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Ministry of Public Health Republic of Uzbekistan Centre of development of the medical education Tashkent Medical Academy «Application of the case-technology at the faculty therapy studies on a theme «Systemic lupus erythematosus» (The teaching and methodological guide for students of IV courses of medical universities) Tashkent 2012 1 Ministry of Public Health Republic of Uzbekistan Centre of development of the medical education Tashkent Medical Academy “Approved” Head of the Chief Department of science and educational institutions of MPH RUz Professor Sh.E. Atahanov ___________________________ “____” ________________ 2012 № of the report «Application of the case-technology at the faculty therapy studies on a theme «Systemic lupus erythematosus» (The teaching and methodological guide for students of IV courses of medical universities) Tashkent 2012 2 Authors: Djuraeva E.R. – department of faculty and hospital therapy of the faculty of general medicine and internal diseases for medical prophylaxis faculty, associate professor. Ziyaeva F.K. – department of faculty and hospital therapy of the faculty of general medicine and internal diseases for medical prophylaxis faculty, assistant. Reviewers: Yakubov A.V. – department of clinical pharmacology of ТМА, professor, doctor of medical science Rahimov S.M. – department of hospital therapy and propedeutics of internal diseases of TashPMI, professor, doctor of medical science The teaching and methodological guide is examinationed and confirmed at the session of ТМА CMC (report № _____ “_____” _____ 2012). Chairman of the CMC, professor M.Sh.Karimov The teaching and methodological guide is confirmed on the Scientific Council of ТМА and is recommended to publication (report № _____ “_____” _____ 2012). The scientific secretary, doctor of medical science, professor Salomova F.I. 3 Theme: Systemicic lupus erythematosus 1. The study venue and equipment Departments of rheumatology, cardiorheumatology and common therapy, department of laboratory and instrumental diagnostics, educational rooms. Blood, serologic analyses, clinical and biochemical analyses, immunologic examinations, acute phase tests, X-ray examinations, ECG, FCG, EchoCS, educational and supervising tests, thematic patients, distributing material. - ТV-video, overhead, multimedia, charts, slides, informational computer program. 2. Duration of the lesson Time for interpretation of the yielded theme - 270 minutes 3. The study purpose: Teaching students of the etiology, pathogenesis, clinical symptomatology, laboratory-instrumental diagnostics and rational therapy, preventive maintenance of complications, follow-up care. The training purpose – development and hardening of theoretical knowledge: The educational purpose – formation in doctor training the interest corresponding to the world standards for a speciality, a sense of responsibility, education of interest to the knowledge enhancement, formation of the deontologic educational level, formation of caution in the course of practical work, lucidity and responsibility. The development purpose – formation of self-maintained thinking and discussion at students, development of critical thinking in students (e.g. clinical and prophylaxis). Briefing 1. 2. 3. 4. 5. Definition of a Systemic lupus erythematosus (SLE). SLE etiology. SLE pathogenesis. SLE classification. Clinical pattern of SLE: the subjective data, common examination, palpation, percussion and auscultation data, the inference of the laboratory-instrumental methods of examination. 6. Differential diagnostics of SLE 7. Main principles of treatment of SLE 8. Course and the SLE prognosis. The student should know: - SLE etiology - SLE pathogenesis - SLE classification - Methods of diagnostics of SLE - Main principles of treatment 4 The student should be able: - To collect the anamnesis, complaints of the patient, to perform the common examination, palpation, percussion and auscultation - To compound the plan of the patient examination - To interpret the laboratory data indexes - To interpret the data of X-ray examination - To prove the clinical diagnosis step-by-step - To write the prescription on drugs and explain their mechanism and side effects 4. Motivation The present studying of a systemic lupus erythematosus has huge value, the SLE can lead to the patient lifethreatening complications. 5. Interdisciplinary and intradisciplinary communication Interdisciplinary communication: To integrate with following subjects: I. On vertical 1. Normal anatomy 2. Normal physiology 3. Histology 4. Pathologic anatomy 5. Pathologic physiology 6. Propedeutics of internal diseases II. On horizontal 1. Radiologic diagnostics 6. The lesson content. Theoretical part Bunch of general diseases of a connective tissue concern: Systemic lupus erythematosus Systemic scleroderma Dermatomyositis Diffuse fasciitis Rheumatic polymyalgia Relapsing panniculitis Relapsing polychondritis Sjogren’s syndrome and disease Mixed diseases of connective tissue Antiphospholypid syndrome SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) - chronic polysyndromic disease of preferentially young women and the girls, educing upon genetic caused irregularity of immune managing processes leading to uncontrollable production of antibodies to natural cells and their components, with development of the autoimmune and immune complex chronic inflammation. 5 Epidemiology Annually in different regions 1face per 400-2000 affected Disease more often educes at women (10-20:1) 50-70 recently affected per 1 million population in a year 70% fallen ill at the age of 14 - 40 years, "peak" by 14 – 25 years The SLE etiology is not determined yet. A viral infection contamination, genetic, endocrine and metabolic factors are supposed to educe the SLE development. In patients with SLE the lymphotoxic antibodies and antibodies to the double-helical DNA are often found, which are being markers of a persistent viral infection. In an endothelium of capillaries of the damaged tissues the virus-like incorporations are being revealed. The fact of family prevalence of the disease considerably exceeding the population testifies to the genetic predisposition to SLE, high frequency of rheumatic diseases at relatives, cases of disease at twins. Connection between SLE and presence of certain HLA-antigenes (DRj, DRj, Bg), deficit of С4component of the complement, genetic determined insufficiency of N-acetyltransferase enzyme metabolizing a series of medicines is established. The depression of immune tolerance to the natural antigens is in the basis of the disease, leading to uncontrollable synthesis of set of autoantibodies to natural tissues of an organism, especially to the nuclear antigens. Disturbance of immune tolerance arises due to the congenital or acquired defect as in the system of T-lymphocytes (depression of T-supressors activity, reduction of interleukin-2 production), as well as the B-system (polyclonal activation). Autoantibodies render direct (on erythrocytes, thrombocytes etc.) and mediated (through formation of cell-bound immune complexes) damaging activity. At SLE the deep disturbances in the processes cell-bound immune complexes elimination from an organism are stated. The antibodies to native DNA and the circulating cell-bound immune complexes sedimenting on the basal membranes of kidney glomerular capillaries, skin and other organs and tissues have their pathogenetic value. Thus they have the damaging effect accompanied by development of typical inflammatory response. Prevalence of young women among patients with SLE, the frequent beginning of disease after the delivery or abortions, disturbance of the estrogens metabolism