First-line immunosuppressive treatment in children with aplastic anemia: rabbit antithymocyte globulin.

Immunosuppressive therapy is the treatment of choice in children with acquired severe aplastic anemia (AA) and no HLA-matched family donor. The paper presents results of a multicenter study of 63 children with AA treated with rabbit antithymocyte globulin (r-ATG) and cyclosporine A as the first line treatment in the years 1996-2012. Therapeutic effects were evaluated at Days 112, 180, and 360. At Day 112, remission was achieved in 28 out of the 63 patients (44.4 %), complete remission in 10 patients (15.9 %), and partial remission in 18 (28.5 %). At Day 180, 31 patients (49.2 %) were in remission including 15 cases in complete (23.8 %), and 16 cases in partial remission (25.4 %). One year after therapy onset, 34 patients (64.9 %) were in remission including 24 patients (38.0 %) in complete and 10 (15.9 %) in partial remission. Relapse occurred in 4 patients, from 8 months up to 2 years and 2 months after remission. One child, 5 years after remission, was diagnosed with paroxysmal nocturnal hemoglobinuria. The estimated 10-year overall survival rate and 10-year event-free survival rate were 67 % and 57 %, respectively.

Educational pathways of childhood cancer survivors-a parental cohort.

PURPOSE: Using the International Standard Classification of Education (ISCED), we examined the educational and vocational pathways of two comparable, parental cohorts: childhood cancer survivors (CCS) and their siblings. Both cohorts had previously entered parenthood. The aim of the study was to elucidate whether childhood cancer and treatment affect the educational pathways chosen by parents who are former patients. METHODS: We analysed data that was collected from childhood cancer survivors and their siblings regarding their offspring's health within the FeCt Multicentre Offspring Study (conducted 2013-2016). We evaluated and compared the professional pathways of (i) all participating survivors and all participating siblings and those of (ii) survivors and their biological siblings. RESULTS: Overall information on parental gender, age, and education were available from 1077 survivors and 246 siblings (group (i)). The majority of participants were female with a mean age of 35.2 (survivor) and 37.9 (sibling) years at time of survey. For subgroup (ii), analysis information was available on 191 survivors and 210 siblings. Fathers achieved university degrees significantly more often than mothers (p = 0.003 (i), p < 0.001 (ii)). The distribution of professional education was not significantly different between cancer survivors and siblings in either cohort (i) or (ii). CONCLUSIONS: Regarding our research on the educational and vocational trajectory of CCS, patients can be reassured that family planning and vocational education are well compatible. Inequalities regarding gender-specific educational pathways remain to be addressed. IMPLICATIONS FOR CANCER SURVIVORS: CCS should monitor their fertility status regularly and, if necessary, cryopreserve germ cells or tissue in order to optimize their family planning. Educational opportunities should be pursued as desired and with confidence. Local as well as European aftercare programs can assist with family planning and education.

[New bioplastic materials for reconstructive surgery].

Results of creation and clinical application of bioplastic materials using specimens from the tissue bank of the Institute of Traumatology and Orthopedics are presented. The use of materials of the new generation, such as perfoost, alomatrix-implant, and osteomatrix, is illustrated by examples of the treatment of various bone diseases. High biocompatibility and efficiency, osteoconductive and osteoinductive properties of these materials are reported. Technical developments in modern bioimplantology are analysed with reference to their status in the Institute's tissue bank.

Does the concentration of alpha 1-proteinase inhibitor reflect the transformation of liver cirrhosis to liver carcinoma?

Serum concentration of alpha1-proteinase inhibitor (alpha1-PI) was determined by nephelometric method in forty seven patients with liver cirrhosis (LC) and fifteen patients with hepatocellular carcinoma (HCC). Our data show an increase in the concentration of alpha1-PI in the group with decompensated LC by 17% and in HCC by 29%. The level of alpha1-PI higher than (220 mg%) may be indicative of the disease progression towards decompensated LC or HCC. In the conclusion, an increase in alpha1-PI concentration in patients with LC may be considered as an alarming factor, but is not sufficiently specific to become a diagnostic tool for the detection of HCC development.

