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UDK: 61 ISSN 1409-9837 ZAMM MAMM ACTA MORPHOLOGICA PUBLIKACIJA NA ZDRU@ENIETO NA ANATOMI I MORFOLOZI NA MAKEDONIJA PUBLICATION OF MACEDONIAN ASSOCIATION OF ANATOMISTS AND MORPHOLOGISTS Vol.3 (2) 2006 1 ACTA MORPHOLOGICA Medicinsko spisanie na Zdru‘enieto na anatomi i morfoloyi na Makedonija (ZAAM) Izdava~: Instituti-Medicinski fakultet,Skopje Izleguva: Dva pati godi{no Glaven i odgovoren urednik: Dobrila Tosovska Lazarova Redakciski odbor: Kostandina Korneti -Pekevska An|a Strateska -Zafirovska-Zamenik glaven i odgovoren urednik Dobrila Tososka-Lazarova Stojmir Petrov Nata{a Janevska-Na}eva Marija Papazova Julija @ivadinovi}-Bogdanovska-sekretar Vlatko Ilievski Vesna Janevska Nada Miteva Nevena Kostova Tehni~ka redakcija: Julija @ivadinovi}-Bogdanovska Rubens Jovanovi} Elizabeta ^adikovska Pe~ati: Arhiepiskopska pe~atnica “Sinaj” -Skopje Adresa na redakcijata i kontakt: Institut za anatomija, Medicinski fakultet, 50 Divizija 6,Skopje, R.Makedonija Tel/faks:++389 2 3125304 e-mail:acta_morphologica @yahoo.com 2 ACTA MORPHOLOGICA Medical journal of Macedonian Association of Anatomists and Morphologists (MAAM) Publisher: Instituti-Medical Faculty Skopje Published: Twice a year Editor in Chief: Dobrila Tosovska-Lazarova Editorial Committee: Kostandina Korneti-Pekevska Anga Strateska-Zafirovska-Assistant Editor in Chief Dobrila Tosovska-Lazarova Stojmir Petrov Natasha Janevska-Nakeva Julija Zhivadinovik-Bogdanovska-secretary Vlatko Ilievski Vesna Janevska Nada Miteva Nevena Kostova Pre-Press Julija Zhivadinovik-Bogdanovska Rubens Jovanovik Elizabeta Chadikovska Print: Archiepiscopial printing office”Sinaj”-Skopje Corresponding address: Institute ofAnatomy,Medical Faculty,50 Divizija 6,Skopje,R.Macedonija Tel/fax:++389 2 3125304 e-mail:[email protected] 3 SODR@INA 7. BAZI^NI STUDII Crnodrobna arteriska anatomija so pregled na slu~aite sokongenitalna arteriska anastomoza Jurkovi} Dragica 19. Dimenzii na fetalnite bubrezi vo oddelni gestaciski nedeli: Jovevska Svetlana, Matveeva N, @ivadinovi} J, Zafirova B,^adikovska E 22. Anatomski karakteristiki na ostiumot na koronarniot sinus: @ivadinovi} Julija, Lazarova D, Papazova M, Matveeva N, Bojaxieva B, Pavlovski G 25 Plantarni dermatoglifi kaj mladata makedonska populacija od ma{ki pol: ^adikovska Elizabeta, Lazarova D, Na}eva N, Papazova M, Zafirova B, @ivadinovi} J, Bojaxieva B 30 MNSs i Kel krvno grupni sistemi kako genetski markeri kaj ~etiri populacii koi ‘iveat vo Republika Makedonija:Efremovska Qudmila, Nikoloska –Dadi} E, [midt H, [eil H-G 35. 39 46. PRIKAZ NA SLU^AJ Skeletna scintigrafija so 99m Tc Mdp – detekcija na metastatska kalcifikacija: prikaz na slu~aj: Stojanoski Sini{a , Pop \or~eva D, Ristevska - Miceva S, Tripunoski T, [ubevska Stratrova S Tretman na ispadi na n. facialis - liceva simetri~nost vo mir: Tuxarova-\orgova Smiqa, Peneva M, Karaxinova S SPORTSKA MEDICINA Vlijanieto na trena@niot proces vrz telesniot sostav, indeksite na ishranetost i testosteronkortizol odnosot kaj profesionalni fudbaleri: Hanxiski Zoran, Maleska V, Petrovska S, Nikoli} S, Hanxiska E 51. SUDSKA MEDICINA Odreduvawe na vremeto na nastapuvawe na smrtta so Henssge Nomogram: Poposka Verica, Janeska B, Gutevska A, ^akar Z 55. NEVROLOGIJA Korelacija na intrakranijalnata so ekstrakranijalnata karotidna ateroskleroza i ishodot posle mozo~niot udar: Arsovska Anita, Popovski A, Orov~anec N, Vr~akovski M 60. PEDIJATRIJA Evolucija i karakteristiki na raniot pubertet kaj makedonskite devoj~iwa: KrstevskaKonstantinova Marina, Ko~ova M, Gu~ev Z 63. EPIDEMIOLOGIJA Epidemiolo{ka studija za ulogata na pu{eweto, nasledniot faktor i stresot vo nastanuvaweto na belodrobniot i laringealniot karcinom: Pavlovska Irina, Orov~anec N, Stefanovski T, Tau{anova B, Zafirova-Ivanovska B 70. Vlijanie na demografskite karakteristiki za pojava na endometrijalniot kancer vo op{tina Bitola – case-control studija: Adamovska Eleonora, Zafirova B, Adamovski P, ^ipurova E 75. UPATSTVO ZA AVTORITE 80. IZJAVA 4 CONTENT 7. BASIC STUDIES Hepatic Arterial Anatomy with Survey of the Cases With Congenital Arterial Anastomosis: Jurkovik Dragica 19. Dimensions of Fetal Kidneys in Different Gestational Weeks: Jovevska Svetlana, Matveeva N, Zhivadinovik J, Zafirova B, Chadikovska E 22. Anatomic Features of the Ostium of the Coronary Sinus: Zhivadinovik Julija, Lazarova D, Papazova M, Matveeva N, Bojadzhieva B, Pavlovski G 25. Plantar Dermatoglyphics in Young Macedonian Population of Male Gender: Chadikovska Elizabeta, Lazarova D, Nakeva N, Papazova M, Zafirova B, Zhivadinovik J, Bojadzhieva B 30. Mns and Kell Blood Type Systems as Genetical Markers in Four Populations in the Republic of Macedonia: Efremovska Ljudmila, Nikoloska-Dadik E, Schmidt H, Sheil H-G 35. 39. CASE REPORTS Detection of Metastatic Calcification with 99m Tc-Mdp Scintigraphy : Case Report: Stojanoski Sinisha, Pop Gjorceva D, Ristevska - Miceva S, Tripunovski T, Shubevska - Stratrova S Facial Nerve Paralysis Treatment: Facial Symmetry at Rest: Tudzharova-Gjorgova Smilja, Peneva M, Karadzhinova S 46. SPORT MEDICINE The Influence of Training Process on Body Composition, Indexes of Nutrition and Testosterone-Cortisol Ratio in Professional Soccer Players: Handzhiski Zoran, Maleska V, Petrovska S, Nikolik S, Handziska E 51. FORENSIC MEDICINE Estimation of Time Since Death by the Henssge-Nomogram: Poposka Verica, Janeska B, Gutevska A, Chakar Z 55. NEUROLOGY Correlation Between Intracranial and Extracranial Carotid Atherosclerosis and Stroke Outcome: Arsovska Anita, Popovski A, Orovchanec N, Vrchakovski M 60. PEDIATRICS Evolution and Characteristics of Early Puberty in Macedonian Girls: Krstevska-Konstantinova Marina, Kocova M, Gucev Z 63. EPIDEMIOLOGY Epidemiological Study For The Role Of Smoking, Genetic Factor And Stress In Lung And Laryngeal Cancer Occurrence: Pavlovska Irina, Orovchanec N, Stefanovski T, Taushanova B, Zafirova-Ivanovska B 70. The Influence of Demographic Characteristics on The Appearance of Endometrial Cancer in the Municipality of Bitola-Case Control Study: Adamovska Eleonora, Zafirova B, Adamov P 77. INFORMATIONS FOR AUTHORS 80. AN EXCLUSIVE STATEMENT 5 6 Acta morphol.2006; Vol.3(2):7-18 UDK: 611.136.41 CRNODROBNA ARTERISKA ANATOMIJA SO PREGLED NA SLU^AITE SO KONGENITALNA ARTERISKA ANASTOMOZA Jurkovi} Dragica Institut za anatomija, Medicinski fakultet, Skopje, R. Makedonija Izvadok Ovoj trud se bazira na detalnite opservacii od deset akrilni kalapi na elementite od aferentnata crnodrobna petelka, koi imaat za cel da gi utvrdat razli~nite modeli na crnodrobnata arteriska anatomija i soodnosot na crnodrobnite arterii so grankite na portalnata vena. Vo isto vreme, se oceneti pojavuvaweto, mestopolo`bata i morfolo{kite tipovi na kongenitalnite anastomozi pome|u crnodrobnite arterii. Edinstvena posebna crnodrobna arterija e prisutna kaj ~etiri slu~ai. Desna i leva crnodrobna arterija od zamenski tip se prisutni kako oddelni arterii kaj ~etiri slu~ai. Kaj preostanatite dva slu~ai crnodrobnite arterii se injicirani parcijalno, kaj edniot od niv samo desnata crnodrobna arterija, a kaj drugiot samo lateralnata segmentalna arterija. Vo modelot na razgranuvawe od desnata crnodrobna arterija se najdeni pet razli~ni morfolo{ki tipovi, a ~etiri kaj istiot od levata crnodrobna arterija. Arteriskoto snabduvawe na desnoto porcio od opa{kastiot rezen e samo od desniot crnodroben arteriski sistem, a za levoto porcio samo od leviot ili samo od desniot crnodroben arteriski sistem. Opi{an e soodnosot na crnodrobnite arterii so grankite od portalnata vena. Na ispituvanite kalapi kongenitalnite anastomozi pome|u crnodrobnite arterii se pojavuvavaat vo 50 procenti. Anastomozite se obrazuvani bilo pome|u crnodrobnite arteriski granki ili pome|u steblata od arteriite ili pome|u steblata i grankite od arteriite. So izgled na anastomotska arkada najdeni se kaj ~etiri slu~ai, a prav tip kaj eden slu~aj. Site slu~ai so kongenitalni anastomozi, osven eden, se vo vrska so arteriskoto snabduvawe na opa{kastiot rezen i opa{kastiot prodol‘etok. [to se odnesuva do nivnoto razmestuvawe, tie se ekstrahilarno (1 slu~aj), vnatre vo hilusot na crniot drob (2 slu~ai), vo umbilikalnata puknatina (1 slu~aj) i intraparenhimno (1 slu~aj). Samo edna{ e opservirana intraheparna anastomoza od izvitkan tip, pome|u dve arterii {to go snabduvaat medijalniot segment. Smetame deka taa e ste~ena imaj}i ja predvid nejzinata abdominalna patologija. Klu~ni zborovi: crn drob, anatomija, posebna crnodrobna arterija, kongenitalni anastomozi HEPATIC ARTERIAL ANATOMY WITH SURVEY OF THE CASES WITH CONGENITAL ARTERIAL ANASTOMOSIS Jurkovik Dragica Institute of Anatomy, Medical Faculty, Skopje, R. Macedonia Abstract This study is based on detailed observations of ten acrylic casts from the elements of hepatic afferent pedicle, aiming to establish different patterns of hepatic arterial anatomy and relationship of hepatic arteries with portal vein branches. At the same time, incidence, location and morphological types of congenital anastomoses between hepatic arteries were evaluated. A single proper hepatic artery was present in four cases. The right and left hepatic arteries of replacing type were present as separate arteries in four cases. In the remainning two cases hepatic arteries were partly injected; in one of them only a right hepatic artery and in the other only a lateral segmental artery. In the branching pattern of the right hepatic artery, five different morphological types were found and four in the branching pattern of the left hepatic artery. Arterial supply to the right portion of the caudate lobe was only from right hepatic arterial system and to the left portion only from left or only from right hepatic arterial systems. Relationship of hepatic arteries with portal vein branches has been described. Congenital anastomoses between hepatic arteries were noticed with an incidence of 50 per cent on the examined casts. Anastomoses were formed either between the hepatic arterial branches or between the trunks of the arteries, or between the trunks and branches of the arteries. Anastomoses had anastomotic arcade look in four cases and in one case there was straight anastomosis. All cases with congenital anastomoses, except one, were in relation to the arterial supply to the caudate lobe and to the caudate process. As to the their disposition, they were extrahilary (1 case), within the liver hilum (2 cases), in the umbilical fissure (1 case) and intraparenchymatously (1 case). Only once, there was an intrahepatic anastomosis of tortuous type between two arteries that supplied the medial segment. We assume that it was acquired concerning its abdominal pathology. Key words: liver, anatomy, hepatic artery, congenital anastomoses 7 Jurkovik D. Hepatic Arterial Anatomy Introduction Detection of anatomic anomalies in liver circulation, including especially congenital arterial anastomoses, is of essential importance to perform safe resective interventions in abdominal surgery. The authors who studied intraparenchymatous ramification of vasculo-biliary elements of the liver did not notice any anastomoses of sufficient calibre – Goldsmith and Woodburne (1957), Gupta and Gupta (1976), Gupta et al. (1977), Sales et al. (1984) . On the other hand, Matusz and Niculescu (1996) pointed out the presence of intrasegmentary and intersegmentary vascular anastomoses, while according to angiographic study of Ibukuro et al. (2000) congenital anastomoses were always located in hepatic hilus and not in the center of the liver. Material and Methods As a study material we used 10 isolated specimens of human liver from patients died from causes not related to the liver pathology, except for one patient with diagnosis- rectorrhagio. On four specimens the three elements of portal triad – proper hepatic artery, portal vein and biliary duct were injected. In the remainning six specimens only the proper hepatic artery and portal vein were injected. Precise observation of acrylic casts by using a magnifying glass enabled determination of : 1. Intrahepatic branching pattern of proper hepatic artery 2. Relationship of hepatic arteries with portal vein branches 3. Incidence, location and morphological types of congenital anastomoses between hepatic arteries Results and Discussion Proper hepatic artery A single proper hepatic artery which divided into right and left branches was present in four of ten cases. The site of division was always extrahepatic. Van Damme and Bonte (1990) described that the division of the hepatic artery into its right and left hepatic branches may took place at any point between the liver hilum ( porta hepatis ) and the origin of the hepatic artery itself. In the other four cases the proper hepatic artery was absent, the right and left hepatic arteries of replacing type were present as separate arteries. In the remainning two cases hepatic arteries were partly injected; in one of them only a right hepatic artery was found and in the other one only a lateral segmental artery. These vessels are defined as aberrant (substitutive or accessory ) hepatic arteries. From the anatomic point of view, it is correct to define these vessels as ’ accesory ’ when present together with the right and left hepatic arteries or ’ substitutive ’ in the absence of the abovementioned vessels – Guadagni et al. (1995) . We could not determine the origin of proper hepatic artery as well as the origin of the right and left hepatic arteries when they were independent branches since we used fresh, isolated autopsy specimens. Thus, it 8 was impossible to compare our results with the results of other authors presented in the literature – Daseler et al. (1947), Van Damme et al. (1969), Guadagni et al. (1995), Yamashita et al. (1997) and Mc Nulty (2000). Right hepatic artery – branching pattern Analysis of the branching pattern of the right hepatic artery enable description of five morphological types ( table 1 ) . Type I presented a normal branching pattern of the right hepatic artery observed also by Gupta and Gupta (1976) in 76 of cases (89,41%) .However, other morphological types found in our series were not observed in their study. They found that in 7 cases (8,24%) the right hepatic artery gave also origin to a posterior inferior area artery and in 2 cases (2,35%) to an anterior superior area artery. As to the origin of subsegmental arteries, we noticed that posterior segmental artery in all cases of Ist and Vth types had classical division into posterior superior area artery and posterior inferior area artery. In type II the posterior segmental artery gave also origin to its usual branches, but the posterior superior area artery gave origin to a second posterior inferior area artery. In the IIIrd and IVth types of our series both subsegmental arteries were direct branches of the right hepatic artery. Branching of anterior segmental artery into its area arteries, one anterior superior area artery and one anterior inferior area artery, was seen in four cases. Only once this artery gave origin to 4 subsegmental arteries, two anterior inferior area arteries and two anterior superior area arteries. In two cases it was a bouquet of inferior and superior area arteries. In a single case, it firstly gave origin to an anterior inferior area artery and then ended with bouquet of subsegmental arteries. Therefore, the total number of its area arteries ranged from 2 to 4 or it was a bouquet of subsegmental arteries.As shown in Table 1, a second anterior segmental artery originating from posterior segmental artery was present in one case. In addition to usual anterior segmental artery as direct branches of right hepatic artery were seen one anterior superior area artery or one anterior inferior area artery . The right hepatic artery usually gives origin to an extrahepatic branch. This branch was a cystic artery observed in our series in five cases as a branch of a normal or replacing right hepatic artery and in one case as a branch of left hepatic artery anastomosed with branch for caudate lobe originating from the right hepatic artery. Left hepatic artery – branching pattern Analysis of the branching pattern of the left hepatic artery enabled description of four morphological types. As shown in Table 2 a normal branchig pattern of the left hepatic artery ( type I ) was observed in 3 cases of our series, while in that described by Gupta and Gupta ( 1976 ) in 63 cases ( 74,12 % ). The IInd and IIIrd types present in our series, were not observed in their study. In type IV of our series, the medial segment of the liver was supplied from two branches, the first took origin from the proper hepatic artery, while the second Jurkovik D. Hepatic Arterial Anatomy Table 1.Variations in the branching pattern of the right hepatic artery TYPE I II III IV V PATTERN No. of cases 1. posterior segmental artery 2. anterior segmental artery 1. anterior inferior area artery 2. anterior segmental artery 3. posterior segmental artery 1. posterior inferior area artery 2. posterior superior area artery 3. anterior segmental artery 1. anterior superior area artery 2. posterior inferior area artery 3. anterior segmental artery 4. posterior superior area artery 1. anterior segmental artery 2. posterior segmental artery a) anterior segmental artery b) posterior inferior area artery c) posterior superior area artery 4 1 1 1 1 TOTAL 8 Table 2.Variations in the branching pattern of the left hepatic artery TYPE I II III IV PATTERN 1. medial segmental artery 2. lateral segmental artery a) lateral superior area artery b) lateral inferior area artery 1. medial segmental artery 2. lateral inferior area artery a) medial inferior area artery b) lateral superior area artery 1. lateral superior area artery a) lateral inferior area arteries 2. medial segmental artery a) lateral inferior area artery 1. lateral superior area artery a) lateral inferior area artery 2. lateral inferior area artery TOTAL from the anterior segmental artery (Fig.7). According to Gupta and Gupta (1976 ) the medial segmental artery, though in majority of cases arising from the left hepatic artery, as one of its terminal branches, may arise in several other ways and in rare cases it can even arise from one of the segmental arteries of the right hepatic arterial system. There was a single case not classified in any morphological type where a separate left hepatic artery ramified into medial and lateral segmental arteries. But, the lateral segmental artery forming an anastomotic arcade with the branch of anterior segmental artery, gave origin only to arteries for caudate lobe (Fig.3). Couinaud ( 1952 ) noticed four different types in the intrahepatic distribution of the left hepatic artery. As type I he also described a common pattern in which two No. of cases 3 1 1 1 6 branches were present; the first one for segment IV and the second that gave origin to arteries for IInd and IIIrd segments. His type II may be compared with the same type in our classification, while type III corresponded to our type IV. However, as type IV he described cases with abundance of arteries originating from the left gastric artery. Left hepatic artery supplied only segment IV in two cases of this type. As shown in Table 2, the lateral segmental artery in all cases of type I had classical division into lateral superior area artery and lateral inferior area artery. But, in one of them, the origin of accessory lateral superior area artery and lateral inferior area artery before the main division was noticed. In another case, one branch of lateral superior area artery that supplied IIIrd subsegment 9 Jurkovik D. Hepatic Arterial Anatomy Table 3. Variations in the origin of the branches to the caudate lobe No. of case 1 2 3 4 5 site of origin right hepatic artery posterior superior area artery right hepatic artery lateral segmental artery anterior segmental artery left hepatic artery lateral superior area artery right hepatic artery branch of the ant. seg. artery lateral segmental artery right portion No. of branches 1 2 3 * left portion No. of branches 1 2 * * * TOTAL 3 3 * * 3 * * * * * 5 4 * Table 4. Variations in the origin of the branches to the caudate process No. of cases 1 2 3 4 5 6 Site of origin Anterior segmental artery (branch only to the caudate process) 1 Anterior segmental artery (common trunk of the medial segmental artery and branchto the right portion of the caudate lobe and caudate process) 1 Branch to the right portion of the caudate lobe (originating from branch of the anterior segmental artery) 1 Anterior superior area artery 1 Posterior superior area artery (common trunk to the right portion of 1 the caudate lobe and caudate process) Right hepatic artery (branch to the right portion of the caudate lobe) Anastomotic Posterior segmental artery arcade (branch to the caudate process) Right hepatic artery (common trunk of branch to the gallbladder, branchto the left portion and branch to the right portion ofthe caudate lobe and caudate process) descended on the anterior surface of the umbilical part of the left portal vein to give origin firstly to a branch which ran to the right to reach the initial part of an arcuate medial superior portal vein branch, then to the left forked into branch which accompanied one lateral inferior portal vein branch originating from the anterior surface of abovementioned branch and branch which ended near the right horn of recess of Rex from there arose one medial inferior portal vein branch tended to left. In spite of their extension none of these branches crossed over the intersegmental fissure between the medial and lateral segments of the liver because the fissure itself lied next to the right border of the umbilical part of the left portal vein. In the IInd and IIIrd types, one of the left subsegmental arteries arose directly from the left hepatic artery together with the medial segmental artery. In type II, there was one lateral inferior area artery which gave origin firstly to one medial inferior area artery and then to one ascendant branch from which one small lateral inferior area artery took origin and crossed on the anterior surface 10 No. of branches 2 4 1 of umbilical part of the left portal vein branch. It continued as a lateral superior area artery. The intersegmental fissure lied obliquely from left to right, at the level of the umbilical part of the left portal vein. In type III there was a lateral superior area artery which gave origin to two lateral inferior area arteries. Both of them were left to the umbilical part of the left portal vein branch, but one branch derived from the first one passed on the anterior surface of the umbilical part of the left portal vein and its terminal branches accompanied two lateral inferior portal vein branches. The terminal part of this branch also accompanied one lateral inferior portal vein branch, which arose from the right horn of recess of Rex tended to left. The second branch was arcuate. In the same case one collateral branch of lateral superior area artery descended as lateral inferior branch which crossed over the plane of the left portal fissure (Fig.8). In type IV, both subsegmental arteries arose directly from the left hepatic artery. But, one accessory lateral inferior area artery originated from the lateral Jurkovik D. Hepatic Arterial Anatomy Fig. 1. Anastomotic arcade below the liver hilum (arrows); lateral inferior area artery and its collateral branches (arrows); horizontaly situated semicircle Fig. 2. Anastomotic arcade within the liver hilum (arrows) Fig. 3. Anastomosis of straight type and vascular reticle within the liver hilum (arrow); arterial-venous anastomosis (arrows) Fig. 4. Anastomotic arcade and vascular reticle in the umbilical fissure (arrow) Fig.5. Portal and hepatic arterial reticles within the liver hilum (arrows); vertically situated semicircle between two medial inferior area arteries (arrows) Fig. 6. Anastomotic arcade rounds initial part of the posterior superior portal vein branch (arrows) 11 Jurkovik D. Hepatic Arterial Anatomy Fig. 7. Intrahepatic anastomosis of tortuous type between arteries that supply the medial segment (right hepatic artery and medial segmental arteries are marked with arrows); portal vascular net which accompanies subsegmental hepatic arteries (arrows); lateral inferior area artery on the posterior surface of the umbilical part of the left portal vein branch (arrow) Fig. 8. Lateral superior area artery gives origin to two lateral inferior area arteries (arrows) and to the branch which crosses over the plane of the left portal fissure (marked with grosser arrow) superior area artery. This branch coursed obliquely on the anterior surface of the umbilical part of the left portal vein branch and gave origin firstly to a collateral branch that ramified left to the mentioned portal branch and then to a branch that ramified to the right on its anterior surface . Its terminal branches accompanied two portal vein branches, which arose from the right horn of recess of Rex but, supplied IIIrd subsegment. This case was important from the portal vein circulation point of view since there were no main portal vein stems for IInd and IIIrd subsegments and for left portion of the caudate lobe except those arising from the right horn and all collateral accompanying portal vein branches arose from the portal vascular reticle which accompanied hepatic arteries for these subsegments (Fig.7). The lateral superior area artery was a long single branch in four cases or short and bifurcated in two cases and only once it was double. As a unique case it arose from the lateral inferior area artery as a long ascendant and terminaly bifurcated branch (Fig.1). The lateral inferior area artery was seen as a long single branch which forked along the portal vein branch for subsegment III in four cases. In two cases the forking was along the left side of the umbilical part of the left portal vein branch. Only once it was on the posterior surface of this portal vein branch. The accessory lateral inferior area artery originating from lateral superior area artery was seen as running obliquely from left to right on the anterior surface of the umbilical part of the left portal vein branch in two cases. In other two cases, one arcuate accessory branch descended on this surface. Finally, two accessory lateral inferior area arteries were seen left to the umbilical part of the left portal vein branc , the first descendent and the second arcuate in another case. The medial segmental artery as a single trunk took origin from the left hepatic artery in six cases. In one case it was double originating from the proper hepatic artery and anterior segmental artery. This segmental artery gave origin to medial superior area arteries and medial inferior area arteries in 4 cases and only to medial inferior area arteries in 3 cases. Only one case had accessory medial inferior area artery originating from the lateral inferior area artery (Fig.1). Analysis of the branching pattern of the medial segmental artery enabled description of the following four morphological types : 1. A separate origin of one medial superior and three medial inferior area arteries was seen in one case. In this kind of division, one arcuate superior area artery arose near the angle of the left portal vein branch and 3 medial inferior area arteries arose near the right horn of recess of Rex. One of inferior area arteries coursed to right to the main medial inferior portal vein branch, which arose from the right horn of recess of Rex. The remainning two arteries descended parallely and an oblique portal vein branch originating from the right horn of recess of Rex passed between them. 2. A separate origin of one medial superior area artery and mutual origin of medial inferior area arteries which gave origin to one medial superior area artery was seen in two cases. In the first case, the medial superior area artery arose near the angle of the left portal vein branch and bifurcated into one arcuate medial superior branch and one branch that passed on the anterior surface of the angle. Two medial inferior area arteries took origin from mutual site by one short medial superior branch next to the right border of the umbilical part of the left portal vein branch. 12 Jurkovik D. Hepatic Arterial Anatomy In the second case, medial superior area artery took origin from the medial segmental artery under the part transverse of the left portal vein branch and then passed anteriorly to it to accompany an arcuate medial superior portal vein branch. Three medial inferior area arteries arose from mutual site near the angle of the left portal vein branch. Two of them accompanied portal vein branches, which arose from the right border and right horn of umbilical part of the left portal vein branch, while the third branch ramified into one arcuate medial superior area artery and one medial inferior area artery that passed on the anterior surface of the umbilical part of the left portal vein branch and gave origin to a branch, which accompanied one portal vein branch originating from the right horn of recess of Rex. This case had one accessory medial inferior area artery from lateral inferior area artery, which gave origin to collateral branch and then forked. The two terminal branches and collateral branch crossed between initial part of portal vein branches that arose from the right horn of recess of Rex. Also, the trunk of medial segmental artery with the trunk of lateral inferior area artery formed crossing as horisontally situated semicircle (Fig.1). 3. A common origin of one medial inferior area artery and common stem of one medial superior and one medial inferior area arteries was seen in one case. Both medial inferior area arteries descended and passed one anteriorly and the other posteriorly to medial inferior portal vein branch. At the level of this branch they crossed and their proximal parts formed one vertically situated semicircle. One arcuate medial superior portal vein branch passed through this semicircle and was accompanied by medial superior area artery, which crossed posteriorly from left to right (Fig.5). 