[Disability assessment for the statutory pension insurance: significance, need for research, and opportunities]. / Sozialmedizinische Begutachtung im Rentenverfahren: Stellenwert, Forschungsbedarf und Chancen.

Disability assessment is a complex and multifaceted process of exploration and evaluation, which in terms of legal evidence can be of far-reaching consequence for the claimant, the statutory pension insurance and finally for society as well. In the article the specifics of the assignment, the assessment situation, and the process of evaluation are described. Based upon an analysis of the so far only little research activities, the future need for research is subdivided into 4 thematic groups: 1 Operationalization and validation of central dimensions of evaluation; 2 Investigation of the structure of the expert decision-making process and the factors influencing it; 3 Investigation of the influence of sociopolitical, labour market-related and economical aspects on the evaluation; 4 Quality assurance. On the other hand the article describes the special quality of disability assessment. In a unique way it offers an integrated reflection of the medical history, limitation in capacity and participation and options for treatment and rehabilitation. Beyond the assessment of functional capacity, it could be of use for the development of innovative forms of support for the rehabilitation of working capacity.

[Rehabilitation in the view of small and midsized enterprises: knowledge, appreciation and possibilities to cooperate - results of the KoRB-project]. / Rehabilitation aus der Sicht kleiner und mittlerer Unternehmen: Wissen, Wertschätzung und Kooperationsmöglichkeiten - Ergebnisse des KoRB-Projektes.

UNLABELLED: The experiences of small and midsized enterprises (SME) with medical rehabilitation were investigated in the KoRB-Study (KoRB= KOoperation Rehabilitation und Betrieb) for the first time. Opportunities for a targeted cooperation between the statutory pension insurance and these enterprises were explored. Based on explorative interviews, Westphalian employers, members of the works council, occupational health practitioners and employees were interrogated about the image of and their appreciation of medical rehabilitation in the work setting. Experience with rehabilitation and the level of information on rehabilitation were recorded as well as the compatibility of rehabilitation with operative processes in the working site. In addition rehab hospitals were asked about their experience in cooperating with enterprises. 697 employers of small and midsized enterprises, 458 members of the works councils, 73 occupational health practitioners, 47 rehab hospitals and 3 509 employees, who are members of the German Pension Fund of Westphalia, took part in the survey. RESULTS: Especially employers perceived rehabilitation positively and reported good experiences. Among the employees, those who had taken part in rehabilitation showed the highest appreciation. Occupational health practitioners were more restrained in their appraisal. Some of them complained about a lack of sustainability. The different target groups of the survey felt differently well informed about rehabilitation - best ratings came from the occupational health practitioners, worst ratings from the employees. All groups would welcome more accessible information in case of need. Medical rehabilitation in its standard form of "3 weeks full-time" often causes severe logistic problems in SME (e. g., replacement of employee, loss of experience). However the financial burden is perceived as less problematic. Employers favour alternative rehab models, which allow part-time working. Many employees, who expressed a need for rehabilitation, refrained from applying for rehabilitation on account of worries about loosing their employment. Both rehab clinicians and occupational health practitioners argued in favour of improved communication and cooperation in order to adapt medical rehab to the specific requirements of the working place and to assure a smooth reintegration into work.

[The IREPRO List of Indicators--a tool for systematic evaluation of the prognosis for reintegration and the need for rehabilitation in the course of psychiatric disability pension assessment]. / Die IREPRO-Indikatorenliste--eine Arbeitshilfe zur systematischen Beurteilung von Reintegrations-Prognose und Rehabilitationsbedürftigkeit in der psychiatrischen Rentenbegutachtung.

There is little research on the process of decision making in sociomedical expert opinion especially on prognostic issues. Experts therefore have to rely upon experience and their own routines of judgement. The IREPRO List of Indicators offers a systematic scheme for the sociomedical exploration and evaluation of the prognosis for reintegration and the need for rehabilitation in claimants for disability pension due to mental illness. A set of ten indicators was defined and its practical use tested in an expert-based process of development. In a manual each indicator is thoroughly described in a standardized manner including a five-point rating scale. In a profile sheet the ratings of all ten indicators are visualized, appropriate therapeutical and rehabilitative means are assigned, and the final judgement of prognosis is deduced. At present the IREPRO List of Indicators offers a good tool to structure the process of decision making and contributes to enhancing transparency and uniformity of the process. It can also be used to discuss cases among colleagues. The basic principle can be transferred to other fields of sociomedical expert opinion-building. The article describes requirements and difficulties in psychiatric disability assessment, the list of indicators and experiences gained from the process of development.

