Topical corticosteroids normalize both skin and systemic inflammatory markers in infant atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is the most common inflammatory skin disease. It is highly heterogeneous in clinical presentation, treatment response, disease trajectory and associated atopic comorbidities. Immune biomarkers are dysregulated in skin and peripheral blood. AIMS: We used noninvasive skin and peripheral biomarkers to observe the effects of real-world topical corticosteroid (TCS) treatment in infants with AD, by measuring skin and blood biomarkers before and after therapy. METHODS: Seventy-four treatment-naïve infants with AD underwent 6 weeks of TCS treatment. Stratum corneum (SC) and plasma blood biomarkers as well as SC natural moisturizing factor (NMF) were measured before and after TCS therapy. Immune markers included innate, T helper (Th)1 and Th2 immunity, angiogenesis, and vascular factors. AD severity was assessed by the Scoring Atopic Dermatitis index, and skin barrier function by transepidermal water loss (TEWL). Twenty healthy infants were recruited as controls. RESULTS: TCS therapy predictably led to improvement in disease severity. Levels of immune markers in the skin and in the peripheral blood showed significant change from baseline, though most did not reach healthy control levels. The most prominent change from baseline in the SC was in markers of innate immune activation, interleukin (IL)-18, IL-8 and IL-1α, and the Th2 chemokines C-C motif chemokine (CCL)17 and CCL22. In blood, the largest changes were in Th2-skewed biomarkers: CCL17, IL-13, CCL22, IL-5, and CCL26. TEWL decreased after therapy; no significant changes from baseline were found for NMF. CONCLUSIONS: The profound impact of topical therapy on systemic biomarkers suggests that the skin compartment generates a major component of dysregulated systemic cytokines in infant AD. There may be long-term beneficial effects of correcting systemic immune dysregulation through topical therapy.

Monitoring of antibiotic consumption and development of resistance by enterobacteria in a tertiary care hospital.

WHAT IS KNOWN AND OBJECTIVE: Antibiotics are the most frequently used drugs in hospitalized patients, but studies have shown that the prescribed antibiotics may be inappropriate and may contribute to antibiotic resistance. We carried out a survey of antibiotic consumption and antibiotic resistance in our tertiary care university hospital, from 2005 to 2013. We focus on cephalosporins, one of the most prescribed groups of antibiotics in the tertiary health care. The objective was to identify any relationship between ceftriaxone consumption and resistance by enterobacteria. METHODS: Antibiotics consumption and antimicrobial resistance were monitored in the tertiary care university hospital from 2005 to 2013. Data on the use of antibiotics in surgical inpatients were obtained and expressed as defined daily doses per 100 bed days. Bacterial resistances were given as percentages of resistant isolates. RESULTS AND DISCUSSION: There was an increasing trend in cephalosporins consumption from 9·56 DBD (2005) to 23·32 DBD (2013), with ceftriaxone as the most frequently used cephalosporin, 3·6 DBD (2005) to 10·78 DBD (2013). E. coli and P. mirabilis resistance to ceftriaxone increased significantly from 22% in 2005 to 47% in 2013 and from 31% in 2005 to 60% in 2013, respectively. We found a significant correlation between ceftriaxone consumption and E. coli resistance (r = 0·895, P < 0·05). WHAT IS NEW AND CONCLUSION: Our study shows that cephalosporin consumption increased from 2005 to 2013, with ceftriaxone as the most prescribed antibiotic. E. coli and P. mirabilis resistance to ceftriaxone increased significantly over the study period. E. coli resistance increased with ceftriaxone consumption.

Late-intervention study with ebselen in an experimental model of type 1 diabetic nephropathy.