4. A common origin of two medial inferior area arteries from the medial segmental artery was seen in three cases. In the first case, both medial inferior area arteries descended and formed crossing above the main medial inferior portal vein branch originating from the right horn of recess of Rex.The crossing was like vertically situated semicircle through which one small direct portal vein branch passed. The distal part of the first medial inferior area artery accompanied anteriorly and to right main medial inferior portal vein branch, while the second branch bifurcated and its terminal branches coursed posteriorly to it. From one of them one ascendent branch ramified and coursed until the centre of recess of Rex (Fig.2). In the second case, two medial segmental arteries had different origin; one from the proper hepatic artery and the other from the anterior segmental artery.They anastomosed and from there one common trunk descended, which gave origin to two divergent medial inferior area arteries .The trunk of afferent medial segmental arteries with three crossings created three semicircles before their joining like triangle (Fig.7). In the third case, medial segmental artery gave origin to two medial inferior area arteries which coursed parallely and ended by bifurcation (Fig.4). Branches to the caudate lobe Our analysis of the arterial supply to the right and left portions of caudate lobe was performed in five cases ( Table 3 ). According to Gupta and Gupta (1976) the right portion of the caudate lobe was supplied by the right hepatic arterial system in 51 cases (60 %) and by the left hepatic arterial system in 34 cases (40%); the left portion of the caudate lobe received its arterial blood from the left hepatic arterial system in 78 cases ( 91,77%) and from the right hepatic arterial system in 7 cases ( 8,23% ) . This is not in agreement with our results, which suggest that the arterial supply to the right portion of the caudate lobe was only from the right hepatic arterial system, and to the left portion only from the left or only from the right hepatic arterial systems. Couinaud (1952) also stated that the arteries of the caudate lobe took origin from the left and right hepatic arteries as two or three small posterior trunks , but most frequently they arose from an anastomotic arcade formed between the left hepatic artery or one of its branches and right hepatic artery. Such manner of arterial supply to the caudate lobe was observed in one of our specimens in which an anastomotic arcade was formed between lateral segmental artery and branch of anterior segmental artery. It was located anteriorly to the part transverse of the left portal vein branch. The other question is whether the arterial supply to the caudate lobe has been unilateral or bilateral in each separate specimen. Goldsmith and Woodburne (1957) described that arteries and ducts may also be derived bilaterally from the right and left branches of each system in a manner that is comparable to the portal vein branches of the caudate lobe. From the previous investigations of portal vein circulation to the caudate lobe – Couinaud (1952), Jurkovik (1994), it may be concluded that when portal vein bifurcation was located in the right part of the hilum the branches to the caudate lobe took origin unilaterally from the left poratal vein branch, but when it was in the middle part of the hilum the branches to the caudate lobe took origin bilaterally from the left and right portal vein branches. However, the companion arterial vessels as may be concluded from this study, took origin unilaterally only from the right hepatic arterial system (two cases) or bilaterally from the right and left hepatic arterial systems (three cases) . Couinaud (1952) noticed also that one branch always originated from the right hepatic artery and that the arterial bifurcation was always to the left. Arterial supply of the caudate process The arterial supply of the caudate process was investigated in six cases. As it may be concluded from Table 4, it was separate only in one case and in relation with arterial supply of the right portion; right and left portions; right portion of the caudate lobe and medial 13 Jurkovik D. Hepatic Arterial Anatomy segment of the liver; right and left portions of the caudate lobe and gallbladder in all remaining specimens. Relationship of hepatic arteries with portal vein branches Relationship of hepatic arteries whit portal vein branches was determined by the pattern and site of ramification of the hepatic arteries itself. On the studied material, the right hepatic artery was inferior to the right portal vein branch in almost all cases (eight out of ten). But, in one of them, the initial part of this artery was tortuous and posterior to the left portal vein branch (Fig.7). The division of the right hepatic artery into anterior and posterior segmental arteries always went before the right portal vein branch divides into its segmental branches. Thus, in their course segmental hepatic arteries usually crossed from inferior to anterior to the accompanyuing portal vein branches. As to the anterior segmental artery, it passed anterior to the anterior portal vein branch in 3 cases, in other 3 cases it was on the left side of this branch and only once it was inferior to it. In one case that almost had no right portal vein branch, anterior segmental artery entirely ascended and terminaly ramified right to the portal trunk (Fig.3). In a single case with a second anterior segmental artery, the main segmental artery was on the left side of the anterior portal vein branch while the second originating from the posterior segmental artery on the right. When anterior superior area artery was the first and direct branch of the right hepatic artery it coursed anteriorly to the right portal vein branch. Also , when anterior inferior area artery arose directly from the right hepatic artery it descended left to the companion anterior inferior portal vein branch. Anterior superior area arteries usually reached left side of the companion portal vein branches in cases in which they were present in a total number of two. In a single case, one anterior superior area artery crossed posterior portal vein branch anteriorly to continue right to the anterior superior portal vein branch. Its terminal branches accompanied that branch like’V’ one anteriorly and the other posteriorly. Anterior superior area artery which crossed companion portal vein branch obliquely and anterior from the left to the right was encountered in one case. In two cases, anterior superior area arteries formed a bouquet of terminal branches; most of them coursed left to the subsegmental portal vein branches and rarely superior or inferior to it. Anterior inferior area arteries were seen as short bifurcated or single long branches. One single anterior inferior area artery was observed inferior to the anterior inferior portal vein branch; two left to the companion portal vein branches; two bifurcated and crossed with potral vein branches anteriorly or posteriorly; two ramified and their collateral branches ranged in number from 3 to 8 coursing to the right,to the left, anterior or superior to the companion portal vein branches. In cases with terminal bouquet of 14 ramification of anterior segmental artery in one case two anterior inferior area arteries were seen right to the portal vein branches and in another one two anterior and two left to it. The posterior segmental artery as we could determine coursed from the inferior to the anterior to the short posterior portal vein branch and there ramified into its terminal branches, the posterior superior and posterior inferior area arteries in one case. In three cases this artery lied and terminaly divided inferior to the posterior portal vein branch. But, in one of them there was no right portal vein branch. When the posterior portal vein branch was absent, the posterior segmental artery coursed and divided into its terminal branches inferior to the right portal vein branch. As to the posterior superior area artery, in all cases with present artery it was unique long branch always ending with bifurcation. In three cases, it coursed from inferior to anterior to the posterior superior portal vein branch, while one of its terminal branches coursed to the left and one anterior and right to it. In other two cases, it crossed anteriorly and obliquely to the posterior portal vein branch. From there, it ascended left to the posterior superior portal vein branch in one of them, while in another case it firstly gave origin to a second posterior inferior area artery and then ascended anterior to the posterior superior portal vein branch until its bifircation. As a direct branch derived from the right hepatic artery, posterior superior area artery crossed firstly anterior to the posterior inferior portal vein branch and then anterior to the posterior superior portal vein branch to reach its left side where it forked into two branches. One of them continued left to the portal stem and another crossed anterior and right to it. In another case, as a direct branch of the right hepatic artery it ascended anteriorly to the right portal vein branch and then continued to the right above the posterior portal vein branch. From there it ascended left to the posterior superior portal vein branch. The terminal branches of the posterior superior area artery were very constant. One of them always continued main stem to the left and the other to the right to cross anteriorly to the posterior superior portal vein branches. The collateral branches of this subsegmental artery crossed to the right anterosuperiorly and to the left inferiorly to the companion portal vein branches. The posterior inferior area artery was a unique branch in all cases with present artery but there was one in which a second artery originating from the posterior superior area artery was seen. As a long branch it coursed on the left side of the posterior inferior portal vein branch in two cases; on the anterior surface of the same branch in one case and once it crossed the initial part of this vein and continued superior to it. In two cases, it was shorter than the companion portal vein branch and on its anterior surface terminaly bifurcated into two long branches. Jurkovik D. Hepatic Arterial Anatomy In the case with two posterior inferior area arteries, one was on the left side while the other on the anterior side of the posterior inferior portal vein branch. At the level of terminal branches, a spiral crossing of two arterial branches was noticed, the first posterior and the second anterior to the anterior inferior portal vein branch, both tended from the left to the right in one case. Accordingly, the usual topography of hepatic arteries in the right lobe of the liver in relation to the portal vein branches was inside it. The left hepatic artery (as a branch of proper hepatic artery or as a single artery) coursed inferior to the part transverse of the left portal vein branch in three cases. In only one specimen, it crossed from inferior to posterior to the above-mentioned portal vein branch, and in another one strictly posterior to it. In the remaining specimens, the left hepatic artery was very short or absent. The division into its segmental branches was in 3 cases inferior and in 2 cases posterior to the part transverse of the left portal vein branch at a different point between forking of the portal trunk and angle of the left portal vein branch. It was situated on the posterior surface of the angle of this branch in two cases. The medial segmental artery as a long tortuous or arcuate trunk arising from the different site of division coursed in 4 cases inferiorly to the part transverse of the left portal vein branch, to reach the right side of the umbilical part of the same branch. In one case as a short straight trunk, it descended posterior to it. This artery as a short tortuous trunk coursed posteriorly to the angle of the left portal vein branch in two cases. In its further course, it also reached the right side of the umbilical part of the left portal vein branch. Crossing of this artery with other arterial trunks was clinicaly important relation. In the case with two afferent medial segmental arteries, the first of them originating from the anterior segmental artery firstly crossed twice the trunk of the right hepatic artery, which was tortuous and formed two conversely posed semicircles.This branch then continued to the left and anterior to the left hepatic artery and with the trunk of the right hepatic artery it formed one triangle. Finaly, with other medial segmental artery originating from the proper hepatic artery that was tortuous, formed three semicircles and one very small triangle (Fig.7). In another case, the trunk of medial segmental artery was arcuate and above the trunk of lateral inferior area artery, which as a direct branch from the left hepatic artery coursed obliquely to the left and posterior to the umbilical part of the left portal vein branch. So, they crossed and formed one horizontaly situated semicircle (Fig.1). The subsegmental arteries may be derived into medial superior and medial inferior area arteries. The medial superior area arteries consisted of branches, which arose directly from the medial segmental artery or from the one of medial inferior area arteries.They were arcuate branches, which ran to the right and then rounded the part transverse of the left portal vein branch from the inferior to the anterior. In two cases, such arcuate branch was seen on the anterior surface of the umbilical part of the left portal vein branch as a branch of common trunk with medial superior or medial inferior area arteries. The medial inferior area arteries arose as group of branches, at different level along the right border or right horn of the umbilical part of the left portal vein branch. One of them usually coursed to the right to accompany the main medial inferior portal vein branch which arose from the right horn of recess of Rex. When this artery took origin at the level higher than the right horn of recess of Rex, its initial part turned over certain portal vein branch and then continued to the right to reach main medial inferior portal vein branch. At this level, it crossed with other medial inferior area artery and formed vertically situated semicircle.The other medial inferior area arteries descended almost parallely but separated with portal vein branches, which arose from the right horn of recess of Rex. Most of them ended by bifurcation.Only in one case, a medial inferior area artery on the anterior surface of umbilical part of the left portal vein branch was seen. At the level of terminal branches, a spiral crossing of an arterial branch from the right to the left anteriorly to the branch of medial inferior portal vein branch was noticed. The lateral segmental artery was observed in five cases. In three of them, it crossed obliquely or trasversely posterior to the angle of the left portal vein branch. In a single case, this artery passed obliquely and posterior to the part transverse of the left portal vein branch. Once it was seen as arising anteriorly to the mentioned portal vein branch. The site of division into its subsegmental branches was found left to the angle of the left portal vein branch, more exactly above the initial portion of the portal vein branch for subsegment II in 3 cases. In this way of division, the lateral superior area artery always coursed superiorly to the mentioned branch for subsegment II, while the lateral inferior area artery crossed it anteriorly and passed by the left side of the umbilical part of the left portal vein branch.From there, the lateral inferior area artery ran superiorly to the portal vein branch for subsegment III. The site of division was on the posterior side of the angle of the left portal vein branch only once. Then the lateral superior area artery turned over the angle from the posterior to the anterior while the lateral inferior area artery crossed it obliquely and posteriorly to reach the left side of umbilical part of the left portal vein branch. In this case, one accessory lateral inferior area artery originating from the lateral superior area artery descended on the anterior surface of the umbilical part of the left portal vein branch and at a level of angle it crossed the trunk of the lateral inferior area artery like ’X’. Thus, at the same time, the lateral inferior area arteries on both surfaces of the umbilical part of left portal vein branch were present. When the lateral segmental artery was absent, the lateral inferior area artery originated from the medial segmental artery (type III) or from the left hepatic artery 15 Jurkovik D. Hepatic Arterial Anatomy (IInd and IVth types); it crossed the umbilical part of the left portal vein branch obliquely and posteriorly (Fig.1 and Fig.7). In type III, one of the accessory lateral inferior area arteries descended anterior to the lateral inferior portal vein branch and main lateral inferior area artery and formed with them one crossing like ’ X’. At the same time, one collateral branch from this artery passed on the anterior surface of the umbilical part of the left portal vein branch, in spite of main lateral inferior area artery that was on the posterior surface. In type II, the lateral inferior and medial inferior area arteries on the anterior surface of the umbilical part of left portal vein branch were present. In type IV, the crossing like ’X’ of main lateral inferior area artery by accessory lateral inferior area artery that descended on the anterior surface of umbilical part of the left portal vein branch was seen. In a single case, on the anterior surface of this branch one accessory lateral inferior area artery and one medial superior area artery were seen. There was one rare case where parallel to the main lateral inferior area artery, one collateral branch from other lateral inferior area artery coursed above the lateral inferior portal vein branch and then passed the main artery posteriorly and the other lateral branch anteriorly. Another special case presented with the origin of one lateral superior area artery from the lateral inferior area artery ( type II) where it rised the left side of the umbilical part of the left portal vein branch anterior to its collateral branches. This artery was also seen as passed anterior or posterior to the companion portal vein branch and only once there were two divergent lateral superior area arteries. Collateral branches which in turn arose from the subsegmental arteries coursed superior or inferior to the companion portal vein branches. In the examined material, as shown in Table 3, the branches to the caudate lobe arose from the right hepatic artery in 3 cases. They crossed from the right to the left anterior to the part transvrese of the left portal vein branch in two cases and posterior to it in one case.These branches then rised to accompany the portal vein branches to caudate lobe originating from the part transverse of the left portal vein branch. In one of them, one branch crossed anterior to the right portal vein branch to reach the portal vein branch to caudate lobe originating from the right portal vein branch. Arterial branches to the caudate lobe in two cases originated from the anterior segmental artery. In one of them, one arterial branch ascended anterior to the right poratl vein branch, while in the other case it crossed transversely anterior to the portal trunk and then obliquely on the anterior surface of the part transverse of the left portal vein branch to form anstomotic arcade by lateral segmental artery. Only once two branches took origin from the posterior superior area artery. One of them originating from the initial part of this artery coursed obliquely to the left, anterior to the right portal vein branch. The second branch ramified above the right portal vein branch. 16 We found branches to the caudate lobe that supplied the left portion of the caudate lobe as branches of the lateral segmental artery in two cases. These branches crossed anterior or posterior to the part transverse of the left portal vein branch. In only one case, the branches arose from the left hepatic artery and lateral superior area artery and crossed posterior to the above mentioned portal vein branch. Incidence, location and morphological types of congenital anastomoses between hepatic arteries Congenital anastomoses between hepatic arteries were noticed with an incidence of 50 per cent (5 cases ) of the total number of arteries ( ten ) on the examined casts. According to Ibukuro et al. ( 2000 ) there are two types of location for anastomoses : between the hepatic artery branches and between the trunk of the arteries. Also, anastomoses can appear either as straight or tortuous. In our material the anastomoses were formed either between the hepatic artery branches or between the trunk of the arteries, or between the trunk and branches of arteries. An anastomotic arcade which joined the cystic artery originating from the left hepatic artery and branch to the caudate lobe deriving from the right hepatic artery was located below the liver hilum in one case. This arcade gave origin to a small branch which supplied the right part of biliary fossa and proximal portion of anterior inferior subsegment- V(Fig.1). The terminal branches of cystic artery and anastomotic arcade were accompanied by one subvesical hepato-radicular duct that drained bile from surface of the gallbladder, right half of its fossa and parenchyma of proximal portion of anterior inferior subsegment directly into the posterior segmental ductJurkovik (2002). In other two cases such anastomotic arcades were located within the liver hilum, but extrahepaticaly. The first case presented an anastomotic arcade formed between the branch to the right portion of caudate lobe originating from the right hepatic artery and branch to the caudate process which arose from the posterior segmental artery. It was located posteriorly and all around the portal trunks in the liver hilum. Along this arcade, four collateral branches originated and supplied caudate process. The longest of them was accompanied by portal vein branch and biliary duct. This biliary duct was beginning to an accessory hepatic duct from the right lobe that entered the right side of the common hepatic duct (Fig.2). In the second case, anastomotic arcade joined one branch of anterior segmental artery and the trunk of lateral segmental artery. It was located on the anterior surface of the part transverse of the left portal vein branch. Strictly, it was one straight anastomosis above its superior border. At the same time, this arcade presented unique origin for arteries that supplied caudate lobe including caudate process and for several small collaterals which formed an anastomotic vascular reticle (Fig.3). Jurkovik D. Hepatic Arterial Anatomy According to Couinaud (1952) these small branches were destined to great biliary ducts of the liver hilum which formed second anastomotic juxta-biliary way. In addition to this case, one A-V anastomosis was noticed. It transversely joined the portal vein branch to the left portion of caudate lobe, which arose from the part transverse of the left portal vein branch and hepatic artery branch originating from the lateral segmental artery (Fig.3). In another case, anastomotic arcade and vascular reticle were formed between the trunk of medial segmental artery and lateral inferior area artery. There were located on the posterior surface of umbilical part of the left portal vein branch that corresponded to umbilical fissure (Fig.4). In a single case with intrahilar location one portal and one hepatic arterial reticle were seen. They were formed between two hepatic artery branches that supplied left portion of the caudate lobe, one from the right hepatic artery and the other from the posterior superior area artery, accompanied by stems and reticle of portal vein branches that arose from the part transverse of the left portal vein branch. It was located on the anterior surface of part transverse of the left portal vein branch (Fig.5). In the same case, an anastomotic arcade was formed between two branches that arose from the posterior superior area artery. One of them firstly gave origin to the branches that supplied right portion of caudate lobe and caudate process and then anastomosed with the second branch. Both branches rounded initial part of the posterior superior portal vein branch. Therefore, the arcade was probably disposed in the liver parenchyma next to the right part of the liver hilum. This anastomotic arcade gave origin to the branches, which formed vascular reticle along the terminal branches of the right portal vein branch (Fig.6). An intrahepatic anastomosis was observed in one case between arteries that supplied the medial segment of the liver. One of them arose directly from the proper hepatic artery while the second from the branch to caudate lobe arising from the anterior segmental artery. Both had long tortuous courses before their joining , which was previously described (Fig.7). Anastomoses between hepatic arteries may be with appearance of an anastomotic arcade which gave origin to collateral branches that supplied some part of the liver (4 cases), as straight type ( 1 case) or as tortuous type (1 case). As to the their disposition they were extrahilary (1 case), within the liver hilum (2 cases), in the umbilical fissure (1 case) and intraparenchymatously (2 cases). The anastomotic arcades gave origin to the collateral branches that formed periportal vascular reticle which may be in the liver parenchyma, in the umbilical fissure or within the liver hilum. The branches that supplied one structural unit of the liver parenchyma may anastomose in its parenchyma. Consequently, the four cases which had extrahepaticaly located anastomotic arcade (below or in the liver hilum or in the umbilical fissure) presented congenital anstomoses. From the cases with intrahepatic anastomoses one of them also presented congenital anastomosis, while the other was acquired concerning its abdominal pathology. All cases with congenital anastomoses, except one, were in relation with arterial supply to the caudate lobe and to the caudate process.The collaterals of hepatic arteries formed periportal vascular reticle. Contrary to this, Ibukuro et al. (2000) encountered ten patients with congenital anastomoses between hepatic arteries who underwent hepatic artery angiography for evaluation of hepatocellular carcinoma. The anastomoses shown in their study were only demonstrated in the patients who had replaced right hepatic artery from superior mesenteric artery and middle hepatic artery (A4) or left hepatic artery. Furthermore, the anastomoses were thick and there was one artery in each patient and always located at the hepatic hilum, not in the center of the liver.In their opinion these anastomoses were congenital. The diameter of the anastomoses was larger than that of the acquired anastomoses which were fine and numerous. Van Damme and Bonte (1990) stated that after ligation of the hepatic artery, two kinds of collaterals develop – collaterals in the liver hilum and extrahepatic collaterals. Conclusion The intrahepatic branching pattern of proper hepatic artery allows description of different morphological types at the level of its two terminal branches. Relationship of hepatic arteries with portal vein branches is determined by the pattern and site of ramification of the hepatic arteries. Congenital anastomoses between hepatic arteries may appear as anastomotic arcade or as straight type, while the acquired ones as tortuous type. References 1. 2. 3. 4. Goldsmith NA, Woodburne RT. The surgical anatomy pertaining to liver resection. Surg Gynecol Obstet 1957; 105: 310-18. Gupta CD, Gupta SC. Evaluation of intrahepatic arterial branching patterns in corrosion casts. J Anat 1976; 122(1): 31-41. Gupta SC, Gupta CD, Arora AK. Subsegmentation of the human liver. J Anat 1977; 124(2): 413-23. Sales JP, Hannoun L, Sichez JP, Honiger J, Levy E. Surgical anatomy of liver segment IV. Anat Clin 1984; 6: 295-304. 17 Jurkovik D. Hepatic Arterial Anatomy 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 18 Matusz P, Niculescu V. The content of hepatic fissures- A study on corrosion pieces. Folia anatomica 1996; vol.24, suppl.2: 94, Book of Abstracts of 24 Congress of YAA with international participants, Novi Sad (Abstr.). Ibukuro K, Tsukiyama T, Mori K, Inoue Y. The congenital anastomoses between hepatic arteries: angiographic appearance. Surg Radiol Anat 2000; 22: 41-5. Van Damme JP, Bonte J. Vascular anatomy in abdominal surgery. Stuttgart, New Jork; Thieme, Medical Publishers, Inc, 1990: 7-20. Guadagni S, Gola P, Marsili L, Catarci M, Mancini E, Agnifili A, De Bernardinis G, Sano T, Maruyama K. Arterial vasculature of the stomach and oncologic gastrectomies. Surg Radiol Anat 1995; 17: 269-76. Daseler EH, Anson BJ, Hambley WC, Reimann AF. The cystic artery and constituents of the hepatic pedicle: A study of 500 specimens. Surg Gynecol Obstet 1947; 85(1): 47-63. Van Damme JP, Bonte J, Van der Schueren G. A revaluation of hepatic and cystic arteries: the importance of the aberrant hepatic branches. Acta Anat 1969; 73: 192-209. Yamashita N, Ito M, Tachibana K, Tsujita N. Some variations in branching of the celiac trunk. Mak med pregled 1997; 51(5-6): 156-61. Mc Nulty JG. Total anomalous arterial supply to the liver and gallbladder from the gastroduodenal artery: a case report. Surg Radiol Anat 2000; 22: 123-4. Couinaud C. Hepatectomies gauches lobaires et segmentaires (Etude des conditions anatomiques). J Chir 1952; 68(11): 697-715. Jurkovik MD. Determination of portal vascular segmentation in liver. Master’s thesis; Skopje, 1994. Jurkovik MD. The biliary drainage of the liver- A case report of an accessory bile duct. Mak med pregled 2002; 1-2: 76-9. Acta morphol.2006; Vol.3(2):19-21 UDK: 611.61.061 - 053.13 DIMENZII NA FETALNITE BUBREZI VO ODDELNI GESTACISKI NEDELI Jovevska Svetlana, Matveeva N, @ivadinovi} J, Zafirova B,^adikovska E, Institut za anatomija, Medicinski fakultet, Skopje, R. Makedonija Izvadok Dimenziite na fetalniot bubreg poka`uvaat brojni varijacii koi zavisat od polot, vozrasta, telesnata konstitucija, fiziolo{kata sostojba na bubregot i patolo{kite promeni na negoviot parenhim. Razvojot na ~ove~kiot fetalen bubreg minuva niz serija od kontinuirani i me|usebno zavisni promeni vo koj period bubregot ja zadr`uva svojata morfolo{ka i funkcionalna zrelost. Ova istra`uvawe ima za cel da gi proceni promenite vo goleminata na bubregot za vreme na periodot na razvojot na fetusot od 15-ta do 25-ta gestaciska nedela i da se presmeta dinamikata na rastot. Vrednostite na bubre`nite dimenzii na leviot i desniot bubreg vo odnos na gestaciskata starost bea odredeni kaj 120 fetusi (70 ma{ki i 50 `enski )koj bea podeleni vo ~etiri grupi. Podatocite bea statisti~ki obraboteni.Pri toa bea koristeni statisti~kite metodi: analiza na varijansa (ANOVA) kako i neparametarskiot Mann-Whitney U Test. Za statisti~kata obrabotka koristena e kompjuterskata programa STATISTIKA VERSION 7. Vrednostite p < 0.05 se smetaat za signifikantni (c), p < 0.001 za zna~ajno signifikantni i p > 0.05 za nesignifikantni. Klu~ni zborovi: fetus, gestaciska starost, bubreg DIMENSIONS OF FETAL KIDNEYS IN DIFFERENT GESTATIONAL WEEKS Jovevska Svetlana, Matveeva N, Zhivadinovik J, Zafirova B, Chadikovska E Institute of Anatomy, Medical Faculty, Skopje, R.Macedonia Abstract Dimensions of the fetal kidney demonstrate numerous variations that depend on the gender, age, body constitution, physiological condition of the kidney and pathological changes of its parenchyma. Development of the human fetal kidney runs through a series of continual mutually dependent changes during which the kidney obtains its morphological and functional maturity. The aim of this study was to estimate the changes in kidney size during gestation in fetuses from 15 to 25 gestational weeks and to evaluate he dynamics of kidney growth. Kidney dimensions in relation to gestational age, were determined in 120 preterm infants (70 males and 50 females). They were divided in four groups. The results were statistically analyzed. Analysis of variance (ANOVA) and Mann-Whitney U Test were applied. Statistical analysis was done by using the computer program STATISTICA VERSION 7. Key wards: fetus, gestational age, kidney Introduction Owing to the progress in diagnostics, our picture of the development of the fetus continually changes. It can be seen that the development of a fetus is not just a proportional growth of its organs, but each period in a fetus life has specific features and differences (Kurjak et al;1991). The identification of one or both kidneys is possible in 90% of cases in the 17th week of gestation and in 95% of cases after the 20th week (Lawson et al.,1981). However, advanced echosonographic techniques have enabled the study of fetal kidney development in early gestation, which is possible as early as in 12th gestational week (Zalel et al., 2002). Renal abnormalities are not uncommon in fetal life. Polyctic kidneys, fetal hydronefrosis, dysplasia, hypoplasia and other anomalies can by established by prenatal ultrasound. For some lethal anomalies, like polycystic kidney, renal dysplasia or bilateral renal agenesis, termination of the pregnancy may be the appropriate choice. Thus, it is very important to know the normal values of fetal kidney dimensions during each period of gestation. The aim of this study was to establish the average values of the dimensions of fetal kidneys and to evaluate the dynamics of their growth. Material and Methods Material for this investigation was obtained from the collection of the Institute of Anatomy, Medical FacultySkopje and it contained 120 fetuses of both sexes (70 males and 50 females) with gestational ages from 12 to 25 weeks. Fetuses were divided into four groups: Group I, with gestational age from 15-18 weeks (38 fetuses) Group II, with gestational age from 19-21 weeks (30 fetuses) Group III, with gestational age from 22-23 weeks (35 fetuses) Group IV, with gestational age from 24-25 weeks (17 fetuses) Fetuses with congenital anomalies were included in the research. Gestational age was determined as by last menstrual cycle. Macroscopic examinations were made 19 Jovevska S et al. Dimensions of Fetal Kidneys in Different Gestational Weeks in the laboratory of the Institute of Anatomy. Fetal dimensions (length, width and anteroposterior diameter) were measured by using ruler.The parametars were statistically processed by using statistical methods: analysis of variance (ANOVA) and Mann-Whitney U Test. Results The following results were obtained from the measurments: GN 15-18 19-21 22-23 24-25 All groups N 38 30 35 17 Left kidney length mean SD min 1.29 0.22 1.0 1.97 0.18 1.8 2.48 0.10 2.4 2.87 0.10 2.8 max 1.6 2.2 2.6 3.0 mean 1.32 1.99 2.50 2.91 Right kidney length SD min max 0.22 1.0 1.7 0.18 1.8 2.3 0.11 2.4 2.7 0.11 2.8 3.1 120 2.04 3.0 2.06 0.60 ANOVA GN 15-18 19-21 22-23 24-25 All groups F = 474.07 N 15-18 19-21 22-23 24-25 All groups ANOVA 1.0 p = 0.0001; F = 442.0 1.0 3.1 p = 0.0001 38 30 35 17 Left kidney width mean SD min 0.65 0.11 0.5 0.99 0.09 0.9 1.24 0.05 1.2 1.43 0.05 1.4 max 0.8 1.1 1.3 1.5 mean 0.67 1.0 1.25 1.46 Right kidney width SD min max 0.11 0.5 0.9 0.09 0.9 1.2 0.06 1.2 1.4 0.07 1.4 1.6 120 1.02 1.5 1.04 0.30 ANOVA GN 0.60 0.30 F = 474.02 N 0.5 p = 0.0001; F = 395.47 0.5 1.6 p = 0.0001 38 30 35 17 Left kidney APD mean SD min 0.29 0.07 0.2 0.45 0.05 0.4 0.60 0.00 0.6 0.70 0.00 0.7 max 0.4 0.5 0.6 0.7 mean 0.31 0.47 0.61 0.72 Right kidney APD SD min max 0.08 0.2 0.5 0.07 0.4 0.6 0.03 0.6 0.7 0.04 0.7 0.8 120 0.48 0.7 0.49 0.16 0.16 F = 404.38 0.2 p = 0,0001; F = 247.205 0.2 0.8 p = 0.0001; Boxplot by Group kidney length 2,8 20 2,6 2,4 2,2 length / cm Analysis of variance (ANOVA) has shown statistically significant differences between groups (formed according to gestational weeks ) about the length ,width and anteroposterior diameter of left and right kidney..Analysis with Mann-Withney U Test has shown that there were no statistically significant differences between length (U=7042 Z= -0.2938 p= 0.7689; graph 1, width (U=6980 Z= -0.4081 p= 0.6831 ; graph 2 and anteroposterior diameter ( U= 6814.5 Z= -0.7168 p= 0.4734 ; graph 3 between left and right kidney in relation to gestational weeks. There were no statisticall differences between kidney dimensions and sexes. 2,0 1,8 1,6 1,4 1,2 1 2 left right ±Std. Dev. ±Std. Err. Mean Chart 1. Graphic presentation of length mean values between left and right kidney Jovevska S et al. Dimensions of Fetal Kidneys in Different Gestational Weeks Boxplot by Group Boxplot by Group kidney width kidney anteroposterior diameter 0,70 1,3 0,65 1,2 0,60 anteroposterior diameter / cm 1,4 width / cm 1,1 1,0 0,9 0,8 0,7 0,6 1 left 2 ±Std. Dev. ±Std. Err. Mean right 0,55 0,50 0,45 0,40 0,35 0,30 1 left 2 ±Std. Dev. ±Std. Err. Mean right Chart 2. Graphic presentation of width mean values between left and right kidney Chart 3. Graphic presentation of mean values of anteroposterior diameter between left and right kidney Discussion Greater congenital anomalies of kidney, for example, infantile polycystic kidney disease, bilateral agenesis or fetal hydronephrosis, could be found by prenatal US measuring of kidney dimensions (Kurjak and Zmijanac, 1991). For this reason it is necessary to precisely establish the normal fetal kidney size. A simple ultrasonographic method, i.e., measurement of the kidney length, can detect a renal abnormality as early as the 14th gestational week (Zalel et al., 2002). Measuring the fetal kidney size can also help in determining the gestational age, especially in cases where the date of mother’s last period is unknown, and routine methods have shown contradictory results (Cohen et al., 1991; Konje et al., 2002). Gupta AK, Anand NK, Lamba IM, 1993 compared kidney dimensions in relation to gestational age in 100 healthy fetuses with gestational age between the 26th and 41st weeks. Chiara A, Chirico G, Barbarini M, et al., 1993 measured kidney volume in different gestational age. The importance of this study may, in our opinion, be monitoring the dynamics of kidney growth by determining the average values of fetal kidney dimensions, which on the other hands, could be used as standard values in obstetrics. References 1. 2. 3. 4. 5. 6. 7. 8. 9. Gupta AK, Anand NK. Lamba IM. Ultrasound evaluation of kidney dimensions in neo-nates. Indian Pediatr 1993; 309 (3): 319-24 Chiara A, Chiroco G, Barbarini M, De Vecchi E, Rondini G. Ultrasonik evaluation of kidney volume in term and preterm infnts. Am J Perinatal. 