[Manifestations of visceral and ocular symptoms of toxocariasis in a 6-year-old boy]. / Pojava visceralne i okularne klinicke slike toksokarijaze kod sestogodisnjeg decaka.

In the past 10 years we have examined 137 cases of toxocariasis, predominantly in children. Three cases were with unilateral ocular involvement. The article reviews a 6-year-old boy with left side strabismus and granulomatous chorioretinitis. Laboratory examinations revealed blood eosinophylia 24% and IgG against Toxocara canis larvae in titer 1:320 by indirect immunofluorescent assay. In epidemiologic anamnesis we concluded that about 4, 5-year-long geophagia was the source of infection.

Effect of serum from thrombocytopenic patients on platelet count in blood of mice.

Estimation of the effect of sera obtained from patients suffering from several forms of megakaryocytic (immune) thrombocytopenia (19), and those with acute non-lymphoblastic leukemia (13), on the platelet count in the peripheral blood of mice was carried out. Several groups of mice were injected intravenously with 0.2 ml of patients' sera, and the platelet count was followed up for 10 days. A marked and highly significant decrease of platelet count in recipient mice was established even 6 hours after the application of both groups of patients' sera. In the control group of mice receiving pooled serum of healthy persons this decrease was not registered. It can be presumed with great probability that the mechanism of development of thrombocytopenia in both groups of patients is very similar: there is an extremely increased destruction of platelets in the peripheral blood in cases with immune thrombocytopenia by antibodies, and in cases with acute leukemias by antibodies and/or other cytotoxic substances. In further investigations the influence of thrombopoietin on this phenomenon will be tested.

[Idiopathic thrombocytopenic purpura in children]. / Idiopatska trombocitopenijska purpura u dece.

INTRODUCTION: Idiopathic (immune) thrombocytopenic purpura (ITP) is the most frequent hemorrhagic disease in children. It represents the acquired megakaryocytic thrombocytopenia with the shortened life of platelets because of immunologic damage (antibodies absorbed by platelets). In the case of this acquired hemorrhagic disorder, in spite of compensatory increased function of the bone marrow, there is a reduced number of platelets because of their increased destruction by the reticuloendothelial system (destructive thrombocytopenia). There are three forms of ITP: acute, chronic and intermittent. The acute form occurs in 80-90% of cases with bleeding episodes lasting a few days or weeks, but no longer than 6 months. The chronic form occurs in 10-15% of children, while the rarest-intermittent form is characterized by periods of normalization in regard to the number of platelets but also with relapse in intervals of 1-3 months. The disease is caused by an immunological disorder in the sense of an imbalanced immune response. Immunologic damages of platelets cause shortening of the opsonized platelets life span. The most frequent platelet opsonins are the immumoglobulin G (IgG) antibodies directed at the platelet membrane in the form of autoantibodies, alloantibodies or possibly absorbed antigen caused by microorganism infection or drug intake. CLINICAL MANIFESTATIONS: It is typical for the phenomenon of bleeding that it starts suddenly and without any other sign of illness. The most frequent acute form appears between the second and fourth year, and is characterized by seasonal occurrence usually after acute viral infections. Children older than 10 years of age, like adults, often have the chronic form associated with other immunologic disorders. The disease affects girls more often than boys (about three times more often) with moderate and constant increase of antiplatelet antibodies. Hemorrhagic manifestations include: petechiae, purpura, epistaxis, gastrointestinal and genitourinary bleeding. They depend on the grade of thrombocytopenia, although there is no strict correlation between the number of platelets and volume of bleeding. Low mortality of the acute ITP is almost exclusively due to intracranial hemorrhage. LABORATORY STUDIES: Thrombocytopenia represents a decrease in the number of blood platelets being a basic abnormality of the blood count. The half-life of platelets in ITP is shortened. Detection of antiplatelet antibodies is connected with technical difficulties, so they are established in about 30% of cases. Bleeding time is prolonged and so is the coagulum retraction which may be completely missed. The Rumpel-Leede test is positive. Clinical differentiation of drug-induced thrombocytopenia is not possible. However, other differential diagnostic possibilities are thrombotic-thrombocytopenic purpura and hemolytic-uremic syndrome. A child with aplastic anemia or acute leukemia, beside thrombocytopenia, has a characteristic finding of white and red blood cell count. Thrombocytopenia with absent radii syndrome is associated with skeletal system abnormalities. TREATMENT: New knowledge about the role of the immune system in ITP determines the modern therapeutic modalities. In cases of acute ITP in children, there are two therapeutic options or therapies of choice: corticosteroids and high doses of intravenous immunoglobulin. Immunosupressive therapy means anti Rh(D) immunoglobulin, cyclosporine, cytostatics, danazol, loaded platelets. In cases of distinctive hemorrhagic syndrome there are also indications for platelet transfusion. Nowadays splenectomy is more restricted, because one third of cases is unsuccessful, whereas plasmapheresis is rarely used in children because of possible complications. CONCLUSION: ITP is the most frequent hemorrhagic disease in children. The disease is basically caused by an immunologic disorder with platelet destruction due to increased immunoglobulin on their membrane. (ABSTRACT TRUNCATED)