Activation of blood platelets in chronic hepatitis and liver cirrhosis P-selectin expression on blood platelets and secretory activity of beta-thromboglobulin and platelet factor-4.

BACKGROUND/AIMS: Blood platelets are cells that quite often undergo damage in chronic liver diseases. Endotoxemia and hyperkinetic circulation influence platelets in an active manner. The role of platelets in the development of hepatitis and liver fibrosis is speculative. The aim of the study was to determine the influence of chronic liver diseases on platelets morphologic parameters, their secretory activity and P-selectin expression. METHODOLOGY: The examination was completed in the group of 29 patients with chronic hepatitis and 27 with liver cirrhosis of postinflammatory etiology (HBV, HCV). Liver biopsies were carried out in all patients. Thirty-two healthy individuals were the control group. Platelets morphological parameters (number, volume, platelet crit, micro- and macrothrombocyte fraction) were estimated. beta-thromboglobulin concentration and platelet factor 4 in blood serum as well as P-selectin expression on resting platelets and after thrombin activation were also examined. RESULTS: Number, volume, and platelet crit decreased with the advancement of a liver disease. Megathrombocyte fraction increased inversely with the severity of liver damage. The concentration of beta-thromboglobulin and platelet factor 4 alpha-granule contents in blood serum was higher 2- and 7-times, respectively than in healthy controls. P-selectin expression on resting platelets was considerably higher. After stimulation with thrombin, P-selectin expression was equal (chronic hepatitis) or higher (liver cirrhosis) than in the control. CONCLUSIONS: There are changes of platelet morphological parameters, with accompanying megathrombocyte fraction increase that occur in chronic liver diseases. Thrombocytes in chronic liver diseases and liver cirrhosis are more activated. Platelet sensitivity to stimuli in these ailments is higher (liver cirrhosis) than in the healthy controls.

MR and 1H MR spectroscopy of the brain in patients with liver cirrhosis and early stages of hepatic encephalopathy.

BACKGROUND/AIMS: Hepatic encephalopathy is a serious problem in patients with liver cirrhosis and precise pathophysiological mechanisms responsible for encephalopathy are not fully understood. Magnetic resonance imaging and magnetic resonance spectroscopy can be used to detect specific morphological and metabolic abnormalities in the brain even in patients with early stages of hepatic encephalopathy. METHODOLOGY: Twenty patients with liver cirrhosis and 14 patients with grade I-II hepatic encephalopathy were studied with magnetic resonance and proton magnetic resonance spectroscopy. Localized magnetic resonance spectra were acquired in the parietal gray/white matter regions and basal ganglia. Control group consisted of 20 healthy volunteers. RESULTS: Frequency and degree of brain atrophy and bilateral signal hyperintensities in globus pallidus were similar in groups with liver cirrhosis and with encephalopathy. Decreased myoinositol, choline and increased glutamine levels were noted in both groups whereas N-acetylaspartate levels were unchanged. The statistically significant differences between cirrhotic and encephalopathic groups were observed only in myoinositol/creatine ratio in basal ganglia. There were no significant differences in metabolic concentrations between parietal and basal ganglia regions. CONCLUSIONS: Metabolic brain alterations occur earlier than clinical evidence of hepatic encephalopathy but there is no correlation between presence of symptoms encephalopathy and magnetic resonance and magnetic resonance spectroscopy findings.

[Identification of genes induced to chondrocytes by nitric oxide]. / Poisk i identifikatsiia genov, indutsiruemykh v khondrotsitakh pod deistviem okisi azota.