1993; 10(2): 109-11 Lawsonb TL, Foley WD, Berland LL, Klark KE. Ultrasonig evaluation of fetal kidneys. Radiology 1981; 138 : 153 –6 Cohen HL, Cooper J, Eisenberg P, et al. Normal length of fetal kidneys: Sonographic study in 397 obstetric patients. AJR – 1991; 157:545-548. Bertagnoli L, Lallata F, Gallicchio R, et al. Qantitative characterization of the growt of the fetal kidney. J Clin Ultrasound 1983; 11:349-356. De Veries L, Levine MI. Measurement of renal size in preterm and term infants by real ime ultrasound Arch Dis Child 1983; 58:145 – 147. Konus OL, Ozdemir A, Akkaya A, et al. Normal liver, spleen and kidney dimensions in neonates, infants and children: evaluation with sonography. Am J Roentgenol 1998; 171: 1693-8 Sureyya K, Soyupak, Nejat Narh, et al. Sonographic measurements of the liver, spleen and kidney dimensions in the healthy term and preterm newborns. Eur J of Radiology 2002; 43: 73-78 Zerin JM, Blane CE. Sonographic assessment of ranal length in children: a reappraisal. Pediatr Radiol 1994;24:1016 21 Acta morphol.2006; Vol.3(2):22-24 UDK: 616.127 ANATOMSKI KARAKTERISTIKI NA OSTIUMOT NA KORONARNIOT SINUS @ivadinovi} Julija1, Lazarova D1, Korneti K1, Papazova M, Matveeva N1, Bojaxieva B1, Pavlovski G2 1 Institut za anatomija , Institut za sudska medicina i kriminalistika2, Medicinski fakultet, Skopje, R. Makedonija Izvadok Ostiumot na koronarniot sinus (OSC) e zna~aen element za orientirawe vo anatomijata na desnata pretkomora i pretstavuva edna od stranite (baza) na triagolnikot na Koh. Del od ostiumot, naj~esto e pokrien so zalistok, ozna~en kako Tebesiev zalistok (Thebesius` ili Thebesian valve). Cel na studijata e da se prika`at goleminata na OSC, negovata polo`ba vo sostav na bazata na triagolnikot na Koh i razvienosta na Tebesieviot zalistok. Analizata e napravena na 70 humani srca fiksirani vo 10% formalin, a dobieni po autopsii na pacienti koi ne po~inale od srcevi zaboluvawa. Rezultatite poka`aa deka dol`inata na bazata na triagolnikot na Koh (strana b) iznesuva 21,6 ±3,8mm (min 14; max 25), na segmentot b1 – 9,5 ±3,3 mm (min 2; max 15), b2 – 8,8 ± 2,1 mm (min 5; max 13), b3 – 3,4 ±1,8 mm (min 1; max 10). Dijametarot na OSC se sovpa|a so b1 segmentot, {to zna~i deka iznesuva 8,8 ± 2,1 mm (min 5; max 13). Analizata na stepenot na razvienost na Tebesieviot zalistok poka`a deka zalistokot ne postoi kaj 9 (12,9%) preparati, umereno e razvien i pokriva pomalku od 15% od OSC kaj 21 (30%) preparati i dobro e razvien i pokriva pove}e od 15% od OSC kaj 34 (48,6%), a kaj 6 (8,6%) od preparatite e fenestriran. Klu~ni zborovi: Triagolnik na Koh, Tebesiev zalistok, elektrofiziologija. ANATOMIC FEATURES OF THE OSTIUM OF THE CORONARY SINUS Zhivadinovik Julija1, Lazarova D1, Papazova M1, Matveeva N1, Bojadzhieva B1, Pavlovski G2 Institute of Anatomy1, Institute for forensic medicine and criminalistic2, Medical Faculty, Skopje, R. Macedonia Abstract The ostium of the coronary sinus (OCS) is a significant landmark in the anatomy of the right atrium, forming one of the sides (the base) of the triangle of Koch. Part of the ostium is often covered with a valve named as Thebesius‘ or Thebesian valve. The aim of this study was to present the diameter of OCS, its location inside the base of the triangle of Koch and the degree of development of the Thebesian valve. The examination was made on 70 human hearts obtained after autopsies of patients died from no cardiac reasons and fixed in 10% formaldehyde. The post mortal measuring showed that the main value of the length of the base of the triangle of Koch (side b) was 21,6 ±3,8mm (min 14; max 25), of the segment b1- 9,5 ±3,3 mm (min 2; max 15), b2 – 8,8 ± 2,1 mm (min 5; max 13), b3 – 3,4 ±1,8 mm (min 1; max 10). The diameter of the OCS was congruent to b1 segment - 8, 8 ± 2, 1 mm (min 5; max 13). The analysis of the degree of development of the Thebesian valve revealed that the valve was absent in 9 (12,9%) cases, residual - moderately developed covering less than 15% of OCS in 21 (30%) cases, partial - well developed covering more than 15% of OCS in 34 (48,6%) cases and fenestrated in 6 (8,6%) cases. Key words: Triangle of Koch, Thebesian valve, electrophysiology 22 Introduction The ostium of the coronary sinus (OCS) is a significant landmark in the anatomy of the right atrium. The coronary sinus is a venous blood vessel located in the left half of the coronary sulcus (sulcus coronarius). It is the conduit for return of most of the venous blood from the heart, although some atrial veins drain directly to the right of left atrial chambers. The coronary sinus continues v. cordis magna, and receives as contributories v. cordis parva, v. cordis media, v. obliqua atrii sinistri and v. posterior ventriculi sinistri. Ostium of the coronary sinus (OCS) is often guarded by thin fold of endocardium, forming semicircular valve, named as Thebesian valve, which covers different percent of the ostium (1). The upper limb of this valve joins with the Eustachian valve and, from this commissure, a tendinous structure runs into the sinus septum (septum between the coronary sinus and the oval fossa). The tendinous structure, called tendon of Todaro, runs forward to insert into the central fibrous body (2). Tendon of Todaro and OCS form the sides of the triangle of Koch (3, 4, 5, and 6). OCS is a part of the base of the triangle (side b), which is the distance from the septal leaflet of the tricuspid valve (at the right angle to the leaflet) through the coronary sinus to the tendon of Todaro. So, the base could be divided into 3 segments: b1, b2 and b3 (4). Dimensions of these three segments of the side b vary, changing the location of the OCS inside the base of the triangle. Zhivadinovik J et al. Anatomic Features of the Ostium of the Coronary Sinus The aim of this study was to present the diameter of the OCS, its location inside the base of the triangle of Koch and the degree of development of the Thebesian valve. Material and Methods The examination was made on 70 human hearts obtained after autopsies of patients older than 18 years, died from no cardiac reasons and fixed in 10% formaldehyde, for at least 72 hours. The right atrium was opened through an incision between the superior and inferior caval venous orifices, and then by extending the incision perpendicular to the first along the lateral wall of the atrium into the right appendage. The dimensions of the segments of the base of the triangle of Koch, including the diameter of the OCS, were measured using the ruler. Side b was divided into 3 segments: b1 – the distance between the septal leaflet of the tricuspid valve and the nearest point of the free edge of OCS; b2 – OCS and b3 – the distance between the OCS and tendon of Todaro. The results were statistically analyzed and expressed as mean value ± standard deviation. The degree of development of the Thebesian valve was classified as: absent, residual (covering less than 15% of the OCS area), partial (covering more than 15% of the OCS area) and fenestrated. Fig. 2. OCS white fibers, that look like chordae tendinae, connecting Eustachian valve with inferior part of the OCS, and passing over the orifice Results The post mortal measuring of the 70 heart specimens gave the following results: The mean value of the length of the base of the triangle of Koch (side b) was 21, 6 ±3,8mm (min 14; max 25), including segment b1 – 9, 5 ±3, 3 mm (min 2; max 15), b2 – 8, 8 ± 2, 1 mm (min 5; max 13), b3 – 3, 4 ±1, 8 mm (min 1; max 10). Diameter of the OSC was equal to b1 segment, which meant it was 8, 8 ± 2, 1 mm (min 5; max 13). Fig. 3. OCS with moderately developed Thebasian valve Fig. 4. OCS with well developed Thebasian valve Fig.1. OCS without Thebasian valve Analyzing the degree of development of the Thebasian valve showed that the valve was absent in 9 (12, 9%) cases (Fig.1). One of these specimens had thin, white fibers, that looked like chordae tendinae, connecting Eustachian valve with inferior part of the OCS, and passing over the orifice (Fig. 2). The valve was moderately developed, covering less than 15% of the OCS in 21 (30%) Fig. 5. OCS with fenestrated Thebasian valve 23 Zhivadinovik J et al. Anatomic Features of the Ostium of the Coronary Sinus cases – residual valve (Fig. 3) and well developed covering more than 15% of the OCS in 34 (48,6%) cases – partial valve (Fig. 4). Six of the cases 6 (8, 6%) had fenestrated valve (Fig. 5). Discussion The right and left venous valves of the sinoatrial orifice regulate the flow of blood from the sinus venosus to the atrium in pisces, amphibians, and reptiles. In aves, mammals and humans, the venous valve loses its hemodynamic function, receiving attention only when congenital anomalies occur that are related to it. The right venous valve persists in humans as the crista terminalis, Thebasian and Eustachian valves (7). Thebesian valve is a small fold of endocardium that is located at the OCS, for the first time described by Thebesius tree centuries ago. According to literature the degree of its development varies. There are different classifications that describe the development of the Thebesian valve. In 1991, Jatene et al. published an anatomic study of the Thebasian valve in 94 human hearts. They described four categories of development of the valve: absent, residual – covering less than 15 % of the OCS, partial– covering more than 15 % of the OCS and trabecular or double (1). Karaca et al. described the degree of development of the Thebasian valve as negative and positive. The last one, according to the shape, can be crescent, semilunar or band shaped (8). In this study, we described the valve as: absent, residual – covering less than 15 % of the OCS, partial– covering more than 15 % of the OCS and fenestrated. The results of the examination of the degree of development of the Thebasian valve showed that the valve was present in 91% of the cases. The valve was moderately developed (residual) in 30%, well developed (partial) in 48,6% and fenestrated in 8,6% of the cases. The mean value of the diameter of the OCS was 8,8mm. These results are in agreement with the published ones (1, 7). Well developed Thebesian valve can be associated with other congenital malformations (hypoplastic right heart, tricuspid atresia and stenosis, transposition of the great heart vessels, atrial and ventricular septal defects), some of them manifested with cyanosis (9, 10). The position of the OCS inside the base of the triangle of Koch varies. The measurements obtained that the lengths of the b1 and b3 segments were different among the specimens. The variations of the position of the OCS change the distance between the ostium ant the tissue of the AV node, which is located at the apex of the Koch’s triangle. The authors, who apply radiofrequent catheter ablation, use OCS as landmark considering that AV node is located 1cm in front of the orifice (11, 12). The knowledge of the anatomy of the OCS, as a part of the triangle of Koch and the right atrium is necessary for successful realization of therapeutic and diagnostic methods in cardiology. References 1. D‘Cruz, Shirwany A. Update on electrocardiography of coronary sinus anatomy and physiology. Echocardiography 2003; 20(1):87- 95. 2. Gabella G. Chapter 10 Cardiovascular system in Gray’s Anatomy. Churchill Livingstone 1995; 1477. 3. Ueng K.C., Chen S.A., Chiang C.E. et al.: Dimension and related anatomical distance of Koch’s triangle. Journal of Cardiovascular Electrophysiology 1996; 7 (11): 1017 – 1023. 4. Inoue S., Becker AE. Koch’s triangle sized up; anatomical landmarks in perspective. PACE 1998; 21 (8): 1553 – 1558. 5. Ho S.Y., Anderson R.H. How constant anatomically is the tendon of Todaro as a marke. Journal of Cardiovascular Electrophysiology 2000; 11 (1): 83 – 89. 6. McGuire M.A., Johnson D.C., Robotin M. et alDimensions of the triangle of Koch in humans. The American Journal of Cardiology 1992; 70 (7): 829-830. 7. Victor S, Nayak VM. An anomalous muscle bundle inside the right atrium possibly related to the right venous valve. J Heart Valve Dis. 1997; 6 (4): 439-40. 8. Karaca M, Bilge O, Dinckal MH, Ucerler H. The anatomic barriers in the coronary sinus: implications for clinical procedures. J Interv Card Electrophysiol. 2005; 14(2):89-94. 9. Raffa H et al. Central cyanosis due to prominence of the Eustachian and Thebesian valves. Ann Thorac Surg 1992; 54 (1):159-160. 10. Schutte DA et al. Prominent venous valves in hypoplastic right hearts. Am Heart J 1997;134:527-31. 11. Rakovec P., Gjorgov N. Atrioventricular conduction disturbances as complications following catheter ablation of supraventricular tachycardias. Ital Heart J 2004; 5 (1): 18-22. 12. Gjorgov N., Reiser W., Lazarov L. Catheter ablation of the slow pathway in the treatment of atrioventricular nodal reentry tachycardia. Journal of the Macedonian Medical Association 1994; 48 (5-6): 151-157. 24 Acta morphol.2006; Vol.3(2):25-29 UDK: 572.524 - 055.1 (497.7) PLANTARNI DERMATOGLIFI KAJ MLADATA MAKEDONSKA POPULACIJA OD MA[KI POL ^adikovska Elizabeta, Lazarova D, Na}eva N, Papazova M, Zafirova B, @ivadinovi} J, Bojaxieva B Institut za anatomija, Medicinski fakultet, Skopje, R. Makedonija Izvadok Da se utvrdat plantarnite dermatoglifski karakteristiki kaj mladata ma{ka populacija od makedonska nacionalnost. Bilateralni otisoci na stapalata na 200 ispitanici od ma{ki pol bea napraveni spored metodot na Cummins i Midlo , ~itani i klasificirani spored Henri- evata klasifikacija. Presmetan e Denkmeijer -ovit indeks; ispituvani se razlikite me|u dvete stapala. Na prstite na dvete stapala kaj prisytnite mostri najzastapeni se fibularnite jamki i lakovi, krugovite se najmnogubrojni na prviot pa na tretiot prst, slo`enite mostri na tretiot prst. Kaj interdigitalnite prostori, vo I-ot najzastapeni mostri se distalnite jamki i krugovi, vo II-ot prostor proksimalnite pa distalnite jamki, vo III-ot distalnite jamki i krugovi. Od osnovnite triradiusi, najzastapeni se d, a i b, a od dopolnitelnite pm, p’, p” na dvete stapala. Osven za vtoriot prst, nema signifikantni razliki me|u dvete stapala. Populacionite sporedbi ne ni demonstriraa jasni rasni razliki na plantarnite dermatoglifi. Ovaa antropolo{ka studija gi dava normalnite dermatoglifski karakteristiki na ma{kata makedonska populacija. Iako najmnogubrojni etni~kite ispituvawa se u{te ne ni davaat podatoci za golem broj regioni. Ovie podatoci ovozmo`uvaat nivno natamo{no koristewe vo antropolo{kite istra`uvawa, potenciraj}i ja osobenosta na plantarnite mostri pri sporedba na rezultatite so onie od drugite populacii ako voop{to gi ima. Klu~ni zborovi: dermatoglifi, plantogrami, antropologija PLANTAR DERMATOGLYPHICS IN YOUNG MACEDONIAN POPULATION OF MALE GENDER Chadikovska Elizabeta, Lazarova D, Nakeva N, Papazova M, Zafirova B, Zhivadinovik J, Bojadzhieva B Institute of Anatomy, Medical faculty, Skopje, R. Macedonia Abstract To establish plantar dermatoglyphic characteristics in young male population of Macedonian nationality. Bilateral sole prints of 200 male examinees were taken using Cummin’s and Midlo’s method; they were recorded, studied and classified using Henry’s method. Denkmeijer’s index was calculated and bilateral differences were examined. Digital pattern types have shown predominance of fibular loops and arches; whorls were present in large number on the first and then on the third digit and complex patterns were most frequent on the third digit of both feet. In the interdigital areas, most frequent patterns were distal loops and whorls in the I-st space, in the II-nd one proximal and distal loops and in the III-rd one distal loops and whorls.From basic digital triradii d, a and b prevailed and from accessory triradii pm, p’ ,p’’ in both feet. Except for the second digit, no other bilateral differences were observed. Population comparisons did not demonstrate a clear racial difference in plantar dermathoglyphics. This antropological study has provided us normal dermatoglyphic features in male Macedonian population. Although there are vast ethnic examinations, we still have no results for a number of regions. Data obtained in this study can be further used in anthropological examinations and researches, emphasizing the uniqueness of plantar ridge patterns and distinguishing differences between population groups, if there are any. Key words: dermatoglyphics, sole prints, anthropology Introduction Dermatoglyphics is the science of the patterned traceries on the skin surface on fingers, palms and soles. Plantar surface of the feet and toes is characterized with presence of skin ridges (cristae superficiales). They are divided between themselves with shalow ridges (sulci cutanei, sulci superficiales). On prints the ridges leave marks known as papillar lines, they are mainly parallel, but in some topographic regions they form distinctive drawings called patterns, highly variable and characteristic for each individual (1). Although the importance of the prints for personal identification has been recognized a long time ago, their significance for anthropology was determined when a number of print samples were collected from many diverse people from different populations, and the genetic basis for the variations observed was accounted. Among other aspects of the dermatoglyphics, anthropologists are 25 Chadikovska E et al. Plantar Dermatoglyphics in Young Macedonian Population of Male Gender interested in billateral differences in one individual are intresting for anthropologists (2). Although some methodological questions are still open, detailed history of the dermatoglyphic population studies has demonstrated the usefulness of information provided by these researches in understanding the evolution and genetic structure of subdivided human population (3). A few scientists studied epidermal ridges of the feet.The First recorded documents were made by Wilder (4), the founder of the etnical dermatoglyphic studies, who examined plantar dermatoglyphics, worked on their classification, nomenclature and made comparisons between twins and different races. The first researches increased the interest among other scientists whose future plantar dermatoglyphic studies have provided us with useful information about anthropological characteristics, their affinities and differences among population groups, although race could not be determined only by reading plantograms (5). Palmar dermatoglyphic examinations in many times exceed plantar ones in number. Lack of data for plantar dermatoglyphics among Balkan populations has induced us to carry out this study of dermatoglyphic features in young Macedonian population of male gender and provide us with useful anthropological data. Material and Methods The sample consisted of 200 examinees of male gender aged 16 – 20 years, selected by random choice. All participants were of Macedonian nationality determened by the conducted poll. Bilateral plantograms were taken using inking method of Cummins and Midlo (1). There are eight plantar configurational areas: hallucal (representing the distal thenar and first interdigital combined), second, third and fourth interdigitals, fibular region of the sole equivalents to the hypothenar area and divided into distal and proximal sections, tibial region as homologue to the thenar and also divided into distal and proximal sections and calcar area in the heel region. We determined configuration types and classified them by Henrie’s method (Fig.1); recorded them and expressed as percentages. We analyzed the presence of digital triradii named a, b, c, d, e and according to Wilder lower or p triradius ( proximal in relation to the other digital triradiiFig.1). Billateral differences were recorded. Dankmeijer’s – index (DI) was calculated. The DI is the total frequency of arches divided by the total frequency of whorles x 100 (6) .We compared our findings with the results from other authors. loop arch whorl complex patterns Fig. 1. Fibular loops,complex patterns and whorls were most prevalent patterns on the third digit. Among the patterns on the fourth digit, arches and fibular loops were the most common. A strong dominance of arches was found on the fifth digit. Distribution of the present triradii on the left foot in males is shown in Table 2. From the basic triradii the most common was d triradius,followed by a, b, p and e. From the accessory triradii pm, p’, p’’ were predominant. In the interdigital spaces, distal loops, whorls and tibial loops were predominant, in the first space.In the second one proximal loops, in the third-distal loops, and in the fourth interdigital space distal loops were also most frequent. Results The distribution of the examined patterns on the left foot in males is shown in Table 1. Fibular loops,whorls and arches were dominant on the fist digit. Fibular loops and arches were predominant among patterns on the second digit. 26 Fig. 2. There were no patterned traceries on the thenar and hypothenar region.On hypothenar distal region we found some tibial loops and arches, proximal and fibular Chadikovska E et al. Plantar Dermatoglyphics in Young Macedonian Population of Male Gender Table 1. Distribution of patterns –male/left feet Patterns First Num. Lf 131 Lt 7 Lp / W 25 A 26 Wd 8 Wcpl 3 Wlpl / Sum 200 Second % Num. 65.5 123 3.5 1 / 2 12.5 5 13.0 54 4.0 12 1.5 / / 3 100 200 Toes Third % Num. 61.5 83 0.5 / 1.0 / 2.5 7 27.0 45 6.0 41 / / 1.5 18 100 200 % 44.5 / / 3.5 22.5 20.5 / 9.0 100 Fourth Num. 81 3 / / 106 6 / 4 200 % 40.5 1.5 / / 53.0 3.0 / 2.0 100 Fifth Num. 4 / / / 196 / / / 200 % 2.0 / / / 98.0 / / / 100 Table 2. Distribution of triradii-male/left feet triradii present Num. % absent Num. % 180 176 57 188 74 96 90 88 28.5 94 37 48 20 24 143 11 126 104 10 12 71.5 5.5 63 52 1 29 38 38 92 0.5 14.5 19 19 46 199 171 162 162 108 99.5 85.5 81 81 54 Fibular loops, whorls and arches were dominant on the fist digit. Fibular loops,folowed by arches were predominant among patterns on the second digit. Most present patterns on the third digit were fibular loops,and from the other patterns arches, double loops, lateral pocket loops from the complex patterns as well as whorls were found. Arches and fibular loops were prevalent patterns on the fourth digit . A strong dominance of arches was present on the fifth digit. Distribution of the present triradii on the right foot in males is shown in Table 4. From the basic triradii the most frequent type was b triradius, followed by d, a and p . basic a b c d e p accessorii d’ e’ p’ p” pm Table 3. Distribution of patterns-male- right foot Patterns Lf Lt Lp W A Wd Wcpl Wlpl Sum First Num. 145 6 / 22 19 4 / 4 200 % 72.5 3.0 / 11.0 9.5 2.0 / 2.0 100 Second Num 150 1 1 5 37 4 / 2 200 % 75.0 0.5 0.5 2.5 18.5 2.0 / 1.0 100 Toes Third Num 116 / / 17 28 27 1 11 200 % 58.0 / / 8.5 14.0 13.5 0.5 5.5 100 loop and in the calcar region few tibial loops were present, all of them in small number. DANKMEIJER’s index –left foot Toes - 213,5% ⋅ 100 = 1154,05 18,5% The distribution of the examined patterns on the right foot in males is shown in Table 3. Fourth Num 81 / 1 2 109 3 / 4 200 % 40.5 / 0.5 1.0 54.5 1.5 / 2.0 100 Fifth Num 2 / / / 198 / / / 200 % 1.0 / / / 99.0 / / / 100 From accessory triradii pm, p’, p’’ were the most common ones. In the interdigital spaces, distal loops, whorls and tibial loops were predominant in the first space.In the second one proximal loops, in the third distal loops were the most present, and there are few whorls and proximal loops, whereas in the fourth interdigital space distal loops were most common patterns. 27 Chadikovska E et al. Plantar Dermatoglyphics in Young Macedonian Population of Male Gender Table 4. Distribution of triradii- male/right foot Triradii Present Num % Absent Num % 175 180 57 178 70 106 87.5 90.0 28.5 89.0 35.0 53.0 25 20 143 20 94 94 12.5 10.0 71.5 10.0 47.0 47.0 2 36 41 44 86 1.0 18.0 20.5 22.0 43.0 / / 159 156 114 / / 79.5 78.0 57.0 basic a b c d e p accessorii d’ e’ p’ p” pm Table 5. Differences: male-left/right foot Parameter U/D Z p-level p Sig./N.Sig. first second third fourth fifth 18531.50 17486.00 D = 0.135 19829.00 19800.00 1.270172 2.174471 0.147906 0.172989 0.204024 0.029670 p<0.10 0.882417 0.862660 p>0.05 p<0.05 p>0.05 p>0.05 p>0.05 N.Sig. Sig. N.Sig. N.Sig. N.Sig. 19500.00 19600.00 19943.00 19199.00 19383.00 19000.00 19700.00 19400.00 19400.00 0.432472 -0.345978 -0.049302 0.692821 -0.533671 -0.864945 -0.259483 -0.518967 0.518967 0.665398 0.729360 0.960679 0.488423 0.593570 0.387070 0.795262 0.603784 0.603784 p>0.05 p>0.05 p>0.05 p>0.05 p>0.05 p>0.05 p>0.05 p>0.05 p>0.05 N.Sig. N.Sig. N.Sig. N.Sig. N.Sig. N.Sig. N.Sig. N.Sig. N.Sig. 19942.50 19168.00 18857.00 19215.00 -0.049734 0.719634 -0.988632 -0.678982 0.960334 0.471751 0.322844 0.497150 p>0.05 p>0.05 p>0.05 p>0.05 N.Sig. N.Sig. N.Sig. N.Sig. 20000.00 19830.00 20000.00 0.00 0.000000 -0.147041 0.000000 0.000000 1.000000 0.883100 1.000000 1.000000 p>0.05 p>0.05 p>0.05 N.Sig. N.Sig. N.Sig. N.Sig. Toes Triradii a b c d e p p1 p2 pm Interdigital Hal/Thd second third fourth Other regions Thp Hyd Hyp Cal There were no patterned traceries on the thenar and hypothenar region.On hypothenar distal region we found some tibial loops and arches, proximal and fibular loop and in the calcar region few tibial loops were present, all of them in small number. DANKMEIJER index - right foot Toes28 195,5% ⋅ 100 = 850 23% The difference between analyzed atributive parameters of the left and right feet in males is shown in Table 5. The significant difference among the analyzed patterns was observed on the second digit for U=17486 ( Z= 2.17 ) and p < 0.05. The difference originates from the larger number of patterned tracerries registered on the second digit on the left foot, especially larger number of arches, while in the distribution of other patterns there Chadikovska E et al. Plantar Dermatoglyphics in Young Macedonian Population of Male Gender was no big difference. No significant difference has been recorded in the other analyzed parameters. Discussion The majority of the presented plantar ridge patterns were consistent with those found in other races and ethnical groups, which indicated that race could not be determined only by describing dermatoglypics.We have outlined the established characteristics for the male Macedonian population and the differences with the already existing data on other populations. The most frequent patterns on the toes of both feet were fibular loops and arches, whereas whorls and complex patterns were less present. In the interdigital spacies the most frequent were: in the 1-st interdigital region distal loops and whorls, in the 2-nd proximal loops, in the third distal loops and whorls. From the basic triradii, predominated d, a, b and p triradius and from the accessories pm, p’ and p’’ on both feet in males. The value of the Dankmeijer’s index was lower for the right foot compared to the left ones. We compared our results with those obtained by the other authors. Igbibi and Didia (7) examined plantar dermathoglyphics on 212 males among the Urhobs in south Nigeria. Igbibi and Msamati (8) studied skin patterns in 150 males in Zimbabve. Digital patterns showed bigger presence of loops than arches, and the least were whorls that were more abundant on the third digit. Loops were more frequent on the right foot. The results obtained in our study for the digit patterns were similar with those of Fox and Plato (9) who studied 168 males in America. Except for the tibial loops present on the first digit which were few in our study, these authors found largest percentage of whorls on the third digit, equal number of fibular loops as in our study except for the third digit where we had very few of them. In the study of Flugel, Greil and Sommer (10) who examined Germans, the results are equal with ours for most fibular loops, then whorls on the first digit, arches on the fifth digit, whereas complex patterns were more present folowed by fibular loops as compared to our study on the third digit. On the second digit fibular loops, complex patterns were the same as in our examinations, on the fourth digit fibular loops and complex patterns were more present than in our results where there were more arches, followed by fibular loops and complex patterns. In the Fox and Plato (9) study of 168 males in America, the presence of the basic triradii coincided with our study, and the accesory triradii were more present in male examinees, p triradius was more frequent on the right foot as in our study. The results for the I-st interdigital regions in agreement with those of Fox and Plato (9), Flugel, Greil and Sommer (10) shoing that distal loops are most frequent, followed by whorls, and tibial loops among male participants. According to the results for the II, III and IV interdigital region in the study of Igbibi and Msamati (8), plantar patterns showed presence of more loops than arches, and more arches than whorls;a special characteristic being the absence of whorls in the second interdigital space. Our results are identical with the Fox’s and Plato’s (9) ones. According to Flugel, Greil and Sommer (10) in the second interdigital region arches were more present than proximal loops, in the third interdigital space distal loops, arches and whorls, in the forth interdigital region again arches, than distal and proximal loops and the least were whorls. Our data for the thenar and hypothenar region distal coincade with those of the mentioned authors, except of the Fox’s and Plato’s (9), who found more tibial loops and arches in the hypothenar region. In the Flugel,Greil and Sommer reports (10) more distal, tibial and proximal loops were found in the calcar region, and tibial loops in the hypothenar proximal region. This study has elucidated the normal dermatoglyphic features in young male Macedonian population. Digital patterns, however, could better differentiate population groups related to the plantar patterns and they could be used in further anthropological examinations (11). References 1. Cummins H,Midlo C:”Finger prints,Palms and Soles”An introduction to dermatoglyphics ,New York :Dover Publicationes,1961 2. Pollitzer W,Plato C:Birth Defects:Original Article Series,1979;XV(6): 211-223. 3. Craford M.,Duggirala R.,:Digital dermatogliphic patterns of Eskimo and Ameridian populations:relationsiphs between geographic,dermatoglyphic,genetic and linguistic distances.Human Biology:1992;64:683-704. 4. Wilder HH:Racial differneces in palm and sole configuration.Am Anthropology,1904;6:244-292. 5. Penrose LS,Loesch D:Dermathoglyphic sole patterns:a new attempt at classification.Human biology,1969;41(3):427 428. 6. Dankmeijer J.Some anthropological data on finger prints.Amer.J .Phys.Anthrop.1934:23:377-380. 7. Igbibi P.S.,Didia B.C.:Plantar Dermatoglyphic Features of the Urhobbos Of Southern Nigeria,East African Medical Journal,1999;76:672-675. 8. Igbibi P.S.,Msamati B.C.:Plantar and digital Dermathogliphic Characteristics of Zimbabwean Subjects,East African Medical Journal,2001;78:536-539.S 9. Fox M.Kathleen and Plato C. Chris : Toe and Plantar Dermatoglyphics in Adult American Caucasians . Am J Physical Anthropology ,1987;74:55-64. 10. Flugel Bernard,Greil Holle, Sommer Karl : Antropologischer Atlas ,Berlin: Verlag Trubune,1986. 11.Malwalwala J:Dermathogliphics:Looking forward to the 21-st century.Progress in dermatoglyphic research,1982;p:13-23. 29 Acta morphol.2006; Vol.3(2):30-34 UDK: 575 (497.7) MNSs I KEL KRVNO GRUPNI SISTEMI KAKO GENETSKI MARKERI KAJ ^ETIRI POPULACII KOI @IVEAT VO REPUBLIKA MAKEDONIJA Efremovska Qudmila1, Nikoloska –Dadi} E1, [midt H2, [eil H-G3 Institut za fiziologija so antropologija, Medicinski fakultet Skopje, Makedonija1, Institut za humana genetika i antropologija, Ulm, Germanija2, Institut za humana genetika i antropologija, Diseldorf, Germanija3 Izvadok Vo ovoj trud daden e prikaz na rezultatite {to se odnesuvaat na MNSs i Kell sistemite kako klasi~ni genetski markeri kaj ~etiri populacii vo republika makedonija , i toa : Makedonci, Albanci, i dve populacii na Vlasi. Odreduvawe na antigenite od MNSs i Kell sistemite be{e izvedeno so komercijalni antiserumi (SERAK-Manfred R. Hofmann, Bad Homburg). Presmetana be{e najdena i o~ekuvana frekvencija kaj sekoj fenotip, kako i nivna haplotipna i alelna frekvencija. Dobienite rezultati od ovaa studija ni ovozmo‘uvaat osvrt na distribucijata na haplotipovite od MNSs i Kell sistemite kaj del od populaciite koi ‘iveat vo R. Makedonija. Rezultatite uka‘uvaat na postoewe na razliki me|u site 4 populacii, koi najverojatno se dol‘at na nivnoto izolirano ‘iveewe i me|usebno neme{awe. Klu~ni zborovi: populaciona genetika, MNSs, Kell, alelna frekvencija, krvni grupi. MNSs AND KELL BLOOD TYPE SYSTEMS AS GENETICAL MARKERS IN FOUR POPULATIONS IN THE REPUBLIC OF MACEDONIA Efremovska Ljudmila1, Nikoloska-Dadik E1, Schmidt H2, Sheil H-G3. Institut for physiology and anthropology , Medical faculty , Skopje , Makedonija1, Institut for human genetics and anthropology , University Ulm, Germany2 Institut for human genetics and anthropology , University Dusseldorf , Germany3 Abstract This study presents the results regarding MNSs and Kell systems as the classical genetic markers in four ethnic groups in the Republic of Macedonia (Macedonians, Albanians, and two Vlach populations). The determination of antigens of MNSs and Kell systems was performed with commercial antiserums (SERAC, Manfred R. Hofmann, Bad Homburg). Observed and expected frequency of every phenotype was calculated, as well as their haplotype and allele frequencies. The obtained results of this study provide insight into the haplotype distribution of MNSs and Kell systems in some populations living in the Republic of Macedonia. These results are different for all four examined populations, which is probably attributed to their separate living and low interaction. Key-words: population genetics, MNSs, Kell, allele frequency, blood types Introduction Currently, according to the Population Census for 2002, there are 2. 022. 