BACKGROUND AND AIM: Previous studies have shown that preventive treatment with the antioxidant, ebselen, in experimental models of type 1 diabetic nephropathy resulted in an attenuation of structural and functional damage in the kidney. However, evidence for the effectiveness of ebselen in late-intervention studies is lacking. Thus, we aimed to investigate the effects of ebselen in attenuating established renal injury in type 1 diabetic nephropathy using the Akita mouse model. METHODS: Baseline blood glucose and albumin-to-creatinine ratio (ACR) were measured in wild-type (WT) and heterozygous Akita mice at 9 weeks of age. At 10 weeks of age, WT and Akita mice were randomized to receive either vehicle (5% carboxymethyl cellulose) or ebselen by oral gavage at 10mg/kg twice daily. Kidney and urine were collected after 16 weeks of treatment with ebselen for histological and functional analyses. RESULTS: At 9 weeks of age, Akita mice displayed well-established renal dysfunction with significant increases in ACR and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels when compared with WT controls. After 16 weeks of treatment with ebselen, oxidative stress, as measured by nitrotyrosine immunostaining and urinary 8-OHdG levels, was significantly reduced in the Akita mice. Furthermore, gene expression of the major reactive oxygen species-producing nicotinamide adenine dinucleotide phosphate enzyme, Nox4, was also reduced by ebselen. However, ebselen had no effect on ACR and glomerulosclerosis. CONCLUSION: Chronic treatment with ebselen significantly reduced oxidative stress in the Akita mice. However, ebselen failed to attenuate functional or structural kidney damage in this late-intervention study using the Akita mouse model.

Three-dimensional pharyngeal airway changes in orthodontic patients treated with and without extractions.

OBJECTIVE: To evaluate and compare three-dimensional pharyngeal airway changes in orthodontic patients treated with and without extractions. MATERIAL AND METHODS: Pharyngeal airway was analyzed for 31 subjects (15 males, 16 females) treated with extractions of four first premolars and 31 age- and gender-matched controls (15 males, 16 females) treated without extractions. The mean age of subjects was 12.97 ± 1.15 years at the beginning and 15.69 ± 1.28 years at the end of treatment. The mean age of controls was 12.86 ± 0.74 years at the beginning and 15.18 ± 0.86 years at the end of treatment. Nasopharyngeal (NP) and oropharyngeal (OP) volumes, area of maximum pharyngeal constriction (AMPC), and upper arch perimeter were measured on T0 and T1 cone beam computed tomography (CBCT) scans. Paired samples t-test was used for analyzing statistical significance of changes (p ≤ 0.05). RESULTS: There were no statistically significant differences in the pharyngeal airway values between the extraction and non-extraction groups at neither T0 nor T1. The extraction group showed a statistically significant increase for NP and OP volumes and AMPC values. Such increase was also noted in the non-extraction group, without statistical significance for AMPC values. CONCLUSIONS: The findings suggest that an extraction or non-extraction choice for orthodontic treatment would not affect the pharyngeal airway.

Burnout in Belgrade orthopaedic surgeons and general practitioners, a preliminary report.

BACKGROUND: Burnout syndrome (BOS) is caused both by psychological-emotional and physical stress. It is associated with decreased job performance and low career satisfaction. BOS has a significance influence both to physicians' performance in health care system, and in their private life. Until now, there was no data about this aspect of orthopaedic surgeon condition and health in our community. AIM: To assess the level of the burnout syndrome in orthopaedic surgeons and general practitioners (GPs), and the relations of their demographic features, job characteristics to the burnout syndrome DESIGN: Questionnaire-based survey METHODS: The sample consisted of 30 orthopaedic surgeons from the University Clinical Centre, and 40 GPs from the primary health care centres. The Burnout syndrome was measured by the Maslach Burnout Inventory (MBI). In addition to the MBI, the demographic data were collected and analyzed (age, age of practicing, gender, marital status) in relation to BOS. RESULTS: Both groups expressed moderate to high rate of emotional exhaustion, depersonalization and low personal accomplishment. However, statistical significance between the groups had not been demonstrated. Neither gender nor years of practice or marital status did express statistically significant impact on the BOS items, i.e. they were not predictors of the BOS. Our results showed that about 70% of the physicians were emotionally exhausted considering both groups. On the other hand, orthopaedics demonstrated slightly higher depersonalisation level (55%) than GPs (38%). While GPs expressed lower personal accomplishment (48%) comparing to orthopaedics (29%). DISCUSSION: The obtained MBI scores in this study were similar to those registered in US among residents, but when comparing to physicians in West Europe, which have similar health care system, our results demonstrated higher rates of BOS items. CONCLUSION: The Burnout syndrome represents an important problem for actively practicing physicians. The results of this and other similar studies should be used to evaluate medical training, practice, professional relations and introduce necessary changes.