with rise of their activity, presence of hyperprolactinemia testifies to participation of hormonal factors in pathogenesis of the disease. Quite often at the SLE diseased patients the symptoms specifying in a depression of adrenal function are noted. Catarrhal diseases, labours, abortions, pregnancy, ultraviolet radiance, intolerance of medicines, vaccines, serums etc. can be the provoking factors in SLE development. Pathomorphology. In the loci of the connective tissue damage the amorphous masses nuclear substance, coloured by hematoxylin in purple-blue colour (hematoxylin bodies). The neutrophils captured these bodies in vitro term as LE cells. Cell-bound immune complexes in a connective tissue and vessel walls consisting of DNA, antibodies to DNA and compliment components, are coloured (as well as fibrine) by eosine, forming a pattern of the fibrinoid necrosis. Clinical pattern. Systemic lupus erythematosus is a disease of young women in childbearing age. Men are ill in 10-15% of cases. Polymorphism of clinical symptoms is bound with the systemic pathological process. Disease more often begins with an articular syndrome, fever, dermal rashes, trophic disturbances and astenovegetative syndrome. Within several months for no apparent reason the patient can grow thin for 10 and more kilograms. Gradually all new organs and organism systems are iHbolved in process, yielding the conforming clinical semiology. 6 The joints lesion occurs at 90-95 % of patients and becomes apparent by arthritis or migrating arthralgias. All joints of arms and feet, but more often the palmar joints can be iHbolved in process. The periarticular edema is distinctive. At a chronic clinical course the deformation of palmar fingers, an atrophy of interosseous muscles can educe. The arthritis at SLE is well treated by corticosteroids. Integuments at SLE clinically are impaired less often than joints. The symptom of "butterfly" erythematous rashes on face and in the field of cheeks, the nose ridge, superciliary arcs are most typical. Dermal lesions can become apparent also by a facial diffuse erythema and open parts of a body, elements of discoid lupus, pemphygoid rash etc. The part of the patients have in the field of palms and fingers can have net teleangiectatic erythema (capillarites) which also have its diagnostic value. The lesion of serous membranes, mostly the pleura and pericardium, meets approximately at 90% of patients. Pleurites and pericardites are often dry, more rarely with a small amount of ecssudate and its prompt iHbolution. X-Ray examination often shows traces of the carried serositespleuropericardial commissures or a pleura thickening. At SLE the cardiovascular system is often iHbolved in pathological process. Clinically it can proceed in the form of a myocardial dystrophy, myocarditis or endocarditis with a lesion of the valval apparatus (endocarditis of Liebmann-Sax). Myocardium lesions are become apparent by pains in the heart area, dyspnea, dumb heart beats, tachycardia, noises, rhythm disturbances. The lesion of lungs proceeds as a pneumonitis (dyspnea, cough, facial cyanosis, at auscultation fine moist rhales) or pneumosclerosis. X-Ray showings indicate intensifying and the strain of the vascular pattern, alternating infiltrates, the fibrosis locus, preferentially in the inferior departments of lungs are observed. The small focal dissemination in lungs at SLE demands differential diagnostics with tubercular process. Kidneys are impaired not less often than at every second patient with SLE. Clinically it can become apparent by a pattern of glomerulonephritis or glomerulonephritis with nephrotic syndrome. At the long-term treatment of patients the corticosteroid hormones can educe the secondary pyelonephritis. Appearance of a renal pathology in a disease debut is especially prognostically unfavorable. The pathology of a gastrointestinal tract is not often revealed. Cheilites (lesion of lips), aphthous stomatites can be observed. The lesion of the nervous systems is most often expressed by the astenovegetative syndrome (weakness, malaise, rapid fatigue, adynamia, irritability, headache, sweating). Polyneurites are less often diagnosed. Development of meningoencephalopolyradiculoneuritis is one of the prognostically most adverse signs. Mental disturbances - labile mood, insomnia, memory depression, epileptiform attacks are possible to diagnose. At many patients with SLE the lymphadenopathy becomes perceptible. Trophic disturbances are characteristic: loss of body weight, reinforced hair fall, alopecia, sometimes full baldness, lesion of fingernails, xeroderma. Laboratory data. In a peripheric blood leukopenia, stab shifting, hypochromic anaemia, ESR substantial increase. Development of hemolitic anaemia and thrombocytopenia is possible. Detection of a great number of lupoid cells (LE-cages), rising of ANF titres and antibodies to native DNA are typical dysproteinemia with augmentation of the gamma globulins content. At the majority of patients in a process of actuation the complement level drops. The false positive Wassermann reaction is sometimes noted. Its development in this case is caused by production of antibodies to phospholipids, first of all to the cardiolipin which is the basic antigen of response. The degree of laboratory indexes changes depends on degree of activity and acuteness of lupoid process course. 7 Diagnostics. For statement of the reliable diagnosis it is necessary to use diagnostic criterias of the American rheumatologic association (1982): 1. Rashes on cheekbones (the “lupoid butterfly”), the fixed erythema (flat or uplifted), tending to diffusion to the nasolabial region. 2. Diskoid rash - erythematic uplifted plaques with adjacent scales and follicular corks; atrophic scars on the old foci. 3. Photosensitization the dermal rash as a result of a sunlight skin exposure (in anamnesis or doctor’s examination) 4. Erosions and ulcers in oral cavity ulcerations in oral cavity or nasopharynx, routinely painless (the doctor should register) 5. Arthritis not erosive arthritis of 2 or more peripheral joints expressed by tenderness, edema and exudate. 6. Serosites pleuritis: pleural pains, pleural rub noise and-or presence of a pleural exudate; pericarditis: documented by an echocardiography, or a pericardial rub noise auscultated by the doctor 7. Kidney lesion a proof proteinuria more than 0,5 g/day or cylinders (erythrocyte, canalicular, granular, mixed) and hematuria. 8. CNS lesion: seizures – in the absence of drug intake or metabolic disturbances (uremia, ketoacidosis, electrolytic disbalance); psychosis – in the absence of drug intake or electrolytic disturbances 9. Hematological disturbances leukopenia less than 4 * 109/l, not less than 2 times registered; lymphopenia less than 1,5 * 109/l, not less than 2 times registered; thrombocytopenia less than 100 * 109/l, not associated with drug intake. 