547 inhabitants in the Republic of Macedonia: 64.18% Macedonians, 25.17% Albanians, 3.85 Turks, 2.66% Vlachs, 1.78% Serbs, 0.84% Bosniacs, and 1.04% others. Such diversity in the ethnic structure is the result of tempestuous historical past of this region (1). Republic of Macedonia is characterized with different cultural and political influences over the centuries, therefore, even today remnants of antique castles, early Christian basilicas, medieval churches, 30 mosques and fortifications stand next to one another, like witnesses of the rich history of this region. In the existing literature dealing with the populations living in the Republic of Macedonia, it is rather difficult to get full account of certain systems of classical genetic markers, and therefore it is hard to utilize them in population genetics studies. The data for certain systems of erythrocyte antigens incorporated in studies for other purposes (2) are exception from the above mentioned, as well as in the studies of serum proteins (3, 4, 5), and investigations of HLA system (6). In this study, we present part of the results related to MNSs and Kell systems as classical genetic markers of the four ethnic groups living in the Republic of Macedonia. This study was part of the International Project of Ethno-history and Population Genetics of the Balkan populations, in the period of 2002-2003, supported by DFG (Deutsche Forschungsgemeinschaft Germany). Material and Methods The study involved 129 respondents of Macedonian nationality (with equal distribution in all parts of the Republic of Macedonia), two population units of Vlach ethnical group (108 from the region of Ovce pole and 95 from Krushevo) and one population unit of Albanians (98 respondents from the region of Skopje, Tetovo and Kumanovo). The respondents were not blood related. The affiliation with a certain population group was determined based on statements given during the Efremovska Lj et al. MNSs and Kell Blood Type Systems as Genetical Markers filling in of demography cards. In those cards, the subjects confirmed their affiliation to their population group at least as far as three previous generations, following the origin of both parents. From each subject 8ml of blood with 10% EDTA was obtained, and within 48 hour period the erythrocyte antigens of MNSs and Kell systems were determined. Determination of antigens of MNSs and Kell systems was performed with commercial antiserums (SERAC, Manfred R. Hofmann, Bad Homburg). Based on the obtained results, the frequency of certain phenotypes was determined (referred to as observed frequency). For every mark the phenotype frequency was calculated in conditions when the population is in genetic equilibrium (Hardy Weinberg equilibrium). This frequency is referred to as expected frequency. Using the Ç2 test for each mark we determined whether the observed frequency of this mark deviates from the expected frequency of the same. When there is no deviation from the expected frequency we conclude that the loci are in genetic equilibrium. Conversely, when significant deviation appears, we determine the direction of deviation and the reason for this deviation. This is especially the case when deviations occur for significant number of loci. Individual haplotype and allele frequencies of every population were calculated for MNSs and Kell systems. We compared the results of our investigations of different population units within our study, and we also compared them with the results from other examined populations within the broader scope of the Project. Results Observed frequencies for phenotype MNSs and Kell systems in populations examined in this study, as well as their expected frequencies when populations are in genetic equilibrium are shown in Tables 1 and 2. The results obtained by x2 test are also shown. It was determined that the populations of Vlachs from Krushevo and Ovche Pole are in Hardy Weinberg equilibrium. Populations of Macedonians and Albanians did not achieve genetic equilibrium. This result may be expected in samples obtained from large cities or samples obtained from different areas (combined samples), if the sample is not big enough. The most frequent phenotypes in all examined populations are MNSs and MNss. The rarest phenotype is NNSS which was found in only one respondent of Vlach population in Ovche Pole (Table 1). The obtained results for Kell system suggest that phenotype kk (cellano, cellano) is of highest frequency in all four populations, and it is the unique phenotype for the Vlach population in Krushevo (Table 2). Phenotype KK (Kell, Kell) is not observed in Macedonian population. Since there are three possible phenotypes (kk, KK, kK) in a sample of small size, the degree of freedom for this system is not sufficient to statistically determine that the populations are in equilibrium for that allele (the test of Hardy-Weinberg equilibrium is impossible). Since the observed and expected frequencies are approximately equal, it could be assumed that these phenotypes are in equilibrium as well. Regarding the haplotype frequencies of MNSs system (Table 3) we conclude that within each haplotype there are differences among the examined populations. The most frequent allele in the Macedonian population and Krushevo Vlach populations is Ms (0.3768, 0.3470), and in the Albanian and Ovche Pole Vlach populations is Ns (0.3236 , 0.3618). Haplotype NS is the rarest within each of the populations. Kell system allele frequencies in our sample are shown in Table 4. It can be observed that the value of k (Cellano) frequency is over 0.95 in each of the populations. In Krushevo Vlach population it equals 1.00. Discussion Different allele frequencies of blood type systems in human populations, as well as different allele frequencies in general, come as a result of the effects of natural selection, genetic drift, migrations and selective meeting (7). Two big alleles of MN system belong to the gene responsible for glycophorin A synthesis (GYP A) (8), which is most frequent glycoprotein receptor on the erythrocyte membrane surface. Glycophorin B (GYP B) is responsible for Ss system. Extremely high number of receptor glycoprotein structures on the membrane surface cannot be explained solely with the primary function of erythrocytes (oxygen supply to tissues) (8). Other factors probably influence this, such as the evolution of genes responsible for their synthesis in conditions of natural selection and microorganism influenced selection which they contacted. Evolution of these genes is generally the fastest evol˜utionary process of human genes (9, 10). MNSs system is one of the most frequently used classical genetic markers, and is determined by two loci responsible for part of the structure of glycophorine A and B. There are two alleles appearing on each locus, and they combine to give four haplotypes (MS, Ms, NS, Ns). These four haplotypes can be found in each human population with different frequency. The world map of single gene frequencies for haplotypes of MNSs shows that their distribution differs (7). Figure 1 shows that two haplotypes MS and NS in domicile population of Australia are nonexistent, and MS is rare haplotype (0.01) in the region of Pacific and New Guinea. Increased frequency of these two haplotypes can be observed when going from East Asia towards Europe. The other two haplotypes of MNSs (Ms and Ns) are generally found (present) in all populations with different degree of variation in their distribution (7). The results obtained in this study provide an insight into the distribution of haplotypes of MNSs system in some of the populations living in the Republic of Macedonia. The calculated haplotype frequencies show that there are differences among all four examined 31 Efremovska Lj et al. MNSs and Kell Blood Type Systems as Genetical Markers Table 1. Frequencies of phenotypes of MNSs system and results of the test for Hardy-Wainberg equilibrium in population sample studied Macedonians Phenotype MMss MMSs MMSS MNss MNSs MNSS NNss NNSs NNSS n x2 Obser. 23 14 12 27 30 7 13 3 0 129 Albanians Expec. 18.31 24.41 8.14 28.56 26.65 5.08 11.13 95.94 0.79 129.01 9.9644 df=4 2.5 < p < 5 Obser. 13 8 11 18 22 8 14 3 0 97 Aromuns Aromuns (Ovce Pole) (Krusevo) Expec. Obser. Expec. Obser. Expec. 9.35 9 9.14 15 11.44 16.07 6 11.97 15 19.80 6.91 9 3.92 11 8.57 19.49 25 22.74 18 18.07 22.72 26 24.74 14 20.82 5.13 5 6.45 9 4.48 10.16 14 14.14 10 7.14 6.22 13 12.25 3 4.09 0.95 1 2.65 0 0.59 97 108 108 95 95 13.5172 df=4 1 < p < 2.5 5.4324 df=4 20 < p < 30 7.2208 df=3 5 < p < 10 Table 2. Frequencies of phenotypes of Kell system and results of the test for Hardy-Wainberg equilibrium in population sample studied Macedonians Phenotype KK Kk kk n x2 Obser. 0 10 119 129 df=0 Expec. 0.19 9.61 119.19 129.01 Albanians Aromuns Aromuns (Ovce Pole) (Krusevo) Obser. Expec. Obser. Expec. Obser. Expec. 2 0.21 1 0.04 0 0 5 8.59 2 3.93 0 0 91 89.21 104 103.04 95 95 98 98.01 107 107.01 95 95 df=0 df=0 df=0 Table 3. Haplotype frequencies of MNSs system in population sample studied Haplotype Macedonians Albanians MS Ms NS Ns Total 0.2511 0.3768 0.0783 0.2938 1.0000 0.2669 0.3104 0.0991 0.3236 1.0000 Aromuns (Ovce Pole) 0.1905 0.2910 0.1567 0.3618 1.0000 Aromuns (Krusevo) 0.3004 0.3470 0.0786 0.2741 1.0000 Table 4. Haplotype frequencies of Kell system in population sample studied Haplotype K k Total 32 Macedonians 0.0388 0.9612 1.0000 Albanians 0.0459 0.9541 1.0000 Aromuns(Ovce Pole) Aromuns(Krusevo) 0.0187 0 0.9813 1.0000 1.0000 1.0000 Efremovska Lj et al. MNSs and Kell Blood Type Systems as Genetical Markers populations, which are attributed to their separate living and low interaction. The transmembrane protein of erythrocyte membrane known as Kell protein (transmembrane zincdependent endopeptidase for cleaving endothelin-3) is responsible for antigens of Kell (also known as KellCellano) system. Three pairs of alleles are responsible for different antigene of Kell system. In population genetics studies the pair of co-dominant alleles K (Kell) and k (Cellano) are most frequently used. The world map of distribution of these alleles is shown in Figure 2. It can be seen that allele k (Cellano) in all examined populations has a value higher than 0.9, and allele K (Kell) has a value of 0.0001 in Australia and 0.05 in India. Our obtained frequencies fall within the range of variation of European values. 33 Efremovska Lj et al. MNSs and Kell Blood Type Systems as Genetical Markers Based on the results in this study, it can be concluded that there are significant differences among the studied populations in the Republic of Macedonia: Macedonians, Albanians and two Vlachs populations, determined through the MNSs and Kell-Cellano systems of genetic markers. In order to determine the genetical distances among the chosen populations and to draw out the dendrograms, more examinations of other classical genetic markers are necessary. References 1. 2. Stoianovich T. Balkan worlds: the first and last Europe. New York ; Sharpe press, 1994: 1-35 Stefanovska V, Stojceski N, Trajkov A. Distribution of MNS blood group in SRM . God. Zbornik Med Fak 1983; 29: 173-4 ( in Macedonian ) 3. Scheil HG, Schmidt HD, Efremovska L, Mikerezi I , Huckenbeck W. Phenotype and allelefrequencies of some serum protein polymorphisms in populations of the Balkan. Anthropol Anz 2004 ; 62(4): 429-34 4. Schmidt HD, Scheil HG, Huckenbeck W, Huckenbeck W, Efremovska L.. Genetic studies in south Balkan populations. Coll Anthropol. 2003; 27 (2): 501-6. 5. Scheil HG, Scheffrahn W, Schmidt HD, Huckenbeck W, Efremovska L, Xirotiris N. Population genetic studies in the Balkan.I. Serum proteins. Anthropol Anz 2001 ; 59 (3): 203-11. 6. Kolevski P, Ivanovski N, Hristova Dimceva A, Penev M, Cakalarovski K, Lekovski L, Popov Z.: Epidemiology of the major histocompatibility complex-human leukocyte antigen in the Macedonian population. Ann Yrol 2000; 34 (5): 306-11. 7. Cavalli-Sforza LL, Menozzi P, Piazza A. The history and geography of human genes. Princeton University Press , 1994 8. Blumenfeld O, Huang H. Molecular genetics of glycophorin MNSs variation. Transfus Clin Biol 1995; 4 :357-65. 9. Baum J, Ward HR, Conway JD. Natural selection on the erythrocyte surface. Mol Biol Evol 2002; 19 (3) : 223-9. 10. Hurng W, Hua Tang CK, James S, ChungW. Rapidly evolving genes in human. I The glycophorins and their possible role in evading malaria parasites. Mol Biol Evol 2003; 20 (11): 1795-804. 34 Acta morphol.2006; Vol.3(2):35-38 UDK: 616.71 - 006.6 - 033.2 - 073.916 SKELETNA SCINTIGRAFIJA SO 99m Tc MDP – DETEKCIJA NA METASTATSKA KALCIFIKACIJA: PRIKAZ NA SLU^AJ Stojanoski Sini{a 1 , Pop \or~eva D 1 , Ristevska - Miceva S 1, Tripunoski T 1, [ubevska Stratrova S 2 Institut za patofiziologija i nuklearna medicina 1 , Klinika za endokrinologija, dijabetes i bolesti na metabolizmot 2 , Medicinski fakultet, Skopje, Makedonija Izvadok Metastatskata kalcifikacija pretstavuva generaliziran fenomen na talo`ewe na kalciumovi soli vo intersticiumot na prethodno intaktni meki tkiva. Vo osnovata na ovoj proces le`i sozdavaweto na hidroksiapatitni kristali asocirani so hiperkalcemija i naru{en kalcium / fosfaten metabolizam. Prika`uvame slu~aj na 65-godi{en ma` so adenom na paratiroidna `lezda i konkomitantna metastatska kalcifikacija. Pri rutinska scintigrafija so 99mTc-MDP (metilen difosfonat), pokraj osteoliti~ni skeletni promeni, kako slu~aen naod, registrirani se i opse`ni mekotkivni depoziti vo belite drobovi i srceto. Dijagnozata na osnovnata bolest e postavena vo korelacija so anamnesti~kite podatoci, klini~kata slika, laboratoriskite naodi i primenata na soodvetnite nuklearno-medicinski immaging modaliteti. Slu~ajniot naod na mekotkivna akumulacija na osteotropnite traseri pri koskena scintigrafija uka`uva na postoewe na dopolnitelen patolo{ki supstrat i potreba za pravovremeno isleduvawe na istiot. Intenzitetot na uptake-ot ovozmozuva determinirwe na aktivnosta na gorespomenatiot proces. Klu~ni zborovi: metastatska kalcifikacija, 99m Tc , MDP DETECTION OF METASTATIC CALCIFICATION WITH 99m Tc-MDP SCINTIGRAPHY : CASE REPORT Stojanoski Sinisha1, Pop Gjorceva D1, Ristevska - Miceva S1, Tripunovski T1, Shubevska - Stratrova S2 Institute of Pathophysiology and Nuclear Medicine 1, Clinic for Endocrinology, Diabetes and metabolic diseases 2, Medical Faculty, Skopje, Macedonia Abstract Metastatic calcification represents a generalised phenomenon of calcium deposition into the interstitium of previously undamaged soft tissues. The pathogenesis of this process underlines the hydroxyapatit crystal formation associated with hypercalcemia and impaired calcium / phosphate metabolism. We present a case of a 65-year - old male patient with parathyroid adenoma and concomitant metastatic calcification. Upon performing a routine 99mTc-MDP bone scintigraphy, not only osteolytic skeletal findings, but also incidental substantial lung and heart soft tissue uptake has been observed. The diagnosis of the underlying disease was established by correlating the anamnesis data, patient‘s clinical history, laboratory findings and the use of the appropriate nuclear-medicine imaging modalities. Incidental findings of soft tissue tracer accumulation by bone scintigraphy indicate the presence of additional, previously unexpected, active disease process. Furthermore, the intensity of tracer localization in bone tracer specific imaging may help evaluate the activity of the metastatic calcification findings. Key words : metastatic calcification, 99m Tc , MDP Introduction Imaging with bone specific radiolabeled tracers can often lead to the dicsovery of incidental unexpected soft tissue uptake. Findings like these indicate the presence of calcium deposition outside the skeletal system – process known as soft tissue calcification (1). First described by Virchow in 1855, metastatic calcification, being just one type of soft tissue calcification, is associated with hypercalcemia caused by various disease processes: osteolytic tumors, chronic renal failure – secondary hyperparathyroidism (2-4); primary hyperparathyroidism - parathyroid adenoma (5), parathyroid carcinoma (6); vitamin D intoxication (7); steroid therapy or multiple myeloma (8), Hodgkin‘s lymphoma, sarcoidosis (9), Waldenstrom‘s macroglobulinemia, myositis ossificans, milk-alkali Sy (10). 99m Tc diphosphonate complex adsorb at the surface of hydroxyapatit crystals, predominantly in the skeletal system, but in certain conditions found also outside the bones, demonstrating the presence of unsuggested soft tissue calcium deposition. The selected case is a patient where analysis of the bone scan helped in the diagnosis of a previously unknown pulmonary and heart metastatic calcification. 35 Stojanoski S et al. Detection of Metastatic Calcification with 99m Tc-Mdp Scintigraphy : Case Report Case report B.S. 65-year old male patient, with incoming diagnosis: Osteoporosis; Hyperparathyroidismus a causa ignota, from the Clinic for Endocrinology, University Clinical Center – Medical Faculty, Skopje, was admitted and routine radionuclide bone scintigraphy was performed (740 MBq 99mTc-MDP injected i.v. into the venous system of the right hand). The disease was diagnosed taking into consideration the previous laboratory findings – high PTH levels (972 pg/ml; normal values 9,5 – 78 pg/ml), osteocalcin levels (27,1 ng/ml; normal values 3,1 – 13,7 ng/ml) and the increase of the levels of ionised calcium from 1,71 mmol/l up to 3,20 mmol/l (2,1 - 2,8 mmol/l). Although the anamnesis data did not indicate presence of concomitant kidney disorder, the laboratory findings presented borderline values of urea blood level - 8,9 mmol/ l (up to 8,3 mmol/l) and slightly increased values of serum creatinin - 173 ¼mol/l (up to 109 ¼mol/l) with mixed type proteinuria (nonselective glomerular and complete tubular proteins), classified as ++, 380 mg/l, combined with postrenal haematuria. The bone scintigram (Fig.1), performed 3 hours after the application of 99mTc-MDP, using standard positions (AP/PA), revealed pathological skeletal tracer accumulations into the mandibula and both zygomatical bones – diffuse type and into the right clavicula, the first and the eight rib – focal type. No pathological findings were observed on any of the other bones. However, on both AP and PA positions, pathological soft tissue accumulations have been observed in both lungs ( left with higher intensity ) and ,, ring ” heart accumulation. The final decision was classified as a finding typical for hyperparathyroidism with possible osteolytic changes and extensive soft tissue calcium depositions. and pulmonary emphysema with initial stage of right heart overloading ( Rtg of the lungs ). CT of the neck region was without any pathological findings. In order to detect and confirm the underlying reason for the impaired calcium metabolism and the evidently present hyperparathyroidism, the patient was instructed to complete the additional examination of the parathyroid glands with ultrasonography and 99mTc-MIBI (methoxy isobutil isonitrile) scintigraphy. The ultrasonography examination revealed presence of hypoechogenous oval formation 15 mm in diameter, just beneath the left thyroid lobe – very indicative to be an enlarged parathyroid gland – ( parathyroid adenoma? ). The parathyroid glands scintigrams ( Fig.2 ), obtained by using standard protocol (early scintigram 20 min., late scintigram - 2,5 hours after i.v. injection of 740 MBq 99mTc-MIBI), revealed the radiotracer,s increased uptake in the region just beneath the left thyroid lobe. These findings were classified as most probably indicative for a parathyroid adenoma. Fig. 2 99mTc-MIBI scintigraphy – increased radiotracer uptake in both early and late images The surgical procedure, Extirpatio adenomatis gl.parathyroideae inferioris sinistri, was performed 1 month after the diagnosis was confirmed. Fig. 1. 99mTc-MDP scintigraphy – soft tissue lungs accumulation (gradus III) and heart (gradus II). Additional morphological findings of the potentially affected organs revealed presence of a few small stones in both kidneys and one larger stone 10 mm in lenght in the left kidney pyelon ( CT of the abdomen ) 36 Discussion Soft tissue calcification can be classified into three major types: metastatic, dystrophic and idiopathic. Dystrophic calcification occurs as a result of tissue damage and is usually associated with normal calcium and phosphate plasma levels. This type of soft tissue calcification includes also some metabolic disorders – amiloidosis, connective tissue disorders – sclerodermia, infestation – cysticercosis and different types of vasculitis. Metastatic calcification, however, is always associated with impaired calcium/ phosphate metabolism, previously undamaged soft tissues and often presents itself affecting the lungs, heart, stomach, blood vessels and periarticular soft tissues (11). The pathogenesis of this process underlines the hydroxyapatit crystal formation with different chemical composition and structure depending on the etiology and the target organ. The main constituent of the visceral organ calcifications, especially in chronic kidney failure, is [ ( Ca Mg )3 (PO4)2 ], presented as amorphous substance or small crystals. On the other Stojanoski S et al. Detection of Metastatic Calcification with 99m Tc-Mdp Scintigraphy : Case Report hand, calcifications outside visceral organs have pyrophosphate as one of their main components. The pathogenesis of metastatic calcification was introduced for the first time by Wells in 1906 and was related to the organs which ,, excrete acid fluid into their cavities” (12) leaving their walls relativly alcaline, which on the other hand reduces the calcium solubility and creates preferable conditions for its deposition. This mechanism, at least theoreticaly, explains why the lungs, heart, kidneys and stomach are the most common target organs. It has been generally accepted that the metastatic calcification is associated with increased calcium/phosphate product (milimolar calcium concentration x milimolar anorganic phosphate concentration) (12). Values higher than 5 ( normal bellow 5 ) are considered to be pathological. Calcium deposition is increased also with increased tissue perfusion and interstitial fluid expansion. (13). After i.v. injection,78% of the 99mTc-MDP injected dose diffuses from the vascular space into the interstitium. The uptake of the 99mTc diphosphonate complex depends upon the tissue calcium content (Silberstein et al. 1975). Biodistributional studies have proven that in physiological conditions, in tissues with low calcium content (muscles – 0.005% and thyroid gland – 0.03%) the uptake of 99mTc - diphosphonate complex is just 0.005% ID/gr, whereas in tissues with high calcium content (14-24%) it can be up to 0.7% ID/gr. The presence of soft tissue calcification can have a substantial effect and can change these parameters. The uptake of the radiotracer is higher in the early stages of amorphous deposits compared with old hydroxyapatit crystals. In general, the earliest stages of calcium deposition are characterised with low calcium/ phosphate molar ratio, bigger adsorption capacity, high levels of complex hidration and low deposit density. The presence of magnesium ions into the deposits considerably lowers the 99mTc-MDP adsorbtion. Iron ions, if present in soft tissues, increase the uptake. According to the intensity of tracer‘s uptake into soft tissues, the following scale has been accepted (14): Gradus 0 – no uptake Gradus I – uptake lower than the bone Gradus II – uptake same as the bone Gradus III – uptake higher than the bone The soft tissue accumulations in our patient were classified as gradus II into the heart and gradus III into the lungs. Although the target organs for soft tissue calcium deposition have been determined by their own local conditions, it has been proven that the stage and activity of the process ( early deposits ) rather than the process localization ( older deposits ) determine the intensity of the tracer‘s uptake (15). The lungs are in 75% the target organ of metastatic calcification presentation.(16). The low pp CO2 into the extracellular fluid that surrounds the alveoli creates a tendency towards alkaline local environment, which favours the calcium deposition process, most frequently confined to the alveolar septum (16). This phenomenon is presented in a form of pulmonary edema or nonspecific infiltration process when radiographic diagnostic modality is being used. Rtg detection of these soft tissue calcifications is almost impossible considering the fact that in most cases the deposits are microscopic in size. Taking these facts into consideration, 99mTc-MDP scintigraphy could be used in the process of screening the occult lung calcification, although substantial controversy can be found concerning the specificity and sensitivity of this method (17). Certain entities, which present themselves with high MDP lung uptake and are by no means related to impared calcium/phosphate metabolisam, must be taken into consideration: Wegener‘s vasculitis (18), primary amiloidosis (19), Pneumocistis carini pneumonia (20), in order to avoid the unnecessary diagnostic mistakes. If detected on time and treated properly, metastatic calcification may be completely reversible (5-7). Calcium lung deposits could increase the probability of restrictive type pulmonary disease developement and consecutive pulmonary hypertension (21). Conclusions Our case is an example of soft tissue calcium deposition in a patient with primary hyperparathyroidisam caused by parathyroid adenoma. Incidental findings of soft tissue tracer accumulation by bone scintigraphy indicate the presence of additional, previously unexpected, active disease process. Considering the fact that the process of metastatic calcification is reversible and it could be cured with the appropriate treatment of the underlying disease, the early detection is essential. Furthermore, the intensity of tracer localization may help evaluate the activity of the metastatic calcification findings and enable follow up of patients who are at risk. References 1. Low RD, Hicks RJ, Arkles LB, Gill G, Adam W : Progressive soft tissue uptake of Tc-99 MDP reflecting metastatic microcalcification.Clin Nucl Med 1992;17:658 2. Di Leo C, Gallieni M, Bestetti A, et al.: Cardiac and pulmonary calcification in a hemodialysis patient: partial regression 4 years after parathyroidectomy. Clin Nephrol. 2003;59:59–63. 3. Taylor RE.: Multifactorial uptake of Tc-99m methylene diphosphonate in chronic renal failure. Clin Nucl Med. 2003;28:939–940. 4. Braga FJ, Miranda JR, Lucca LJ, et al.:Heart and lung accumulation of Tc-99m MDP with normal radiographs in patients undergoing hemodialysis. Clin Nucl Med. 2000;25:377–378. 5. Hwang GJ, Lee JD, Park CY, Lim SK: Reversible extraskeletal uptake of bone scanning in primary hyperparathyroidism. J Nucl Med 1996; 37:469 37 Stojanoski S et al. Detection of Metastatic Calcification with 99m Tc-Mdp Scintigraphy : Case Report 6. Davidson RM, Dhenkne RD, Moore WH, Butler DB :Metastatic calcification in a patient with malignant parathyroid carcinoma. Clin Nucl Med 1990; 15:692 7. Rosenthal DI, Chandler HL, Azzizi F, Schneider PB :Uptake of bone-imaging agents by diffuse pulmonary metastatic calcifications.Am J Roentgenol 1977;129:871 8. Eagel GA, Stier SA, Wakem C: Nonosseous bone scan abnormalities in multiple myeloma associated with hypercalcemia. Clin Nucl Med 1988;14:869 9. Krubsack A: Three phase bone scan in muscular sarcoidosis. J Nucl Med 1991; 32:1829 10. Castaigne C, Martin P, Blocklet D.: Lung, gastric, and soft tissue uptake of Tc-99m MDP and Ga-67 citrate associated with hypercalcemia. Clin Nucl Med. 2003;28:467–471. 11. Wheat D, McCarthy P: Metastatic pulmonary, gastric, and renal calcification demonstrated on bone scintigraphy in a patient with malignant melanoma and renal failure. Clin Nucl Med 1998;23:824 12. Velentzas C, Meindok H, Oreopoulos DG: Visceral calcification and the Ca x P product. Adv Exp Med Biol 1978;102:195 13. Du Cret RP, Boudreau RJ, Block JB, et al. : Exercise-induced muscle uptake of technetium-99m MDP. Clin Nucl Med. 1987;12:354–355. 14. Kok M, Case D, Billingsly J.: The use of bone scintigraphy to evaluate metastatic calcification caused by endstage renal disease and secondary hyperparathyroidism. Clin Nucl Med 2003; 28: 144"145. 15. Turklas Ozturk C, Guven M, Ugur P, Erzen C: Pulmonary alveolar microlithiasis in the absence of Tc-99mMDP uptake in the lungs. Clin Nucl Med 1988;13:883 16. Shigeno, Fukunaga M, Morita R: Bone scintigraphy in pulmonary alveolar microlithiasis: a comparative study of radioactivity and density distribution. Clin Nucl Med 1982;7:103 17. Nizami MA, Gerntholtz T, Swanepoel CR.: The role of bone scanning in the detection of metastatic calcification: a case report. Clin Nucl Med. 2000;25:407–409. 18. Kuynenhoven JD, Ommeslag DJ, Ackerman CM, Hilderson JM, Troch ME: Lung uptake on technetium-99mMDP bone scan in Wegener’s vasculitis. J Nucl Med 1996;37:857 19. Zwas ST, Shpilberg O, Huszar M, Rozenman J: Isolated ectopic lung uptake of technectium 99m methylene diphosphonate on bone scintigraphy in primary amyloidosis. Eur J Nucl Med 1990;17:282 20. Vaquer RA, Dunn EK, Bhat S, et al: Reversible pulmonary uptake and hypertrophic pulmonary osteoarthropathic distribution of technetium-99m methylene diphosphonate in a case of Pneumocystis carinii pneumonia. J Nucl Med 1989;30:1563 21. Margolin RJ, Addison TE: Hypercalcemia and rapidly progressive respiratory failure. Chest 1984;86:767 38 Acta morphol.2006; Vol.3(2):39-45 UDK: 616.833.17 - 009.11 TRETMAN NA ISPADI NA N. FACIALIS - LICEVA SIMETRI^NOST VO MIR Tuxarova-\orgova Smiqa1, Peneva M1, Karaxinova S2 Klinika za Plasti~na i Rekonstruktivna hirurgija1, Klini~ki centar- Skopje Ambulanta Akus Medikus2-Skopje, R. Makedonija Izvadok Mnogubrojnite traumi koi rezultiraat so nagrduvawa vo predelot na liceto i vratot, limfnite disekciite na vrat, kako i estetskite intervencii vo predelot na liceto i vratot mo‘e da dovedat do povreda na nekoja od grankite na liceviot nerv. Negovata pareza i paraliza ostavaat porazuva~ki funkcionalni i psihol{ki sekveli kaj pacientite, se gubi normalnata ekspresija na ~uvstavata, naru{ena e za{titnata uloga na o~nite kapaci , a leceviot deformitet e naj~esto nepovraten. Kompletnoto razbirawe na naru{uvawata na liceviot nerv ovozmo‘uva adekvatna primena na planot za rekonstrukcija. Nekolku mo‘nosti se dostapni za rehabilitacija na paraliti~noto lice. Adekvatnata procedura ja odbirame preku determiniraweto na etiologijasta na bolesta, fizikalniot pregled na pacientot, utvrduvawe na stepenot na paralizata, vozrasta i op{tata sostojba na pacientot. Tretmanot na licevata pareza i paraliza vsu{nost pretstavuva prevencija na komplikaciite, restavracija i rekonstrukcija na licevite dvi‘ewa, restavracija i podobruvawe na estetskiot izgled na liceto. Vo na{ata serija se opfateni 30 pacienti na vozrast od 20-60 godini. Pacientite se tretirani operativno (8 pacienti) i konzervativno (22 pacienti ambulantski se tretirani so elektrostimulacii). Nova operativna tehnika za prv pat primeneta kaj nas be{e lifting tehnikata - ”Contour Thread lift”. Site proceduri za lekuvawe na povredite na liceviot nerv imaat zna~ajna uloga i edinstvena cel korekcija na deformitetot i vospostavuvawe na funkcijata, licevata simetri~nost i licevata estetika vo mir. Klu~ni zborovi: liceva paraliza, liceva simetrija, hirur{ki tehniki, “Contour lift”, elektrostimulacija FACIAL NERVE PARALYSIS TREATMENT: FACIAL SYMMETRYAT REST Tudzharova-Gjorgova Smilja1, Peneva M1, Karadzhinova S2 Clinic of Plastic and Reconstructive Surgery1, University Clinical Center, AKUS Medikus2, Skopje, R. Macedonia Abstract Multiple trauma that result in facial and neck injury, lymph node neck dissections, and aesthetic procedures in the region of the face and neck may cause injures of the facial nerve branches. Its paresis and paralysis leaves devastating functional and aesthetic problems with loss of facial expression and inadequate function of the eyelids, Complete understanding of the facial nerve disorders is prerequisite for proper choice of the adequate reconstructive procedure for the paralyzed face. The etiology of the disorder, physical examination of the patient, age, general condition, and the stage of the paralysis are the chief factors that influence the management method. Most important treatment objective for individuals with facial nerve paralysis are prevention of complications, restoration with reconstruction of facial movement, and improvement of facial aesthetics. In our study 30 patients were included at the age of 20-60 years. Eight patients (26.7%) were operatively treated, and 22 patients (73.3%) were conservatively treated in the outpatient department with Transcutaneous Electric Nerve Stimulation (TENS). “Contour Thread Lift” technique is a new operative procedure that is used for the first time at our clinic. All the procedures used in the treatment of the paralytic face are equally important and have unique goal that is correction of the deformity and establishing facial symmetry, adequate function and facial aesthetics at rest. Key words: facial paralysis, facial symmetry, surgical techniques, Transcutaneous Electric Nerve Stimulation (TENS), Contour Thread lift, Introduction Facial nerve, or the VIIth intracranial nerve, consists of motor, sensitive and parasymapthic fibers, with the motor part being most developed. The motor fibers of the facial nerve innervate the facial expression muscles of the head and face, two of the suprahioid muscles and one muscle from the middle ear. The sensitive and parasymapthic fibers coming from the facial nerve are less developed and are known as n. intermedius. The sensitive fibers are responsible for the sense of taste for the first two thirds of the tongue, while the parasymapthic fibers innervate gl. submandibularis, gl. sublingualis, gl. lacrimalis, gll. palatinae and gll. nasales (1). The etiology of the facial nerve palsy is a major aspect that impacts the timing and the choice of the operative treatment. The stage of the paralysis as well as its symptoms can help determine its’ etiology. In addition, facial nerve paralysis can also be caused by viruses (Herpes simplex and Herpes Zoster, Coxackie virus, Epstein-Barr, Parotitis), bacteria (TBC, Lyme Borelia), congenital (Mobius Sy.), middle ear infections, trauma, tumors, systemic disorders, (diabetes, hypertension), 39 Tudzharova-Gjorgova S et al. Facial Nerve Paralysis Treatment: Facial Symmetry at Rest neurological autoimmune disorders, toxic damage and rare syndromes (Melkersson-Rosenthal) (2). Facial nerve injury according to its’ localization can be intracranial, intratemporal and extratemporal (in the parotid region, submandibular or temporomandibular region). Additionally facial nerve paralysis can be central or peripheral. Central paralysis is due to damage of supranuclear pathways and cerebral nuclei of the facial nerve. When this type of paralysis is present, the patient can elevate the eyebrows. On the other hand, the peripheral paralysis of the facial nerve can be either incomplete (paresis) or complete (paralysis). During peripheral paralysis, the patient can not elevate the eyebrows. The most known type of peripheral facial nerve paralysis is Bell’s paralysis that is characterized with facial asymmetry, inability to elevate the eyebrows, inability to close the eye, effacement of the nasolabial fold, oral incompetence with drooling, decreased tear production, change of the taste in the mouth, dry mouth, and hyperacusia. The most prevalent etiology for this facial nerve paralysis is viral (3, 4). There are 7 zones of possible facial nerve injury (5). Zone 1: - n. facialis, n. auricularis magnus - injury in this zone provokes insensibility of one third of the ear and of the upper third of the lower jaw Zone 2: - n. facialis, n. temporalis - injury in this zone provokes brow depression and visable assimetry when the forehead is lifted Zone 3: - n. facialis, n. marginalis mandibulae these patients can not show the theets and there is depression of the mouth angle Zone 4: - n. facialis, nn. Buccales - in this injury when the patient is laughting the afected side is not elevating. If this injury is not recognised, mustakes can be made when diagnosing of the side of the facial nerve injury Zone 5: - n. facialis, n. supraorbitalis, n. supratrochlearis - injury in this zone results with parestesia in the upper eyelid as well as in the part of the ferehaad Zone 6: - n. facialis, n. infraorbitalis - injury in this area results with parestesia in the lower eyelid, a part of the nose and the upper lip and the chick Table. 