Prevalence and risk factors of hepatitis C virus infection in haemodialysis patients: a multicentre study in 2796 patients.

BACKGROUND: Hepatitis C virus (HCV) infection is a significant problem in the management of haemodialysis patients. A high prevalence of HCV infection in haemodialysis patients has been reported. Risk factors such as the number of blood transfusions or duration on haemodialysis have been identified. AIM: To determine the prevalence of HCV by antibody testing and HCV-RNA determination by polymerase chain reaction (PCR) in haemodialysis patients. Furthermore, liver function tests were performed and epidemiological data were obtained to determine risk factors for HCV in this cohort of patients. RESULTS: A total of 2796 patients from 43 dialysis centres were enrolled. The overall prevalence of HCV (HCV antibody and/or HCV-RNA positivity) was 7.0% (195 patients). Antibody positivity occurred in 171 patients (6.1%). Viraemia was detectable in 111 patients (4.0%). Twenty four of 111 HCV RNA positive patients (21.6%) were negative for HCV antibodies. Thus 0.8% of the entire study population was HCV positive but could not be diagnosed by routine HCV antibody testing. Major risk factors identified by a standard questionnaire in 1717 of 2796 patients were the number of blood transfusions individuals had received and duration of dialysis, the latter including patients who received no blood transfusions. Sequencing of the 5'untranslated region of the genome showed a dominant genotype 1 (77.6%) within the cohort. Further reverse transcription-PCR of the NS5b and core region were performed to document phylogenetic analysis. Comparing nucleic acid sequences detected by PCR, no homogeneity was found and thus nosocomial transmission was excluded. CONCLUSIONS: HCV is common in German haemodialysis patients but screening for HCV antibodies alone does not exclude infection with HCV.

Does prolonged oral treatment with sustained-release morphine tablets influence immune function?

UNLABELLED: Opioids such as morphine are the mainstay of acute and chronic pain treatment. The purpose of this study was to investigate the immunosuppressive effects of morphine in patients with pain syndromes. We investigated 10 patients with chronic pain syndromes undergoing treatment with oral sustained-release morphine (30-240 mg/d) before and after 1,4, and 12 wk of treatment compared with healthy control subjects without morphine treatment. Immunological variables of the cellular and humoral immune axis showed that 1) total lymphocyte counts and the distribution of lymphocyte subpopulations, including helper T-cell/suppressor cytotoxic T-cell ratios (CD4/CD8 ratios), did not change compared with baseline or healthy control subjects; 2) proliferation of peripheral mononuclear cells (PMC) was not impaired by morphine treatment; 3) interleukin 2 production increased after 4 wk of treatment with morphine; and 4) immunoglobulin (Ig) production was reduced before initiation of therapy in pain patients and decreased further during morphine treatment, whereas Ig concentrations in the circulation remained at normal levels. These results indicate that treatment with oral, sustained-release morphine does not have a suppressive effect on overall PMC function. On the other hand, Ig production was impaired in patients with chronic pain and was further suppressed by morphine. Whether this suppression of humoral immune function has a clinical impact on the immune system as a whole remains to be determined. IMPLICATIONS: Treatment of patients with chronic pain with oral, sustained-release morphine does not influence cellular immune function, but it suppresses the already attenuated production of immunoglobulins.

Effect of renal function on cytokine secretion of monocytes and lymphocytes.

The effect of renal function on cytokine secretion capacity of mononuclear cells was analysed in patients who had not been subjected to any form of renal replacement therapy. The aim of the study was especially to determine whether there is a defect of monocyte function. The patients were divided into three groups of 12 on the basis of renal function: group I, serum creatinine 1.5-3 mg/dl; group II, 3-6 mg/dl; and group III, > 6 mg/dl. Serving as controls were 36 age- and sex-matched healthy volunteers. IL-1 beta, IL-6, TNF-alpha, IL-2 and IF-gamma concentrations were measured in the supernatants of stimulated and unstimulated cells isolated from the blood. Renal function was not found to have any effect on the secretion capacity of IL-2 and IF-gamma. However, the secretion capacity of IL-1 beta of lipopolysaccharide (LPS)-stimulated monocytes was reduced in patients of group III to 214 +/- 290 pg/ml, compared with 501 +/- 327 pg/ml in controls (P = 0.047). The effect was even more accentuated for IL-6 (group III: 5422 +/- 5116 pg/ml; controls: 16,319 +/- 12,474 pg/ml; P = 0.019). Spontaneous secretion levels did not change for any of the cytokines, and LPS-stimulated TNF-alpha secretion was also normal. Highly purified blood monocytes/macrophages were stained for CD14, HLA-DR, CD11c, and CD4. Neither the percentage of positive cells nor the fluorescence intensity, as measured by FACS, was influenced by renal function, and no correlation could be established between function and phenotype.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigenemia, immunoblotting, and enzyme immunoassay for early diagnosis of cytomegalovirus infection in renal transplant patients.