Potential of information technology in dental education.

The use of information technology (IT) in dentistry is far ranging. In order to produce a working document for the dental educator, this paper focuses on those methods where IT can assist in the education and competence development of dental students and dentists (e.g. e-learning, distance learning, simulations and computer-based assessment). Web pages and other information-gathering devices have become an essential part of our daily life, as they provide extensive information on all aspects of our society. This is mirrored in dental education where there are many different tools available, as listed in this report. IT offers added value to traditional teaching methods and examples are provided. In spite of the continuing debate on the learning effectiveness of e-learning applications, students request such approaches as an adjunct to the traditional delivery of learning materials. Faculty require support to enable them to effectively use the technology to the benefit of their students. This support should be provided by the institution and it is suggested that, where possible, institutions should appoint an e-learning champion with good interpersonal skills to support and encourage faculty change. From a global prospective, all students and faculty should have access to e-learning tools. This report encourages open access to e-learning material, platforms and programs. The quality of such learning materials must have well defined learning objectives and involve peer review to ensure content validity, accuracy, currency, the use of evidence-based data and the use of best practices. To ensure that the developers' intellectual rights are protected, the original content needs to be secure from unauthorized changes. Strategies and recommendations on how to improve the quality of e-learning are outlined. In the area of assessment, traditional examination schemes can be enriched by IT, whilst the Internet can provide many innovative approaches. Future trends in IT will evolve around improved uptake and access facilitated by the technology (hardware and software). The use of Web 2.0 shows considerable promise and this may have implications on a global level. For example, the one-laptop-per-child project is the best example of what Web 2.0 can do: minimal use of hardware to maximize use of the Internet structure. In essence, simple technology can overcome many of the barriers to learning. IT will always remain exciting, as it is always changing and the users, whether dental students, educators or patients are like chameleons adapting to the ever-changing landscape.

Inefficiency of storm water inlets as a source of urban floods.

The paper attempts to explain sources of surplus storm water runoff in urban areas, particularly in relation with functioning of inlets. Inlet capacity (quantity of captured water) and inlet efficiency (portion of the approaching flow rate) have been defined and their relationship with relevant parameters (approaching flow, longitudinal and lateral street slopes) was established through laboratory measurements. Effects of clogging of inlets on inlet capacity were also investigated in laboratory conditions. As a consequence of decreased inlet efficiency, there is a portion of approaching flow that is not captured by the inlet (pass-over flow). If the pass-over flow is considered along a street having numerous inlets, it is easy to estimate the quantity of flow that would accumulate on the pavement. Inlet inefficiency can be significant when overestimation of inlet capacity results in increased distance between consecutive inlets, and when clogging of grates or inadequate placing of inlets causes significant decrease in inlet capacity.

Peculiarities of the sural nerve complex morphologic types in human fetuses.

The sural nerve is the most frequently used sensory nerve in nerve transplantation. It can be transplanted alone or together with the other elements of the neurovascular stalk within the superficial sural flap. The aim of this study was to define the morphologic types of the sural nerve complex, as well as to describe their specific characteristics. Microdissection was performed on 100 human fetuses (200 calves) after 10% formalin fixation. Five morphologic types of sural nerve complex with different incidence were defined. Two morphologic types dominated: type I (58.5%) in which the sural nerve was formed by merging of a fibular communicating branch and the medial sural cutaneous nerve, and type III (26%) in which the medial sural cutaneous nerve took over the function of the sural nerve. Other morphologic variations were less common.