1 Segment Supranuclear Brain stem Meatal segment Labyrinthine segment Tympanic segment Mastoid segment Extratemporal segment Location Cerebral cortex Motor nucleus of facial nerve, superior salivatory nucleus of tractus solitarius Brain stem to IAC 40 NA 13-15 Fundus of IAC to facial hiatus Geniculate ganglion to pyramidal eminence Pyramidal process to stylomastoid foramen 3-4 8-11 10-14 Stylomastoid foramen to pes anserinus 15-20 The facial nerve pathway can be divided into 6 segments. Fig. 1. Length, mm NA Zone 7: - n. facialis, n. mentalis (thirth branch of n. trigeminus) - injury in this zone results with numbness and hyperestesia of the lower lip and the chin. These patients can not play instruments that need blowing The neurological deficit evident at rest becomes even more noteworthy when the patient is asked to performa a certain mimic. The aim of this study is to present the advantages of the “Contour Thread Lift” technique in reconstruction of the paralytic face. Its simple operative procedure can be used under local anesthesia making this procedure suitable also for children as well as an outpatient surgical procedure. Matherials and Methods In our study we analyzed 30 patients between the age of 20 and 60 years. Eight patients were treated operatively, while the other 22 patients were managed with electrostimulation. All patients underwent a detailed physical examination that included: face observation at rest; presence of facial expressions: reflex and emotional expressions; symmetry during movement: establishing the stage of synkinesia, the stage of brow ptosis, the ectropion, and the oral commissural competence, by differentiating whether the facial nerve paralysis is central or peripheral. Tudzharova-Gjorgova S et al. Facial Nerve Paralysis Treatment: Facial Symmetry at Rest Patients were also evaluated for audiometric function (tympanometry, acustic reflexes), neurohysiological function (electroneurography, electromyography); and with radiographic examinations (Rtg, CT, MRI). Surgical techniques used for facial nerve paralysis reconstruction are: transfers fascia m temporalis and fascia lata transfer), “Contour Thread Lift” –technique of tissue suspension with special surgical suture (6). Static procedures have one goal, suspension of a part of the face. Commonly used autologous materials for correction of the lower third of the paralyt. All of the tissues are harvested with relative ease and provide adequate length and tensile strength for use in the face (7) Static procedures of facial nerve paralysis treatment involve suspension of the orbicularis oris muscle to the temporal fascia using autologous or alloplastic material. The standard approach is through an incision in the temporal region aided by an incision at the nasolabial fold. A subcutaneous channel is then formed between the temporal fascia and the nasolabial fold through which the fascia lata strip is brought trough. The inferior end of the sling can be split into two tongues and each of them can be fixed to orbicularis oris fibers of the upper and lower lip. The position of the mouth on the unaffected side is used to determine the vector of suspension, and the proximal end of the facial sling is then fixed to the temporal fascia using non absorbable sutures. Some degree of overcorrection is necessary to account for postoperative relaxation of the autologous tissue. Disruption of the buccal branches of the facial nerve results in paralysis of the nasal muscle with collapse of the nostril. Patients may complain of unilateral nasal airway obstruction. The problem can be solved with static lateralization, suturing a fascia lata strip between the deep tissues of the lateral alar base and the temporal fascia or with a cartilage graft harvested from the ear. In both instances lifting of the nasal ala is accomplished (8). Oral commissural suspension and nasal lateralization may be achieved in a single procedure using multiple slings of fascia lata. Multiple slings with different vectors of tension generally produce superior results, as ideal positioning of both the ala and the oral commissural is difficult to achieve with a single vector. It’s worth mentioning that the “Contour lift” technique uses non absorbable sutures for face suspension (9). In this technique two tunnels between the temporal and the nasolabial region are made, using cannula through out which the sutures are passed and afterwards fixed with certain amount of tension in order to achieve symmetry. Transcutaneous electric nerve stimulation (TENS) in combination with Acupuncture provokes a biologic answer both locally and distantly. During this procedure physiologic response is activated either at the periphery or in the brain. Endogen opioids have important part when TENS is used for analgesia. However when this procedure is used for stimulation, the process goes through activation of the pituitary gland and the hypothalamus which in turn secrete neuro hormons. Percutaneous stimulation of the facial nerve pathways also provokes muscle contraction. If the above mentioned procedure incites an answer, then one can expect nerve regeneration to occur. If evoked electromyography doesn’t provoke an answer, then surgical operation is advocated. Nerve excitability was determined using the NET test (nerve excitability test), During TENS results are compared between the affected and normal facial area. Electro acupuncture needles were used for measuring the evoked potential of the facial muscles. EMG registrates muscle answer. Fibrillation of potential is present when the muscle is denervated, with poliphase potential present when the muscle is reinervated. Complete electrical silence is seen in case of fibrosis and facial nerve injury. Presentation of our cases: Case 1 Patient with a facial nerve paralysis due to removal of facial nerve tumor. Six years after the removal of the tumor a static suspension of the face structures is performed using autologous tissue, fascia lata. Photograph taken before the operation. (Figure 2) Fig. 2. Lagophthalmos phenomenon. (Figure 3) Fig. 3. A part of fascia lata will be used for suspension of the facial structures. Photograph taken intraoperatively (Figure 4) 41 Tudzharova-Gjorgova S et al. Facial Nerve Paralysis Treatment: Facial Symmetry at Rest Fig. 4. The procedure of static suspension. Photograph taken intraoperatively. (Figure 5) Fig. 7. Fig. 5. Two years after the operation. Facial symmetry is maintained. (Figure 6) . Fig. 8 Fig. 6. Cases 2 and 3 Patients with a Bell’s palsy, treated with TENS. (Figure 7-11) Fig. 9. 42 Tudzharova-Gjorgova S et al. Facial Nerve Paralysis Treatment: Facial Symmetry at Rest In this patient, the facial suspension was performed with the use of “Contour Thread Lift” technique. Suspension of the upper and lower lip was performed. Photograph after the operation. (Figure 13) Fig. 13. Photograph 2 years after the operation. Facial symmetry is maintained, there is no additional sagging of the facial structures. (Figure 14) Fig. 10. Fig. 11. Case 4 Patient with congenital facial nerve paralysis. Photograph taken before the operation. (Figure 12) Fig. 14. Case 5 Patient with congenital facial nerve paralysis. Photograph taken before the operation. The patient under general anesthesia. . (Figure 15) Fig. 12. Fig. 15. 43 Tudzharova-Gjorgova S et al. Facial Nerve Paralysis Treatment: Facial Symmetry at Rest In this case too, “Contour Thread lift “technique was applied. Fig. 16. Photograph taken after the operation. (Figure 16) Results The House-Brackmann Facial Nerve Grading System (stage1-6) is used to determine the spectrum of facial dysfunction and the stage of facial paralysis. (Table 2) According to the House-Brackmann Facial Nerve Grading System (stage I - normal function, stage VIcomplete paralysis) we have the following results: out of 30 patients included in our serial 10 were in stage III and 12 in stage IV. Eight of our patients were surgically treated: 5 of them in stage V, and 3 in stage VI “Contour Thread Lift” technique is a new operative technique that can be used in conjunction with local anesthesia and leaves no visible scars. It allows correction of the oral commissure and accomplishes facial symmetry at rest. It is one day surgery and the operative technique can be used in children as well. The patient was followed up for 2 years. The TENS treatment lasts for 21 days. In 7 patients the treatment was repeated until complete correction of the oral commissure was achieved. During electric stimulation, neuron metabolic activators are stimulated that excite the axons, make progression of the myelin, enhance the potential and consequently return the function of the facial muscles. Objective measurement of facial symmetry we made using photographs and videos. We also evaluated the psychological reactions of the patients before and after the treatment and we noticed positive answer and return of the confidence. Discussion Patients with complete unilateral facial nerve paralysis have facial asymmetry, depression of the eyebrows, inability to close the eye (Lagophthalmos), lower eyelid paralysis (Ectropion), decreased tear production, corneal damage, depression of the mid face, effacement of the nasolabial fold, nasal obstruction secondary to collapse of the nasal ala, inability to smile (asymmetry), oral incompetence and drooling,. Static suspension is possible with the lifting technique as with the other standard surgical techniques. Lifting the oral commissure establishes facial symmetry at rest and improves oral competence. Closing of the eye with golden plate and medial canthotomy establishes surgical canthal symmetry. According to Peitersen, facial nerve paralyses of less than 18 - 24 month duration can successfully be treated with electric stimulations (TENS), leading to restoration of the predominance of facial nerve function. Slow progressing paralysis suggests malignant disease, where as sudden onset of paralysis is a sign of a Bell’s palsy. If the paralysis is due to malignant disease or due to resection Table 2. House-Brackmann Facial Nerve Grading System Stage 44 characteristics I normal Normal facial function in all areas II Mild dysfunction Slight weakness noticeable on close inspection; may have very slight synkinesis III Moderate dysfunction Obvious, but not disfiguring, difference between 2 sides; noticeable, but not severe, synkinesis, contracture, or hemifacial spasm; complete eye closure with effort IV Moderately severe dysfunction Obvious weakness or disfiguring asymmetry; normal symmetry and tone at rest; incomplete eye closure V Severe dysfunction Only barely perceptible motion; asymmetry at rest VI Total paralysis No movement Tudzharova-Gjorgova S et al. Facial Nerve Paralysis Treatment: Facial Symmetry at Rest because of malignancy, the treatment and the reconstruction are different. According to Peitesen, in patients with partial paralysis the nerve recovery with electro stimulations is complete. In patients with trauma or surgical lesion, the nerve reconstruction should be made in period no longer than 30 days. The most important treatment objective for individuals with facial paralysis is prevention of complications, restoration and reconstruction of facial movement, restoration and improvement of facial aesthetics. The protocol of facial symmetry reconstruction includes: facial symmetry at rest, adequate facial function including oral competence and eye closure, spontaneous facial expression, absence of synkinesis or mass movement. Conclusion Facial nerve paralysis is a serious problem for the patient and a great challenge for the surgeon. The aim of the reanimation is facial symmetry including adequate eye closure, oral competence,spontaneous facial expressions, and absence of synkinesis. In the reconstruction of the paralytic face, both static and dynamic operative procedures find their place. Facial suspension can be employed together with the dynamic procedures, when the dynamic procedures have failed or as a single procedure. No matter the mode of their use, static procedures have important place in reestablishing facial symmetry and aesthetics at rest. References 1. 2. 3. 4. 5. 6. 7. 8. 9. Anica Kargovska Klisarova, Josif Josifov: Anatomy. Head and neck. 1984;94-98 Facial Nerve Paralysis, Static Reconstruction, www.emedicine.com/plastic/topic221.htm B. Radojcic: Klinicka neurologija Facial nerve paralysis, www.plastic-surgery-options.com Brooke R Seckel: Facial danger zones,QMP,1994 Christopher Stone, Plastic Surgery Facts John Marquis Converse, et al: Reconstructive Plastic Surgery,second edition, p.1174-1867 May M: Regional reanimation: nose and mouth. In: The Facial Nerve: May’s Second Edition. 2000;775-795 Konior RJ: Facial paralysis reconstruction with Gore-Tex Soft Tissue Patch. Arch Otolaryngol Head Neck Surg 1992 Nov; 118(11):1188-94 45 Acta morphol.2006; Vol.3(2):46-50 UDK: 796.332.071.2.015 - 056.25 VLIJANIETO NA TRENA@NIOT PROCES VRZ TELESNIOT SOSTAV, INDEKSITE NA ISHRANETOST I TESTOSTERON-KORTIZOL ODNOSOT KAJ PROFESIONALNI FUDBALERI Hanxiski Zoran, Maleska V, Petrovska S, Nikoli} S, Hanxiska E Institut za fiziologija so antropologija, Medicinski Fakultet, Skopje, R. Makedonija Izvadok Novite istra‘uvawa poka‘uvaat deka maksimalnata sila i izdr‘livost na muskulite se namaluva za vreme na natprevaruva~kata faza od profesionalniot fudbalski trena‘en proces. Vi{okot na masna komponenta, zaedno so promenata na nekoi indeksi na ishranetost, mo‘at u{te pove}e da gi potenciraat gorenavedenite promeni preku namaluvawe na eksplozivnosta i brzinata. Ako ovie promeni se prosledeni so namaluvawe na testosteron-kortizol odnosot toga{ mo‘ebi stanuva zbor za nesoodvetno prilagoduvawe ili pojavuvawe na znaci na akutno prekumerno optovaruvawe ili “overtraining”. Cel na ovaa studija e da se evaluiraat promenite na telesniot sostav, nekoi indeksi na ishranetost i testosteron-kortizol odnosot kaj profesionalni fudbaleri vo tekot na edna natprevaruva~ka polusezona. Vo ovaa studija bea vklu~eni 30 profesionalni fudbaleri od eden tim od prvata fubalska liga. Ispituvawata bea sprovedeni vo tri to~ki: vo po~etokot na podgotvitelniot period, pred po~etokot na natprevaruva~kiot period i po zavr{uvawe na natprevaruva~kiot period. Apsolutnata i relativna muskulna i masna masa i indeksite na ishranetost (masna i muskulna povr{ina na nadlakticata i BMI) bea odredeni so antropometriski merewa i soodvetni predvideni formuli. Pred i posle maksimalen ergometriski test be{e zemena venska krv i odredeni serum koncentracii na testosteron i plazma koncentracii na kortizol so pomo{ na RIA. Iako nema{e zna~itelni razliki vo komponentite na telesniot sostav i indeksite na ishranetost pome|u trite periodi od trena‘niot proces, namaluvaweto na muskulnata i zgolemuvaweto na masnata komponenta e nepovolen efekt od trana‘niot proces i dietetskite naviki vo odnos na fudbalskata igra. Ne postoe{e zna~itelna povrzanost na telesniot sostav i indeksite na ishranetost so testosteron-kortizol odnosot, ~ie pak zna~itelno namaluvawe na krajot od natprevaruva~kiot period mo‘ebi e povrzano so nesoodvetna adaptacija i zamor. Klu~ni zborovi: telesen sostav, indeksi na ishranetost, testosteron, kortizol, fudbal. THE INFLUENCE OF TRAINING PROCESS ON BODY COMPOSITION, INDEXES OF NUTRITION AND TESTOSTERONE-CORTISOL RATIO IN PROFESSIONAL SOCCER PLAYERS Handzhiski Zoran, Maleska V, Petrovska S, Nikolik S, Handziska E Institute of Physiology with Anthropology, Medical Faculty, Skopje, Republic of Macedonia Abstract Recent researches show that the maximal strength and endurance of muscles have been decreased during the competition phase of the professional soccer training process. The excess of fat mass, together with the change in some of the nutritional indexes, could additionally reduce the explosiveness and speediness, thus enhancing the above mentioned changes. If these changes are accompanied with decrease of testosterone-cortisol ratio than it could possibly be the case of inadequate adaptation or first signs of overreaching or “overtraining”. The aim of this study is to evaluate the changes of body composition, some indexes of nutrition and testosterone-cortisol ratio in professional soccer players during a competition half-season. This study included 30 professional soccer players recruited in a soccer team. The researches were conducted in three points: at the beginning of the 46 preparation period, before the start of the competition period and after the ending of the competition period. Absolute and relative muscle and fat mass and indexes of nutrition (muscle and fat surface of upper arm, BMI) were obtained with anthropological measurements and some predictive formulas. The venous blood was taken before and after maximal exercise test and serum levels of testosterone and plasma levels of cortisol were measured by RIA. Despite insignificant differences of body composition and indexes of nutrition between the three periods of training process, decreasing of muscle mass and increasing of fat mass are undesirable effect of training process related to soccer game. There were insignificant relationships between body composition and indexes of nutrition and testosterone-cortisol ratio. The significant decreasing of this ratio at the end of competition period could be connected with inadequate adaptation and fatigue. Handzhiski Z et al. The Influence of Training Process Key words: body composition, indexes of nutrition, testosterone, cortisol, soccer. Introduction Muscle strength and power are the keys for explosiveness and endurance in modern soccer game. The new researches show that the muscle strength and endurance during the competition phase of training process, when a lot of games take place, decreases with the decline of sports form (1). On the other side, the excess of fat mass is “undesirable” effect that compromises the speediness and explosiveness of soccer player. Although BMI is regularly determinated in soccer clubs, some other indexes of nutrition, as muscle and fat surface of upper arm, are of interest in evaluation of the effects of training process and nutrition advices. Therefore, the changes of these indexes and body composition, in correlation with changes in testosteronecortisol ratio, could give the first sings of overreaching or “overtraining”. This ratio suggests eventually the positive effects of training process when increased concentration of testosterone increases the muscle mass, strength and endurance. The decrease of this ratio for more than 30% suggests that there is an inadequate adaptation of hypothalamo-pituitary axis, and is one of the signs of clinically undefined syndrome of “overtraining”. Some new studies suggest that at the end of the competition season, 10-30% of soccer players have some signs of “overtraining”. The aim of this study is to evaluate the changes of body composition, some indexes of nutrition and testosterone-cortisol ratio in professional soccer players during a competition half-season. . Material and Methods The body composition, absolute and relative muscle (MM kg; MMP%) and fat mass (FM kg; FMP%), some indexes of nutrition, muscle and fat surface of upper arm (MMA cm2 and FMA cm2) and BMI, in 30 professional soccer players of a soccer club were obtained by anthropometric parameters and prediction formulas by Mateigka and Frischenko. Venous blood was taken before and after maximal progressively increased ergometric test for determining the serum concentration of testosterone and plasma concentration of cortisol by RIA, from which the testosterone-cortisol ratio (T/C) was obtained. These researches were conducted in the morning, at the Institute of Physiology with Anthropology, in the week of decreased intensity and volume of physical load, at: the beginning of phase of preparation (phase I), beginning of phase of competition (phase II) and after finishing the phase of competition (phase III). Descriptive statistic, ANOVA and correlations were used (p<0.05). Results The mean values and standard deviations of muscle and fat mass, as their differences between three phases of training process, are presented in Table 1. There is no significant difference in body composition between the three phase of the training process, despite the decrease Table 1. Changes of Body Composition of Professional Soccer Players During a Competition Half-season. Phase of training process MM kg MMP % FM kg FMP % p<0.05 Before preparation (phase I) Before competition (phase II) After finishing the half-season (phase III) 42.13 ± 4.13 55.19 ± 2.04 10.64 ± 1.17 13.56 ± 0.63 n.s. 41.73 ± 4.75 54.53 ± 2.05 10.71±1.16 13.92 ± 0.69 n.s 42.28 ± 4.63 54.66 ± 2.52 11.03 ± 1.03 14.26 ± 0.93 n.s Table 2. Changes of Indexes of Nutrition of Professional Soccer Players During a Competition Half-season. Phase of training process MMA sm2 FMA sm2 BMI kg/m2 p<0.05 Before preparation (phase I) Before competition (phase II) After finishing the half-season (phase III) 57.30 ± 7.59 9.80 ± 2.36 23.89 ± 1.40 n.s 57.00 ± 8.13 10.71 ± 2.24 24.04 ± 1.20 n.s 64.61 ± 12.85 10.91 ± 2.86 23.13 ± 4.85 n.s 47 Handzhiski Z et al. The Influence of Training Process 0.14 0,06 exercise induced answer of testosterone/cortisol ratio of muscle mass after the phase I and continuously increase of fat mass at the and of phase of competition The mean values and standard deviations of muscle and fat surface of upper arm and BMI, as their differences between three phases of training process, are presented in Table 2. There are no significant differences in indexes of nutrition between the three phase of training process, despite the increase of muscle and fat surface of upper arm at the and of phase of competition. The differences of testosterone-cortisol ratio before and after maximal ergometric test between three phases of training process are presented on Chart1. There were significant differences in this ratio between all three phases of training process. There is significant increase of this ratio after phase of preparation (phase I) and significant decrease after the phase of competition (phase III). The decrease of testosterone-cortisol ratio is more that 30%. 0,05 0,04 I phase 0,03 II phase 0,02 III phase 0,01 0 1 three phases of training process Chart 2. Changes of Maximal Egometric Exercise Induced Response of Tesosterone/cortisol Ratio in Professional Soccer Players During a Competition halfseason (p < 0.05 between and II phase and II and III phase of training process). 0.12 testosterone/cortisol 0.1 0.08 I phase 0.06 II phase III phase 0.04 0.02 0 at re st afte r e xe rcise Chart 1. Changes of Testosterone-cortisol Ratio at Rest and After Maximal Ergometric Test in Professional Soccer Players During a Competition Half-season (p < 0.05 between I, II and II phase of training process). The differences of maximal ergometric exercise induced response of testosterone-cortisol ratio between the three phases of training process are presented on Chart 2. There are significant differences between I and II phase and II and III phase. Namely, there is significant increase of this response after the phase of preparation and its significant decrease after ending the phase of competition. The changes of body composition and some indexes of nutrition were not significant connected with the changes of testosterone-cortisol ratio, before and after maximal exercise, in the three phase of training process (Table 3). Discusion The insignificant differences of muscle mass between all phases of training process provoke the necessity of new strategies in training process, especially in training of strength. It is necessary to redesign the 48 phase of preparation of training process that should increase muscle mass (2). The relative fat mass of 13-14% in soccer players of this club is too high compared with elite European soccer players of 8-10% (3,4). New nutrition efforts are necessary in education of professional soccer players due to increasing of fat mass at the end of phase of competition. Although insignificant, the increase of muscle and fat surface of upper arm at the end of phase of competition suggest on increased protein and energetic income or on decreased intensity and volume of training process which regularly happened at the end of phase of competition (5,6,7). New strategies of training and nutrition would be necessary for the next season, especially for the phase of competition. The significant increase of testosterone-cortisol ratio and its maximal exercise induced response after the phase of preparation, although not connected with body composition and indexes of nutrition, suggest on positive effect of training process in phase of preparation (8). This effect is maybe connected with the level of intensity and volume of training process and the week of decreased intensity of training, when these investigations were conducted (9). Accordingly, with the new data and studies, the insignificant decrease of testosterone-cortisol ratio and its maximal exercise induced response are maybe expected and are connected with the fatigue and the depletion of reserves of adaptation at the end of season. On the other side, the decrease of this ratio more than 30%, compared with phase I and II, although not connected with body composition and indexes of nutrition, may indicate overreaching or “overtraining”(10,11,12). Nevertheless, without information on other hormonal answers, specific field tests of soccer performance and psychological tests, these changes should suggest high risk of lack of adaptation or stagnation in training process (13,14). Handzhiski Z et al. The Influence of Training Process Table 3. Correlations Between Testosterone-cortisol Ratio Before and After Maximal Ergometric Test and Body Composition and Indexes of Nutrition in Professional Soccer Players During a Competition Half-season. Phase of training process I phase II phase III phase MM (kg) MMP (%) FM (kg) FMP (%) MMA (sm2) FMA (sm2) BMI (kg/m2) MM (kg) MMP (%) FM (kg) FMP (%) MMA (sm2) FMA (sm2) BMI (kg/m2) MM (kg) MMP (%) FM (kg) FMP (%) MMA (sm2) FMA (sm2) BMI (kg/m2) Testosterone-cortisol ration before maximal exercise test Testosterone-cortisol ratio after maximal exercise test 0.15 0.32 -0.01 -0.11 0.06 -0.11 0.05 0.41 0.28 0.24 0.05 0.37 -0.09 0.31 0.33 0.35 -0.11 0.20 0.15 -0.15 0.26 0.10 0.32 -0.05 -0.23 0.09 -0.19 -0.11 0.03 -0.04 -0.12 0.07 -0.01 -0.09 -0.01 0.21 0.11 0.16 -0.19 0.18 -0.11 0.28 r = o.42; p<0.05 (n.s) Conclusion There are insignificant changes of absolute and relative muscle and fat mass of professional soccer players during a competition half season, although there is a trend of continuous increase of fat mass at the end of the phase of competition. There are insignificant changes of muscle and fat surface of upper arm and BMI of professional soccer players during a competition half season, although there is a trend of continuous increase of muscle and fat surface of upper arm at the end of phase of competition. There is significant increase of testosteronecortisol ratio after the phase of preparation and its significant decrease at the end of phase of competition, more than 30%. There are insignificant correlations between the changes of testosterone-cortisol ration and the changes of body composition and indexes of nutrition. References 1. Stolen T, Chanari K, Castagna C, Wisloff V. Physiology of soccer. Sports Med 2005; 35(6):501-536. 2. Vanderford M, Meyers M, Skelly W, Stewart c, Hamilton K. Physiological and sport-specific skill response of Olympic youth soccer athletes. J Strenght & Conditioning Research 2004; 18(2):334-342. 3. Thomas V, Reilly T. Fitness assessment of English League soccer players throughout the competitive season. Br J Sports Med 1979; 13:103-109. 4. Wilmore J.H, Haskell W.L. Body composition and endurance capacity of professional football players. J App Physiology 1972; 33:564-567. 5. Ramadan J, Byrd R. Physical characteristics of elite soccer players. J Sports Med Phys Fit 1987; 27:424-428. 6. Raven P, Gettman L, Pollock, Cooper K. A physiological evaluation of professional soccer players. Br J Sports Med 1976; 109:209-216. 7. Bangsbo J. Energy demands in competitive soccer. J Sports Sci 1994; 12(Suppl):S5-S12. 8. Banfi G, Maineii G, Roi S, Agape V. Usefulness of free testosterone/cortisol ratio during a season of elite speed skating athletes. International Journal of Applied Physiology 1993; 14:373-9. 9. Bosco C, Colli R, Bonomi R, Duvilard SP, Viru A. Monitoring of strength training. Neuromuscular and hormonal profile. Medicine and Science in Sports and Exercise 2000; 32:202-8. 10. Urhausen A, Gabriel H, Kinderman W. Impaired pituitary hormonal responses to exhaustive exercise in overtrained athletes. Medicine and Science in Sports and Exercise 1998; 30:407-14. 49 Handzhiski Z et al. The Influence of Training Process 11. Lehmann M, Foster J, Steinacker W, Lormes J, Steinacker M, Liu Y, Optiz-Gress A, Gastman U. Training and overtraining: overview and experimental results. Journal of Sports Medicine and Physical Fitness 1997; 37:7-17. 12. Urhausen A, Gabriel H, Kinderman W. Blood hormones as markers of training stress and overtraining. Sports Medicine 1995; 20:351-76. 13. Viru A, Viru M, Karelson K, Janson T. Hormones in biochemical monitoring of training. Journal of Physiology and Pharmacology 50 1999; (Suppl.1):101. 14. Hooper SL, Mackinnon LT, Howard A. Physiological and psychometric variables for monitoring recovery during tapering for major competition. Medicine and Science in Sports and Exercise 1999;31:1205-10. 50 Acta morphol.2006; Vol.3(2):51-54 UDK: 340.66:616 - 036.88 ODREDUVAWE NA VREMETO NA NASTAPUVAWE NA SMRTTA SO HENSSGE NOMOGRAM Poposka Verica, Janeska B, Gutevska A, ^akar Z Institut za sudska medicina i kriminalistika, Medicinski fakultet, Skopje, Republika Makedonija Izvadok Odreduvaweto na vremeto na smrtta vo sudko medicinskata ekspertiza e pra{awe od golem interes, osobeno vo slu~ai na nasilna smrt so nepoznat storitel. Postmortalnoto ladewe na teloto pretstavuva eden od va`nite parametri pri odreduvaweto na vremeto na smrtta vo raniot postmortalen period. Vo ovoj trud e prika`ano odreduvaweto na verojatnoto vreme na smrt so upotreba na nomogramot po Henssge. So sporeduvawe na dobienite rezultati vo odnos na vistinskoto vreme na smrtta, napraven e obid da se utvrdi preciznosta pri odreduvaweto na vremeto na smrtta so primenetiot metod. Vo trudot se analizirani 50 slu~ai obducirani vo Institutot za sudska medicina i kriminalistika vo Skopje, so poznato vreme na smrt. Izvr{eno e merewe na rektalnata temperatura na teloto so digitalen termemetar. Istovremeno e izvr{eno merewe na temperaturata na sredinata, telesnata te`ina na teloto i zabele`ano e dali e teloto oble~eno ili golo. So sporedba na poznatoto vreme na smrtta so vremeto na smrtta dobieno so primenetiot nomogram, utvrdeno e otstapuvawe od nekolku ~asa. Klu~ni zborovi: vreme na smrt, rektalna temperatura, ambientalna temperatura, nomogram ESTIMATION OF TIME SINCE DEATH BY THE HENSSGE-NOMOGRAM Poposka Verica, Janeska B, Gutevska A, Chakar Z. Institute of Forensic Medicine and Criminology, Faculty of Medicine, Skopje, R Macedonia Abstract Estimation of time since death in the field of forensic medicine expertise is an issue of high interest, especially in case of violent death caused by unknown executor. Post mortem cooling of the body is one of the pertinent parameters in estimation of time since death during the early postmortem period. The estimation of possible time of death with Henssge nomogram is presented in this paper. To determine preciseness of time of death by the applied method, the results were compared with the true time of death. This paper presents the analysis of 50 cases autopsied at the Institute of Forensic Medicine and Criminology in Skopje, with known time of death. Rectal temperature was taken with digital thermometer. Simultaneously, environment temperature was measured as well as the body weight; it was recorded whether the body was covered or naked. Comparison of the known time of death with the time obtained by the applied nomogram, has shown a discrepancy of few hours. Key words: time of death, rectal temperature, ambient temperature, nomogram Introduction In the forensic medicine expertise the precise time of death is an issue of special interest in many cases after finding the body of the diseased. Preciseness of answers is substantial in the reconstruction and clarification of circumstances, particularly in murder cases, un-witnessed, killer unknown; in traffic accidents of carhit casualties with driver escaped from the scene; and many other cases. Estimation of time since death in the forensic medicine practice includes two expertises, one considering the early postmortem period (24-48 h) and the other the late postmortem period when body has started to decompose. Preciseness of estimation of time since death decreases as time interval since death increases.(1,2) Approximately, time of death in the early postmortem period is routinely estimated by conventional methods of corpse examination by observing the development of postmortem changes.(3) Postmortem cooling of the body is one of the important parameters upon estimation of time since death. Body cooling is a complex issue and it is difficult to estimate the time since death based on it, due to the fact that there is a variety of circumstances that have impact on it: body volume; body surface; body position; covered/ naked body; environment temperature and the medium.(4,5,6) Purpose of this paper is to determine possible time of death with Henssge nomogram, compare obtained results with true time of death and determine preciseness in estimation of time of death by the applied method. Materials and Work Method 50 cases have been analyzed in this paper, autopsied at the Institute of Forensic Medicine and Criminology - Faculty of Medicine, Skopje, with known time of death. 51 Poposka V et al. Estimation of Time Since Death by the Henssge-Nomogram The group is non-homogenous in regard to time since death, as shown in the attached Table 1. For the needs of analysis, following has been recorded: time of death, clothing condition (body covered or naked), sex and age. Then measuring has been done of: body weight, body height, rectal temperature and environment (ambient) temperature. Henssge Nomogram Henssge nomogram allows for fast and precise estimation of time since death. It has been applied over the last ten years. Nomogram method is based on a formula which follows the sigmoid shape of the cooling curve, as obtained by taking the rectal temperature. This formula contains two exponential parts. The first represents the post mortem plateau and the second constant shows the exponential drop of t after the plateau according to Newton’s law on cooling (Fig. 1). Using previously announced data and findings stating that relative length of postmortem plateau depends on the t of the environment, Henssge made two nomograms, one for below 23°C and the other for above 23°C. Fig. 1 shows an example of its use. In the nomogram there is an addition for the impact of ambient temperature over the speed of cooling and the impact of body weight (7,8,9). In order to determine the possible time of death for each individual case, a line is drawn that links the rectal and environment temperatures. Through the cross-point obtained by the oblique line, a line is drawn and afterwards, taking into consideration the body weight expressed in kg, the possible time of death expressed in hours is read on the nomogram. Fig. 1. 