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Biomedical subjects

K M Koch

Publications and source records attributed to K M Koch.

At least 73 records · Page 4Linked to original sources
PubMed1996

The long-term course of hepatitis C after kidney transplantation.

Patients with chronic hepatitis run the risk of developing progressive liver disease during immunosuppressive therapy after kidney transplantation. To determine the impact of chronic hepatitis C on morbidity and mortality we analyzed 162 anti-HCV positive of 1241 renal-grafted patients (prevalence 13.1%; 84.9% HCV RNA positive) regularly surveyed in our outpatient clinic between 1992 and 1994. The mean age at transplantation was 44.5 (6-69) years, and follow-up after grafting was 7.4 (0.1-23.9) years. The immunosuppressive regimen and frequency of rejection episodes in HCV-infected patients were comparable to the total population. Only 4.3% (5/117) of the anti-HCV positive, HBV negative patients living with functioning grafts developed a markedly compromised liver function. Fifteen (9.3%) of the HCV-infected patients died, but none suffered from posthepatitic cirrhosis. An additional retrospective analysis of causes of death after transplantation prior to 1992 revealed that liver disease had only been responsible for 2% of the deaths (7 of 324) in the HBsAg negative population (n= 1901). In contrast, the predominant cause of death in the HBsAg positive population (n=76) was posthepatitic cirrhosis in 58% (15 of 26). Thus, kidney transplantation in patients with replicative hepatitis C and normal liver function appears to be justified because of low early and late morbidity and mortality due to chronic liver disease. HBV infection and hemosiderosis substantially increase the risk of chronic liver disease in renal transplant recipients with hepatitis C.

Adolescent↗
PubMed1996

Incidence of Pneumocystis carinii pneumonia after renal transplantation. Impact of immunosuppression.

The incidence and potential risk factors of Pneumocystis carinii pneumonia (PCP) in our population of renal transplant recipients were analyzed retrospectively. Of 1427 patients who received transplants between January 1986 and June 1994, 1192 were evaluated. Four different immunosuppressive regimens were applied: (1) cyclosporine (CsA) + prednisolone (Pred), (2) CsA + azathioprine (Aza, 2 mg/kg/day) + Pred, (3) CsA + Aza + antithymocyte globulin, and (4) (after December 1, 1993, European multicenter trial) FK506 + Aza (1 mg/kg/day) + Pred. No prophylaxis against PCP was performed. Before December 1, 1993, three PCPs in 494 patients on protocol 2 or 3 occurred (0.6%). Afterward, seven PCPs in 77 patients occurred (9%): three in 38 patients on protocol 2 (7.8%) and four in 28 patients on protocol 4 (14.3%). Comparing patients with PCP on CsA and FK506, the mean Aza dose was 2.40 and 1.32 mg/kg/day, five and two patients received additional steroids, antibody treatment was used in three and no patients, and CMV infections occurred in five and two patients, respectively. The incidence of PCP with a moderate CsA-based immunosuppressive regimen is low and seems to occur only in cases of additional immunosuppressive cofactors. Despite a general increase of PCP, its incidence was highest in patients on FK506 with fewer immunosuppressive cofactors. Thus, prophylaxis against PCP after renal transplantation should be performed, if not in every renal transplant recipient, at least in case of treatment with additional steroids, antibodies, or FK506.

Adult↗
PubMed1996

How best to use tacrolimus (FK506) for treatment of steroid- and OKT3-resistant rejection after renal transplantation.

Nineteen patients with biopsy-confirmed ongoing acute rejection of renal allografts were converted from standard immunosuppression to FK506. Eight grafts showed vascular rejection and 11 had cellular rejection on biopsy. All patients had already received intravenous high-dose steroid treatment. Ten patients also had additional OKT3 rescue therapy. Initial FK506 doses were 0.13 +/- 0.06 mg/kg/day; the FK506 whole blood trough level after 3 days of treatment was 9.3 +/- 4.5 ng/ml. After conversion to FK506 all but four patients also received azathioprine, 1.5-2 mg/kg/day, and all patients received oral prednisolone. Concomitant with initiation of FK506, an anti-infective prophylaxis was prescribed, consisting of ganciclovir and trimethoprim/sulfamethoxazole. Sixteen out of 19 of the grafts (84%) were rescued successfully, including two grafts of patients already on hemodialysis at the time of conversion. Graft function of the responders improved from an average serum creatinine level of 364 +/- 109 mumol/L to 154 +/- 49 mumol/L. Of the patients receiving high-dose steroids alone prior to FK506 initiation, 8/9 responded to FK506 treatment, compared with 8/10 of those who had also received OKT3. During the mean follow-up of 35 weeks after conversion, no clinically apparent cytomegalovirus infection and no pneumonia were seen. Treatment with FK506 may successfully suppress ongoing acute rejection, even if antilymphocyte preparations have failed. FK506 can be used at a lower dose than so far recommended without impairing the antirejection potential. An additional anti-infective prophylaxis seems effective in preventing severe complications in the first months after rejection therapy.