[Hematologic characteristics of leishmaniasis]. / Hematoloske karakteristike lajsmanijaze.

INTRODUCTION: Leishmaniasis is a chronic infectious disease from the group of anthropozoonoses. It is caused by protozoa in the genus leishmania flagellate. There are five major foci of this disease in the world: India, Mediterranean countries, East Africa, South China and South America. Endemic regions in the Balkans are as follows: Montenegro, Macedonia, Herzegovina and the Morava's valley (1,2). Reservoirs of infection are infected humans and animals (dogs and rodents). Infection is transmitted by insects the most significant representative of which is a sandfly. The course of the disease may be acute, subacute and chronic and several forms are differentiated such as visceral, cutaneous and mucocutaneous. Signs of disease are elevated temperature, gastrointestinal disorders, splenomegaly and hepatomegaly and rarely generalized lymphadenomegaly. Laboratory findings point to pancytopenia. The diagnosis is established on the basis of parasitological findings in macrophages of the bone marrow and is confirmed by serologic tests (4,5). However, mortality is decreased to 5% after the application of 5-valent antimony and amphotericin B (6,7). CASE REPORT: A female patient aged 19 year from Novi Sad was admitted at the Clinic of Hematology due to unclear febrile state lasting 3 months accompanied by pancytopenia and enlarged spleen. The first discomforts were experienced in the second half of August in 1997 upon the patient's return from Sutomore. The disease started gradually with uncharacteristic manifestations. Firstly, discomforts developed in the region of the gastrointestinal tract and were characterized by loss of appetite, nausea, and vomiting in addition to drastic weight loss. Secondly, fatigue occurred during effort, later on at rest as well, accompanied by increased body temperature. Temperature increased twice a day and was followed by shuddering, fever, shivering and very often by nocturnal sweating. Antibiotics and antipyretics were used, but without fall of temperature. Subjective discomforts were increasingly pronounced, so that due to unclear febrile state and in addition to the present pancytopenia the patient was referred to hospital treatment and was therefore admitted at the Clinic of Hematology. Febrile state, tachycardia, a striking paleness of the skin and visible mucosa as well as splenomegaly were confirmed. Basic laboratory findings (Table 1) pointed to pancytopenia. Apart from anemia and mild thrombocytopenia, leukopenia with neutropenia, lymphocytosis and monocytosis were pronounced. Sternal puncture was the most significant diagnostic procedure on the basis of which the diagnosis was established. In hypocellular bone marrow in macrophages, both intra- and extracellular, protozoa were found in smaller and greater groups which resembled leishmaniasis (Figure 1). The diagnosis was confirmed by serologic tests to leishmaniasis, antibody titre was > 1:32. In order to exclude other infections and hematologic diseases, other diagnostic tests were performed (Table 1) and the findings were normal. After the establishment of diagnosis the patient was transferred to the Clinic of Infectious Diseases where the causal therapy with 5-valent antimony was introduced, parenterally. As early as the first week of therapy, the patient was afebrile, subjective discomforts disappeared, she regained appetite and put on weight. Also, the decrease of the spleen was observed as well as improvement in hematological findings. DISCUSSION AND CONCLUSION: This paper predominantly deals with hematological findings which are characteristic for leishmaniasis on the basis of which the diagnosis of this disease has been quickly established (1,2). Hematological findings were the key of diagnosis being confirmed by serologic and other tests. The disease is very rare in this region, so that there is a difficulty in recognizing it. In our case, the diagnosis was made on the basis of sternal puncture survey, because protozoa were found in hy

Prevention of autoimmune diabetes by oral administration of syngeneic pancreatic extract to young NOD mice.