52 Results and Discussion Estimation of possible time of death after the Henssge Method represents an estimation by a nomogram which includes temperature plateau, ambient temperature and body weight (9,10). Results obtained by the Henssge nomogram show discrepancy from true time of death as shown in Chart 1. 25 20 15 ho urs 10 5 0 -5 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 Cases Henssge Chart 1. Discrepancies obtained by Henssge Analyzing obtained results, it was observed that discrepancies from true time of death have been less (from -2 to +3 hours) with postmortem period up to 15 hours, which applies to 34 cases. When postmortem period increases above 15 hours, discrepancies from true time of death are bigger and range between +7 to +20 hours. This refers to cases nos. 35 - 50, but we must consider that with these cases the differences between the rectal and ambient temperatures were very small, i.e. about 1OC. Cases nos. 44, 45 and 46 are exceptional - discrepancies for postmortem of 20 hours was +3 and +4 hours, but here Poposka V et al. Estimation of Time Since Death by the Henssge-Nomogram Table 1. Cases with known time of death Case Age 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. 51 54 54 26 16 49 35 38 20 55 58 69 52 44 35 53 75 76 60 59 44 62 38 60 29 57 40 42 44 74 54 53 67 32 36 60 53 37 32 37 25 25 20 24 75 34 31 44 24 58 Sex Time since death (h) M 4 F 4 M 4 F 4 M 4 M 5 M 5 M 6 F 6 M 6 M 6 M 6 M 6 F 7 M 7 M 7 M 7 M 7 M 7 M 7 M 7 M 8 M 8 M 8 M 9 M 10 M 10 M 12 M 13 M 13 M 13 M 14 F 14 F 14 M 15 M 15 M 15 M 15 M 16 M 17 M 19 M 19 M 19 M 20 M 20 M 20 F 21 M 22 M 24 M 24 T°C T°C Body Body Covered rec- ambi- weight height tum ent (kg) (cm) 34,9 34,4 35,1 34,7 35,9 33 36,5 32,8 32,2 34 33,2 33 34,1 32 30,6 32,5 33 33,9 33,8 33 35,4 32 32,4 32,6 32 31,6 30,9 27,2 29,6 28,8 28,1 28,4 27,2 27,5 27 25,9 24,1 24,5 24 23,5 23 23,5 23 22,7 22,5 22,5 22 21,6 21,3 21,8 17 22 19,3 22,5 22,4 24 21 22,4 22 21 16,5 20 24,5 21 16 21,3 24 24 24 22,5 30 21 21,2 21 24 19 23 15,7 24 21 16,5 18 20,6 20 23 24,4 23,6 20 21 23 19 22 22 17 17 17 20,5 21 20 21 65 65 78 75 65 75 80 80 58 75 60 78 70 57 80 80 78 82 84 70 75 72 55 85 50 78 80 75 80 83 80 75 54 45 75 76 75 80 73 95 80 95 85 75 70 76 65 73 80 60 168 160 180 166 175 176 175 174 165 172 158 173 166 160 175 172 176 175 178 164 177 168 159 180 159 174 180 173 178 180 179 172 151 166 174 175 180 181 166 187 184 180 184 180 173 175 155 175 178 163 + + + + + + + + + + + + + + + + + + + + + + + + + + + + - Causa mortis Infarctus myocardii Schock traumaticus Vulnera explosiva Electrocutio Contusio cerebri Intoxicatio cum pesticidi Vulnera sclopetaria Vulnera sclopetaria Schock traumaticus Embolia pulmonis Tamponada cordis Vulnera punctata Infarctus myocardii Intoxicatio cum HCl Schock traumaticus Insufitientio myocardii Schock traumaticus Schock traumaticus Schock traumaticus Schock traumaticus Electrocutio Embolia trombotica Infarctus cerebri Meningitis Asphixio propt. Aspiratio Suspensio Vulnera sclopetaria Schock traumaticus Schock traumaticus Schock haemorrhagicus Insufitientio myocardii acuta Ruptura aneurismae aortae Schock traumaticus TBC Vuln. Schlopet. capitis Schock traumaticus Canalis punctum cordis Canalis sclop. Cerebri Vulnera sclopetaria Vulnus sclopet. Thoracis Schock traumaticus Schock traumaticus Schock traumaticus Vulnera sclopetaria Vulnera sclopetaria Vulnera sclopetaria Insufitientio myocardii acuta Contusio pulmonum Intoxicatio cum opiati Contusio cerebri 53 Poposka V et al. Estimation of Time Since Death by the Henssge-Nomogram we had bigger difference between rectal and ambient temperatures. From Graph no. 1 it is possible to see that with a total of 8 cases (cases nos. 1, 5, 11, 13, 18, 19, 21 and 32) there was no discrepancy of obtained possible time and the true time of death. We can conclude that by Henssge nomogram which includes the postmortem temperature plateau and the effects of ambient temperature and body temperature over body cooling, good results have been obtained, i.e. discrepancy varied between –2 to +3 hours. Henssge nomogram cannot be applied with cases where rectal and ambient temperatures are close in value. Conclusion Estimation of possible time of death by using Henssge nomogram show that preciseness of results depends on the length of postmortem period. Mainly discrepancies range between -2 to +3 hours but only in cases where the difference between the rectal and ambient temperatures is several degrees. It is impossible to estimate possible time of death by Henssge nomogram in case of small difference between the rectal and ambient temperatures, i.e. when body temperature has approximated the environment temperature because it results in big discrepancies. References 1. Zeèeviæ D i suradnici, Sudska medicina i deontologija, 4.obnnovljeno i dopunjeno izdanje, Medicinska Naklada Zagreb, 2004, 31-36. 2. Di Maio D.J, Di Maio V.J.M. Forensic Pathology, 1Id ed., CRC Press LLC 2000, 21-41 3. D i suradnici, Sudska medicina i deontologija, 4.obnnovljeno i dopunjeno izdanje, Medicinska Naklada Zagreb, 2004, 31-36. 4. Di Maio D.J, Di Maio V.J.M. Forensic Pathology, 1Id ed., CRC Press LLC 2000,21-41 5. Janeska B., Chakar Z., Stankov A., Boshkovski K., Belakaposki M., Duma A. Ulogata na veshto lice pri uvid na mestoto na nastanot. Policijata, Javnoto Obvinitelstvo, Sudot, Advokaturata vo Pretkrivichnata Postapka, AD Kosta Abrash, Ohrid, 2000, 397-400 6. Poposka V, Chakar Z, Gutevska A, Davcheva N, Duma A. Odreduvanje na vremeto na nastapuvanje na smrtta. Policijata, Javnoto Obvinitelstvo, Sudot, Advokaturata vo Pretkrivichnata Postapka. AD Kosta Abrash, Ohrid, 2000,401-406. 7. Brown A, Marshall TK. Body temperature as a means of estimating the time of death. Forensic Sci. 1974; 4:12533. 8. Joseph A, Schickele E. A general method for assessing factors controlling postmortem cooling. J. Forensic Sci. 1970; 15:364-91 9. Henssge C, Knight B, Krompecher T, Madea B, Nokes L: The Estimation of the Time Since Death in the Early Postmortem Period, Edvard Arnold, London, 1995 10. Green MA, Wright JC. Postmortem interval estimation from body temperature data only. Forensic Sci. Int. 1985; 28:35-46. 11. Henssge C. Death time estimation in case work – I. The rectal temperature time of death nomogram. Forensic Sci. Int. 1988; 38:209-36. 12. Henssge C. Rectal temperature time of death nomogram: dependence of corrective factors on the body weight under stronger thermic insulation conditions. Forensic Sci. Int. 1992; 54:51-56. 54 Acta morphol.2006; Vol.3(2):55-59 UDK: 616.133 - 007.271:616.831 - 005.1 KORELACIJA NA INTRAKRANIJALNATA SO EKSTRAKRANIJALNATA KAROTIDNA ATEROSKLEROZA I ISHODOT POSLE MOZO^NIOT UDAR Arsovska Anita¹ , Popovski A¹ , Orov~anec N² , Vr~akovski M³ Klinika za nevrologija¹ , Institut za epidemiologija i biostatistika² , Institut za radiologija³ , Medicinski fakultet, Skopje, Republika Makedonija Izvadok Celta na ovaa studija e se sporedi prisustvoto na intrakranijalnata so ekstrakranijalnata karotidna ateroskleroza i ishodot posle mozo~niot udar. Naj~esta pri~ina za ishemi~en mozo~en udar e aterosklerozata na krvnite sadovi {to go snabduvaat mozokot. Okluzivnite zaboluvawa na karotidnite arterii mo`at da predizvikaat i do 30% od ishemi~nite mozo~ni udari, i se po~esti kaj ma`ite postari od 65 godini. Ateroskleroti~nata intrakranijalna stenoza e odgovorna za ishemi~niot mozo~en udar kaj 5-10% od belcite i kaj 33% od Azijatite. Pacientite so simptomatska intrakranijalna ateroskleroza koi pretrpele mozo~en udar imaat mnogu visok procent na recidivanten mozo~en udar ili smrten ishod. Kaj 50 pacienti so ishemi~en mozo~en udar bea evalvirani ekstrakranijalnite i intrakranijalnite arterii so pomo{ na ekstra i transkranijalnata kolor dupleks sonografija (extracranial and transcranial color coded sonography – ECCS / TCCS), kako i so magnetna rezonantna angiografija (magnetic resonance angiography-MRA) vo period 1-5 dena posle sonografijata. Pri priemot i pri kontrolniot pregled be{e odreden i nevrolo{kiot deficit, bodiran preku National Institute of Health Scale Score (NIHSS). Spored TCCS naodot, pacientite bea podeleni vo slednive grupi: I) ureden TCCS naod; II) okluzija na grankite na arteria cerebri media (ACM); III) stenoza na stebloto na ACM i IV) okluzija na stebloto na ACM. Spored ECCS/MRA naodot na karotidnite arterii, pacientite bea podeleni vo slednive grupi: A) ureden naod; B) nesignifikantna karotidna stenoza (<70%); V) signifikantna karotidna stenoza(>70%) i G) okluzija na karotidnata arterija. NIHS skorot se dvi`e{e od 0-42 poeni, a namaluvaweto za 4 poeni se smeta{e kako pokazatel za signifikantno podobruvawe. Rezultatite poka`aa deka te`inata na intrakranijalnata ateroskleroza silno korelira so stepenot na ekstrakranijalnata ateroskleroza, kako i so te`inata na nevrolo{kiot deficit. Zaklu~okot naveduva deka TCCS naodot ima sposobnost da ja predvidi klini~kata evolucija. Normalniot bazi~en TCCS e predikativen za dobar dolgotraen ishod, dodeka pak otkrivaweto na intrakranijalna okluzija vo akutnata faza na mozo~niot udar e silen predikator na lo{iot ishod. Bidej}i vaskularniot status vo raniot tek na mozo~niot udar e povrzan so goleminata na posledovatelniot mozo~en udar i nevrolo{kiot ishod, TCCS mo`e da se upotrebi kako ran vodi~ za terapevtskite odluki. Klu~ni zborovi: intrakranijalna ateroskleroza, ekstrakranijalna karotidna ateroskleroza, ishemi~en mozo~en udar CORRELATION BETWEEN INTRACRANIALAND EXTRACRANIAL CAROTID ATHEROSCLEROSIS AND STROKE OUTCOME Arsovska Anita¹, Popovski A¹, Orovchanec N², Vrchakovski M³ Clinic of Neurology¹, Institute of Epidemiology and Biostatistics², Institute of Radiology³, Medical Faculty, Skopje Abstract The most common cause for strokes is atherosclerosis of the blood vessels that supply the brain. Occlusive diseases of the carotid arteries can cause up to 30% of ischemic strokes, and are more frequent with men age over 65. Intracranial atherosclerosis is responsible for ischemic strokes of 5- 10% of Caucasians and of 33% of Asiatics. With patients with symptomaticatherosclerosis who have had a stroke is very high the degree of recurrent strokes or a lethal outcome. The purpose of this study is to correlate the presence of intracranial with extracranial carotid atherosclerosis as well as with the stroke outcome. Fifty patients with ischemic stroke, the extracranial and intracranial arteries were examined with extracranial and transcranial color coded sonography – ECCS / TCCS), and also with magnetic resonance angiography-MRA within 1-5 days after sonography. The neurological deficit was determined also and it was measured by the National Institute of Health Scale Score (NIHSS) on admission of the patients as well as the control examination. According to theTCCS findings, patients fell within the following groups: group I) those with normal findings; group II) with occlusion of middle cerebral artery 55 Arsovska A et al. Correlation Between Intracranial and Extracranial Carotid Atherosclerosis and Stroke Outcome (MCA) branches; group III) with MCA stenosis and group IV) with occlusion of MCA trunk. According the ECCS/MRA findings of the carotid arteries, patients fell within the followinggroups: group A) those with normal findings; B) with no significant carotid atherosclerosis (<70%);C) with significant carotid atherosclerosis (>70%) and group D) with carotid occlusion. NIHSS was between 0-42, and of 4 points decrease was considered a sign of significant improvement. The results showed that the level of intracranial atherosclerosis in a large extent correlates with the degree of extracranial atherosclerosis and the neurological deficit. TCCS findings can predict clinical evolution. Normal basic TCCS predicts of a good long-term outcome, while detecting intracranial occlusion in the acute stroke phase could be a strong predictor of a bad outcome. Because the vascular status in early course, is connected with the extension of stroke and neurological deficit, TCCS could be used as an early guide for therapeutic decisions. Key words: intracranial atherosclerosis, extracranial carotid atherosclerosis, ischemic stroke Introduction Ischemic stroke is a syndrome with multiple etiology, with different patophysiological mechanisms and different clinical manifestations. Prognosis of stroke depends on several factors, such as: age, sex, non-regulated hypertension, heart failure or diabetes, as well as the stroke type or lesion location. The most common cause for strokes is atherosclerosis of the blood vessels that supply the brain. Occlusive diseases of the carotid arteries can cause up to 30% of ischemic strokes, and are more frequent in men age over 65 (1). Intracranial atherosclerosis is responsible for ischemic strokes in 5-10% of Caucasians and 33% of Asiatics (2). With patients with symptomatic atherosclerosis who have had a stroke is very high the degree of recurrent strokes or a lethal outcome (3). The purpose of this study is to correlate the presence of intracranial with extracranial carotid atherosclerosis as well as with the stroke outcome. Material and Methods A total of fifty patients with ischemic stroke in the anterior circulation were examined (18 female and 32 male, age 58-76). The extracranial and intracranial arteries were tested in all patients with extracranial and transcranial color coded sonography (ECCS/TCCS), and also with magnetic resonance angiography (MRA) within 1-5 days after sonography. The neurological deficit was measured on admission of the patients and also and 7 days after their hospitalization according to the National Institute of Health Scale Score (NIHSS). Patients who died before the second examination were classified as the worst score of 42. The decrease of NIHS score for 4 or more points was defined as a neurological improvement. According to the TCCS findings, patients fell within the following groups: group I) those with normal findings; II) with occlusion of middle cerebral artery (MCA) branches; III) with MCA stenosis and group IV) with occlusion of MCA trunk. 56 According to the ECCS/MRA findings of the carotid arteries, patients fell within the following groups: group A) those with normal findings; B) with no significant carotid atherosclerosis (<70%); C) with significant carotid atherosclerosis (>70%) and group D) with carotid occlusion. NIHS score was between 0-42, and of 4 points decrease was considered a sign of significant improvement. All data was statistically analyzed with the program STATISTICA 7.1 / 2005 and Epi 6.0, i.e. a correlation was made between TCCS findings and the neurological deficit, as well as with the findings of the carotid arteries. The Spearman Rank Correlation was used, while value of p<0.05 was considered as a significant difference. Results According to the TCCS findings, the following results were obtained: I) 16 (32%) patients had normal TCCS findings; II) 8 (16%) patients had occlusion of MCA branches; III) 15 (30%) had MCA stenosis and IV) 11 (22 %) had occlusion of MCA trunk. According the ECCS/MRA findings of the carotid arteries, the following results were obtained: A) 10 (20%) patients had normal findings; B) 23 (46%) patients had no significant carotid atherosclerosis (<70%); C) 9 (18%) patients had significant carotid atherosclerosis (>70%) and D) 8 (16%) patients had carotid occlusion. All patients from the first group (A) had normal findings of the carotid arteries, as well as of the TCCS examination. From the second group (B) 5 (21, 7%) patients had a normal TCCS examination, 1 patient (4, 3%) had a distal MCA branch occlusion, 13 patients (56, 6%) had MCA stenosis, while 4 patients (17, 4%) had an occlusion of MCA main trunk. In the third group 2 (22, 2%) patients had normal TCCS findings, with 3 (33, 3%) patients MCA branch occlusion was diagnosed, 2 (22, 2%) patients had MCA stenosis, while the rest of 2 (22, 2%) patients had MCA main trunk occlusion.From the fourth group, with 3 (37, 5%) patients an occlusion of MCA branches was diagnosed at TCCSexamination, while 5 (62, 5%) patients had an occlusion of MCA main trunk. In a large number of patients with carotid occlusion, on TCCS a presence of collateral flow, i.e. reversible direction in the ipsilateral anterior cerebral artery (ACA), was evident with an increased blood flow velocity in the contralateral ACA and posterior cerebral artery (PCA).The statistical analysis of the parameters in this study showed that the degree of carotid arteries pathological changes correlates with the degree of the lesions that were found in TCCS examination. Patients with intracranial atherosclerosis meet with higher risk than patients who have no intracranial atherosclerosis, while patients with a combined intracranial and extracranial occlusive diseases face the worst outcome. The association between the diseases of the carotid arteries /TCCS findings is presented in Figure 1, and for R=0.55, there is a strong and a significant (p<0, 05) correlation, i.e. the degree of carotid arteries diseases Arsovska A et al. Correlation Between Intracranial and Extracranial Carotid Atherosclerosis and Stroke Outcome correlates with the degree of the pathological TCCS findings. (p<0.05) correlation, i.e. the severity of the neurological status correlates with the degree of pathological TCCS results. Karotidi / T CCS: Spearman Rank Correlations = 0.55 (p < 0.05) SN / TCCS: Spearman Rank Correlations = 0.58 (p < 0.05) KAROTIDI SN TCCS TCCS Fig. 1. Carotid arteries/TCCS Fig. 2. NS/TCCS NIHSS 1 in the first group was within the interval 8.00 ± 3.50. At the control examination, NIHSS 2 was 4.56 ± 4.11 (Table 1). So, patients with normal initial TCCS examination, had significantly better initial and control neurological examination (p<0.05) in comparison with the patients in the other groups. NIHSS 1 in the second group varied in the interval 17.25 ± 5.75. Control NIHSS 2 was 18.12 ± 10.07 (Table 2). In this group, control neurological status showed a significant improvement with 1 patient, with 6 patients was the same the condition, while 1 patient deteriorated and had a lethal outcome. In the third group, NIHSS 1 was in the interval 17.26 ± 2.93, while control NIHSS 2 was 15.13 ± 4.50 (Table 3). With 4 patients, the control examination showed an improvement, with 8 patients the condition was unchanged, and with 3 patients a deterioration of the neurological status was registered. NIHSS 1 in the fourth group was in the interval 18.54 ± 1.69, while control NIHSS 2 was in the interval 20.81±12.38 (Table 4). With 3 patients the control examination showed an improvement, with other 3 the condition was the same, while with 5 patients a deterioration of the neurological status was registered, and 2 of them had a lethal outcome. The neurological status on admission didn’t show significant changes among the patients with pathological TCCS findings (p>0,05), although a higher NIHS scores were registered with those who had ACM occlusion. The control neurological status showed higher NIHS scores in patients with blood flow velocity reduction and ACM occlusion, and the values of NIHSS 2 in the fourth group were significantly higher in comparison with the other groups (p<0.05). Thus, a significant trend towards a worse prognosis was shown with patients who had an occlusion, than those with stenosis, whose prognosis was worse than the one of the patients without stenosis. The assocciation between NS/TCCS is shown in Figure 2, and for R=0.58, there is a strong and a significant Discussion There are several studies published abroad that discuss the presence of extracranial and intracranial stenoocclusive carotid diseases in patients with ischemic stroke. Suwanvela et al (4) found that in patients with extracranial stenosis, 98% had an associated intracranial disease, while no one of those with intracranial stenosis had more than 50% reduction of extracranial carotid arteries. Liu et al (5) found that about 1/3 of the symptomatic Chinese patients had intracranial artery diseases. About 24% of the patients had only extracranial carotid diseases, while about 26% had only intracranial diseases. With their study Liu et al, confirmed the racial difference between the Chinese and the Caucasians in the location of lesions in cerebrovascular steno-occlusive diseases. According to the data found in the available literature (6), if the urgent TCCS is normal, there is a 89% chance that the control examination will not reveal stenoocclusive artery diseases. Although normal TCCS can not completely exclude existance of the pathologic artery lesions, the data in the present study, as well as in the available literature, suggests that TCCS parameters are sufficient to exclude urgent angiography in many patients. As it was previously shown, normal TCCS examination is also a good prognostic sign (7). Progression of steno-occlusive MCA diseases is associated with a number of subsequent vascular diseases after the initial stroke.So, for patients with progressive MCA occlusive diseases the risk from clinical cerebrovascular or cardiovascular events after stroke is increased. Consequently, the progression of MCA lesions can serve as a marker for progression of a generalized atherosclerotic process. This is the reason why, control TCCS examinations are appropriate ones in order to identify patients who meet with an especially high risk, in order that adequate therapeutic and preventive measures should be taken. 57 Arsovska A et al. Correlation Between Intracranial and Extracranial Carotid Atherosclerosis and Stroke Outcome Table 1. NIHSS with patients of the first group (I) Parameter NIHSS1 NIHSS2 Valid N 16 16 Mean 8.00 4.56 Confid. - 95.0% 6.13 2.37 Confid. Min. +95.0% 9.86 4.00 6.75 1.00 Max. SD 17.00 15.00 3.50 4.11 Max. SD 28.00 42.00 5.75 10.07 Max. SD 23.00 22.00 2.93 4.50 Max. SD 22.00 42.00 1.69 12.38 Table 2. NIHSS with patients of the second group (II) Parameter NIHSS1 NIHSS2 Valid N 8 8 Mean 17.25 18.12 Confid. Confid. Min. -95.0% + 95.0% 12.44 22.05 10.00 9.70 26.54 11.00 Table 3. NIHSS with patients of the third group (III) Parameter NIHSS1 NIHSS2 Valid N 15 15 Mean 17.26 15.13 Confid. -95.0% 15.63 12.64 Confid. Min. + 95.0% 18.89 12.00 17.62 10.00 Table 4. NIHSS with patients of the fourth group (IV) Parameter NIHSS1 NIHSS2 Valid N 11 11 Mean 18.54 20.81 Confid. - 95.0% 17.40 12.49 Confid. Min. + 95.0% 19.68 16.00 29.13 7.00 Conclusion - The degree of pathological findings of the carotid arteries correlates with the severity of intracranial lesions; - Patients with intracranial atherosclerosis meet with a higher risk than patients who have no intracranial atherosclerosis; - Patients with a combined intracranial and extracranial occlusive disease face theworst outcome; - TCCS findings have the ability to anticipate the clinical evolution; - The normal basic TCCS is predictive of good longterm outcome; - The TCCS finding of intracranial occlusion is a strong predictor of a bad stroke outcome; - Because the vascular status in the early stroke course is associated with the severity of consequent stroke and neurological outcome, TCCS can be as pplied as an early guide in the therapeutic decisions, the planning of further diagnostic procedures and the risk estimation of recurrent strokes. References 1. 2. 3. 4. 5. 58 Bornstein NM, Norris JW: “Management of patients with asymptomatic neck bruits and carotid stenosis,” in: Barnett HJM and Hachinski VC ed, Neurologic Clinics; Cerebral Ischaemia: Treatment and Prevention. VB Saunders. Philadelphia: 1992, 269. Wityk R, Lehman D, Klag M, et al. “Race and sex differences in the distribution of cerebral atherosclerosis”. Stroke 1996; 27:1974–80. Thijs V, Albers G. “Symptomatic intracranial atherosclerosis. Outcome of patients who fail antithrombotic therapy”. Neurology 2000; 55:490–7. Suwanwela NC, Chutinetr A : “Risk factors for atherosclerosis of cervicocerebral arteries: intracranial versus extracranial”. J Ultrasound Med 24:451-457. Liu HM, Tu YK, Yip PK, Su CT. “ Evaluation of intracranial and extracranial carotid steno-occlusive diseases in Taiwan Chinese patients with MR angiography: preliminary experience”. Stroke 1996; 27:650–653. Arsovska A et al. Correlation Between Intracranial and Extracranial Carotid Atherosclerosis and Stroke Outcome 6. 7. Alexandrov AV, Bladin CF, Norris J. “Intracranial blood flow velocities in acute schemic stroke”. Stroke. 1994; 25:1378 –1383. Toni D, Fiorelli M, Zanette EM, Sacchetti ML, Salerno A, Argentino C, Solaro M, Fieschi C. “Early spontaneous improvement and deterioration of ischemic stroke patients: a serial study with transcranial Doppler ultrasonography”. Stroke. 1998;29:1144 –1148 59 Acta morphol.2006; Vol.3(2):60-62 UDK: 612.661 - 055.25 (497.7) EVOLUCIJA I KARAKTERISTIKI NA RANIOT PUBERTET KAJ MAKEDONSKITE DEVOJ^IWA Krstevska-Konstantinova Marina, Ko~ova M, Gu~ev Z Oddel za endokrinologija i genetika, Klinika za detski bolesti, Skopje, R. Makedonija Izvadok Raniot pubertet kaj devoj~iwata se karakterizira, spored odredeni avtori, so pojava na sekundarni seksualni karakteristiki pome|u vozrasta od 8 i 9 godini. Vo poslednava dekada se po~esto se javuva vo na{ata sredina. Vistinskiot predvremen pubertet ili centralen predvremen pubertet, koj mo‘e da bide organski ili idiopatski se karakterizira so pubertetska maturacija pred osma godina od ‘ivotot. Vo literaturata, se po~esto se obrnuva vnimanie na raniot pubertet vo odnos na eventualen tretman, vo sporedba so centralniot predvremen pubertet koj se tretira so GnRH agonisti. Celta na na{ata studija e da se proceni pubertetskiot razvoj, vremetraewe i evolucija na raniot pubertet kaj makedonskite devoj~iwa. Vo na{iot trud nie evaluiravme klini~ki i auksolo{ki karakteristiki na 35 devoj~iwa. Sleden e pubertetskiot razvoj za vreme od 3 godini po dijagnozata. Vo vreme na dijagnozata hronolo{kata starost na devoj~iwata be{e 8.8 ± 0.5 godini. Visinata vo standardni devijacii (SDS) be{e 0.6 ± 0.9, indeksot na telesnata masa (BMI SDS) be{e 3.2 ± 2.2, dodeka koskenata maturacija iznesuva{e 9.4 ± 1.5 godini. Kaj dve devoj~iwa ve}e ima{e menarha na vozrast od 8.5 i 9 godini. Od 35 devoj~iwa, 18 imaa samo unilateralen rast na gradi M2 do M3. Ostanatite 17 devoj~iwa imaa bilateralen rast na gradi kako i pubi~na i aksilarna vlaknatost. Po 3 godini, visinata SDS (1.0 ± 0.4) i telesnata masa SDS (3.1 ± 2.1) ostanaa sli~ni, koskenata maturacija se zabrza na 12 ± 1.3 godini. 20 devoj~iwa dobija menarha na sredna vozrast od 11.3 ± 0.9 godini. Ostanatite 15 devoj~iwa imaa usporen pubertetski razvoj. Ultrazvu~niot pregled na genitaliite pri dijagnozata i po 3 godini be{e pubertetski. Raniot pubertet e se po~est vo na{ata zemja. Prete‘no normalno progredira pubertetot vo narednite godini. No sepak, pove}eto od devoj~iwata se pokrupni i imaat zabrzana koskena maturacija. Klu~ni zborovi: ran pubertet, pubertet, predvremen seksualen razvoj EVOLUTION AND CHARACTERISTICS OF EARLY PUBERTY IN MACEDONIAN GIRLS Krstevska-Konstantinova Marina, Kocova M, Guchev Z Department for Endocrinology and Genetics, Pediatric Clinic, Skopje, R. Macedonia Abstract Early puberty in girls is characterized, according to some authors, by the appearance of secondary sexual development between the age of 8 and 9 years. It is becoming more frequent in our country in the last decade. Central precoAious puberty, which may be of organic or idiopathic origin, is characterized by pubertal maturation before the age of eight years. In the literature, early puberty is becoming more important reffering to eventual treatment, in comparasion with central precoAious puberty, which is treated with GnRH agonists. The aim of our study is to assess the pubertal development, duration and evolution of early puberty in Macedonian girls. We have studied clinical and auxologic characteristics of 35 girls. We have followed the pubertal development during 3 years after diagnosis. At diagnosis CA (chronological age) of the girls was 8.8 ± 0.5 years. Height SDS was 0.6 ± 0.9, body mass index was 3.2 ± 2.2 and bone age was 9.4 ± 1.5 years. In two girls menarche has already occurred at the age of 8.5 and 9 years. Out of 35 girls, 18 girls had solely unilateral breast development M2 to M3. The other 17 girls had 60 besides bilateral breast enlargement, also pubic and axillary hair development. After 3 years, height SDS (1.0 ± 0.4) and body mass index (3.1 ± 2.1) remains similar, bone age advanced to 12 ± 1.3 years. Menarche occurred in 20 girls with the mean age of 11.3 ± 0.9 years. The remaining 15 girls had a slow rate of pubertal development. Ultrasonographic appearance of genitalia at diagnosis and after 3 years was generally pubertal. Early puberty is common in our country. Normal completion of puberty usually occurs regularly. However, most of the girls are heavier and have accelerated bone maturation. Key words: early puberty, puberty, premature sexual development Introduction In girls, puberty usually occurs after 8 years of life, while before this period it is called central precocious puberty. Concerning early puberty, the range of age is between 8 and 9 years. The appearance of menarche in girls before the age of 10 years also shows a premature event. These criteria has been revised recently, accepting the age of 7 years for breast development in white girls Krstevska-Konstantinova M et al. Evolution and Characteristics of Early Puberty in Macedonian Girls and 6 years in black girls (1), on basis of the knowledge of American pediatricians (2), in about 17,000 american girls. In developed countries it is thought that the secular trend of earlier age of menarche has stopped in the last decades, but that the development of breasts and menarche occur 1 year earlier in American black girls in contrast to white girls (3). In the other countries of the world, in the last years, such kind of studies has not been performed regarding early appearance of puberty in girls. The aim of our study was to assess the pubertal development, timing, and evolution of early puberty in Macedonian girls, in comparison with girls from other countries and ethnic groups. Breast Development 20 18 17 16 12 8 4 0 Breast development M2-M3 Bilateral breast development with pubic and axillary hair Chart 2. Bone age regarding the study period Materials and Methods The study period was 3 years, in which 35 girls were evaluated, and sent for evaluation from their family doctors for premature sexual development to the Department for Endocrinology and Genetics at the Pediatric Clinic in Skopje. We evaluated the height, weight and the pubertal stadium of the girls. The criteria for inclusion in the evaluated group were a breast development (M2) and/ or pubic hair (P2) and axillary growth of hair before the age of 8 years. The clinical and auxologic characteristics were studied, while the pubertal stage was followed-up for a time period of 3 years in intervals of 3 months. At diagnosis, the chronological age of the girls was 8.8 ± 0.5 years. The height was in the normal range during the first examination and remained in the same frames in the evaluation period. (Chartr 1) The height was registered in standard deviations (SDS) according to Tanner (4). The body mass index (Body mass index SDS) showed elevated values in these girls (Chart 1), and did not change during the study period. This parameter was taken into consideration due to the hypothesis of Frich, which proves a need of a sufficient amount of body fat and weight with witch the puberty may commence (5). Breast Development 18 17 16 12 8 4 0 Breast development M2-M3 Bilateral breast development with pubic and axillary hair Chart 1. Height and body mass index of the girls at diagnosis and after three years Body mass index 3.5 3.2 3.1 At Diagnosis After 3 years 3 2.5 2 1.5 1 1.0 0.6 0.5 0 At Diagnosis Results 20 Height SDS After 3 years Chart 3. Breast development regarding the pubertal stage and presence of other sexual characteristics The bone age (Chart2), also evaluated and compared according to the atlas of Greulih and Pyle (6), showed a slight advancement during the evaluation period in all 35 girls (100%). The breast development was different in most girls (Chart 3), unilateral in 18 girls (51,4%) and bilateral in 17 girls (48,5%). One half of the patients (50%) had pubic and axillary hair development. Two girls had menarche at the age of 8.5 and 9 years (5,7%). After 3 years, menarche occurred in 20 girls (57,1%) at the mean age of 11.3 ± 0.9 years. Slow developing puberty had the rest 15 girls. The ultrasound examination of the genitalia in all girls at the diagnosis and after 3 years was pubertal. Ovaries above 15 mm in the diagonal section with up to three follicles in either ovary. The girls were sent for evaluation from different cities in Macedonia, without any predilection of regions. Discussion In the Republic of Macedonia there is no data of the timing of puberty and menarche of the girls. In the literature today, there is not enough information about the characteristics of early puberty of girls, which may be in the normal range, slow, or accelerated. According to our clinical observations, more girls are being referred for clinical evaluation of their premature sexual development. Mostly this situation is caused by improved life-style in some segments of our society. Still, our study group, was 61 Krstevska-Konstantinova M et al. Evolution and Characteristics of Early Puberty in Macedonian Girls not socially endangered, while their material status was different. Tanner and Davies in the year of 1985, in England, reported of a mean age of 10.9 years for the beginning of breast development (4), which is a later period than our group. According to american authors, similar mean age was found of 9.7 years for M2, in white American girls (7). Later, the same authors report for a late age of 10.4 years in white girls and 9.5 years in black girls in different groups of the whole cohort. The mean age of menarche in France and other Mediterranean countries (9,10,11,12,13) is lower than the rest of the Western European countries (14,15,16,17,18). According to Eveleth and Tanner (19), this indicates a geographical difference which includes at the same time, genetic or ethnic factors, as well as environmental factors. Our present limited study is an announcement for a larger References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 62 evaluation of the pubertal development which would be performed in the Republic of Macedonia. In our study, the girls were heavier, which is similar with a study from the literature, where between 1974 and 1994, the body mass of the girls increased for 22% at the age of 5 to 14 years and resulted in accelerated maturation (20). Also, there is an existing dilemma for eventual treatment of the fast developing puberty where the target height of the girls would be low. The slow developing variant of puberty, as well as the normal variant does not require treatment. Conclusion Early puberty is becoming more frequent in our country. Completion of puberty, even if it starts early develops regularly. Still, most girls with early puberty are with a greater body weight, have accelerated bone age, and early menarche (21). Kaplowitz PB, Oberfield SE, and the Drug and Therapeutics and Executive Committees of the Lawson Wilkins Pediatric Endocrine Society: Reexamination of the age limits for defining when puberty is precocious in girls in the United States: implications for evaluation and treatment. Pediatrics 1999, 104: 936-941 Herman-Giddens ME, Slora EJ, Wasserman RC et al. Secondary sexual characteristics and menses in young girls seen in office practice: a study from the Pediatric research in Office Settings Network. Pediatrics 1997, 99: 505-512 Hergenmoeder AC, Hill RB, Wong WW, et al. Validity of self-assessment of pubertal maturation in AfricanAmerican and European American adolescents. J Adolesc Health 1999, 24:205 Tanner JM, Davies PSW. Clinical longitudinal standards for height and height velocity for North American children. Pediatrics 1985, 107:317-329 Frisch RE, Revelle R, Cook S. 1973 Components of weight at menarche and the initiation of the adolescent growth spurt in girls: estimated total water, lean body weight and fat. Hum Biol 45: 469-483 Kreiter M, Burstein S, Rosenfield RL et al. Preserving adult height potential in girls with idiopathic true precocois puberty. J Pediatr 1990, 117: 364-370 NHANES 3 : NHANES 3 Reference manuals and reports (CD Rom). Analytic and reporting guidelines: the Third National Health and Nutrition Examination Survey (1988-94), Hyattsville MD: National center for Health Statistics, Centers for Disease Control and Prevention. Sun SS, Schubert CM, Chumlea WC et al. 2002 National estimates of the timing of sexual maturation and racial differences among US children. Pediatrics 110: 911-919 de la Rochebrochard E 1999. Les ages a la puberte des filles et des garcons en France. Population 54: 933-962 Borneman M, Vienna A, Tommaseo M et al. 1995 Menarcheal age and environmental factors in a sample from the province of Rome. Acta Med Auxol 27: 97-104 de la Puente ML, CAnela J, Alvarez J et al. 1997 Cross-sectional growth study of the child and adolescent population of Catalonia (Spain) Ann Hum Biol 24:435-452 Rueda C, Labera C, Boldova C,et al. 2002 Spanish longitudinal study of growth and development standards. Horm Res 58 (Suppl 2):36 (abs) Papadimitriou A, Gousia E, Pitaoili E, et al. 1999 Age at menarche in Greek girls. Ann Hum Biol 26:175-177 Rimpela AH, Rimpela MK 1993 Towards an equal distribution of health, Socioeconomic and regional differences of the secular trend of the age of menarche in Finland from 1979-1989. Acta Pediatr 82: 87-90 Lindgren LW, Degerfois IL, Friedrikson et al. 1991 Menarche 1990 in Stockholm school girls. Acta Paediatr Scand 80:953-955 Helm P, Grolund L 1998 A halt in the secular trend towards earlier menarche in Denmark. Acta Obstet Gynecol Scand 77: 198-200 Buchler J 1990 A longitudinal study of adolescent growth. London: Springer-Verlag Raes M 1993 Menarche when and why. Lancet 342; 1375-1376 Eveleth PB, Tanner JM 1990 Worldwide variation in human growth. 