10. Immunologic disturbances detection of a lupoid coagulant; false positive response of the Wassermann test during at least 6 months at proved absence of syphilis by the immobilisation reactions of a pale treponema and the fluorescent absorption of the treponeme AB. 11. Antinuclear AB titre rising noted by a method of immunofluorescence or a similar method and lack of drugs reception iHboking the SLE-similar syndrome. The patient can be classified to SLE in the presence of any 4 and more criteria from 11 offered. Diagnostic measure can be presented consistently or simultaneously, to any season of observation. There are the following variants of SLE course (acute, subacute, chronic at first diseases and to the further advance). At acute course there are the sudden onset of disease, high body temperature, acute polyarthritis with the acute joint pain, the expressed dermal changes, serious polyserosites, kidneys lesion, nerve system, trophic disturbances, weight loss, acute augmentation of an ESR, pancytopenia, considerable quantity of LEcells in blood, high caption of ANF are characteristic. Duration of disease 1-2 years. Subacute сourse is characterised by gradual development, articular syndrome, normal or subfebrile body temperature, dermal changes. Activity of process during the considerable time underload, remissions are long (before half a year). However process become gradually generalized, the plural lesion of organs and systems are revealed. Chronic course is expressed by mono- or some syndromic for many years. The common state remains satisfactory for a long time. At early stages the dermal changes, articular syndrome are observed. Process slowly progresses, and many organs and systems further are impaired. Taking into account clinical and datas of laboratory there are three degrees of activity evolved: high (III), moderated (II), minimal (I). 8 Degree of activity Index III II I Body temperature 38о and more Less 38о The normal Weight loss Expressed Moderated - Trophic disturbance Expressed Moderated - Skin lesion "Butterfly" and an erythema of lupoid type Ecssudative erythema Diskoid foci Polyarthritis Acute, subacute Subacute Deforming, arthralgias Pericarditis Exudative Dry Adhesive Myocarditis Diffuse Focal Cardiosclerosis, myocardium dystrophia Endocarditis Lesion of many valves Lesion (routinely mitral) valve Insufficiency of the mitral valve Pleuritis Exudative Dry Adhesive Pneumonitis Acute (vasculitis) Chronic (interstitial) Pneumofibrosis Nephritis Nephrotic syndrome Nephrotic or urine syndrome Chronic glomerulonephritis The nervous system Acute encephaloradiculonephritis Encephalonephritis Polyneuritis Crises (hemolitic, nephrotic, adrenal, etc.) + - - Haemoglobin, g/l Less than 100 100-110 120 and more ESR, mm/H 45 and more 30-40 16-20 Fibrinogen, g/l 6 and more 5 5 Albumines, % 30-35 40-45 48-60 α2 13-17 11-12 10-11 γ 30-40 24-25 20-23 Globulins, % 9 LE-cells 5:1000 leukocytes and more (1-2:1000 leukocytes Individual or absent The antinuclear factor (АНФ) 1:128 and above 1:64 1:32 Luminescence type Edge Homogeneous and edge Homogenous Antibodies to nDNA (titres) High Average Low Working classification of clinical variants of SLE course (Nasonova V. A. 1972 - 1986) The clinic-morphological characteristic of lesions Charact er of course Phase and degree of activity Acute Subacute Chronic Phase: Active Degree of activity: High(III) Moderate (II) Minimal(I) Phase: inactive Skin Symptom of “butterfly” Ecssudative erythema, Dermal purpura Discoid lupus. Joints Arthralgias Polyarthritis Serous membra nes Polyserositis: pleuritis/ pericarditis Heart Myocarditis Endocarditis Lungs Kidneys Nerve system Pneumonitis Pneumofibrosis LupusNephritis (With nephrotic syndrome, isolated urine syndrome) Meningoencephalopolyradiculoneuritis, polineuropaty Treatment. Not less difficult problem, than diagnostics of this many-sided disease, is SLE treatment. Treatment of patients is referred to the repressing the immune complex pathology and restoration of function of the affected organs and systems. Basics of medicamentous therapy of SLE compound GCS hormones which are terrain clearancely shown at an establishment of the reliable diagnosis. Prednisolonum, Methylprednisolonum (Medrolum, Urbazonum), Triamcinolonum (Polcortolonum), Dexamethasone (Dexasonum), Betamethasone can be prescribed. The dose of corticosteroid hormones to each patient is selected individually. It depends on acuteness of pathological process, degree of activity, character of visceral lesions. 10 Except corticosteroid hormones to the majority of patients with SLE are prescribed aminochinolone drugs (Delagilum, Plaquenilum, Chingaminum, Chloroquine etc.). Delagilum is taken over in the evening after meal on 1-2 tablets (0,25-0,5 g/day), Plaquenilum - for 0,2-0,4/days are necessary within many months or years. Aminohinoline drugs are most shown to the patients with SLE accompanied by the skin lesion and at chronic course of the disease. The wide spread in SLE treatment suffices have received cytostatic drugs which immediately depress pathologic immune organism responses. Indications to application of cytostatics are: 1) presence of progressing lupoid nephritis at patients or a lesion of the nervous system with neurolupus type; 2) high immunologic activity of disease or presence of lupoid crisis; 3) necessity promptly to reduce an overwhelming dose of corticosteroid hormones because of the bad shipping or expression of side effects; 4) futility of previous therapy; 5) resistance to corticosteroid therapy. Most often at patients with SLE Azathioprinum (Imuranum) or Cyclophosphanum (cyclophosphamide CF) in a dose of 2-3 mg/kg a day is applied. In a medical dose the drug is prescribed on 3-4 months, and then it is necessary to transfer to reception of maintenance doses of 50 100 mg/day within many months and even years. Azathioprinum is taken over inside, and Cyclophosphanum – parenteral (intramuscular or intravenous). At high immunologic activity of SLE it is possible to begin treatment with parenteral application of Cyclophosphanum for reception of more prompt therapeutic effect, and later 2-3 weeks to transfer to the further reception of Azathioprinum. Antimetabolites (Azathioprinum) are better for prescribing daily, and for alkising drugs (Cyclophosphanum) is more preferable to use an alternating mean of introduction. Cyclophosphanum, as a rule, is applied on 200 mg intravenously in-jet every other day or 400 mg 2 times a week. Presence of nephritis at the patient with SLE of any degree of manifestation or signs of a generalised vasculitis is the indication for incorporation in complex therapy with Heparin and Dipiridamolum. Heparin, being direct action anticoagulant, depresses intravascular coagulation, besides, reduces activity of complement, has anti-inflammatory effect, reduces vascular permeability. On the background of its effects the arterial pressure drops, the diuresis is enlarged. Heparin is prescribed with 20000-30000 MU per day. It is more preferable to introduce it subcutaneously in the abdominal area for 5000 MU 4 times a day or under other scheme 10000 MU intravenously droply, and the remained daily dose subcutaneously in the abdominal area - in 2-3 injections. Duration of a heparin course should compound 3-10 weeks. Heparin is introduced under control of a blood clotting time and (or) tolerances of plasma to heparin. Dipiridamolum (Curantylum) as disaggregant interferes with aggregation of thrombocytes due to that efficiency of application of heparin raises. It is prescribed in a daily dose of 150-400 mg within 3-8 months. Courses of Heparin-Curantylum schemas at patients with a lupus-nephrite 2-3 times a year are recommended to make courses of treatment. It allows to conserve function of kidneys in a satisfactory state for a long time. Despite the reached successes, conducting patients with SLE remains one of the most challenges. On a combination of efficiency and safety the drugs influencing immune inflammation GCS, CPh, Azathioprinum, Chlorbutinum and others not always satisfy clinicians. Besides, at many patients early administration of adequate doses of GCS and cytotoxic drugs does not allow to avoid an irreversible damage of vitals and systemic (first of all kidneys and the central nervous system), and also quite often associates with development of serious, potentially lethal side reactions (an intercurrent infection contamination, a cytopenia, a hemorrhagic cystitis, osteoporotic fractures, growth of number of malignant growths and so forth). All it spots necessity of studying of new approaches to SLE pharmacotherapy. Perfection of action methods on immune process descends in two directions: change of traditional regimens of their application and introduction in practice of new drugs. 