[Clinical use of thrombopoietin (c-Mpl Ligand)]. / Klinicka upotreba trombopoetina (c-Mpl LIGANDA).

INTRODUCTION: Results in clinical use of thrombopoietin have been published later than of other hematopoietic growth factors, because until recently the research was the least understood aspect of blood cell development. Reasons for this time gap were numerous, from inconvenient methods for measurement of thrombopoietin activity, to difficulties of its chemical purification. It is claimed recently that the understanding of platelet production has been profoundly advanced by the recombinant-gene synthesis and characterization of c-Mpl ligand (Megakaryocyte Growth and Development Factor), a substance which strongly enhances the proliferation of megakaryocytic line and the production of platelets. In this paper, some historical facts and biology of thrombopoietin are briefly discussed as well as the recent of the clinical use of thrombopoietin. THE HISTORY OF RESEARCH AND PRODUCTION OF THROMBOPOIETIN: The concept that the platelet production is underlying humoral regulation was first promoted by a group of Hungarian authors and they also named that humoral regulator--thrombopoietin. Further research followed in several countries including our own, and the initial studies proved that the serum of thrombocytopenic animals induced proliferation and maturation of megakaryocytic cell line and thrombocytosis in the peripheral blood of recipient animals. Later, when in vitro techniques were developed, it was shown that this humoral regulator has also a colony stimulating activity on megakaryocytic precursors. During the following two decades, studies of megakarycytopoiesis supported the hypothesis that two types of factors are involved in platelet production: early acting--megakaryocyte colony stimulating factors (Meg-CSF), and late acting--megakaryocyte potentiators, first of all thrombopoietin (TPO). However, extensive attempts on the purification of substances that either stimulate megakaryocyte development or augment platelet production failed to yield a homogeneous protein adequate for protein sequencing and cDNA cloning, the usual route which led to the production of other hematopoietic growth factors. Furthermore, a large number of other cytokines were described that possessed activity in various assays of megakaryocyte development. In spite of great number of accumulated data, it seemed in early 1990s that the production of a distinct, clinically useful lineage specific thrombopoietin will not be soon possible to achieve. The breakthrough occurred in 1994, when four groups of investigators published simultaneously their successful results on production of c-Mpl ligand, a substance which specifically binds to the Mpl receptors on megakaryocytes and has a very potent thrombocytopoietic effect. This production is based on genetic engineering and two companies (Kirin and Amgen) are already able to produce recombinant human thrombopoietin in large amounts, for clinical use. Although this substance is not commercially available yet, it passed the preclinical and clinical trials whose results are presented here. RESULTS OF THE PRECLINICAL TRIALS OF RECOMBINANT THROMBOPOIETIN: The chemical structure of human recombinant thrombopoietin (rTPO) is well defined, it is a glycoprotein consisting of 353 amino acids and molecular weight of 30 kD. The biologic actions of this molecule are in vitro: stimulation of megakaryocyte colony forming, endoreduplication of chromosomes and megakaryocyte maturation, and in vivo: increase of the number of progenitors and of megakaryocytes in the bone marrow, and an extensive elevation of platelet count in the peripheral blood 4-7 days after its application. Also, in synergism with other pluripotent cytokines, it can stimulate the proliferation of other progenitors including CD34+ stem cells. Based on these data it is considered that c-Mpl ligand is the main physiological humoral regulator of thrombocytopoiesis, having the biological actions both of MegCSF and TPO.

[Clinical use of granulocyte colony stimulating-factors (GM-CSF and G-CSF]. / Klinicka upotreba faktora stimulacije granulocitnih kolonija (GM-CSF i G-CSF).