Nitric oxide (NO) acts as a short-lived paracrine factor and selectively activates transcription of certain genes. The spectrum of inducible genes was studied in primary chondrocytes. A cDNA library was obtained by subtraction hybridization with RNAs isolated from rabbit chondrocytes before and after treatment with nitrosoglutathione, an NO-generating agent. Some of the cloned cDNAs were homologous to known mammalian genes and human EST. NO-dependent transcriptional activation was demonstrated for the stromelysin 1 and cyclooxygenase 2 genes and, for the first time, for mcl1 coding for an apoptosis suppressor.

[Genetic aspects of the reaction of humoral immunity to collagen in humans and animals. Report I. Analysis of polymorphism of autoantibody levels to collagen type I in mice NZB X NZW (F1)]. / Geneticheskie aspekty reaktsii gumoral'nogo immuniteta k kollagenu u cheloveka i zhivotnykh. Soobshchenie I. Analiz polimorfizma urovnei autoantitel k kollagenu I tipa u myshei NZB X NZW (F1).

The study of polymorphism of humoral immunoreactions to the type I (AC) collagen in CBA/Lac, C57B1/6-J inbred mice and NZB X NZW (F1) hybrids showed the presence of genetically determined variability of the above mentioned trait. The analysis of intralinear dispersions of AC levels in NZB X NZW (F1) mice revealed sex dimorphism and age variability of the trait. A suggestion was made that sex hormones are important factors in ontogenic formation and modulation of autoimmunity to the type I collagen in NZB X NZW (F1) mice.

[Protein synthesis and secretion and RNA and DNA synthesis in human skin fibroblasts in a medium with a low serum content]. / Sintez i sekretsiia belka, sintez RNK i DNK u fibroblastov kozhi cheloveka v srede s nizkim soderzhaniem syvorotki.

Human skin fibroblasts, both postnatal and embryonic, were cultured in the stationary phase of growth for 6-10 days in the DMEM with bovine serum (BS), 0.1-0.5% fetal calf serum (FCS) or 1% human serum (HS). On the day 4 of culturing, a considerable increase was observed in the synthesis and secretion of protein by postnatal fibroblasts in the Eagle medium with 0.1-0.5% FCS, or with 0.5% BS, and in medium 199 with 0.1-0.5 BS, or with 0.1 FCS. Maximum synthesis and secretion of 14C-proline labeled protein was observed on day 2 of culturing of cells in the DMEM medium with 1% HS. In the DMEM medium with low serum content, protein synthesis being virtually unchanged, 75-80% of protein was secreted by cells into the culture medium with BS on days 2-4; in the medium with FCS such a high secretion of protein was observed only on day 4. High synthesis of protein by fetal fibroblasts in the DMEM medium with 0.1% BS and high protein secretion in all the media with 0.1% BS or 0.5% FCS were observed. The maximum level of secretion of protein by fibroblasts coincided with a considerable increase in both RNA and DNA syntheses. The data obtained suggest that cells in deep resting state actively react to the composition of the medium as well as to the quality and quantity of the serum. It may also be suggested that the mechanism of protein secretion has an important role in maintenance of the constant level of intracellular proteins in resting cells.

[Snake bites]. / Ukaszenia przez zmije.

Vipera berus is the only viper i.e. venomous (poisonous) snake that is found in Poland. Snakebites occur rarely und usually follow attempts of catching the viper or accidental treading on it. Appropriate treatment consists of administering specific antivenom serum (antivenin). Four cases of snakebites hospitalized in 1989-1995 in the Department of Infectious Diseases of the University Medical School in Bialystok are reported.

[Epidemiology of intra-marital infections with hepatitis B virus (HBV) among the patients hospitalized in the infectious disease clinics in the Bialystok region 1988-1990]. / Epidemiologia zakazen wewnatrzmalzenskich wirusem hepatitis B (HBV) w populacji chorych hospitalizowanych w oddzialach obserwacyjno-zakaznych Bialostocczyzny w latach 1988-1990.