11 Point of application of therapeutic procedures is action on lymphocytes, formation and immune complex deposition and preventive maintenance, and also change of the immune answer by inducing the antigen-specifying tolerances or interactions with the system of cytokines. Last years especially great interest iHbokes cyclosporine A which is examined as one of the most effective medical products with selective immune-suppressive activity. The concrete mechanisms spotting efficiency of cyclosporine A (CsА) at SLE, up to the end are not clear. It is obvious that on character of action the synthesis of cytokines of CsA it is rather close to GCS. It is impossible to exclude that one of important mechanisms of activity of CsA at SLE is bound with inhibition of interpherone synthesis. Ability of CsA to depress an expression of ligand СD40 on T-lymphocytes membrane is interested. Doubtless advantage of CsA in comparison with other drugs, used for SLE treatment, is smaller frequency both immediate, and the remote side effects, first of all infectious complications and malignant growths. Unlike other cytotoxic drugs of CsA possesses underload teratogenious ability. There is data about depression against therapy of CsA of level of anticardiolypin new and antithrombocytal antibodies, and also preventive activity concerning an atherosclerosis forwardness that has huge value for patients with SLE. Encouraging effects are received at patients with SLE of one and more selective immune-supressor Mophetyl mycophenolate. Mophetyl mycophenolate (MMF) (Cellsept) represents synthetic morpholyne-ethyl aether of mycophenole acids and its precursor. After reception of MMF inside hepatic esterases completely transform it into the active bond with mycophenolic acid which is noncompetitive inhibitor of inosinemonophosphatedehydrogenase, the enzyme limiting rate of synthesis of guanosine nucleotide. As the functional activity of lymphocytes in a greater degree, than other promptly divided cells, depends on synthesis purines, the drug yields more expressed the antiproliferative effect concerning lymphocytes and displays cytostatic, instead of cytotoxic activity. Expedient discussion of one more perspective direction of pharmacotherapy of SLE - usage of the drugs quenching a proliferation of B-cells among which the most studied is rituximab (RM) is represented. Advantages of appointment RM consisted in influence practically on all clinic-laboratory parameters of SLE and prompt achievement of effect that is especially actual at development of the critical states immediately menacing to life of patients. Probably, in the future use RM as drug of the first line with the subsequent long-term appointment of a selective immunodepressant will appear the optimum schema of treatment of prognostically unfavorable variants of SLE. Prospects of treatment of patients with SLE, it is doubtless behind biological methods of action, with use of so-called biological agents. These drugs are developed for the purpose of action on specific immunologic processes to which concern activation of T-cells, T-B - cellular interaction, development of antibodies with two-spiral DNA, activation of cytokines and others. In this respect major possibilities are represented by application антииEиотипических monoclones, an intravenous immunoglobulin. Revealing of the raised serum levels IL 10 at patients with SLE and relatives, and also their correlation with activity of disease have formed the establishment for use monoclone antibodies to IL 10. Pre-award effects of several examinations testify to plus influence of antibodies concerning a lesion of a skin, nephroses, an arthritis and a serositis, refractory to GCS therapies. Thus, use of biological agents as the majority of them does not possess generalised immunesupressive activity will be doubtless prospect of treatment of patients with SLE. 12 Now it is necessary to recognise as the most aggressive method of treatment of SLE is the autologic transplantation of stem cells (ATSC). Important direction of pharmacotherapy of SLE is prevention of development or treatment of an accompanying pathology, first of all an early atherosclerosis, an osteoporosis, infectious complications which make not less negative impact on the vital prognosis, than disease. It spots necessity of wider introduction of up-to-date hypotensive, hypolypidemic, antiosteoporotic and hermicides. As some of them, for example, statins, antibiotics and it is possible, bisphosphonates possess anti-inflammatory and immune-modulating activity, their application can potentially raise efficiency of treatment of the inflammatory rheumatic diseases. As the SLE intensive care last years the pulse-therapy by Methylprednisolonum (Solumedrole), is widely applied by betamethasone (Celestonum). From cytostatic drugs for pulse-therapy Cyclophosphanum (cyclophosphamide) is used. The sense of pulse-therapy consists in introduction in an organism of shock superhigh doses of corticosteroid hormones or cytostatics during a short time term. These drugs in a superhigh proportioning render powerful antiinflammatory and the immunodepressive effect, and short term of their application does not allow to educe to terrible iatrogenic complications. Pulse-therapy by Methylprednisolonum it is shown in the presence of the active lupoid nephritis with a nephrotic syndrome, neurolupus, prompt advance of disease, high immunologic activity of process, weak efficiency of usual therapy. For the purpose of intensifying of anti-inflammatory and immunodepressive effects probably carrying out of the combined pulse-therapy. At carrying out of the combined pulse-therapy in the first day 1000 mg methyl-prednizolona and 600-1000 mg (depending on mass of a body of the patient) Cyclophosphanum are intravenously droply introduced. The next 2 days patients receive dropwisely only on 1000 mg of Methylprednisolonum. From by-effects of the combined pulse-therapy it is necessary to note a nausea, unpleasant sensations in the field of heart, a tachycardia, rarely leukopenia and a hair fall. Combined pulse-therapy it should be prescribed under strict indications. It can be made only at patients with a torpid and progressing lupus-nephrite, and also a generalised vasculitis. At the most serious variants of the SLE, becoming complicated development of a lupoid crisis (renal or multiorgan), or resistances to traditional therapy, include in treatment schemas plasmapheresis (PPh, synchronising its carrying out with pulse-therapy CPh). Usage of PPh is referred on excision from a blood of circulating cell-bound immune complexes (Central Electoral Committee), cryoprecipitines, various antibodies, mediators of an inflammation, yields of metabolism etc. At PPh endogenous phagocytosis of the Central Electoral Committee therefore expression of lesions of various organs decreases is labilised, sensitivity of receptors of cells to action of immunodepressants raises. Administration of the isolated extracorporal therapy for patients with SLE is essentially circumscribed because of threat of development of a so-called syndrome of the "rebound" characterised by rough production of autoantibodies in 12-24 h after procedure. Repressing of activity of lymphocytes and "rebound" prevention can be reached by synchronous program application PPh/GCS and pulsetherapy of MT and CPh. The schema of synchronous therapy consists of three sessions of PPh which is carried out in 1st, 2nd and 3rd days of treatment, in 6h after the third session PPh make pulse-therapy CPh (or CPh and MT) which retry in 4th and 5th days of treatment. As indications for appointment of SLE high value of clinical and laboratory indexes of activity of SLE, disease advance, despite made conservative therapy, and the states menacing to life of the patient serve. 