Timely and rapid diagnosis of cytomegalovirus (CMV) infection is important for the management of transplant patients. We compared three serological assays, IgM immunoblot and IgG/IgM enzyme immunoassay (EIA), as well as the detection of CMV antigens in polymorphonuclear blood leukocytes (antigenemia), for their value in the early diagnosis of CMV infection. Thirty-one patients were monitored longitudinally for 3 months after renal transplantation. Laboratory documented CMV infection occurred in 20 patients. All of these cases showed a positive IgM immunoblot result that was confirmed by at least one of the other test assays (IgG EIA 19/20, antigenemia assay 13/20, and IgM EIA 12/20). All of the ten patients whose clinical picture was compatible with symptomatic CMV disease were positive for CMV infection according to IgM immunoblot and IgG EIA, nine were positive according to the antigenemia assay, and seven were positive according to IgM EIA. With reference to the temporal pattern, the antigenemia assay indicated CMV infection significantly earlier than the serological tests (P < or = 0.05). In symptomatic patients CMV antigen-positive leukocytes were, on the average, detected on the day of onset of symptoms, whereas detection by IgM immunoblot, IgG EIA, and IgM EIA followed 8, 13, and 14 days later, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

A microtitre assay system for glucocorticoid receptors: decreased receptor concentration in myocardial infarction.

A major difficulty in determination of glucocorticoid receptor sites is the very complicated assay procedure. Therefore, we describe a microtitre assay system for glucocorticoid receptors which is a whole-cell competitive binding radioassay using [3H]-dexamethasone as radioligand. This modification of a previously described protocol simplifies and reduces laboratory work and allows assay reproducibility to be controlled more reliably. Thus enabled to perform the test on multiple blood samples in parallel, we investigated cardiac infarction patients over a 12-day period to test if glucocorticoid receptor binding is altered in this 'stressful' disease. On the first day of the disease, glucocorticoid receptor capacity was significantly decreased without alteration of the receptor-ligand affinity, whereas on days 4 and 12 the number of receptor sites was normal again. This result fits well into the general observation of stress-induced down-regulation of immune responses.

Temporal patterns of immunoblot-reactive antibodies to cytomegalovirus in transplant recipients.

A total of 234 sera from 44 allograft recipients were compared with 12 sera from 9 immunocompetent patients with symptomatic cytomegalovirus (CMV) infection and with 20 sera of 20 healthy individuals with latent CMV infection. The presence of immunoreactive proteins was not associated with a specific transplant group or with different immunosuppressive regimens but rather with the kinetics of the immune response. Acute phase sera demonstrated early antibodies to proteins p38 and p48, followed by high or still rising antibodies to high molecular weight proteins, particularly p150, and their later decline to persistent lower levels. Convalescent phase sera were identified serologically by the transient appearance of IgG antibodies directed to 22-26 kDa polypeptides. Immunoreactive p44 was present in 85% of all patients with mild disease and in 40% of all patients with severe CMV disease. When tested in parallel, the immunoblot analysis was shown to be a more sensitive indicator of early CMV antibodies in allograft recipients than the ELISA technique.

Rejection prophylaxis with interleukin-2 receptor antibody BT 563: mechanisms of action on human cells.

We investigated the in vitro immunosuppressive effect of BT 563, a monoclonal antibody, against the alpha-chain of the human interleukin-2 (IL-2) receptor (p 55), which has been used to prevent transplant rejection in several clinical trials. We also measured the proliferative T cell alloresponse and pCTL frequencies of BT563-treated kidney transplant patients. In mixed lymphocyte cultures BT 563 caused a reduction of T cell proliferation to about 50%. This could not be reversed by the addition of exogenous IL-2. A more effective reduction (80%) was seen in the generation of cytotoxic T cells from CML cultures and at the clonal level. The specific T cell response after preincubation with antigen and BT 563 was not reduced so that BT 563 did not induce tolerance. The in vitro findings indicated that BT 563 had a significant but incomplete immunosuppressive effect. This correlated with the clinical course and ex vivo analysis of PBL from BT 563-treated patients after kidney transplantation.

Malignant lymphoma of donor origin after renal transplantation: a case report.