Viral hepatitis B infection is worldwide epidemiological and clinical problem with same prophylactic difficulties concerned first of all married patients. The infection routes could be parenteral or homo/heterosexual contact. During 1988-1990 from hospitalized viral hepatitis B all patients (394), married patients was found 9% (34) persons with epidemiological documented viral hepatitis B infection, from his/her sexual married partner.

[Autoimmune thrombocytopenia in chronic liver disease]. / Autoimmunologiczna trombocytopenia w przewleklych chorobach watroby.

Thrombocytopenia (TP) often accompanies chronic liver diseases. The causes are numerous and include impaired production of blood platelets, spleen sequestration, and the immune factors, e.g. antiplatelet autoantibodies. ELISA (GTI-PAKPLUS) examinations were conducted in order to estimate the rate of autoimmune thrombocytopenia occurrence in patients with thrombocytopenia in the course of chronic hepatitis (10 patients) and liver cirrhosis (20 patients). Blood platelet activity was also evaluated as well as the expression of platelet glycoproteins (GPIIb, GPIIIa, and GPIX) in platelets of the patients and the controls. It was observed that autoimmune TP occurred in 30% of patients with liver cirrhosis and in 10% of patients with chronic hepatitis, in which anti-GPIIb/IIIa, GPIa/IIa, and HLA class I antibodies were detected. In all patients there occurred significant/marked platelet activation with CD61P expression. Thrombocytopenia in patients showed a similar activity after thrombin stimulation to that in healthy individuals. Expression on GPIIb platelet receptors was markedly increased and GPIX decreased in patients in comparison to the controls. There was no correlation between the occurrence of certain types of anti-platelet autoantibodies and the expression of GP on thrombocytes in these patients.

[Liver biopsy: the mandatory test in liver diagnosis in adults]. / Biopsja watroby--niezbedny element w diagnostyce chorób watroby u doroslych.

The aim of the study was clinical and morphological analysis patients with liver biopsy. In this work technique of percutaneous liver biopsy, indications, contraindications and complications were presented. Among 547 liver biopsy 56% patients was HCV infected and a 14% patient was HBV infected. Microscopic examination was performed the similar percentage the stage of inflammation and fibrosis. Among patients without viral infection (HBV and HCV) the most finding was steatosis and liver cirrhosis. Agreement of clinical diagnosis with results of microscopic investigations with reference to of inflammable changes carried out 90%, the less agreement with steatosis, cholestasis and hemosiderosis. In 30% patients after biopsy were pains in place executed of intervention and right arm for 6 hours. 0.5% of patients was sub capsular bleeding after intervention. We no observed dangerous complications after liver percutaneous biopsy. Liver biopsy is very important investigation in liver diagnosis, comparatively safety if contraindications are complains.

[Appendicitis and its atypical causes]. / Zapalenie wyrostka robaczkowego i jego nietypowe przyczyny.

The authors analysed 2849 patients who were admitted to the Department of General Surgery, Regional Hospital in Pisz in the years 1980-1989 with symptoms suggestive of appendicitis. In 983 cases surgical intervention was abandoned, because the symptoms regressed spontaneously or were caused by diseases of other organs. The pathological conditions associated with appendicitis are analysed in 1866 surgically treated patients. Cases of appendicitis caused by Oxyuris vermicularis, Salmonella-enteritidis and actinomycosis (one case each) and appendicular carcinoma (2 cases) are described in more detail. Attention is called to the aetiology, pathogenesis and treatment of these rare causes of appendicitis.

[Phagocytic activity of blood platelets in patients infected with Giardia intestinalis]. / Aktywnosc fagocytarna plytek krwi u chorych zarazonych Giardia intestinalis.

Blood platelets take part in immune reactions of the organism, especially in anti-parasitic immunity. We conducted this study measuring the phagocytic activity of blood platelets. The experiments were done on 35 patients infected G. intestinalis. Diagnosis was supported on finding trophozoits in bile cysts and GSA-65 protein in feces. We have found some decrease of blood platelets count and the increase the percentage of phagocytic platelets. Our general conclusion is, the parasite is able to stimulate the phagocytic activity of blood platelets.