13 Preventive maintenance at SLE is referred on the prevention of exacerbations of disease. Essential value has pedantic observance of medical references on reception of medical products of pathogenetic activity, first of all corticosteroid hormones and cytostatics (or aminochinoline drugs). Observance by the patient of certain references on a regimen, character of work and rest is not less important. The patient should avoid action of solar insolation, supercooling, the catarrhal diseases, the bioticly not shown operative measures, inoculation, vaccines, serums. The prognosis. Now the prognosis at patients with SLE was essentially refined. The survival rate of patients with SLE in 10 years after diagnosis statement reaches 80 %, in 20 years–60 %. Nevertheless the mortality of patients with SLE remains in 3 times above, than in population. New pedagogic technologies applied on lesson. CASE Solving the problem of in-time diagnostics of SLE and a choice of rational therapy The pedagogical summary Subject: «Faculty therapy» Theme: «SLE diagnostics and treatment» The purpose of the yielded case: an excavation and dilating of knowledge of the causes of development of SLE. Development of ability of an assessment and the analysis of a situation of treatment patients with SLE. Skills of drawing up of diagnostic algorithm and a choice of tactics of treatment in the conditions of a hospital. Scheduled educational effects – by results of operation with a case students get skills: Assessment and the analysis of common state of patients with SLE Choice of the correct diagnostic algorithm of patients with SLE. Choice of treatment tactics in the conditions of a hospital. For the successful solution of the yielded case the student should know: • Measure of the SLE diagnosis. • To perform differential diagnostics • To number the diagnostic methods, to compound and prove the plan of examination in the hospital conditions • To compound and prove a treatment planning The yielded case reflects a real situation in the hospital conditions. Case references: 1. Internal diseases Martynova A.I., Muhina N.A., Moiseeva A.S., М, medicine, 2004 2. Internal diseases edited by Martynova A.I., Muhina N.A. – M. 2008 3. Rheumatology: the National management / by E.L.Nasonov, V.A.Nasonovoj's edition. - М, GEOTAR-media, 2008. - 720с. 4. Rheumatology: clinical references. / by E.L.Nasonov's edition. - Moscow-005.-262s. 5. Rheumatology secrets. Sterling J.Way. Translation from English. Moscow, 1999. 768с. 6. http://.www.med-site.narod.ru/index.htm The description, diagnostics, treatment of diseases. Pharmaceutics, anatomy. 7. http:// www.recipe.ru Medicine: information resources, databases. 8. http:// www.vh.org 9. http:// www.meddean.luc.edu 14 The encyclopaedia of examination of the patient with set of an illustration, the short description of diseasees, testing. 10. http://embbs.com Case histories, training, the atlas on an electrocardiogram, etc. 11. WWW.TMA.uz. The case performance according to typological signs The yielded case falls into the room, subject genres. It is volumic, structured. It is a case-question. On the didactic purposes the case is training, boosting thinking in a real situation in the hospital conditions. The case can be used on disciplines: therapy, infectious diseases, urgent conditions. I CASE « SLE diagnostics and treatment» Introduction Systemic lupus erythematosus - chronic polysyndromic disease of preferentially young women and the girls, educing against genetic caused irregularity of immunoregulatory processes leading to uncontrollable production of antibodies to natural cells and their components, with development autoimmune and immune complex a chronic inflammation. Annually in different regions 1 per 400-2000 become ill. Disease educes at women (10-20:1) more often. Recurring 50-70 on 1 million population in a year. 70% are ill at the age of 14-40 years, "peak" on 14 – 25 years. The SLE etiology is not positioned till now. In its development participation of a virus infection contamination, and also genetic, endocrine and metabolic factors is supposed. Prevalence among patients with SLE of young women, the frequent beginning of disease after the delivery or abortions, disturbance of a metabolism of estrogens with rising of their activity, presence of hyperprolactinemia testifies to participation of hormonal factors in a pathogenesis of disease. Catarrhal diseases, labours, abortions, pregnancy, ultraviolet light, intolerance of medicines, vaccines, serums can be presented as provoking factors in SLE development etc. Complexity of in-time diagnostics of disease, variety of clinical symptoms, frequent iHbolving from the very beginning of disease of several vitals and systems with the subsequent disturbance of their functions prove necessity of the further studying of disease and knowledge of means of rational therapy. The purpose of the yielded case is development in the student – users of a case of abilities of the analysis of a situation at curation patients with SLE. Skills of a choice of conducting tactics, diagnostics, rendering of rational therapy in the hospital conditions. The solution of a prospective case will allow students to reach following educational effects: To educe abilities of an assessment and the analysis of common state of patients with SLE To fulfil a choice ability of the correct diagnostic algorithm of patients with SLE. To fulfil a choice ability of treatment tactics in stationary conditions Situation: In department of rheumatology the woman of 24 years was admitted with complaints on temperature grow up to 39-400C, rashes of red colour on face and upper half of thorax, pain and radiocarpal and knee joints tumescence, palpitation, edemas on the face and legs, weakness. From the anamnesis morbi: ill for 6 months. Disease has begun in 1,5 months after the delivery. From the anamnesis vitae: 15 • From the underwent diseases - frequent catarrhal diseases • Menses since 13 years, sexual life since 20 years, pregnancy-1, labours-1. • The allergy to medicinal preparations and foodstuff did not become perceptible. • Family/social anamnesis: married, works as the nurse. Bad habits absent. Epid. anamnesis: • In contact to infectious patients was not, • Blood preparations did not receive • Injection therapy negates Physical examination: moderately severe common state. Consciousness clear, standing active. Integuments: on the face in the field of cheeks, malar arches, bridges and the upper half of thorax become perceptible erythematic rashes. The face bloated, standing edemas. Joints: the tumescence of radiocarpal and knee joints, a pain becomes perceptible at palpation and locomotions. Vesicular breath in lungs. Cardiac sounds are dumb, tachycardia, on all points is auscultated systolic hum. A gaste soft, painless. The liver and spleen are not enlarged. Pulse regular–110 bpm. The BP - of 130/100 mm hg. The diurhesis is reduced. The examinations spent in a hospital, have shown: • Common blood analysis: Нb-80 D\л, leukocytes – 3,8, thrombocytes – 150000, a ESR - 30mm/h • Common urine analysis: protein - of 0,132 %, erythrocytes - 20-25/1, leukocytes - 10-15/1, cylinders - 3-4/1. • Blood biochemical analysis: common blood protein – 58g/l, bilirubin-19 mmole/l, AlAT-0,5 and AsAT-0,6 (within norm) Questions and assignments 1. What additional research techniques need to be performed for diagnosis statement? 