2nd Edition. Cambridge, UK: Cambridge University Press Freedman DS, Srinivason SR 1997 Secular increases in relative weight and adiposity among children over two decades. The Bogalusa heart study. Pediatrics 99:42-426 M. Krstevska Konstantinova, M. Kocova, Z Gucev, Evolution and characteristics of early puberty in Macedonian girls. 2005 Hormone research, Vol 64 suppl 1, 217 (Abst.) *Appreciation We would like to thank the colleagues from the Institute of Radiology for the evaluation of the bone age of the children, as well as to the colleagues of the Ultrasound Cabinet at the Clinic of Gynecology and obstetrics, where the ultrasound of the ovaries was performed. Acta morphol.2006; Vol.3(2):63-69 UDK: 616.24 - 006.6 - 02 616.22 - 006.6 - 02 EPIDEMIOLO[KA STUDIJA ZA ULOGATA NA PU[EWETO, NASLEDNIOT FAKTOR I STRESOT VO NASTANUVAWETO NA BELODROBNIOT I LARINGEALNIOT KARCINOM Pavlovska Irina1, Orov~anec N1, Stefanovski T2, Tau{anova B1, Zafirova-Ivanovska B1 Institut za epidemiologija i biostatistika so medicinska informatika1, Klinika za pulmologija i alergologija, Klini~ki centar2, Medicinski fakultet, Skopje, Republika Makedonija Izvadok Celi na studijata se da se utvrdi distribucijata na zabolenite so belodroben i laringealen karcinom spored: pol, vozrast, bra~en status, obrazovanie, etni~ka pripadnost, mesto na ‘iveewe; da se odredi i kvantificira zastapenosta na pu{eweto, naslednosta i stresot kaj belodrobniot i laringealniot karcinom, kako i da se utvrdi zna~ajnosta na razlikata vo prisustvoto na navedenite rizik faktori pome|u dvete grupi. Ispituvaweto go opfa}a periodot od 01.06.2005-01.06.2006 godina. Vo nego se vklu~eni 35 zaboleni so karcinom na beli drobovi i 35 zaboleni so laringealen karcinom. Primenet e deskriptiven i analiti~ki epidemiolo{ki metod. Kaj seriite so atributivni belezi odreduvani se procenti na struktura. Razlikata pome|u seriite so numeri~ki belezi kaj nezavisni primeroci testirana e so ttest za nezavisni primeroci. Mann-Whitney U test koristen e za utvrduvawe na zna~ajnosta na razlikata pome|u dva nezavisni primeroci so atributivni belezi. Anamneza za pozitiven nasleden faktor imaat 28,6% lica so belodroben karcinom (BK), odnosno 40% so laringealen karcinom (LK). Pome|u ispitanicite so BK i onie so LK za Z=-0,23 i p>0,05, ne postoi zna~ajna razlika vo zaboluvaweto vo odnos na genetskiot faktor. Za Z=2,27 i p<0,05 stresot zna~ajno e pove}e prisuten me|u zabolenite so BK. Najgolem broj zaboleni so BK i LK pu{at 21-40 cigari dnevno (48,4%-BK;62,9%-LK). Pome|u zabolenite so BK i LK za Z=-0,58 i p>0,05 ne postoi zna~ajna razlika vo brojot na dnevno ispu{eni cigari. Pu{a~ki sta‘ 31-45 god. imaat najgolem procent pripadnici na dvete grupi (41,9%-BK;51,4%-LK). Rezultatite od studijata ja potvrduvaat ulogata na pu{eweto kako najzna~aen faktor na rizik za nastanokot na belodrobniot i laringealniot karcinom. Glavniot akcent vo prevencijata na ovie zaboluvawa se naso~uva kon zapoznavawe na populacijata so {tetnite efekti od ovaa navika. Klu~ni zborovi: belodroben karcinom, pu{ewe cigari, stres, nasleden faktor. EPIDEMIOLOGICAL STUDY FOR THE ROLE OF SMOKING, GENETIC FACTOR AND STRESS IN LUNG AND LARYNGEAL CANCER OCCURRENCE Pavlovska Irina1, Orovchanec N1, Stefanovski T2, Tausanova B1, Zafirova-Ivanovska B1 Institute of Epidemiology and Biostatics with Medical Informatics1, Clinic for Pulmology and Allergology, Clinical Centre2, Faculty of Medicine, Skopje, R. Macedonia Abstract Objectives of the study are: to determine the distribution of lung and laryngeal cancer patients according to gender, age, marital status, professional training, ethnic belonging, place of residence; to determine and quantify presence of smoking, heredity and stress in lung and laryngeal cancer as well as to determine the importance of difference in presence of the mentioned risk factors between the two groups. Investigation comprised the period from 1st June 2005 up to 1st June 2006, and included 35 lung cancer and 35 laryngeal cancer patients. Data were collected from the Clinic of Pulmology and the Clinic for Othorhinolaryngology. Descriptive and analytical epidemiological methods were applied. Structure percentage was determined in data analysis for the series with attributive features. Difference among the series with numerical features in independent specimens, was tested by t-test for independent specimens. Mann-Whitney U test was used to determine the significance of difference between two independent specimens with attributive features. Anamnesis for a positive genetic factor had 28,6% persons with lung cancer (LC), and 40% with laryngeal cancer (LarC), respectively. There was no significant difference in the disease relating the genetic factor between the interviewees with LC and those with LarC for Z=-0,23 and p>0,05. For Z=2,27 and p<0,05 stress was significantly more present among the diseased with LC. Majority of the diseased patients from LC and LarC smoke between 21-40 cigarettes per day (48,4% with LC;62,9% with LarC). There was no significant difference 63 Pavlovska I et al. Epidemiological Study for the Role of Smoking, Genetic Factor and Stress in the number of the daily smoked cigarettes between the diseased LC patients and those with LarC for Z=-0,58 and p>0,05. Smoking length from 31-45 years had the greatest percent of the participants in the both groups (41,9% with LC;51,4% with LarC). Results from this study proved the role of smoking as the most important risk factor in the occurrence of the lung and laryngeal cancer. Main stress in prevention of these diseases has been directed towards information of the population about harmful effects of this habit. Key words: lung cancer, cigarette smoking, stress, genetic factor. Introduction Cancer is a disease that knows no boundaries. It is on the second place as a death cause in the developed countries, and among the three leading death causes in the developing countries. The cause for 12.5% of all deaths is the cancer. It is more than the percent of deaths caused by HIV/AIDS, tuberculosis and malaria all together (1). Nowadays, 24.6 million persons live with this disease. If the present level of smoking habit and acceptance of the unhealthy lifestyle persist, this increase will be even greater (1). Lung cancer in majority of the industriously developed countries is the most frequent in men, and it appears to be great in women as well. Immediately after lung cancer, larynx cancer comes according to the frequency of occurrence among respiratory tract cancers (2,3). Although the incidence rates of this cancer form are far lower than those of the lung cancer, they still follow the changes of this form. It is supposed that the causes for the increased number of the sick individuals in greater part of the world are the changes of smoking cigarettes habit and alcohol consumption. This form of cancer has been relatively frequent in men, but, up to now, rare in women (4). In the Republic of Macedonia, in the last twenty years, malignant neoplasm’s, due to their high mortality rate, are on the second place in the structure of the death causes, immediately after the cardiovascular diseases (5). A number of epidemiological studies point out the mutual role of some risk factors in occurrence of respiratory system malignant neoplasms, first of all, of the lungs and larynx. The most important of the so called “lifestyle” risk factors are cigarette smoking habit, passive smoking, alcohol consumption and way of nourishment, then from the exogenic causes are exposition to some professional carcinogenic and air pollution, while the endogenous ones are presented by psychosocial and genetic factor (6,7). Cigarette smoking has been the cause for about 85-90% of the cases with bronchogenic and laryngeal cancer. Mutations of oncogenic and suppressor gene tumor, associated with development of lung and larynx cancer occur more frequently as acquired during lifetime than being inherited as inborn mutations. Always when the cell is prepared to split into new cells, its DNK must be copied. This process is not perfect and a copy can bring an error. Fortunately, the cells have repair enzymes, which 64 correct the DNK. Lung and larynx cell mutations often appear due to exposition to cancerogenic substances, present in cigarette smoke (8,9). In the mechanism of cancer genesis, the way of stress reaction, i.e. the form of behaviour in stress situations, has a role of endogenous factor. Humoral mechanism, the change of glucocorticoid and gonadal steroid levels can only partially explain the role of these hormones in expression of cellular oncogenes (10). Purpose of the study - To determine the distribution of the sick individuals of lung and laryngeal cancer according to: gender, age, marital status, degree of education, ethnicity, place of residence; - To determine and quantify representation of smoking, inheritance, and stress in lung and laryngeal cancer as well as to determine the importance of difference in presence of the above mentioned risk factors between the two groups. Material and Methods This investigation comprised a period from 1st June 2005 to 1st June 2006. It included 35 sick individuals of lung cancer, as well as 35 with laryngeal cancer. Data needed for realization the investigation targets were collected from the Clinic of Pulmology and the Clinic of Otorhinolaryngology. Descriptive and analytical epidemiologic method was used. Questionnaire Cigarette smoking habit has been worked out by application of modified questions from the Questionnaire for using cigarettes, recommended by Tobacco Health Programme of the World Health Organization (11). According to this Questionnaire, current smokers are defined as persons, who, during this study performance, smoke every day or occasionally any kind of tobacco product. Concerning the fact that none of the interviewed individuals used another tobacco product, save cigarettes, the following definitions refer only to cigarette smoking. A person who smokes at least one cigarette daily for three months, i.e. a total of approximately 100 cigarettes and more during his/her lifetime, is defined as a current smoker. Ex-smoker is a smoker who used to smoke cigarettes previously, but in the moment does not smoke at least for 6 months. Non-smokers are persons who never lighted cigarette or smoked less than 100 cigarettes in their lives. In order to perceive the role of genetic factor in development of lung and larynx cancer, the interviewees were asked a question if someone in their family was sick of or is sick of malignant diseases, and if so, on which localization. The influence of stress in occurrence of these two kinds of cancer was investigated by questions referring the eventual exposition to some kind of stress, as well as of its time duration. Statistical methods For data elaboration, the following was used: Pavlovska I et al. Epidemiological Study for the Role of Smoking, Genetic Factor and Stress 1. Structure percents were determined in series with attributive features; 2. Difference between two series with numerical features, in independent samples, was tested by t-test for independent samples; 3. Mann-Whitney U test was used for determination of significant difference between two independent samples with attributive features. Data were showed tabulary and graphically. Results Thirty patients sick from lung cancer (LC) and identical number of individuals sick from laryngeal cancer (LARC) were included in the study. There were 28 (80%) men and 7 (20%) women in the group of lung cancer. Ratio of registered men and women was 4:1. There was not even one woman in the group of LARC. Individuals with LC were aged from 39 to 81 years, and those sick from LARC from 41 to 76 years. Age of the interviewees in both groups varies in almost identical interval (59,3±10,2 years for LC; 59,7±7,8 years for LARC). In the group of LC interviewees dominated those old from 60 to 69 years (16 or 45,7%). Among the persons sick of LARC the most represented were those belonging to the age group from 50 to 59 years (15 or 42,9%) and from 60 to 69 years (13 or 37,1%) (Table 1). Total of 77,1% sick from lung cancer, i.e. 82.9% from laryngeal cancer live in town. Taking into consideration the distribution of the sick persons from lung and laryngeal cancer, there is no significant difference in relation to the place of residence, for χ² = 0,36 and p>0,05. Greatest number of the sick persons of both groups is Macedonians (94.3% with LC and 85.7% with LARC). Christians are 94,3% patients with LC, and 91.4% with LARC, respectively. Concerning the marital status, category married dominated in both groups (LC-28 or 80,0%; LARC-34 or 97,1%). Distribution of the interviewees according to education degree shows that in both groups the greatest number are those with completed secondary education (22 or 62,9% with LC; 18 or 51,4% with LARC). After them, individuals with completed primary education follow (17,1% with LC; 25,7% with LARC). There is no significant difference in relation to the education degree between both groups with sick individuals for Z = -0,14 and p>0,05. According to our own epidemiological investigation, of a total of 35 LC patients, anamnesis for positive genetic factor has 10 (28,6%). In the group sick from LARC 14 (40,0%) give evidence that some family member had or has cancer (Table 2). There is no significant difference of the disease in relation to the genetic factor between the interviewees Table 1. Distribution according to age Age (years) <39 40-49 50-59 60-69 70 > Total Investigated group Lung cancer N % 1 2.9 7 20.0 8 22.9 16 45.7 3 8.5 35 100 Investigated group Laryngeal cancer % / 8.6 42.9 37.1 11.4 100 N / 3 15 13 4 35 Table 2. Distribution according to presence of positive familiar anamnesis for malignant disease Hereditary factor Positive Negative Total Investigated group Lung cancer N % 10 28.6 25 71.4 35 100 Investigated group Laryngeal cancer N 14 21 35 % 40.0 60.0 100 65 Pavlovska I et al. Epidemiological Study for the Role of Smoking, Genetic Factor and Stress Table 3. Distribution according to stress exposition Stress exposition No Yes - acute Yes - chronic Total Investigated group Lung cancer N % 19 54.3 2 5.7 14 40.0 35 100 Investigated group Laryngeal cancer N 28 2 5 35 % 80.0 5.7 14.3 100 Table 4. Distribution according to the cigarette smoking habit Habit of cigarette smoking Yes Formerly No Total Investigated group Lung cancer N % 19 54.3 12 34.3 4 11.4 35 100 Investigated group Laryngeal cancer N 24 11 / 35 % 68.6 31.4 / 100 Investigated group Laryngeal cancer N 1 7 22 5 35 % 2.9 20.0 62.9 14.2 100 Table 5. Distribution according to number of daily smoked cigarettes Number of cigarettes per day ≤ 10 11 - 20 21 - 40 > 40 Total Investigated group Lung cancer N % / / 11 35.5 15 48.4 5 16.1 31 100 Table 6. Distribution according to duration of smoking Duration of smoking (years) ≤ 15 16 - 30 31 - 45 > 45 Total 66 Investigated group Lung cancer Investigated group Laryngeal cancer N 1 11 13 6 31 N 1 4 18 12 35 % 3.2 35.5 41.9 19.4 100 % 2.9 11.4 51.4 34.3 100 Pavlovska I et al. Epidemiological Study for the Role of Smoking, Genetic Factor and Stress with lung cancer and those with laryngeal cancer for Z= 0,23 and p>0,05. Greatest number of interviewees of both groups gives an evidence for development of cancer in their fathers (3 or 30,0% LC; 6 or 42,9% LARC). Malignoma appears in both parents only in the group with LC (one interviewee or 10,0%). The most frequent malignoma localization in relatives of the sick persons LC are the lungs, represented by 50,0%. After them, the breast follows in 20,0%. The most represented localization is skin cancer (21,5%), followed by stomach and bones with 14.4% each, in the relatives of the individuals with LARC. There is no significant difference (Z = -1,5; p>0,05) between the interviewees with lung cancer and those with laryngeal cancer in distribution of malignant diseases in relation to the localization of the malignoma in their relatives. Exposed to stress situation are 16 (45,7%) individuals with LC, and 7 (20,0%) with LARC (Table 3), respectively. For Z = 2,27 and p<0,05 stress has been significantly more present among the persons with lung cancer than among those with laryngeal cancer. A greater number of the persons belonging to both groups are exposed to chronical stress (14 or 40,0% with LC; 5 or 14,3% with LARC). There is no significant difference concerning the stress type (acute or chronic) between the individual with lung cancer and those with laryngeal cancer for Z = 0,6 and p>0,05. Time duration of stress in patients with LC ranges in diapason from 3 months to 5 years, while in the individuals from LARC from 4 months to 6 years. Time duration of stress in the sick persons with lung cancer has been longer than in those with laryngeal cancer, however for t = 0,96 and p>0,05 does not exist significant difference in relation to this variable between both groups. Habit of smoking cigarettes is in a great measure present among the individuals with LC (19 or 54,3%) and LARC (24 or 68,6%). Ex-smokers in the groups with LC are 12 (34,3%), and 11 (31,4%) in that with LARC, respectively. There was none nonsmoker among the LARC persons, while the number in those with LC is 4 (11,4%) (Table 4). There is no statistical significance concerning the smoking cigarettes between the patients with lung cancer and laryngeal cancer (Z = -0,36; p>0,05). Greatest number of the persons with lung cancer and laryngeal cancer smoke cigarettes between 21-40 cigarettes per day (c/d) (48,4% with LC; 62,9% with LARC). Followed those who smoke from 11-20 c/d, present with 35,5%, and 20,0%, respectively. The group of the so-called “passionate” smokers (above 40 c/den) makes 16,1% of the sick individuals with LC BK and 14,2% of those with LAR (Table 5). There is no statistical difference in the number of the daily smoked cigarettes between the individuals sick of lung cancer and laryngeal cancer for Z = -0,58 and p>0,05. There is no significant difference among the sick individuals of both cancer localizations in relation to the age when they start smoking cigarettes (Z = 1,33; p>0,05). Smoking length from 31 to 45 years has the members of both groups (13 or 41,9% with LC and 18 or 51,4% with LAR) (Table 6). Due to domination of the length of smoking experience in the categories aged from 31 to 45 years and > 45 years of the sick individuals from laryngeal cancer for Z = -1,96 and p<0,05, there is significant difference. Discussion According to the International Agency for Research Cancer (IARC), malignant tumors of lungs, larynx, oral cavity, pharynx, urinary bladder, kidneys, esophagus, stomach and pancreas are caused from smoking and are denoted as tobacco-related cancers (12). Dosemeci et al. (13) in their case-control study evaluated the risk from cancer development in lungs and larynx in men according to localization and histologic type, in relation to cigarette smoking and alcohol consumption. Results demonstrated significant association of these two cancers with the mentioned risk factors. In smokers, greatest risk has been found for supraglottic region of the larynx (Odds ratio OR=4,1), while in those who consume alcohol, the greatest risk has been found in glottic region (OR=1,7). When both risk factors are taken into consideration together, the relative risk is 12,2 for laryngeal, and 14,1 for lung cancer, respectively, in passionate smokers and alcohol consumer. Kubik et al. (14) on the ground of their research concluded that the most significant risk factor and the main cause for mortality increase from lung cancer in Czech Republic has been cigarette smoking. There is significantly increased risk as well for the current smokers, being 11,20 (OR=11,20 95% CI 5,9-21,2) as for the ex-smokers (OR=10,02 95% CI 5,5-18,4). There is positive association in the number of the daily cigarettes smoked and with the smoking length. Identical results were shown by Haldorsen (15) from Norway. Results from the study made by Freudenheim et al. (16) show that there is significant association between smoking, alcohol consumption and development of the laryngeal cancer. Talamini et al. (17) pointed out the relation between smoking cigarettes and development of laryngeal cancer. Compared to nonsmokers, the current smokers have 19,8, while the ex-smokers have 7,0 times greater risk to become sick. The risk increases with the increase of the number of daily cigarettes smoked (OR=42,9 for >25 c/) and the length of smoking (OR=37,2 for >40 years). According to Menvielle et al. (18) the risk of occurrence laryngeal and hypopharyngeal cancer increases with the increase of the number of cigarettes smoked and time duration of the smoking length (Odds ratio=3-44 for actual smokers). According to our own research, the greatest number of sick individuals from lung cancer and laryngeal cancer smoke between 21 to 40 c/den (48,4% with LC; 62,9% with LARC). Among the sick individuals with lung 67 Pavlovska I et al. Epidemiological Study for the Role of Smoking, Genetic Factor and Stress and laryngeal cancers for Z = -0,58 and p > 0,05 there is no significant difference in the number of the daily cigarettes smoked. Due to domination of the time duration of smoking length in the age categories from 31 to 45 years and > 45 years in individuals sick with laryngeal cancer for Z = 1,96 and p < 0,05, there is significant difference. The role of stress in the mechanism of development the lung and laryngeal cancers has been studied. Results from many researches showed that greater inclination to become sick of cancer have the individuals with the so called low neuroticism. On first glance, it will be logical to expect occurrence of the disease in individuals being extremely neurotic and psychotic (with high neuroticism), i.e. who are supposed to be exposed under the action of prolonged or intensive stress situation. This dilemma Berrino explains with the “inoculation” effect for repeated stress situations, when cumulation of the stress situations makes the individual less sensitive for the coming stresses (19). Epidemiological study made showed that greater number of the sick persons of both groups is exposed to chronic stress (14 or 40% - LC; 5 or 14,3% - LARC). Spasova et al. (20) investigated mutations of Kras codon in lung cancer patients. Results from the study showed that, although K-ras (kodon 12) mutation was a genetic lesion not frequently detected in some sample taken during the procedure of bronchoscopy in cases with clinically suspected lung cancer, its discovery could help to prove the cytologic diagnosis for non-small cell carcinoma or even to make diagnosis in cytologically negative cases. Loss of CD44 molecule expression is a factor for bad prognosis in some tumor types. According to Esteban et al. (21) reduced expression of this molecule represents a marker for a bad prognosis for laryngeal cancer. According to epidemiological study made, lung cancer is four times as frequent in men than in women. There is no one woman in individuals sick from laryngeal cancer. The age in both group members varies in almost identical interval (59,3±10,2 years for lung; 59,7±7,8 years for laryngeal cancer). The disease most frequently appears in the sixth and the seventh decades of life (LC 60-69 years; LARC 50-59 years). Macedonians dominate among the sick individuals from LC and LARC (94,3% with LC and 85,7% with LAR), as well as the individuals with Christian faith. There is no significant difference in relation to genetic cancer between the interviewees with lung cancer and those with laryngeal cancer for Z = -0,23 and p>0,05. For Z = 2,27 and p<0,05 stress has been significantly more present among the sick persons with lung cancer than among those with laryngeal cancer. Greater number of both group members are exposed to chronic stress (14 or 40,0% with LC; 5 or 14,3% with LARC). Smoking is one of the most significant risk factors for occurrence of lung and larynx cancers. So, the time duration of the smoking length has been important. Earlier starting with this habit, greater is the risk from occurrence of this disease. Current smokers among the LC sick individuals are 19 or 54,3%, while those with LARC are 24 or 68,6%. There is none nonsmoker among the sick LARC persons, while the number of those with LC is 4 (11,4%). There is no statistically significant difference in relation to the cigarettes smoking habit between the patients with lung and laryngeal cancers (Z = -0,36; p>0,05). Conclusions References 1. 2. 3. 4. WHO; Global Action Against Cancer: WHO Library Cataloguing-in-Publication Data; 2005. Page 2-15. Tuyns AJ. Laryngeal cancer. Cancer Surv 1994; 19-20: 159-73. Williams MD, Sandler AB. The epidemiology of lung cancer. Cancer Treat Res 2001;105: 31-52. Capocaccia R, Micheli A, Berrino F, Gatta G, Sant M, Ruzza MR, Valente F, Verdecchia A. Time trends of lung and larynx cancers in Italy. Int J Cancer 1994 Apr 15; 57(2): 154-61. 5. Register za rak vo Republika Makedonija 1997. Skopje: Republi~ki zavod za zdravstvena za{tita; 1998. Str. 1024. 6. Berrino F, Crosignani P. Epidemiology of malignant tumors of the larynx and lung. Ann Ist Super Sanita 1992; 28(1): 107-20. 7. CDC. Cigarette smoking among adults—United States, 1999. MMWR CDC Surveill Summ 2001; 50(40): 869873. 8. Abdel-Rahman SZ, El-Zein RA, Zwischenberger JB, Au WW. Association of the NAT1*10 genotype with increased chromosome aberrations and higher lung cancer risk in cigarette smokers. Mutat Res 1998 Feb 26; 398(1-2): 4354. 9. Wu X, Dave BJ, Jiang H, Pathak S, Spitz MR. Lung carcinoma patients with a family history of cancer and lymphocyte primary chromosome 9 aberrations. Cancer 1997 Apr 15; 79(8): 1527-32. 10. Zrilic V. Epidemiologija karcinoma bronha. U Burány B. Opsta i specijalna epidemiologija malignih neoplazmi sa posebnim osvrtom na najucestalije lokalizacije. Novi Sad: Medicinski fakultet; 1984. Str. 106–115. 11. World Health Organization, Tobacco or Health Programme. Guidelines for Controlling and Monitoring the Tobacco Epidemic. Geneva: World Health Organization, 1996. Page 3-9. 68 Pavlovska I et al. Epidemiological Study for the Role of Smoking, Genetic Factor and Stress 12. International Agency for Research on Cancer. Alcohol Drinking. Lyon, France: IARC, 1988; IARC Monogr Eval Carcinog Risk Chem Humans, Vol.44. 13. Dosemeci M, Gokmen I, Unsal M, Hayes RB, Blair A. Tobacco, alcohol use, and risks of laryngeal and lung cancer by subsite and histologic type in Turkey. Cancer Causes Control 1997 Sep; 8(5): 729-37. 14. Kubik A., Zatloukal P., Boyle P., Robertson C., Gandini S., Tomasek L., Gray N., Havel L. A case-control study of lung cancer among Czech women. Lung cancer 2001 Mar;31(2-3):111-122. 15. Haldorsen T., Grimsrud TK. Cohort analysis of cigarette smoking and lung cancer incidence among Norwegian women. Int J Epidemiol 1999;28(6):1032-6. 16. Freudenheim JL, Graham S, Byers TE, Marshall JR, Haughey BP, Swanson MK, Wilkinson G. Diet, smoking, and alcohol in cancer of the larynx: a case-control study. Nutr Cancer 1992; 17(1): 33-45. 17. Talamini R, Bosetti C, La Vacchia C, Dal Maso L, Levi F, Bidoli E, Negri E, Pasche C, Vaccarella S, Barzan L, Franceschi S. Combined effect of tobacco and alcohol on laryngeal cancer risk: a case-control study. Cancer Causes Control 2002 Dec; 13(10): 957-64. 18. Menvielle G, Luce D, Goldberg P, Bugel I, Leclerc A. Smoking, alcohol drinking and cancer risk for various sites of the larynx and hypopharynx. A case-control study in France. Eur J Cancer Prev 2004 Jun; 13(3): 165-72. 19. Berrino F, Crosignani P. Epidemiology of malignant tumors of the larynx and lung. Ann Ist Super Sanita 1992; 28(1): 107-20. 20. Spasova I, Novotna H, Vachtenheim J, Bartosova H, Patek J, Hoserova V, Zatloukal P, Kinkor Z. Low mutational rate of K-ras codon 12 in singular bronchoscopy specimens in suspected lung cancer. Neoplasma 2005; 52(3): 255-9. 21. Esteban F, Bravo JJ, Gonzalez-Moles MA, Bravo M, Ruiz-Avila I, Gil-Montoya JA. Adhesion molecule CD44 as a prognostic factor in laryngeal cancer. Anticancer Res 2005 Mar-Apr; 25(2A): 1115-21. 