Bacterial infections in pediatric hematopoietic stem cell transplantation recipients: incidence, epidemiology, and spectrum of pathogens: report of the Polish Pediatric Group for Hematopoietic Stem Cell Transplantation.

BACKGROUND: Infectious complications are a significant cause of hematopoietic stem cell transplantation (HSCT) failure, especially allogeneic HSCT (allo-HSCT) because of delayed immune reconstitution and graft-versus-host disease (GVHD) occurrence. Identifying the factors responsible for bacterial infections (BI) in patients undergoing HSCT will provide much more effective empirical antimicrobial treatment in this group of patients. OBJECTIVE: The aim of this study was to evaluate the epidemiology and profile of BI in patients after HSCT in 5 centers of the Polish Pediatric Group for Hematopoietic Stem Cell Transplantation in 2012-2013. PATIENTS AND METHODS: In 308 HSCT recipients, we retrospectively analyzed 273 episodes of BI in 113 (36.7%) children aged 0.02-22 years (median age: 7 years), 92 after allo-HSCT and 22 after autologous HSCT (auto-HSCT). We assessed incidence of BI in different HSCT types by calculating the Index of Bacterial Infection (IBI) as a ratio of patients with at least 1 BI to all patients who underwent this type of HSCT in the analyzed period. We assessed the profile of BI with particular emphasis on multidrug-resistant organisms, and impact of underlying disease and of graft-versus-host disease on BI episodes. RESULTS: In the studied group, 273 episodes of BI were diagnosed, including 237 episodes after allo-HSCT and 36 after auto-HSCT. Among allo-HSCT recipients diagnosed with at least 1 BI, the IBI was 0.4 (matched sibling donor-HSCT 0.3; matched donor-HSCT 0.4; mismatched unrelated donor [MMUD]-HSCT 0.8; P = 0.027) and after auto-HSCT 0.3 per 1 transplanted patient. In patient after allo-HSCT because of myelo- or lymphoproliferative diseases and bone marrow failures, the major cause of infections was Enterobacteriaceae, while gram-positive bacteria predominated in the group with primary immunodeficiencies. In all patients after auto-HSCT, the dominant pathogen of BI were Enterobacteriaceae (P = 0.011). Time from each type of HSCT to infection caused by different pathogens did not differ significantly. CONCLUSIONS: The risk of BI does not depend on the underlying disease, but only on HSCT donor type and is the highest after MMUD-HSCT procedure. The profile of BI depends on the underlying disease and HSCT donor type, but does not depend on the occurrence of acute GVHD. Gram-negative bacteria predominated in patients with myelo- and lymphoproliferative diseases, while in patients with primary immunodeficiencies gram-positive strains were predominant.

[The application of membranes and bone substitutes in periodontology]. / Zastosowanie blon i substytutów kosci w periodontologii.

The purpose of the article is to present the repair potential of periodontal tissues using guided bone regeneration. Indications, operating methods, effects of membranes and bone substitutes implantation are presented.

Fetotoxic effect of 2,4-dichlorophenoxyacetic acid (2,4-D) in rats.

The fetotoxic effect of 2,4-dichlorophenoxyacetic acid (2,4-D) was investigated. Histological and histochemical changes in the liver of newborn, jung and adult rats exposed to the herbicide from the prenatal period to the end of an experiment were evaluated. The experiment used 90 male and female, Wistar, aged to 10 weeks rats, divided into two groups: I-control-30 and II-60 animals which received the water solution of 2,4-D acid sodium salt in a daily dose of 250 mg/kg b.w. It was given with drinking water every day. The animals were sacrificed after 24 hours, 4, 6, and 10 weeks of the experiment. The results obtained showed that the administration of 2,4-D acid to rats in the prenatal and postnatal period, in a dose inducing subacute intoxication leads to histological and histochemical changes in the liver. The observed changes indicate disorders in energetic processes in hepatocytes and are morphological exponents of detoxicative processes there. They are most intensified with newborn rats. It suggest also, the pregnants ought not to work with 2,4-D and should avoid any contact with herbicides belongs to the 2,4-dichlorophenoxyacetic acid group.

[Tuberculosis in patients after kidney transplantation]. / Gruzlica u chorych po przeszczepieniu nerki.

Infection caused by Mycobacterium tuberculosis is common among population in Poland. We analyzed the effect of tuberculosis (TB) on patients and graft survival in the group of renal allograft recipients (RAR), treated in our center. Among 1669 renal allograft recipients transplanted from 1981 to 1992, tuberculosis developed in 33 (2%) patients (16 M/17F, age: 22-57 years). The patients were on following immunosuppressive regiments" Pred+Aza+CsA (12 pts), Pred+Aza (12), Pred+CsA (6) and Pred+Aza+CsA+ATG (3). Acute rejection was diagnosed in 27 of them and was treated with methyloprednisone pulses, and in a few cases additionally with ATG (2 pts) or OKT3 (1 pt). In two pts TB had been diagnosed and successfully treated in the past. In 6 pts, on chest X-ray done immediately before transplantation, healed primary lesion (Ghon complex) had been seen. In 16 pts TB developed in the early posttransplant period (median: 3.8 +/- 1.8, range: 1-6 months) and in 17--late after transplantation (median: 31.2 +/- 1.8, range: 13-156 months). In 19 pts symptoms developed soon after treatment of acute rejection. Clinical manifestations include pulmonary TB (30 pts) and extrapulmonary lesions (15 pts): pleural TB (3 pts), miliary TB (5 pts), tuberculous lymphadenitis (1 pt), uveitis (1 pt), renal allograft (2 pts), skeletal (2 pts) and GI tract (1 pt). Diagnosis of TB was made based on clinical presentation and radiologic findings and it was confirmed by positive cultures in 18 pts, by tissue biopsy in 4 pts and by autopsy examination in 9 pts. Treatment regimen included one of the following drug combinations: INH+EMB+RMP (20 pts), INH+RMB+RMP+PZA (10 pts) or INH+EMB+SM (3 pts). Three pts died before TB was recognized and 4 deaths occurred after treatment was started. All these pts developed renal failure. 26 pts were treated for 3-12 months (median, range: 7.8 +/- 2.9) and in 24 of them complete remission was achieved. In this group renal function remained stable in 16 pts and 6 pts developed terminal failure due to chronic rejection. Authors conclude: 1. TB remains a frequent complication in RAR but can be successfully treated when diagnosed early. 2. Extrapulmonary TB is common in RAR. 3. TB deteriorates one year patients (75%) and graft (49%) survivals.