Humoral regulation of granulocytopoiesis was proven 30 years ago by discovery of factors which stimulate production of granulocyte colonies (CSF-colony stimulating factors), while clinical utilization of recombinant human colony stimulating factors (rhGM-CSF and rh-CSF) is present for the last 10 years. On the basis of this, today we have a lot of experience in regard to indications, modes and results of their clinical utilization. Clinical utilization of CSF is divided into three fields: treatment of the neutropenic syndrome, utilization in oncologic patients and in bone marrow transplantation. The best results have been achieved in neutropenic syndrome therapy, both chronic (congenital, cyclic and idiopathic neutropenia, aplastic anemia and myelodysplastic syndrome) and acute (granulocytopenia drug induced, postirradiation neutropenia). In oncologic patients it is used to eliminate neutropenia which occurs after cytostatic therapy with standard doses or high dose cytostatic therapy with better effects on the tumor, but with myeloablation. Granulocyte colony-stimulating factor is also used for stimulating fast granulocytopoiesis in autologous or allogeneic bone marrow transplantation, in unsatisfactory transplants especially. In recent years it has been used for mobilization of progenitor CD34+ cells in the donor in order to perform their transplantation, especially in treatment of chronic myeloid leukemia. At our institution G-CSF has been successfully used in 17 patients.

Detection of malignant cells of epithelial origin in mononuclear cell fractions.

Qualitative and quantitative detection of contaminating malignant cells in stem cell apheresis products intended for supportive therapy after high-dose chemotherapy of sensitive solid tumors is a demanding task for the laboratory. Human breast cancer cells in differing concentrations among mononuclear cells were quantitated by multicolor flow cytometry and immunocytochemistry. Comparing specificity, sensitivity, and laboratory processing time, the immunocytochemical detection of the above-mentioned malignant cells of epithelial origin was demonstrated to be the superior method.

[Problems and perspectives in child health care]. / Problemi i perspektive zdravstvene zastite dece.

Health care protection of children in Vojvodina is of particular importance regarding the negative natural birth rate. In spite of difficult economic situation, health care of children in Vojvodina is permanently carried out and would be significantly better in quality if the education of subspecialized personnel, space facilities, technological innovations, computerization and continuous education were available. Introduction of microanalytic laboratory techniques is essential for monitoring of prematures. Propagation of natural nutrition is an obligation of pediatricians. Respiratory diseases are still on the top of morbidity pyramid but tuberculosis is evidently in increase. An important health care problem is the expansion of allergic diseases. The progressive incidence of insulin-dependent diabetes is also evident. The spheres of juvenile gynecological endocrinology and andrology are still underdeveloped and that also applies to adolescent medicine. Toxicology remains an ongoing problem in pediatrics due to an increased number of accidental poisoning. Pediatricians-gastroenterologists are lacking while paediatric hepatology should be brought into more advanced state. Bone marrow and stem cells transplantation is in the responsibility of the Centre for haematology and oncology. Nephrology department lacks children's haemodialysis, ultrasound biopsy of kidneys, urodynamic analyses and new staff facilities. The increased number of survivals in case of children with with sequeles inevitably asks for better development of rehabilitation, prolonged treatment and teamwork. Intensive care and therapy department requires new staff and high technology capacities. Development of children's surgery department inevitably means the reconstruction of space facilities, modern equipment and new subspecializations. Preventive outpatient service is performed through systematic examinations. ultrasound diagnostics of hips, auditive screening and educational program activities related to addiction and veneral diseases. Genetic health of the population is supremely covered by the Center for Medical Genetics, with the tendenca for development of molecular genetics. It is necessary to develop rehabilitation service, prolonged treatment and teamwork. Diagnostic of convulsive conditions should be advanced with more refined diagnostic methods.

[Clinical use of erythropoietin]. / Klinicka upotreba eritropoetina.

Humoral regulation of erythropoiesis has been known for 100 years, while clinical utilization of recombinant human erythropoietin (rhEPO) only for two decades. It can be said that there is much experience in regard to indications, models and results of its clinical utilization. According to the standpoint of secretion of erythropoietin, anemias can be divided into those where secretion is increased and satisfactory, those where it is increased but not satisfactory and into those where it is not increased or it is even decreased. Anemias of the first group are not an indication for rhEPO utilization, the second group is relative and the third group absolute indication for its utilization. The best results are achieved with absolute indications and it is anemia in chronic renal insufficiency and nonphysiologic anemia of premature babies. Good results can be expected, but not predicted in relative indications, such as anemias in chronic infections, anemias in malignant diseases, myelodysplastic syndrome, aplastic anemia and other secondary anemias. Utilization of rhEPO is useful also in certain states without anemia, especially in transfusiology.