A case of non-Hodgkin's lymphoma of polymorphous centroblastic type presenting in a renal allograft is reported. The kidney graft was explanted 10 months after transplantation because of chronic rejection. No other manifestations of lymphoma were found in the recipient. Since the human leukocyte antigen patterns of the renal allograft and the recipient differed at two loci, the donor origin of the malignancy could be clearly demonstrated by immunohistochemistry.

Discrepant results of different tests for antibodies to hepatitis C in children with malignant diseases and in patients on renal replacement therapy.

The serostatus of hepatitis C in pediatric oncological patients and in individuals on renal replacement therapy was tested for circulating antibodies to the c100-3 recombinant antigen of hepatitis C. Upon prescreening, 12 of 82 patients in the pediatric oncological group, 6 of 108 renal transplant recipients, and 17 of 150 patients on chronic intermittent hemodialysis were repeatedly positive. Further testing of these 35 sera by supplemental test assays revealed conflicting data, mostly in the pediatric oncological group and in renal transplant recipients. Only in 10 sera were identical results obtained, suggesting that positive test results in some groups at risk have only a low predictive value.

[Inferior vena cava compression syndrome in cystic kidney. Duplex ultrasonic diagnosis]. / Vena-cava-inferior-Kompressionssyndrome bei Zystennieren. Duplexsonographische Diagnose.

Four months after renal transplantation for polycystic renal degeneration a 38-year-old man developed breathing-related pain in the left upper lung and a sinus tachycardia (130/min). Lung perfusion scintigraphy demonstrated pulmonary emboli from an acute venous thrombosis of the left lower leg. Polycythaemia and impairment of clot-inhibiting factors were excluded. Ultrasound examination of the abdomen revealed stenosis of the inferior vena cava (IVC) distal to the hepatic veins, dorsal to the liver and ventral of a huge right polycystic kidney which had been left in situ at the time of the renal transplantation. Duplex sonography demonstrated a band-like flow profile in the region of the stenosis. Blood flow was clearly increased (0.62 m/s) and not affected by either heart rate or breathing movements. The findings were confirmed by angiography. The right kidney, weighing 5 kg, was removed at surgery. The IVC stenosis was postoperatively found to be relieved and duplex sonography gave normal findings.

CD4+ memory T cells in peripheral blood are not decreased in patients with atopic dermatitis.

Atopic dermatitis (AD) is a severe and chronic eczematous skin disease, to which increased IgE levels and imbalances of CD4+ T cells are related. CD4+ T cells, however, are heterogeneous and include at least two subpopulations being designated as CD4+ naive and memory T cells. They represent sequential maturational stages (naive into memory) in CD4+ T cell development differing in function and phenotype. Of these two subpopulations the CD4+ memory T cell compartment is a potent producer of gamma-interferon which suppresses IgE synthesis in B cells. Therefore, we speculated whether an inborn maturation defect of CD4+ memory T cells causes the increased IgE production in AD. In patients with AD and age- and sex-matched controls (both n = 10) we analyzed the distribution of both subpopulations in peripheral blood by two-color flow cytometry using monoclonal antibodies against the CD4, CD45RA and CD29 antigen. We provide evidence that the numerical values of CD4+ memory T cells and CD4+ naive T cells are equivalent in both groups. This supports the view that functional disturbances of lymphocytes or lymphocyte subsets are responsible for IgE excess and the pathogenesis of AD.

Measurement of soluble MHC class I molecules in renal graft patients: a noninvasive allograft monitor.

We investigated the biochemistry of naturally occurring major histocompatibility complex (MHC) class I molecules in human serum and established a quantitative enzyme-linked immunoassay (ELISA) to determine soluble human leukocyte antigen (HLA) concentration. Peptides of 46, 40, 37, 35, and 12 kDa were isolated on affinity chromatography columns using two monoclonal antibodies (MoAbs), the anti-heavy chain W6/32 and the anti-beta 2-microglobulin BBM. 1. These peptides were confirmed on Western blots by the HC-10 MoAb, which binds a monomorphic epitope on denatured heavy chains. In detergent-binding experiments, only the 46-kDa peptide could be isolated from solubilized cell membranes. No quantitative differences between serum and plasma HLAs of the same individual were measured. Soluble HLA expression in 12 renal graft recipients was measured over 1-3 mo posttransplantation. A highly significant increase of 50%-100% was noted during rejection episodes. Clinical signs of rejection were accompanied by poor renal function, including elevated creatinine values. After the crises had been managed, class I levels normalized to 0.3-1.5 micrograms/ml, which is the range in healthy persons. Patients who showed no rejection crises maintained constant levels within the period of study. We anticipate the application of soluble HLA measurement in clinical practice as a noninvasive graft monitor.