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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.
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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.
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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.
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1.
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Zagreb, 2004, 31-36.
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2004, 31-36.
4. Di Maio D.J, Di Maio V.J.M. Forensic Pathology, 1Id ed., CRC Press LLC 2000,21-41
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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
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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
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National Health and Nutrition Examination Survey (1988-94), Hyattsville MD: National center for Health Statistics,
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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
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WHO; Global Action Against Cancer: WHO Library Cataloguing-in-Publication Data; 2005. Page 2-15.
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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
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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. Int J Gynecol Obstet 1999; 66 (3): 263-72.
Acta morphol.2006; Vol.3(2)
Informacii za avtorite
Ovie instrukcii se vo soglasnost so “Uniform Requirements for Manuscripts Submitted to Biomedical
Journals “ (Site podatoci se dostapni na veb stranata www.icmje.org.).
Rakopisite }e bidat objaveni samo pod uslov ako nieden materijal , nitu negov del, tabela ili
sli~no ne se i nema da bidat pe~ateni i dadeni nikade za objavuvawe pred nivnoto pe~atewe vo Acta
Morphologica.Ovie pravila ne va‘at za apstrakti ili slu~ai (case report ) prezentirani na nau~ni
kongresi.
Izdava~ite }e gi razgleduvaat prifatenite i neprifatenite trudovi. Avtorite treba da
objasnat kako nivnata rabota se razlikuva od ve}e postoe~kite nivni recenzirani trudovi no vo plik
vo koj se ispra}a trudot.
Rakopis / Op{ti zabele{ki
Rakopisot treba da gi potvrdi instrukciite vo Uniform Requirements 5 th edition , New Engl J Med
1997 ; 336 ( 4 ): 309-315. Trudot mora da sodr‘i ne pove}e od 5000 zbora . Na plikot vo koj se ispra}a se
potpi{uvaat site avtori i ostavaat podatoci (po{.faks, tel. Broj, e- meil), dostapni za ponatamo{no
kontaktirawe. Sekoj avtor mora da potpi{e izjava deka toj ili taa }e gi ispolni kriteriumite na
Uniform Requirements.
Forma na trudot
Se podnesuvaat dve kopii, so disketa (vidi “ Instructiones for Electornic Manuscript Submission” ) na
angliski jazik , so dvoen prored so margini od 5 cm (2 inch) levo. Tekstot treba da sodr`i : Voved,
Metodi, Rezultati, Diskusija, Blagodarnost (Priznanija), Literatura, Tabeli, Ilustracii i Sliki
so Legendi, izvadok so klu~ni zborovi (kratok apstrakt) .
Strana 1 treba da stoi naslov na trudot , ime (wa) na avtorot (ite), institucija kade {to e raboten
trudot i lice za kontakt so kompletna adresa po{.faks, tel.broj, e-mail (adresa za kontakt).
Tabeli-te se davaat na poseben list so dvoen prored, so naslov nad niv i objasnuvawa pod niv. Site
kratenki treba da se objasnat. 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