[Infiltration of the testes in acute lymphoblastic leukemia in childhood--personal experience]. / Infiltracija testisa u toku akutne limfoblastne leukemije decijeg uzrasta--nase iskustvo.

According to various literature data testicular leukemic infiltration occurs in 5-40%, while the mean time for testicular recurrence is 36 months. Hematologic recurrence usually occurs in the interval from 1-6 months. Although testicular leukemic infiltration clinically occurs as an isolated recurrence of leukemia, it usually presents only a clearly marked spot in the general recurrence of the disease. It is a painless enlargement of one or both testes. The diagnosis is made ultrasonographically and by histopathologic examination of the biopsied testicle tissue. This paper deals with 4 patients with acute lymphoblastic leukemia and testicular recurrence. In 2 patients the testicular recurrence occurred as a part of the general recurrence of the disease, while in the other 2 at the time of testicular recurrence diagnosis, the bone marrow was regular. All 4 patients were treated with combined radiotherapy and chemotherapy, in 3 cases successfully.

Quantitation of circulating hematopoietic progenitor cells early after transplantation.

By multicolor flow cytometry CD34 positive blood progenitor cells (BPC) were determined by standard procedures before and after reinfusion. Measurements of circulating progenitor cells after transplantation lead to cell numbers that are considered together with reconstitution potential, especially with the number of transfused apheresis platelet concentrates after transplantation. Decreased concentrations of CD34 positive cells are associated with an increased frequency of platelet transfusions after transplantation.

[Clinical use of hematopoietic growth factors--general principles]. / Klinicka upotreba hematopoeznih faktora rasta--opsti principi.

Biology of haematopoietic growth factors in the process of haematopoiesis is well known, but their clinical utilization started with production of recombinant preparations. Today only preparations of Erythropoietin, GM-CSF and G-CSF are commercially at disposal. Absolute indications for utilization of haematopoietic growth factors are states caused by decreased production of certain classes of blood cells as a consequence of shortage of a growth factor necessary for production of a certain class. As these states are very rare, relative indications spread to other states characterized by a decreased number of blood cells or necessity for stimulation of haematopoiesis due to any other reason. This paper contains results of clinical researches only for those growth factors which are not commercially utilized.: M-CSF, Interleukin 3, PIXY321, SCF, Interleukin 6, Interleukin 11, Interleukin 1, Interleukin 2 and Thrombopoietin. Our institution utilizes only the preparations of Erythropoietin (Eprex) and G-CSF (Neuprogen) in 38 patients.

[Congenital leukemia--personal experience]. / Kongenitalna leukemija--nasa iskustva.

Congenital leukemia is a very rare form of acute leukemia and up to now more than 100 well documented cases have been published. Symptoms and signs of the disease may be faintly differentiated and be a differential diagnostic problem for a long period of time in comparison to other common diseases of the newborn. This is a case report on two newborns with congenital leukemia. It was an acute non-lymphoblastic leukemia in the first case, and acute lymphoblastic leukemia in the second. In both cases there were nonspecific manifestations of the disease (no weight gaining, hemorrhagic enterocolitis). In both cases polyhemotherapeutic protocols were performed. In the first case only partial remission occurred and death occurred during the hemathologic recidive of the disease. In the second case, 15 months after the diagnose of congenital leukemia has been established, complete remission is in course.

[Diagnostic approach to von Willebrand's disease in childhood]. / Dijagnosticki pristup von Willebrandovoj bolesti u decijem uzrastu.

Von Willebrand's disease seems to be the most common hereditary bleeding disorder in children. Every form of this disease is based on quantitative or qualitative disorder of von Willebrand's factor influencing adhesion of thrombocytes (primary hemostasis) and stabilization FVIII:C in circulation (secondary hemostasis). We present contemporary knowledge on epidemiologic investigations, molecular biology, classification and rational diagnostic approach to von Willebrand's disease in children. We also report on evaluating laboratory tests' reliability in 51 examined children with von Willebrand's disease. It can be concluded that most laboratory tests are highly specific and significant for diagnosis. Determination of vWF activity has optimal value for establishing laboratory diagnosis of von Willebrand's disease; RIPA and multimer analysis are valuable for subtype classification.