69 Acta morphol.2006; Vol.3(2):70-74 UDK: 618.14 - 018.7 - 006.6(497.7 - 21) VLIJANIE NA DEMOGRAFSKITE KARAKTERISTIKI ZA POJAVA NA ENDOMETRIJALNIOT KANCER VO OP[TINA BITOLA – CASE-CONTROL STUDIJA AdamovskaEleonora 1, Zafirova B2, Adamovski P1, ^ipurova E3 Zavod za zdravstvena za{tita-Bitola, R. Makedonija1 Institut za epidemiologija i biostatistika so medicinska informatika,Medicinski fakultet, Skopje, R. Makedonija2 Ginekolo{ko oddelenie, Klini~ka bolnica-Bitola, R. Makedonija3 Izvadok Cel na istra‘uvaweto e da se sogleda vlijanieto na demografskite karakteristiki za pojavata na endometrijalniot kancer vo Op{tina Bitola. Istra‘uvaweto e sprovedeno vo vid na case-control studija. Vo nea se obraboteni 60 pacientki so patohistilo{ki potvrden endometrijalen kancer i identi~en broj ‘eni bez maligno zaboluvawe, koi ja so~inuvaat kontrolnata grupa. Zgolemeniot rizik od pojava na zaboluvawe e presmetan so stapki na predimstvo (Odds ratio-OR), a so intervali na doverba (Confidence intervals-CI) e definirana statisti~kata zna~ajnost na ispituvanite varijabli kako faktori na rizik. Vo ispituvanata grupa ‘eni, vozrasta od 60 do 64 godini e najpove}e zastapena (35%). Spored mestoto na ‘iveewe, urbanata sredina deluva protektivno vo odnos na ruralnata sredina (OR=0.33, 95% CI 0.12-0.85). @enite so osnovno obrazovanie imaat signifikantno pogolem rizik da dobijat endometrijalen kancer vo sporedba so onie so sredno obrazovanie (OR=4.21 95% CI 1.45-12.51), i vo sporedba so onie so visoko obrazovanie (OR=5.61 95% CI 1.71-20.01). @enite doma}inki sporedeni so ‘enite zemjodelki imaat nezna~ajno pogolem rizik za 1.23 (95% CI 0.30-4.71). Rizikot za doma}inkite e signifikantno pogolem koga se sporedeni so ‘enite rabotni~ki (OR=4.02 95% CI 1.29-12.75) i ‘enite slu‘beni~ki (OR=6.14 95% CI 2.00-19.24). @enite koi se ma‘eni imaat nesignifikantno pogolem rizik od onie koi se vdovici i razvedeni (OR=1.69 95% CI 0.74-3.90). Makedonkite imaat pogolem rizik za 1.52 (95% CI 0.17-18.84) vo sporedba so drugite nacionalnosti (Albanki i Tur~inki). Klu~ni zborovi: endometrijalen kancer, vozrast, profesija, edukacija. THE INFLUENCE OF DEMOGRAPHIC CHARACTERISTICS ON THEAPPEARANCE OF ENDOMETRIAL CANCER IN THE MUNICIPALITY OF BITOLA-CASE CONTROL STUDY AdamovskaEleonora1, Zafirova B2, Adamovski P1, Cipurova E3 Public Health Institute-Bitola, R. Macedonia1 Institute of Epidemiology and Biostatistics with Medical Informatics, Medical faculty, Skopje, R. Macedonia2 Department of gynecology and obstetrics, Klinical hospital-Bitola, R. Macedonia3 Abstract The aim of the research is to understand the influence of demographic characteristics for the appearance of endometrial cancer in the municipality of Bitola. The research has been made as case-control study. The examine group consists of 60 patients confirmed with pathohystiological verified endometrial cancer and an equal number of women without malignant diseases have been examined. The increased risk of the appearance of the illness is calculated in steps of priority and by intervals of loyalty whereas the risk factor is defined by the statistical importance of the examined variables. The age group of 60 to 64 is mostly present within the examined group of women (35%). According to the place of residence, the urban area is more protected than that of the rural one (OR=0.33, 95%CI 0.12-0.85). Women with primary education have a significantly higher risk of receiving endometrial cancer compared to those with secondary education (OR=4.21 95%CI 1.45-12.51) and those with a higher education (OR=5.61, 95%CI 1.71-20.01). Women housewives compared to women farmers have an 70 insignificant higher risk of 1.23 (95%CI 0.30-4.71). The risk of housewives is significantly higher when compared to women laborers (OR=4.02, 95%CI 1.29-12.75) and women working in service organizations (OR=6.14, 95%CI 2.0019.24). Women who are married have an insignificant higher risk compared to those who are widows or divorced (OR=1.69, 95%CI 0.74-3.90). Macedonian women have a higher risk of 1.52 (95%Ci 0.17-18.84) compared to those of other nationalities (Albanian and Turkish). Key words: endometrial cancer, age, profession, education, nationality Introduction Endometrial cancer is the most common malignant neoplasia within the female tract. It appears worldwide and yearly in 142,000 women, and it is estimated that yearly 42,000 women die from this type of cancer. Most cases are diagnosed after menopause, with a high incidence of the 70s age group (1,2). The increase of incidence of endometrial cancer in Western Europe and USA has continued in the last 30 Adamovska E et al. The Influence of Demographic Characteristics on The Appearance of Endometrial Cancer years. The USA takes forth place of common appearance in the female population. In 1999 37,400 new cases and 6,400 deaths (3) were registered in the USA. A high incidence is registered in developed countries around the world (22.2/100 000 in 1997), while in countries in development the incidence is low (2.5/100 000 in 1997). The incidence in Macedonia is 9.5/100 000 in 1997 (4). A large number of factors contribute to the appearance of endometrial cancer. Some are age, place of residence, education, profession, marital status and nationality have a certain part on the appearance of this cancer in women. The endometrial cancer is mostly present in women with menopause (over 50 years of age) and in women with a post-menopause (over 70 years of age) (5). In some countries such as England and Japan an increase in incidence within young women aged 40 to 45 has been noticed. (6, 7). Many case studies show that most of the diseased women live in urban areas (8, 9) and have a low education (10, 11). Women whose job is connected with sitting have a higher risk than those whose job is manual (12, 13). Some studies show that white women have a lighter clinical picture of the illness than black women do (14, 15). Methods This investigation is a case-control study. A group of women who are diseased with endometrial cancer have been examined (an examined group – EG) and a group of women without malignant infection (control group – CG). The examined group consists of 60 women with a pathohistological verification of endometrial cancer who were operated in the Gynecological ward in the Clinical hospital – Bitola. Patients who have not been operated on with pathohistological diagnosis of endometrial cancer are not included in the research. A certain number of patients refused to be surveyed. The control group consists of 60 women who are hospitalized in the Internal ward because of other illnesses, i.e. women who have no malignant illnesses. The women from the examined and control group live in the area of the municipality Bitola. For the choice of members the method matching by age was used in order to minimize the risk of bias while comparing both groups. Statistical methods From the received information a data base has been created in the statistical program Statistics for Windows 7.0, Epiinfo 6 and SPSS 13.0. For the data analysis the following statistical methods have been used: measures for a central tendency and disperse (an average and standard deviation); a linear trend for arranging the developing tendency of endometrial cancer; Pearsson Chi square test (χ2); Fisher exact-test for testing the importance of the differences between the distributions of the investigated variables; classifying the risks with the help of the odds ratio (OR) for the univariant analysis of the examined risk-factors in the case-control study; the logistic regression analysis of determining the independent influence of risk-factors which have shown statistical significance in the univariant analysis; classifying 95% of intervals of loyalty for the odds ratio (OR) according to Cornfield. For statistically significant differences, a mistake on a lower level than 0.05 (p) was taken. Results In the age analysis, which represents a factor of matching, it has been shown that the amplitude of age within the group of diseased women is between 45 and 84, whereas with the control group it is from 46 from 79. The age group of 60-64 is mostly present in percentage in the examined group (35%) (Chart 1). According to place of residence, a greater number of women from the examined group live in the city (39 or 65%). A great percent of women from the control group also live in the city (51 or 85%). In the analysis the place of residence of diseased women showed that women who live in the city have a significant lower risk of receiving endometrial cancer in comparison to those who live in the villages of the municipality of Bitola (OR=0.33, 95%Ci 0.12-0.85) (Table 1). Education is examined with the analysis of the relations between women with different levels of education (illiterate, primary, secondary and higher school education). This means that education plays a part in the appearance of endometrial cancer in the municipality of Bitola. Women with primary education significantly have 4 times a greater risk of receiving endometrial cancer compared to those who have a secondary education (OR=4.21, 95%CI 1.45-12.51) and 5 times a significant higher risk compared to women with a higher education (OR=5.61, 95%CI 1.71-20.01)(Table 2). According to profession, a significance of risk does not exist in order to receive endometrial cancer in housewives compared to women farmers (OR=1.23, 95%CI 0.30-4.71). Women housewives have significantly 4 times a greater risk compared to women laborers (OR=4.02, 95%CI 1.29-12.75). The comparison between housewives and women who work in services shows that the risk is by 6 times significant in housewives (OR=6.14, 95%CI 2.0019.24) (Table 3). An analysis has been made on the structure of the nationality of women diseased with endometrial cancer. Macedonians have a high percent in the participation of the disease (96.6%). This is present in Albanians and Turkish by a lower percent (1.7%). Statistically no difference exists between the Macedonians and the other nationalities (Albanian and Turkish) (OR=1.53, 95%Ci 0.1718.84) (Table 4). Most of the women in the examined group are married. The number of widows present is of 26.6%. Only 1.7% are divorced. In the control group 60% are married, and 40% are widows. There are no divorced women in this group. There are no single women in both groups. During the analysis of married women and widows, it is shown that the married women have a 1.7 times insignificant greater risk in comparison to the widows (OR=1.79, 95%CI 0.77-4.19). An analysis has been made between married and widows with divorced. Married women have a 1.6 times insignificant greater risk in comparison with the second group (widows and divorced) (OR=1.69, 95% CI 0.74-3.90) (Table 5). The completed logistical regression analysis of the risk-factors for the endometrial cancer shows that 71 Adamovska E et al. The Influence of Demographic Characteristics on The Appearance of Endometrial Cancer Table 1. Determination of the risk for endometrial cancer according to the place of residence place urban rural Investigated group Control group 39 51 21 9 OR1 95%CI2 0.33 0.12-0.85 Odds Ratio-OR1 Confidence interval-CI2 Table 2. Determination of the risk for endometrial cancer according to education education Primary education Secindary education Higher education OR1 1.00 4.21 5.61 Investigated group Control group 40 19 9 18 6 16 95%CI2 1.45-12.51 1.71-20.01 Odds Ratio-OR1 Confidence interval-CI2 Table 3. Determination of the risk for endometrial cancer according to profession profesion Housewives Women farmers Women laborers Women officers Investigated group Control group 27 11 12 6 11 18 10 25 OR1 1.00 1.23 4.02 6.14 95%CI2 0.30-4.71 1.29-12.75 2.00-19.24 Odds Ratio-OR1 Confidence interval-CI2 Table 4. Determination of the risk for endometrial cancer according to nationality nationality Macedonian Albanian and Turkish Investigated group Control group 58 57 2 3 OR1 1.00 1.53 95%CI2 0.17-18.84 Odds Ratio-OR1 Confidence interval-CI2 Table 5. Determination of the risk for endometrial cancer according to the marital status Marital status Married Widows and divorced Investigated group Control group 43 36 17 24 OR1 1.00 1.69 95%CI2 0.74-3.90 Odds Ratio-OR1 Confidence interval-CI2 profession and education have an important influence on the appearance of this type of cancer in the municipality of Bitola (Table 6). Women with primary education have 14.4 (95% CI 2.18-95.1) times a greater risk compared to that of women with secondary education, and 4.65 (95% Ci 0.4-53.6) times a greater risk in those compared to women with a higher school education. Women farmers have 1.37 (95% CI 0.20-9.24) times a greater risk compared to women housewives. But agricultural work decreases the chances 72 of infection by 7.75 times compared to women doing labor work and by 1.46 times compared to professions connected with services. Discussion From the completed case-control study and the logistical regression analysis of the risk factors of endometrial cancer in the municipality of Bitola, results Adamovska E et al. The Influence of Demographic Characteristics on The Appearance of Endometrial Cancer Table 6. Logistic regression analyses of risk factores for endometrial carcinoma Parameters Place of living Education Elementary education Secondary education High education Professional occupation Women farmers Housewives Office-employed women Constant Wald* 0.702 9.766 7.662 1.522 0.212 9.771 0.105 3.420 0.070 0.360 Sig. 0.402 0.021 0.006 0.217 0.645 0.021 0.746 0.064 0.792 0.548 Exp.(B)** 1.984 95.0%.I.for EHP(B) lower higher 0.400 9.854 14.390 4.654 2.031 2.178 0.404 0.100 95.071 53.561 41.384 1.371 0.129 0.685 6.337 0.203 0.015 0.042 9.235 1.130 11.308 *Wald test=statistical operation that is used to test the statistical significance for inclusion of each coefficient in model( General linear model-GLM) ** ExpB=Standardised regression coefficient;This value is a measure how strong each predictor value influences the criterion variable. which have been made agree with a large number of researches made worldwide. Endometrial cancer appears at any age, although it is most common in women with menopause (>50 years) and in women with post menopause (>70 years) (5). Vasilj I et al. show the participation of women from 49 years in the Republic of Bosnia and Herzegovina from 28.4% (16). Scientists in Japan also show that the number of infected women under 40 is continuously increasing (6). An increase is noticed in England in the incidence of diseased in the adult group from 40-45 as in the adult group over 65 years, while with the adult group from 35-54 years the incidence decreases (7). Our own studies show that in Bitola women from 60-64 years are diseased with a greater percent (35%). Our studies also show that the place of residence has an important role in the appearance of endometrial cancer. One study in Croatia stated that most diseased women live in the city than in the village (9). The literature give information about the influence of the place of residence according to the years of survival. Bratos K, et al. shows that surviving 5 years is greater in women who live in the city (81%) rather than those who live in the village (73%) (8). The data of made analysis for school preparation of diseased women are the same with those of the quotes made in books. Our studies show that women with primary school have 14.4 times a greater risk than those with secondary education. La Vecchia et al. give information that, if education is taken into consideration, women with a lower education have 2.8 times increased relative risk of receiving endometrial carcinoma. (10). In a Sweden study, Li C, et al. also show that women with a low education have a greater risk of endometrial carcinoma (11). The study of Strinic T, et al. in Croatia show that women with a lower education were largely present in the examined group (9). Women who do agricultural work have a greater risk of 1.37 compared to women housewives. Although agricultural work decreases the chances of infection by 7.75 times compared to labor work and by 1.46 times compared to a profession in services (p>0.05). In a Finish study, endometrial carcinoma was associated to the exposure of animal dust and work connected with sitting. An insignificant lower risk is noticed in manual professions (13). Kalandidi A, et al. confirmed that there is a low risk of disease in women from Greece, of which their profession is manual (p=0.03) (12). Almost every nationality is diseased by endometrial carcinoma, even though it is highly present in Macedonians (96.6%). This is due to the structure of women in our municipality where Macedonians take part in by 90.7%. From the completed logistical regression analysis it is shown that nationality does not represent a significant risk factor. Anastasiadis PG, et al. examined the endometrial characteristics of women with endometrial carcinoma which belong to the two large ethnical groups (Christian and Muslim) and came up with the conclusion that these two groups have significant statistical differences compared to many epidemical characteristics (17). The completed logistical regression analysis has shown that marital status does not represent a significant risk factor for the appearance of endometrial cancer. In Strinic T, et al. studies in Croatia single and widows were more present in the group of infected women (9). Conclusion The results of the demographic characteristic studies show that independent predictable risk factors for the appearance of endometrial cancer in the municipality Bitola are primary education and profession. The place of residence, marital status and nationality structure of the women, do not highly influence the appearance of this type of cancer. 73 Adamovska E et al. The Influence of Demographic Characteristics on The Appearance of Endometrial Cancer References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 74 Amant F, Moerman P, Neven P, Timmerman D, Limbergen E, Vergote I. Endometrial cancer. Lancet 2005; 366(9484):491-505. Canavan TP, Doshi NR. Endometrial cancer. Am Fam Physician 1999; 59(11):3069-77. Bristow RE. Endometrial cancer. Curr Opin Oncol 1999; 11(5):388-93. Parkin DM, Whelan SL, Ferlay J, Raymond L, Young J. (1997) Cancer incidence in five continents, Vol VII. (IARC Scientific Publications No. 143) Lyon, IARC. Marchetti M, Vasile C, Chiarelli S. Endometrial cancer: asymptomatic endometrial findings. Characteristics of postmenopausal endometrial cancer. Eur J Gynecol Oncol 2005; 26(5):479-84. Yamagami W, Susumu N, Banno K, Hirao T, Kataoka F, Hirasawa A, Suzuki N, et al. Clinicopathologic manifestations of early-onset endometrial cancer in Japanese women with a familial predispisition to cancer. Obstet Gynecol Res 2005; 31(5):444-51. Somove G, Olaitan A, Mocroft A, Jacobs I. Age related trends in the incidence of endometrial cancer in South East England 1962-1997. J Obstet Gynecol 2005; 25(1):35-8. Bratos K, Roszak A, Cikowska-Wozniak E, Niecewicz P. Analysis of epidemiologic risk factors foe endometrial cancer. Ginekol Pol 2002; 73(11):945-50. Strinic T, Bukovic D, Bilonic I, Hirs ZZI, Despot A, Bocan A. Socio-demographic characteristics of women with endometrial carcinoma. Coll Antropol 2002; 27 Suppl 1:55-9. La Vecchia C, Negrii E, Franceschi S, D,Avanzo B, Boyle P. A case control study of diabetes mellitus and cancer risk. Br J Cancer 1994; 70(5):950-3. Li C, Samsioe G, Iosif C. Quality of life in endometrial cancer surivors. Maturitas 1999; 31 (3): 227-36. Kalandidi A, Tzonou A, Lipworth L, Gamatsi I, Filippa D, Terichopoulos D. A case-control study of endometrial cancer in relation to reproductive, somatometric, and life-style variables. Oncology 1996; 53(5): 354-9. Weiderpass E, Pukkala E, Vasama-Neuvonen K, Kauppinen T, Vainio H, Paakkulainen H, Boffeta P, et al. Occupational exposures and cancers of the endometrium and cervix uteri in Finland. Am J Ind Med 2001; 39 (6): 572-80. Madison T, Schottenfeld D, James SA, Schwartz AG, Gruber SB. Endometrial cancer: socioeconomic status and racial/ethnic differences in stage at diagnosis, treatment, and survival. Am J Public Health 2004; 94(12):2104-11. Kost ER, Hall KL, Hines JF, Farley JH, Nycum LR, Rose GS, carlson JW, et al. Asian-Pacific Islander race independly predicts poor outcome in partients with endometrial cancer. Ginecol Oncol 2003; 89(2):218-26. Vasilj I, Cavaljuga S, Strnad M, Znaor A. Endometrial cancer epidemiology and prevention in Federation of Bosna and Herzegovina, B&H. Bosn J basic Med Sci 2004; 4(4): 63-5. Anastasiadis PG, Skaphida PG, Koutlaki NG, Galazios GC, Tsikouras PN, Liberis VA. Epidemiologic aspects of endometrial cancer in Thrace, Greece. 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Da ne se povtoruvaat isti informacii vo tabelite i slikite. Ilustracii-te se podnesuvaat isprintani na paus hartija, sjajni (dve isti mo‘e da se fotokopiraat) so mo‘nost za namaluvawe na rezolucijata ako e potrebno. Maksimalnata golemina na sekoja slika vo pe~ateno spisanie treba da iznesuva 20 x 28 cm (8.25 x 11 inch) . Na pozadinata na sekoja slika , treba da stoi ime na avtorot i broj na slikata, a so strelka ozna~eni gore specijalni mesta na slikite. Sekoja slika treba da e oddelena, so celosno objasnete legenda na slikite; site delovi na slikata, simboli i kratenki treba da bidat definirani. Legendata za slikite treba da e napi{ana na posebna strana; brojot na slikite treba da gi sledi i referencite vo tekstot. Imiwa na lekovi . Treba da se koristat generi~ki imiwa na lekovite: komercijalni imiwa mo‘e da se dadat vo zagradi pri prvoto spomenuvawe, a generi~koto ime treba da se koristi vo natamo{niot tekst. Kratenki. Listata na kratenki dadena vo “ Uniform Requirements for Manuscripts Submitted to Biomedical Journals “ ( del referenci ) treba da se sledi. Za dodavawe kratenki , koristete go CBE Style Manual (available from the Council of Biology Editors, 9650 Rockville Pike , Bethrsda, Maryland 20814, U.S.A.) ili nekoj drug izvor. Literatura Referencite se pi{uvaat kako {to se dadeni vo “ Uniform Requirements for Manuscripts Submitted to Biomedical Journals “ . Literaturnite podatoci treba da se citiraat vo tekstot po broj i da se napi{at kako {to }e bidat citirani. Literaturnite podatoci treba da se pi{uvaat so dvoen prored na krajot na tekstot sledej}i gi dadenite primeri podolu. Kratenkite na spisanijata se vo soglasnost so tie citirani vo Indeks Medikus (dostapni vo Superintendent of Documents, U.S. Goverment Printing Office, Washington , D.C. 20402, U.S.A., DHEW Publication No. NIH 83 – 267; ISSN 0093 – 3821). Se citiraat site avtori ako se sedum ili pomalku; za pove}e od sedum se citiraat prvite tri i se dodava sor. Za makedonski tekst ili “ et all “ za angliski tekst.Avtorot e odgovoren za svoite literaturni podatoci. Trud: 1. Greenblatt DJ, Abernethy DR,Shader Jr RI.Pharmacocinetic aspects of drug therapy in the elderly (commentary). Ther drug Monit 1986; 8 ( 6 ): 249 - 255. Kniga: 2. Mitchell JR, Horning MG (Eds). Drug metabolism and drug toxicity. New York; Raven Press, 1984:1 – 25. Poglavie vo kniga: 3. Kutt H, Pippenberg CE et al. Plasma clearance of non-methsuximide in uremic patient. 223 – 226. In: Levy RH, Public WH ,Meijer J (Eds). Metabolism of antiepileptic drugs. Ney York; Raven Press, 1984. 75 Informacii za avtorite Kniga vo serija: 4. Usdin E,Asberg M,Bertilisson L (Eds) .Frontiers in biochemical and pharmacological research in depression.New York; Raven Press,1984. (Advances in biochemical psychopharmacology; vol 39.) Izvadok Izvadokot treba da se pi{uva na posebna strana so ne pove}e od 250 zborovi. Negovata sodr‘ina treba da pretstavuva nezavisna celina, da se pi{uva vo sega{no vreme , podelena vo pet delovi koi go opf}aat sledniot redosled: Cel, Voved, Metodi, Rezultati, Zaklu~ok. Se koristat celi re~enici. Site podatoci vo izvadokot treba da se pi{uvaat vo sega{no vreme kako i celiot tekst i tabelite. Da ne se koristat pove}e od 3 do 5 klu~ni zborovi. Mo‘e da se koristat zborovi od Index Medicus. Sodr‘inata na apstraktot ne treba da sodr‘i pove}e od 50 zborovi i da ja zadovoli sodr‘inata na dadenite tabeli i prikazi na klini~ki slu~ai. Korekcii Recenziranite trudovi treba da se vratat vo rok od 3 dena; sekoe zadocnuvawe mo‘e da dovede do odlo‘uvawe na pe~ateweto. Ve molime prethodno proverete go tekstot , tabelite, legendite i literaturnite podatoci. Kriteriumi za podnesuvawe na trud vo elektronska forma Trudot se dostavuva na 3,5 inch disk vo MS – DOS forma. Sekoja podnesena disketa treba da e obele‘ana so etiketa na koja se nao|a ime na avtorot , naslov na trudot , naslov na spisanieto, kompjuterski program (verzija) i ime na fajlot. o Rakopisot daden na disketa treba da ja pretstavuva kone~nata verzija i da e vo soglasnost so materijalot podnesen za pe~atewe. Disketata treba da ja sodr‘i samo kone~nata verzija na trudot , a ostanatiot materijal treba da se izbri{e od disketata. Ve molime da se sledat kriteriumite za pi{uvawe na trud dadeni vo “ Kriteriumi za avtorot za pi{uvawe trud”. Tekstot daden vo rakopis za pe~atewe treba da e so dvoen prored, dodeka elektronskata verzija ne treba da sodr‘i formatirani instrukcii. Ne se koristi tabs ili ekstra prostor na po~etokot na tekstot.Ne se podvlekuva vo referencite. Se isklu~uva kop~eto za line spacing. Ne se obele‘uvaat stranite. Vnesete gi korektno “ eden “ (1) ili “ el “ (malo latinsko l) , kako i “ nula “ ( 0 ) i golema bukva “ O “ (O) . Ve molime sledete gi usvoenite pravila. Koristete edna crta za prostor pred za da go obele`ite znakot minus , a koristete dvojna crta ( so prostor pred i po ) za da obele`ite dolga crta vo tekstot i trojna crta (bez prostor) za da gi obele`ite broevite (str. “ 23-45”). Nestandarni karakteristiki ( gr~ki bukvi, matemati~ki simboli i dr. ) treba da se {ifriraat vo kontekst na tekstot. Ve molime napravete lista na koristewe na {ifrite. Avtorite treba da se soglasat so toa {to go bara izdava~ot za pe~ateweto. Avtorite treba da gi izvr{at site merewa sprema usvoenite pravila na Systeme Internacional (SI).Konvencionalnite pravila na koristewe na sliki i tabeli treba da se dadat so legenda za koristewe na istite. Vo elektronskoto pi{uvawe na tekstot se prepora~uva text editor ili (editor T602). Tekstot treba da se pi{uva od levo ( not justified ) , bez crti~ki, bez to~ki za nabrojuvawe, broevi i podvlekuvawa. Eden tip na program Word treba da se koristi vo celiot tekst. Tabeli vo Word: ne koristete vertikalni linii, osven ako toa ne e potrebno. Stavete gi tabelite kako poseben fajl so naslov (ne gi stavajte vo tekstot). Grafikoni vo Exel: stavete gi kako poseben fajl vo Exel. Grafikoni vo Word: stavete gi kako poseben fajl vo Word. Legendata za tabelite i grafikonite stavete ja posebno na krajot od tekstot. Grafikonite da bidat vo crno - bela boja. Grafikonite printani na laser ili na ink printer da ne se koristat kako templates – sekoga{ vo originalen elektronski fajl! Sliki: Originalni ili skenirani. Skenirawe do 600 – 800 dpi!-set to B/W or line art. Sliki- vo crno- bela boja – so dobar kvalitet ili skenirani do 350 dpi. Sliki – vo boja - so visoka rezolucija do 350 dpi. Slikite so pogolema rezolucija od 72 ili 96dpi nema da se pe~atat. Elektonski podgotvenite sliki se primaat vo Tif ili Jpg format (so minimalna rezolucija ). Legendata za slikite se pi{uva kako poseben fajl. Ne se stavaat sliki vo Power Point- tie se koristat za prezentacii i ne mo‘at da se koristat kako dokument za printawe. Sliki od digitalna kamera ne se stavaat vo tekstot. (se koristat vo Tif ili Jpg format ( so minimalna rezolucija). 76 Acta morphol.2006; Vol.3(2) Informations for Authors These guidelines are in accordance with the “Uniform Requirements for Manuscripts Submitted to Biomedical Journals”. (Complete document available at www.icmje.org ) Manuscripts are accepted for processing if neither the article nor any essential part, tables or figures, has been or will be published or submitted elsewhere before presenting in Acta Morphologica. This restriction does not apply to abstracts or press reports related to scientific meetings. The Editors will consider both invited and uninvited review articles. Authors should detail how their work differs from existing reviews on subject in cover letter. Manuscripts/General Guidelines The manuscript should conform the guidelines set forth in the “Uniform Requirements for Manuscripts Submitted to Biomedical Journals”, 5th edition, New Engl J Med 1997; 336 (4): 309–315. Manuscript must contain no more than 5000 words. A cover letter signed by all authors should identify the person (post address, telephone number, and e-mail address) responsible for negotiations. Each author must sign a statement attesting that he or she fulfills the authorship criteria of the Uniform Requirements. Each author must significantly contribute to the submitted work. Form of Manuscript Three copies of each manuscript, along with a disk (see “Instructions for Electronic Manuscript Submission”), must be submitted in English, in double-spaced typewritten form with a 5-cm (2-inch) left margin. (Do not use “erasable” bond.) The text should be written in following sequence: Introduction, Methods, Results, Discussion, Acknowledgement, References, Tables, Illustrations and Figure Legends, Structured Abstract with key words and Condensed Abstract. Page 1 should bear an article title, name(s) of the author(s) and institution where the work was done and a person whom proofs and reprint request should be sent, with complete address (including postal codes), telephone number and e-mail address (address for correspondence). Tables should be typed neatly, each on a separate sheet, with title above and any notes below. All abbreviations should be explained. Do not provide duplicite information in tables and figures. Illustrations should be submitted as clear glossy prints (two duplicate sets may be photocopied), with lettering large enough to be legible if reduced. The maximal final size of any figure in the printed journal will be 20 by 28 cm (8.25x11 inch). On the back of each figure, the name of author and the figure number should be writen, with the top indicated by an arrow. Each figure should have a separate, fully explicit legend; all parts of the figure and all abbreviations and symbols should be clearly defined. Figure legends should be typed on separate pages; figure numbers must follow their reference in text. Drug names. Generic names should be used; trade names may be given in parentheses in the first mention, and generic names should be used thereafter. Abbreviations. The list of abbreviations given in “Uniform Requirements for Manuscripts Submitted to Biomedical Journals” (section References) should be followed. For additional abbreviations, consult the CBE Style Manual (available from the Council of Biology Editors, 9650 Rockville Pike, Bethesda, Maryland 20814, U.S.A.) or other standard sources. References The journal complies with the reference style given in “Uniform Requirements for Manuscripts Submitted to Biomedical Journals”. References should be cited in text by number and numbered in order they are cited. The reference should by written in double-spaced form at the end of the text, following the sample formats given below. For the abbreviations of journal names, refer to the List of Journals Indexed in Index Medicus (available from the Superintendent of Documents, U.S. Government Printing Office, Washington, D.C. 20402, U.S.A., DHEW Publication No. NIH 83-267; ISSN 0093-3821). Provide all names of authors when fewer than seven: when seven or more, list the first three and add et al. Provide article titles and inclusive pages. The author is responsible for the accuracy of reference data. 77 Informations for Authors Article: 1. Greenblatt DJ, Abernethy DR, Shader Jr RI. Pharmacokinetic aspects of drug therapy in the elderly (commentary). Ther Drug Monit 1986; 8 (6): 249-255. Book: 2.Mitchell JR, Horning MG (Eds). Drug metabolism and drug toxicity. New York; Raven Press, 1984: 1-25. Chapter of book: 3. Kutt H, Pippenberg CE et al. Plasma clearance of nor-methsuximide in a uremic patient. 223-226. In: Levy RH, Pitlick WH, Meijer J (Eds). Metabolism of antiepileptic drugs. New York; Raven Press, 1984. Book in a series: 4. Usdin E, Asberg M, Bertilsson L (Eds). Frontiers in biochemical and pharmacological research in depression. New York; Raven Press, 1984. (Advances in biochemical psychopharmacology; vol 39.) Internet: 5.http://www.med.monash.edu.au/medical Structured Abstract A structured abstract should be provided on a separate page with no more than 250 words, presenting essential data in five paragraphs introduced by separate headings in following order: Objectives, Background, Methods, Results, Conclusion. Complete sentences should be used. All data in the structured abstract must be present also in the submitted text or tables. Three to five key words should be added. Terms from Index Medicus should be used. Condensed Abstract (for table of contents) A condensed abstract of no more than 50 words should be provided for the expanded table of contents, stressing clinical implications. Do not include data which are not present in the text or tables. Proofs Proof must be returned within 3 days; late return may cause a delay in publication. Please check text, tables, legends, and references carefully. Instructions for Electronic Manuscript Submission The preferred storage medium is a 3.5 inch disk in MS-DOS compatible format. Each submitted disk must be clearly labeled with the name of the author, article title, journal title, type of the equipment used to generate the disk, word processing program (including version number), and filenames. The manuscript submitted on a disk must be in the final corrected version and must agree with the final accepted version of the submitted paper manuscript. The submitted disk should contain only the final version of the manuscript. Delete all other material from the disk. Please follow the general instructions on style/arrangement and, in particular, the reference style as given in “Instruction to Authors”. Note, that while the paper version of the manuscript must be presented in the traditional double spaced format, the electronic version will be typeset and should not contain extraneous formatting instructions. Do not use tabs or extra space at the beginning of a paragraph or for list entries. Do not indent runover lines in references. Turn off line spacing. Do not specify page breaks, page numbers, or headers. Do not specify typeface. Take care to enter “one” (1) and lower case “el” (1)“, as well as “zero” (0) and capital “oh” (O) correctly. Please note the following conventions on dashes: Use a single hyphen with space before it for a minus sign, use a double hyphen (with space before and after) to indicate a “long dash” in text, and a triple hyphen (with no extra space) to indicate a range of numbers (e.g. “23–45”). Non-standard characters (Greek letters, mathematical symbols, etc.) should be coded consistently throughout the text. Please make a list and provide a listing of the used codes. Authors agree to execute copyright transfer forms as requested. Authors should express all measurements in conventional units, with Systéme International (SI) units given in parentheses throughout the text. Conventional units should be used in figures and tables, with conversion factors given in legends or footnotes. In electronic manuscript submission text editor Word 6 or higher is recommended (editor T602 is possible). Text should be aligned left (not justified), without hyphenation, without bullets, numbering and underlines, without extra hard returns at the end of line (only at the end of paragraphs). One type of Word paragraph should be used throughout the text. Word graphic experiments should not be used. 78 Informations for Authors Word tables : do not use vertical lines, unless it is necessary. Provide tables as a separate file (do not place in text). Excel graphs : provide as Excel file. Word graphs : provide as a separate Word file (do not place in text!) Table and graph legends should be provided separately at the end of the text. Graphs should be processed for black and white print. Graphs printed on laser or ink printers could not serve as templates– always provide original electronic files ! Figures : provide original or scan. Scan to 600-800 dpi ! – set to B/W or line art. Figures – black and white photos – provide high-quality original or scan to 350 dpi ! Figures – color photos — provide high-quality original or scan to 350 dpi ! Figures scanned to 72 or 96 dpi are not suitable for print ! On principle, do not place scans in text ! Always provide original figures in tif or jpg format (with minimal compression). Placing scan in Word text causes a loss of quality! Figure legends should be provided as a separate text file. Do not place figures in PowerPoint – this application is meant for presentations and it is not possible to use it as a template for print ! Figures from digital camera should not be placed in text. Provide them in tif or jpg format (with minimal compression)! Transciption of Macedonian Cyrillic Alphabet into English Latin Aa Bb Vv Gg Dd \| Ee @‘ Zz Yy Ii Jj Kk Ll Qq Mm A a B b Vv Gg D d Gg Ee Zh zh Zz Dz dz II Jj Kk Ll Lj Lj Mm Nn Ww Oo Pp Rr Ss Tt ]} Uu Ff Hh Cc ^~ Xx [{ N n Nj nj O o P p Rr S s T t Kk U u Ff Kh kh Ts ts Ch ch Dzh dzh Sh sh On the basis of ISO Recomandation R-9-1968 International List of Periodical Title Abbreviations (1970) 79 EKSKLUZIVNA IZJAVA ZA OBJAVUVAWE NA AVTORITE KOI PODNESUVAAT TRUD AN EXCLUSIVE STATEMENT FOR PUBLICATION IS NESSESARY WHEN SUBMITTINGAN ARTICLE FOR PUBLICATION Potvrduvam deka nitu eden materijal od ovoj rakopis ne e prethodno objaven ili daden za objavuvawe vo bilo koj vid, osven izvadok (apstrakt) od 400 zbora ili pomalku. I hereby confirm that the materials of this manuscript have neither been previously published nor handed for publishing, except the abstract of 400 words or less. SOGLASNOST ZA PRENOS NA PE^ATARSKI PRAVA TRANSFER OF COPYRIGHTAGREEMENT Pe~atarski prava na trudot so naslov: Copyright to the article entitled: __________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________________________________________________________________________ koj }e se objavi vo spisanieto Acta Morphologica, se prenesuvaat na Acta Morphologica, no avtorite go zadr‘uvaat slednovo: to be published in the journal Acta Morphologica is hereby transferred to the Acta Morphologica, but this authors reserve the following: 1. Site prava na sopstvenost osven pe~atarskite, kako pravoto na patent All proprietary rights other than copyright, such as the patent right. 2. Pravoto za upotreba na del ili site delovi od ovoj trud za svoja li~na rabota The right to use all of the parts of the article in future works of their own. Ime i prezime First and last name ________________________ ________________________ ________________________ Potpis signature VA@I SAMO PO PRIFA]AWE NA TRUDOT VALID ONLY AFTER THE ACCEPTANCE OF THE ARTICLE 80