2. By your opinion, with what pathologies it is necessary to perform the differential diagnostics? 3. Enumerate the diagnostic criteria. 4. What is your diagnosis and how can you prove it? 5. Set the treatment plan. The assignment: On the basis of the state analysis of patients with SLE it is necessary to make the preliminary diagnosis, to spend necessary methods of diagnostics, to accept the well-founded treatment plan. II. Methodical indications for students 2.1 Issue: Diagnostics and treatment of patients with SLE in the stationery conditions 2.2. Subissue 1. The outward analysis 2. The analysis of the anamnesis morbi and anamnesis vitae of the patient 3. The examination analysis 4. Choice of necessary methods of diagnostics 5. The analysis of the received effects of examinations and performing of differential diagnostics 6. Choice of treatment tactics. 2.3. Algorithm of the solution 1. The outward analysis includes following examination - Examination of skin and the visible mucous - Face, body 16 2. The anamnesis analysis - The underwent diseases - The is family-social anamnesis - Duration of disease 3. The examination analysis - Pulse, arterial pressure. - Auscultation of heart and lungs - Abdominal palpation - Examination of joints. 4. A choice of necessary methods of diagnostics - CBA, CUA - Biochemical analysis of blood/X of blood Protein in daily urine Coagulogram Acute phase tests Blood on LE cells and АНА ECG EchoCS Chest fluoroscopy - USI of abdominal organs - A skin biopsy 5. To correlate the received results and to carry out differential diagnostics with: - rheumatoid arthritis - glomerulonephritis - scleroderma 6. A choice of treatment tactics - Application of traditional therapy - Application of pulse therapy - Application of plasmapheresis Work stages 1. Acquaintance with case 2. Acquaintance with the given situation The instruction to independent work on the analysis and the solution of a practical situation Sheet of the situational analysis Recommendations and advises Firstly make acquaintance with a case While reading, do not try to analyze a situation at once Read the information once again, mark the paragraphs which have seemed important to you. Try to characterise a situation. Mark what is important, and what is less. 17 Problem: 3. Revealing, formulation and a substantiation of a key issue and subissues Diagnostics and treatment of patients with SLE At the situation analysis answer following questions: 1. Make definition, enumerate the causes and the mechanism of development of SLE. 2. Enumerate the diagnostic methods of SLE using the patient example. 3. What methods of diagnostics are necessary for diagnosis statement? 4. Compound and prove the examination plan. 5. Formulate the clinical diagnosis and prove it. 6. What nosologies are necessary to eliminate during the differential diagnostics? 7. Define the treatment tactics 4. Diagnostics of the situation analysis 5. A choice and a substantiation of methods and problem resolution means Enumerate the possible means of solution of the yielded problem in the presented situation 6. Development and resolution of a problem situation State the diagnosis, choose the treatment tactics The rating table of individual work with a case Participants The analysis of a current situation max 1,0 Rating criteria and indexes Detailed Choice of Problem methods and development of standards substantiation problem on solution resolution max 0,5 realisation max 0,5 max 0,5 Common mark (max 2,5) * 1. 2. № * 2,0 – 2,5 points – “excellent”, 1,5 – 2,0 points – “good", 1,0 – 1,5 points – “satisfactory", Less than 1,0 points – “unsatisfactory" 18 Rating system of the group problem resolution. 1. Each group receives two estimate points. It can donate them at once all to one candidate solution or part it by two (1:1; 0,5:1,5; etc.), not including the own solution rating. 2. All received points on each candidate solution are summarized. The solution which has achieved the greatest quantity of points wins. In disputable cases it is possible to take voting. The rating table of the group problem resolution, mark Group 1 The alternative candidates of the problem solution 2 3 № 1. 2. № Total Rating of presentation of the offered solution Group Completeness and clearness of presentation (1 – 20) Obviousness of the presentation (1 – 20) Mass activity of group participants (1 – 20) Originality of presented solutions (1 – 20) Recption ability to the legislative norms (1 – 20) Total sum of achieved points (max 100) 1. 2. № III. THE CASE CANDIDATE SOLUTION VARIANT BY THE TEACHER-CASEOLOGIST 1. The symptoms enumerated above in a case specify that there is a systemic disease of the connective tissue, i.e. systemic lupus erythematosus. It is necessary to perform following iHbestigations for the patient: Nechiporenko’s probe, Zimnitsky’s probe, protein definition in daily urine – for acknowledgement of a systemic kidney lesion; acute phase tests, blood on LE-cells, definition of ANA (antinuclear antibodies), the rhematoid factor – for revealing of immunologic disturbances, blood clotting time, coagulogram – for revealing the changes in the coagulating system of blood, an electrocardiogram, EchoCS – for revealing of a systemic heart lesion, thorax X-radiography – for revealing of of lungs lesion and pleuritis, US of abdominal organs– for revealing of liver lesion and ascitis. 19 2. There are not less than 40 diseases similar to SLE, especially in an disease debut. In this case disease is necessary for differentiating with rheumatoid arthritis, acute rheumatic fever, glomerulonephritis, systemic scleroderma, systemic vasculitis. 3. At the yielded patient following disease criterias are noted: 1) erythematic rashes, 2) joints lesion (arthritis), 3) kidneys lesion (edemas standing, diurhesis reduction, proteinuria, microhematuria, cylinderuria), 4) hematological disturbances (anemia, leukopenia, thrombocytopenia, ESR acceleration). Therefore from 11 diagnostic criteria used for statement of the diagnosis 4 criterias were noted and the diagnosis is considered reliable. The diagnosis formulation: Systemic lupus erythematosus, subacute variant of course, activity II, with lesion of skin, joints, heart, kidneys. 4. GCS: Prednisolonum: 30mg/day, considering degree of disease activity. With the antiinflammatory purpose – nonsteroid antiinflammatory drugs, considering presence of lupusdermatitis and arthritis - 4-aminochinoline drugs (Plaquenilum 400mg/day), anticoagulants (heparin 20000 MU/day), antiaggregants (Curantylum 150mg/day). The intensive care: plasmapheresis №2 with the subsequent pulse therapy (Methylprednisolonum 1000 mg+ Cyclophosphanum 1000 mg) intravenously droply №1. It is recommended to avoid solar insolation. IV CASE – TECHNOLOGY OF TRAINING AT THE SEMINAR 4.1 Model of technology of training Theme Diagnostics and SLE treatment Duration – 90 minutes Quantity of the trained: 10 persons The shape of educational lesson Seminar on dilating and an excavation of knowledge, working off of abilities of tactics of conducting patients with SLE 1. Introduction to the educational lesson 2. Actualisation of knowledge 3. Operation with a case in minigroups 4. Presentations of effects The seminar plan 5. Discussion, assessment and choice of the best variant of strategy 6. The inference. An assessment of activity of groups and students, degrees of goal achievement of educational lesson The purpose of educational lesson: an excavation and dilating the knowledge of the causes of development of SLE. Development of rating ability and the situation analysis of criteria at curation patients with SLE. Skills of composing the diagnostic algorithm and a choice of tactics of treatment in 20 