[The effect of erythropoietin treatment on endocrine organ function in patients with terminal-stage kidney failure on hemodialysis]. / Vliianie lecheniia éritropoétinom na funktsiiu éndokrinnykh organov u bol'nykh s terminal'noi stadiei pochechnoi nedostatochnosti, nakhodiashchikhsia na gemodialize.

Eleven hemodialyzed patients with uremia were examined for the effect of erythropoietin (EP) treatment carried out for 3 months on functions of different endocrine organs. EP treatment resulted in a decrease of the initial plasma levels of somatotropin, prolactin, follicle-stimulating and luteinizing hormones. EP treatment being over, there was a decrease in the plasma content of ACTH, cortisol and aldosterone. The treatment with EP was also associated with an insignificant rise of the plasma levels of parathyroid hormone and testosterone. EP treatment did not influence the plasma concentration of calcitonin and 25-OH-D. EP was found to exert no significant effect on the pituitary-thyroid reverse relationship. The 3-month treatment with EP eventuated in plasma renin activity inhibition as well as in an increase of the atrial level of natriuretic peptide in the plasma. EP treatment stimulated insulin secretion and reduced glucagon secretion. Finally, EP decreased the gastrin level and to a less degree the plasma level of pancreatic polypeptide.

Endocrine abnormalities in patients with endstage renal failure.

Data presented in this study suggest existence of hyperendorphinism in uraemic patients. This hyperendorphinism may be regarded both as a primary beneficial compensatory mechanism counteracting disturbances of the internal environment, while causing secondary harmful side effects, which contribute to the uraemic state. Erythropoietin treatment of uraemic, haemodialyzed patients is followed by marked endocrine alterations (suppression of plasma levels of STH, ACTH, prolactin, glucagon, aldosterone, cortisol and plasma renin activity, elevation of plasma insulin and atrial natriuretic levels, lack of influence on plasma PTH, CT and AVP). It remains to be clarified whether the erythropoietin induced endocrine alterations are due to correction of the existing anaemia or reflect a specific effect of this hormone.

Long-term immunosuppressive therapy of idiopathic membranoproliferative glomerulonephritis.

Fifty cases of idiopathic membranoproliferative glomerulonephritis were followed up for an average of 10 +/- 0.9 (SE) years. Forty of them, who presented a nephrotic syndrome, were treated by immunosuppressive drugs (prednisone, azathioprine, chlorambucil, cyclophosphamide) for 79 +/- 9.7 (SE) months. Cumulative survival ratio for 5, 10 and 15 years after enrollment was 0.90, 0.82 and 0.77 and after appearance of first symptoms or signs of kidney disease as determined by anamnestic data 0.97, 0.91 and 0.90 accordingly. Triple-drug therapy (prednisone and azathioprine combined with chlorambucil or cyclophosphamide) was more effective in improving proteinuria than other immunosuppressive regimens. No serious side effects were encountered.

The comparison of antibody-dependent (ADCC) and lectin-induced (LICC) cytotoxic activities of human blood lymphocytes in healthy and diseased subjects.

Antibody-dependent and PHA-induced cytotoxicity of peripheral blood lymphocytes in healthy human subjects and in patients with primary glomerulopathies (non-treated and on immunosuppressive treatment) as well as hemodialyzed and transplanted patients were investigated. Heavy disorders of ADCC and LICC activity in the groups of uremic patients and in patients on immunosuppressive therapy were found. Higher sensitivity to immunosuppressive treatment demonstrated that the lymphocytes exerted an antibody-dependent rather than a PHA-induced cytotoxicity. Results presented suggested the participation of two different lymphocyte subpopulations with ADCC and LICC activity in the regulatory and pathological processes.

The effect of uremia and dialysis on cell-mediated immunity.

Delayed-type hypersensitivity to PPD, two types T rosettes as well as lymphokine production were studied in patients with end-stage renal failure maintained on hemodialysis. A significant impairment of skin reactivity and the lowering of the number of T cells were found, while no definite changes of lymphokine production were detected. No conclusive data are obtained as to the role of hemodialysis in reversing of immunologic deficits noted in uremia.

Studies on the human mixed lymphocyte culture. II. Comparison of one-way and two-way test performed on lymphocytes of patients with end-stage renal failure and their prospective living donors.

The results of DNA synthesis in human one-way and two-way mixed lymphocyte cultures were compared. Twenty patients with chronic renal failure and their twenty six prospective living donors were investigated. Statistical correlation was found on the level alpha = 0.01 between the stimulation index value calculated for one-way and two-way technique. Two-way MLC, the rapid and simple and simple assay detecting lymphocyte activation is a very useful tissue typing test.