Adult↗
PubMed1996

High mortality from urothelial carcinoma despite regular tumor screening in patients with analgesic nephropathy after renal transplantation.

Patients with end-stage renal failure due to analgesic nephropathy have an increased risk of developing a urothelial carcinoma. To determine the impact of renal transplantation on the frequency of urothelial carcinomas, we analyzed 2072 patients who underwent 2371 renal transplantation between 1968 and 1993, including 78 (3.8%) with clinically proven analgesic nephropathy. Before and after transplantation a regular tumor screening was performed in patients with analgesic nephropathy by urine cytology and abdominal sonography. In 11 of the 78 patients with analgesic nephropathy (14.1%; age 51-66 years, 40-108 months after initiation of dialysis treatment, 5-77 months after transplantation), a urothelial carcinoma of the native urinary tract, especially the kidneys, was diagnosed. Therapy comprised nephroureterectomy (n = 6), transurethral resection (n = 6) and/or cystectomy (n = 2). Seven patients died due to tumor progression 16.3 (4-33) months postoperatively and one patient died due to a perioperative complication. Despite regular tumor screening after transplantation, the diagnosis of a urothelial carcinoma was made very late, leading to a high tumor-related mortality. As a consequence, we suggest that a bilateral nephroureterectomy should be performed prophylactically in patients with proven analgesic nephropathy. In addition, a cystoscopy with lavage cytology testing of the bladder should be performed twice a year.

Acetaminophen↗
PubMed1996

Mechanisms involved in the pathogenesis of tubulointerstitial fibrosis in 5/6-nephrectomized rats.

The 5/6 nephrectomy model is used to study pathogenetic mechanisms underlying chronic renal failure. We previously demonstrated that increased mesangial cell proliferation and glomerular PDGF B-chain expression precede glomerulosclerosis in this model. In the present study we have assessed the concomitant changes in the cortical tubulointerstitium. A wave of tubular and interstitial cell proliferation (as determined by immunostaining for PCNA) occurred at week 1 after 5/6 nephrectomy. This wave preceded the peak glomerular cell proliferation by one week. Tubulointerstitial cell proliferation decreased thereafter and reached control values by week 10. In situ hybridization and immunostaining for PDGF B-chain and beta-receptor in sham-operated controls showed labeling of distal tubules and collecting ducts, while no signal was present in the interstitium. PDGF B-chain mRNA and protein expression was markedly increased in tubules at weeks 2 and 4 after 5/6 nephrectomy and in the interstitium (particularly in areas of inflammatory infiltrates) at weeks 2 to 10. Similar changes occurred with PDGF receptor beta-subunit immunostaining. Interstitial expression of desmin and alpha-smooth muscle actin (markers of myofibroblasts) progressively increased after week 1. Interstitial influx of monocytes/macrophages with focal accentuation started at week 2. Counts of lymphocytes, neutrophils and platelets showed only minor changes. In parallel to the monocyte/macrophage influx, progressive interstitial accumulation of collagens I and IV, laminin, and fibronectin occurred. All of these changes were correlated with the increase in serum creatinine, proteinuria and an index of tubulointerstitial damage. We conclude that tubulointerstitial changes after 5/6 nephrectomy show similarities with those observed in the glomeruli. Tubular and interstitial overexpression of PDGF B-chain and its receptor may play a role in mediating fibroblast migration and/or proliferation in areas of tubulointerstitial injury.

Actins↗
PubMed1996

Pharmacokinetics of bismuth and ranitidine following single doses of ranitidine bismuth citrate.

1. The pharmacokinetics of bismuth and ranitidine derived from ranitidine bismuth citrate given in single oral doses ranging from 200 mg to 1600 mg were evaluated in healthy subjects. 2. Bismuth was only minimally absorbed (< 0.5% of the amount dosed) after administration of ranitidine bismuth citrate, and peak plasma concentrations never exceeded 33 ng ml-1 in any subject. Plasma concentrations and urinary recoveries of bismuth at doses up to and including 800 mg were relatively constant and not proportional to dose. Bismuth absorption was increased more than proportionally with the dose at 1600 mg. 3. The pharmacokinetics of ranitidine after administration of ranitidine bismuth citrate were dose-proportional and consistent with previous observations for ranitidine administered alone. 4. Ranitidine bismuth citrate was well-tolerated in single oral doses of up to 1600 mg.

Adult↗
PubMed1996

Pharmacokinetics of bismuth and ranitidine following multiple doses of ranitidine bismuth citrate.

1. The pharmacokinetics of bismuth and ranitidine derived from oral doses of ranitidine bismuth citrate 800 mg given twice daily for 28 days were examined in this double-blind, placebo-controlled, parallel-group study in 27 healthy subjects. 2. Bismuth accumulation in plasma reflected its multicompartmental disposition, achieving the majority of predicted steady state within 14-28 days. Bismuth absorption from ranitidine bismuth citrate is limited (< 0.5% of the dose), and bismuth elimination is predominantly renal secretion. Peak plasma concentrations did not exceed 19 ng ml-1, remaining well below those associated with bismuth toxicity. Bismuth was measurable at low concentrations in plasma and urine for up to 5 months after the last dose. Plasma bismuth concentration-time data and urinary excretion data were best described by separate multicompartmental models, with terminal half-lives averaging 21 days and 45 days, respectively. 3. The pharmacokinetics of ranitidine derived from ranitidine bismuth citrate were similar to those of ranitidine administered alone. Ranitidine did not appreciably accumulate in plasma. 4. Ranitidine bismuth citrate was well-tolerated during 28 days of repeated dosing.