Oral administration of relevant autoantigens is being considered as a realistic approach for the prevention of several autoimmune diseases. In this study we administered, orally, to young female NOD/Ak mice (diabetes incidence, 40%) and NOD/LtJ mice (diabetes incidence, 70%) whole pancreatic extract on days 19, 20, 21, 22, 23, 26, and 27 and studied its effects on the development of diabetes until day 250. The cumulative incidence of diabetes in both the colonies after pancreatic extract treatment was compared with the incidence after oral administration of syngeneic liver extract or in untreated mice. In the NOD/Ak mice, the incidence of diabetes in the pancreatic extract group was significantly lower (6%; n = 34, p = 0.004) and was delayed compared with 33% in the liver group (n = 34) and 44% in the untreated group (n = 18). Significant protection from diabetes and a delay in its onset also were observed in the NOD/LtJ mice treated with pancreatic extract (16%; n = 19, p = 0.002) compared with those liver extract treated (72%; n = 18) and in untreated mice (60%; n = 22). Pancreatic histology at day 90 from all the study groups showed that the protection from diabetes in the pancreatic-extract group was not associated with reduced insulitis. We speculate that the marked disease protection observed in this study with orally administered pancreatic extract may be associated with the presence of immunoregulatory cells with a predominant Th2 cytokine bias. Our studies may have implications for the prevention of insulin-dependent diabetes mellitus (IDDM) in humans.

[Complications in the use of blood transfusions--alloimmunization in polytransfused patients]. / Komplikacija primanja transfuzija krvi--aloimunizacija politransfundovanih bolesnika.

INTRODUCTION: The objective of this paper was to examine the frequency of red blood cell (RBC) alloantibodies in polytransfused hematologic patients. MATERIAL AND METHODS: Blood samples of 2669 polytransfused hematologic patients were examined on clinical significant alloantibodies using antibody screening and identification according to Standards of AABB Technical Manual (1). Available medical charts were reviewed for sex, age and medical history and total number of given transfusions. RESULTS: During a three year period blood samples of 2669 polytransfused hematologic patients were examined for RBC alloantibodies. Alloantibodies were detected in 48 cases with the incidence of 1.79%. 36 patients (1.35%) developed single antibody while in 12 patients (0.45%) multiple antibodies were detected. Antibodies were registered more frequently in females than in males (37:17). In patients with single antibody next specificity was detected: anti-D (38.89%), anti-K (22.22%), antibodies to antigens MNSs system (22.22%), while anti-Le, anti-Fy and anti-P specificity was detected in 13.89%. Patients with multiple antibodies had specificity to Rhesus, Kell, Duffy, MNSs, Lewis and P blood group systems. All patients received more than 10 RBC transfusions. CONCLUSION: The incidence of alloimmunization was 1.79%. Sensibilization occurred more frequently in females than in males. Usually, the discovered alloantibodies were clinically significant and made problems in pretransfusion testings and required special efforts in blood selection for transfusion. For patients with the risk of frequent transfusions we suggest to include blood transfusion charts with complete phenotyping against antigens in Rhesus, Kell, Kidd and MNSs blood group systems and the data of all received transfusions.

The frequency, characteristics and outcome of infections in patients with acute nonlymphoblastic leukemias.

A retrospective study was conducted in 91 patients treated at the Clinic of Hematology in Novi Sad in the period January 1, 1994,-November 15, 1997. The frequency, types, characteristics and outcome of infections were examined. The causative microorganism was determined in 65% of 133 febrile episodes, in 55% Gram-negative bacteria, 39% Gram-positive bacteria and in 6% fungi. Gram-negative bacteria were causative microorganisms in 80% of pneumonia. 77% of skin infections and 93% of urinary infections. Gram-positive bacteria were causative microorganisms in 53% of sepsis, Gram-negative in 41% of sepsis and Candida in 6%. The significant resistance to antibiotics was present in 47% of Gram-negative sepsis (causative microorganisms were Pseudomonas aeruginosa and Acinetobacter species) and in 18% of Gram-positive sepsis (susceptibility to imipenem only in Gram-negative sepsis and susceptibility to vankomycin in Gram-positive sepsis). Infections were the cause of death in 62.8% of patients.