[Methodology of a screening study of the level of mental development of young children]. / Metodika skrining-issledovaniia urovnia psikhicheskogo razvitiia detei rannego vozrasta.

A screening procedure for assessing the level of the psychic development of very young children was developed and tried on 210 healthy children. To evaluate the validity of this method, 50 children with mental retardation (debility) confirmed by extensive clinical examinations were studied. This test allows highly significant differentiation between intellectually intact and mentally retarded children.

[Pulmonary thromboembolism--random analysis of autopsy material]. / Choroba zatorowo-zakrzepowa pluc--analiza nieselekcjonowanego materialu autopsyjnego.

In the study an analysis of 13216 autopsy materials was performed to evaluate a frequency of pulmonary thromboembolism incidence including localisation of detected changes. Pulmonary thromboembolism was determined in 5.5% autopsies, with evident increase in older subjects (up to 31.3% in 70-79 years old group). The most frequently (67.8%) pulmonary thromboembolism was observed in lobar and segmental arteries in a course of atherosclerosis (28.6%), neoplasmas (20.8%) and septic diseases (15.5%). In 25% cases of pulmonary thromboembolism has been diagnosed during clinical observations and has been confirmed by autopsy procedure.

[The NBT test in bacterial infections complicating prednisone-treated nephrotic syndrome]. / Test NBT w infekcjach bakteryjnych wiklajacych zespól nerczycowy leczony enkortonem.

The spontaneous nitroblue tetrazolium reduction test was done in children with nephrotic syndrome treated with prednisone and with secondary bacterial infections and in children with urinary tract infections not treated with prednisone. In healthy children 9.0 +/- 1.3% of polymorphonuclear leucocytes in peripheral blood showed presence of deposits in the NBT test. In children not treated with prednisone the number of NBT (+) leucocytes was increased over fourfold. The value of the NBT test was highest at the beginning of the disease. In children treated with prednisone the value of the NBT test increased slowly. The highest results were obtained in the second week of infection treatment. In relation to controls the proportion of NBT (+) test in peripheral blood was increased threefold.

[Mechanism of the effect of phytohemagglutinin as a stimulator of wound healing]. / K mekhanizmu deistviia fitogemaggliutinina kak stimuliatora zazhivleniia ran.

Phytohemagglutinin (PHA) produced by Difco, USA, (3.3 microgram per 1 mg of unguentum base) was tested as a stimulator of the healing of suppurative skin-muscle wounds 4 cm2 in area in 70 rabbits divided into 3 groups according to reaction to the intracutaneous test with PHA. Enhanced wound healing was observed only in poorly reacting rabbits (20.7 against 31.1 days in control). A considerable increase in the number of activated lymphocytes and cells of monocyte-macrophage group in the wound exudate, increased phagocytosis as well as more rapid and intensive development of proliferative processes were also established. The stimulation mechanism includes the direct PHA effect on inflammation cells and epithelium and a complex chain of both direct and mediated cellular interactions.

[Anticholinesterase activity and toxicity of substituted O,O-dialkyl-S-vinyl phosphates and thiovinyl phosphonium salts]. / Antikholinesteraznaia aktivnost' i toksichnost' zameshchennykh O,O-dialkil-S-vinilfosfatov i solei tiovinilfosfoniia.

A kinetic investigation of the human erythrocyte and housefly head acetylcholinesterase irreversible inhibition with thiovinyl phosphates is performed and an activation effect of thioalkyl alpha-substituents in the vinyl group is observed. Thiovinyl phosphates in vitro are less selective to the insect enzyme than the corresponding oxygen analogues. Their inhibitory potency rises with lengthening of the alkoxyl radicals at a phosphorus atom but the correlation with the toxicity is absent. Phosphonium salts having a thiovinyl substituent inhibit the enzyme via the reversible mechanism typical for onium compounds.