the hospital conditions. Effects of educational activity: Tasks of the teacher: • • To set and deepen the knowledge by rating and analysis of common state of patients with SLE To develop a choice ability of the correct algorithm of activities for diagnosis statement. • To develop skills on rendering the rational therapy • Estimate and analyze a situation and common state of patients with SLE • Choose algorithm of activities for diagnosis statement. • Educe skill of self-maintained decision making at conducting patients with SLE in the hospital conditions. • Develop algorithm of treatment for the patients with SLE Training methods Cases-stages, discussion, practical method Tutorials Case, methodical indications Form of study Individual, face-to-face, operation in groups Training requirements Audience with a hardware, adapted for operation in groups Monitoring and assessment Observation, blitz-poll, presentation, rating The procedure sheet of the educational lesson based on a case. Stage and the operation content Activity Teacher Students Listen Preparational stage Explains appointment of a case-stages and its influence on development of professional knowledge. Distributes the case materials and acquaints with a situation analysis algorithm (see Methodical indicatings for students). Yields the assignment of self-maintained to carry out the analysis and bring the results in the «Sheet of the situation analysis» Independent study of the case content and individually fill the sheet of the situation analysis. 21 I stage. Introduction to educational lesson (10 mins) II stage basic (60 mins) 1.1. Terms the lesson theme, plan, its purpose, tasks and scheduled effect of educational activity. 1.2. Acquaints with the lesson regimen and criterias of results rating (see indications for students) 2.1. Proves the statement of a problem and a situation choice – the urgency. Makes quiz on purpose to activate knowledge trained on a theme: 1. Comprise the SLE definition. 2. Enumerate the causes of occurrence and the mechanism of disease development? 3. Enumerate the course variants of SLE 4. Enumerate the diagnostic criterias of SLE 5. The methods of diagnostics applied to statement of the diagnosis 6. For which nosologies is it necessary to perform differential diagnostics 7. Tactics of management and treatment of patients with SLE 2.2. Divides students into bunches. Reminds the content and case problems. Acquaints (reminds) with operation rules in groups and discussion rules. 2.3. Yields the assignment, improves correctness of perception of the assignment: 2.4. Co-ordinates, advises, refers educational activity. Estimates effects of individual operation: Sheets of the situation analysis. 2.5. Will organise presentations following the results of the done operation under the case solution, discussion. The organizer of discussion: asks questions, replicas, reminds a theoretical stuff 2.6. An organizer - algorithm of activities in the present state of affairs (cascade, lotus) 2.7. Reports the own candidate solution of a case Listen Write down the conforming records Answer questions, discuss, ask defining questions. Are divided into groups Discuss, perform the joint analysis of an individual problem, spot the major aspects of situation, the basic problems and means of their solution, design the solution results Represent candidates solution of a problem of 10-15 mins Questions after the presentation terminal, choose an optimum variant Develop uniform system, discussion 22 III Summarizing the lesson, the analysis and rating 20 mins 3.1. Extends results of educational activity, declares results of individual and teamwork. Listen. Analyzes and rates the group, notes the pro and con moments. Can spend a self-rating and inter-rating 3.2. Emphasises the value of a case-stage and its influence on development of the future expert Express the opinion 7. A quality monitoring of practical skills and theoretical knowledge. 1. Professional inquiry and examination of the patients with systemic lupus erythematosus. The purpose: - Reception of the information necessary for diagnostics; - An assessment of disease probability; - Definition of other sources of the information (relatives, other doctors, etc.); - An establishment of confidential mutual relations with the patient; - An assessment of the face of the patient and its attitude to disease (an intrinsic pattern of disease); - To estimate a state of consciousness and the mental status of the patient, its standing, a habit view, a state of iHbestments and separate fields of a body. Indications: poll strictly for all patients who are in consciousness; examination is made to all patient. Equipment: well lighted boxes, physician offices, incandescent lamps. Performance requirements: no strange persons, confidential situation. Carried out stages (steps): № Action 1 2 3 4 5 6 7 8 9 1 0 Inquiry of passport data Assembly of complaints Assembly of the anamnesis morbi Assembly of the anamnesis vitae The epidemiological, allergic anamnesis Objective examination of the patient Will compound the examination plan The correct statement of the diagnosis Differential diagnostics Compound of a treatment plan Total Was not executed 0 0 0 0 0 0 0 0 0 0 0 Completely and correctly executed 5 15 20 15 5 5 5 5 20 5 100 23 2. Drawing up the dietary references and the treatment program. The purpose: Treatment of disease and remission achievement № Action 1 2 3 4 5 6 Studying the performance of medical tables The correctby choice of a dietary table Pewzner Assessment of a diet accordingoftofull the value diagnosis According to the diagnosis, gravity of According to theappointment diagnosis, gravity of disease and a stage of the basic Preventive actions disease and a therapy stage appointment of symptomatic Totaltherapy Was not executed (0 points) 0 0 0 0 0 0 0 Completely and correctly executed 10 10 20 20 20 20 100 Tests 1. What laboratory indexes are the most informative at diagnostics of a Systemic lupus erythematosus: А lymphocytosis B. thrombocytopenia C hemolitic anaemia D acute augmentation of s-reactive protein E pancytopenia, antinuclear antibodies* 2. What does not enumerate into complications of corticosteroid therapy: А Coushing syndrome B. hyperkaliemia* C hypertonia D osteoporosis E steroid diabetes 3. What changes of the analysis of a blood are characteristic for III degree of activity of a Systemic lupus erythematosus: A.Hb 120 g/l ESR 20 mm/h B.Hb 116 g/l ESR 24 mm/h C.Hb 110 g/l ESR 38 mm/h D.Hb 96 g/l ESR 52 mm/h* E.Hb 96 g/l ESR 35 mm/h 4. What hematological disturbances are included into diagnostic measure of a Systemic lupus erythematosus: А hemolitic anaemia B. leukopenia less than 4ооо / ml C all presented* D thrombocytopenia less than 150 tys/ml E lymphopenia less than 1500/ml 5. What following laboratory disturbances do not fall into the diagnostic criteria of a systemic lupus erythematosus: А a false positive Wassermann reaction B. antibodies to DNA C accelerated ESR* D antibodies to a sm-antigen E all specified datas of laboratory fall into to measure of SLE 24 6. Note not the characteristic dermal exhibitings of a Systemic lupus erythematosus: А allopecia B. Vitiligo C discoid changes D Lupus vulgaris* E photodermatitis 7. At treatment of a Systemic lupus erythematosus following bunches of drugs are used: А cytostatics antibiotics anticoagulants B. antibiotics streptocides glucocorticoids C GCS cytostatics antiaggregants D glucocorticoids angioprotectors immunosuppressors E glucocorticoids drugs 4-aminochinoline cytostatics NSAID* 8. LE-cells are: А autoaggressive lymphocytes B. rosette lymphocytes C neutrophils englobing the rhematoid factor D mature neutrophils englobing nuclear proteins of blood cells * E broken up under the influence of the antinuclear factor 9. Clinical factors of SLE which it is necessary to specify on the work classification (Nasonov V. A) (3): А character of course* B. activity of patoprocess* C the clinic-morphological performance of the affected organs and systems* D a course phase E quantity of the involved joints Е the immunologic performance 10. Variants of SLE course (3): А acute* B. subacute* C chronic* D slow progressive E fast progressive Е lightning 11. Clinic-morphological lesions of a skin at a lupus-dermatitis (5): А lupoid "butterfly" * B. Vitiligo* C Exfoliation* D Hyperpigmentation* E Papilloma* Е Ichtyosis Ж Petechial rashes З Pustular rashes И Bulleous rashes 12. Variants of a lesion of joints at SLE (2): А an arthralgia without arthritis* B. polyartritis* C erosive arthritis 25 D mutilating arthritis 13. Shapes of heart lesions at SLE (4): А myocarditis* B. endocarditis with failures* C cardiosclerosis* D myocardial dystrophy * E amyloidosis F a subendocardial ischemia G subaortal stenosis H stenosis of the pulmonary artery valve 14. Clinic-morphological lesions of lungs at SLE (2): А pneumonitis* B. pneumosclerosis* C emphysema D bronchiectasias 15. The characteristic changes of a peripheric blood at SLE (4): А leukopenia* B. thrombocytopenia* C hypochromic anemia* D rising ESR* E leukocytosis F thrombocytosis G lymphocytosis H hyperglobulia 16. The laboratory indexes having direct diagnostic value at SLE (4): А LE-cells* B. ANF* C antibodies to native DNA* D "a rosella" phenomenon * E. RF F hemolitic anaemia G thrombocytopenia H hypofibrinogenemia 8. Measure of an assessment of monitoring The level of student knowledge A student on the major issues and themes for students' independent work:: Summarizes and makes decisions creative thinking independently analyzed Into practice Shows high activity, a creative approach to the conduct of interactive games Correctly solves the case studies with full justification for the answer Understands the subject matter Knows, says confident Has a faithful representation Progress in % and the score 96-100 Evaluation 5 26 Prepares informative modern visual aids or abstracts of high quality using data from the recent literature of 7-10 sources and the Internet. A student on the major issues and themes on the SIW: creative thinking independently analyzed Into practice Shows high activity, a creative approach to the conduct of interactive games Correctly solves the case studies with full justification for the answer Understands the subject matter Knows, says confident Has a faithful representation Prepares informative modern visual aids or abstracts of high quality using data from the recent literature of 4-6 sources and the Internet. 91-95 5 A student on the major issues and themes on the SIW: independently analyzed Into practice Shows high activity, a creative approach to the conduct of interactive games Correctly solves the case studies with full justification for the answer Understands the subject matter Knows, says confident Has a faithful representation Prepares informative modern visual aids or abstracts of high quality using data from the recent literature of 3-5 sources and the Internet. 86-90 5 A student on the major issues and themes on the SIW: Into practice Shows high activity, a creative approach to the conduct of interactive games Correctly solves the case studies with full justification for the answer Understands the subject matter Knows, says confident Has a faithful representation Prepares informative modern visual aids or abstracts of high quality using data from the recent literature of 3-5 sources and the Internet. 81-85 4 76-80 4 71-75 4 A student on the major issues and themes on the SIW: Shows high activity during the interactive games Correctly solve situational problems, but the justification for an incomplete answer Understands the subject matter Knows, says confident Has a faithful representation Prepares modern visual aids or abstracts using the recent literature data of 1-2 sources. A student on the major issues and themes on the SIW: Correctly solve situational problems, but the justification for an incomplete answer Understands the subject matter Knows, says confident Has faithful representations or 27 A student on the major issues and themes on the CDS: Mistakes in solving situational problems Knows, says uncertainly Has a faithful representation of some issues topic Prepares informative modern visual aids or abstracts of high quality using data from the recent literature of 7-10 sources and the Internet. Prepares modern visual aids or abstracts of high quality using data from the recent literature of 4-6 sources and the Internet. A student on the major issues and themes on the SIW: Understands the subject matter Correctly solve situational problems, but can not justify a response Knows, says confident Has a faithful representation of some issues topic 66-70 3 61-65 3 A student on the major issues and themes on SIW: Knows, says uncertainly Has a partial view 55-60 3 A student on the major issues and themes on SIW: It does not accurately represent Does not know anything Less then 55 2 A student on the major issues and themes on SIW: Mistakes in solving situational problems Knows, says uncertainly Has a faithful representation of some issues topic 9. A chronological card of lesson. № Stages of practical lesson Lesson shapes Duration (minutes) 270 1. Opening address of the teacher (theme substantiation). 2. Discussion of a theme of practical lesson, checkout of basic knowledge of students with use of new pedagogical technologies, a demonstration stuff (slides, audio videocassettes, X-ray patterns, an electrocardiogram, etc.). 3. Discussion end. 10 Poll, explanatories. 60 20 28 4. Allocation of assignments to students for performance of a practical part of lesson. Instructing and the explanatory under the demands shown to practical assignments. Self-maintained curation. Development by means of the teacher of a practical part of lesson. 5. 30 Case study 90 Interpreting of laboratory-instrumental methods of examinations differential diagnostics, treatment and preventive maintenance scheduling. 6. Discussion of theoretical and practical knowledge of students, their reinforcement and assessment of activity of bunch in respect of achievement of an object in view of lesson. Oral poll, the test, discussion, checkout of effects of practical operation. 40 7. The inference of the teacher on the transited lesson, an assessment of activity of each student and the announcement of effects. Working out of assignments for preparation for following lesson (the receiving tank of questions). Questions for selfmaintained operation. 20 10. Questions for control of knowledge 1. Etiology and pathogenesis of a systemic lupus erythematosus (SLE). 2. Clinical pattern of SLE. 3. Diagnostic measure of SLE. 4. SLE classification. 5. Differential diagnostics of SLE 6. SLE treatment. 11. The recommended references The basic: 1. Internal diseases Martynova A.I., Muhina N.A., Moiseeva A.S., М, medicine, 2004 2. Internal diseases edited by Martynova A.I., Muhina N.A. – M. 2008 The additional: 1. Diagnostics of, A.N.Okorokov, M. 2005. 2. Treatment of internal diseases, A.N.Okorokov. M.2005. 3. http://.www.med-site.narod.ru/index.htm The description, diagnostics, treatment of diseases. Pharmaceutics, anatomy. 4. http:// www.recipe.ru Medicine: information resources, databases. 5. http:// www.vh.org 6. http:// www.meddean.luc.edu The encyclopeedia of examination of the patient with set of an illustration, the short description of diseasees, testing. 7. http://embbs.com Case histories, training, the atlas on an electrocardiogram, etc. 8. WWW.TMA.uz. 29