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.

Quantitative analysis of the renal changes in Balkan endemic nephropathy.

The volume densities of the cortical interstitium (CI), glomeruli and proximal tubular epithelium have been investigated on a sample involving 18 patients suffering from Balkan endemic nephropathy (BEN), classified into three groups with regard to the clearance of 99mTc-DTPA. In comparison with the control group, the evolution of the disease is marked by a significant increase of the CI volume (p<0.001), as well as a significant reduction of glomerular (p<0.01) and tubular volume densities (p<0.001). The most intensive changes of CI and glomerular volumes are characteristic of the initial stage of the disease when glomerular filtration (GF) has shown no signs of deterioration yet. On the other hand, a significant reduction of the tubular epithelium volume density is characteristic of the advanced stages. The specified changes, particularly those taking place at the level of interstitium bear the key responsibility for the BEN progression. However, a number of links constituting the chain of BEN morphogenesis remained insufficiently clarified. This urges for a precise quantification of all histological changes taking place in different stages of the disease, starting from the earliest, in order to get a better insight into the order and dynamics of their occurrence.

[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.

[Modern treatment of leukemia and hematopoietic stem cell transplantation]. / Savremeno lecenje leukemija i transplantacija maticne celije hematopoeze.

The paper presents the possibilities of contemporary treatment of acute and chronic leukemia that have been based on new knowledge and experience we have gathered through clinical and scientific work. Contemporary treatment of leukemia is very complex and requires the application of cytostatics, biological therapy and transplantation of hematopoietic stem cells. The treatment of acute leukemia by cytostatics and induction protocols results in a rather high percentage of remissions, but unfortunately most of them cannot be preserved. Allogenic transplantation of hematopoietic stem cells from bone marrow or peripheral blood have given the best results in the treatment of acute and chronic leukemia. Anti-leukemic effect is bound to the previous chemoradiotherapy, particularly to the activity of donor's immunocompetent cells in the transplant, having an effect of a graft against leukemia. The cleansing of the autograft and isolation of stem cells together with the application of IL-2 will be a significant improvement of the efficacy of autologous transplantation in leukemia. It is realistic to expect that the treatment of malignant diseases such as leukemia will in near future, besides the already existing treatment methods, include molecular therapy at various cell levels, which will make possible a correction of the basic disorder in the process of malignant alteration of hematopoietic cells.

[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.

[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.

[Prognosis in patients with myelodysplastic syndromes based on cytomorphologic and clinico-biologic parameters]. / Prognoza obolelih od mijelodisplasticnih sindroma na osnovu citomorfoloskih i klinicko-bioloskih parametara.

Under myelodysplastic syndromes we presume a heterogeneous group of malignant hemopathies with clearly described characteristics of the disease given by a cooperative group of French, American and British authors. Myelodysplastic syndromes most frequently occur at older age. Survival of these patients, after the diagnosis is made, is mostly short because the disease evolves into acute leukemia. Myelodysplastic syndrome is characterized by appearance of refractive anemia, leukemia, thrombocytopenia with signs of expressed dishematopoiesis of the bone marrow. Clear criteria which could define forms with fast or slow course leading to acute leukemia don't exist, so there is a need to group patients into those with good or with bad outcome. The investigation included following parameters important for the outlook of the disease: 1. enlargement of lymph nodes, liver and spleen, 2. biochemical examination of peripheral blood, 3. cytomorphologic changes in the peripheral blood cells and bone marrow. By a follow-up of described parameters a statistically significant influence on survival of the sick concerning the degree of present anemia, absolute number of granulocytes, number of thrombocytes, dishematopoiesis of the peripheral blood and bone marrow, lymphadenomegaly, hepatomegaly and splenomegaly was not found. The percentage of blast in the peripheral blood and bone marrow has a statistically significant influence on patients' short survival.