Adult↗
PubMed1996

Diagnostic aspects of beta 2-microglobulin amyloidosis.

Osteoarticular symptoms and signs, such as carpal tunnel syndrome, periarthritis humeroscapularis, synovial and joint inflammation, lead to the clinical diagnosis of beta 2-microglobulin (beta 2-M) amyloidosis. Radiologically, destructive arthropathy, spondylarthropathy and periarticular cystic bone radiolucencies can be demonstrated by plain X-ray and conventional and computed tomography. Magnetic resonance is used to visualize amyloid masses in special locations such as the cervical spine. Joint ultrasonography demonstrating thickening of synoviae and tendons has become a useful non-invasive diagnostic tool, although it is not specific for beta 2-M amyloidosis, and results depend on observer experience. Efforts to develop more specific methods for demonstration of amyloid deposits have led to two scintigraphic techniques based on the injection of radiolabelled proteins which are incorporated into the amyloid tissue. One method uses serum amyloid P component, a non-specific constituent of all types of amyloid. An alternative imaging technique based on radiolabelled beta 2-M as the specific precursor molecule of beta 2-M amyloidosis appears to be a more sensitive diagnostic method. Both tracer techniques have been used so far only in small single-centre clinical studies, and a more widespread application will require the introduction of recombinant material as the protein source for labelling. The 'gold standard' for the definitive diagnosis of beta 2-M amyloidosis, and also for reference in the evaluation of new diagnostic techniques, remains the histomorphological demonstration of beta 2-M amyloid by Congo red staining, green birefringence under polarized light, positive immunostaining with anti-beta 2-M antibodies, and electronoptic visualization of amyloid fibrils in tissue obtained invasively by biopsy, surgery or autopsy.

Amyloidosis↗
PubMed1996

Bacterial challenge of NISSHO ultrafilter ETF 609: results of in vitro testing.

In hemodialysis, a certain degree of bacterial contamination on the dialysate side is a regular finding. Concern has been growing that this contamination may lead to a chronic inflammatory response in the patient. Ultrafiltration of dialysate can be used to reduce bacterial content and levels of cytokine-inducing substances upstream of the patient's dialyzer. The aim of this study was to test in vitro the rejection capacity of a polysulfone hollow-fiber ultrafilter (ETF 609, NISSHO Co., Osaka, Japan) challenged with bacterial filtrates derived from Pseudomonas aeruginosa PA103. Results showed a reduction of interleukin-1 beta-inducing activity (measured on peripheral blood mononuclear cells) from 5,035 +/- 394 pg/ml prefilter to nondetectable levels postfilter and endotoxin levels (limulus amebocyte lysate assay) of 4,167 +/- 1,079 versus 12 +/- 2 pg/ml, respectively. In conclusion, ultrafiltration of dialysate with the polysulfone ultrafilter ETF 609 leads to a potent reduction of cytokine-inducing activity.

Endotoxins↗
PubMed1996

No significant influence of HLA determinants on susceptibility to hepatitis C virus infection in Caucasian patients with end-stage renal disease.

In hepatitis C, both susceptibility to infection and the course of disease may depend on differences in the immune response. As the major histocompatibility complex (MHC) plays a crucial role in antigen presentation, we investigated a possible relationship between susceptibility to hepatitis C virus (HCV) infection and human leucocyte antigen (HLA) alleles. Therefore, phenotype frequencies of HLA were compared in 186 anti-HCV positive patients with end-stage renal disease (ESRD) to 328 anti-HCV negative patients with ESRD. HLA class I alleles were determined serologically and HLA class II alleles (DRB1, DQA1, DQB1) by the polymerase chain reaction sequence-specific oligonucleotide (PCR-SSO) technique. Additionally, in anti-HCV positive patients we looked for a relationship between the activity of hepatitis C (indicated by elevation of transaminases or the presence of viremia) and HLA determinants. For the three criteria (antibody status, elevation of transaminases and viremia) a significant association to HLA alleles was not found in patients with ESRD. This suggests that neither susceptibility to HCV infection nor the biochemical activity of hepatitis and HCV-RNA positivity seem to be strongly related to HLA status in Caucasian patients with end-stage renal disease.

Adult↗
PubMed1996

Urodilatin is involved in sodium homeostasis and exerts sodium-state-dependent natriuretic and diuretic effects.

Urodilatin is involved in sodium homeostasis exerts sodium-state-dependent natriuretic and diuretic cts. Eight male volunteers participated in a study consisting of three consecutive phases of 7 days each. The volunteers a sodium diet with 52, 172.6, and 347.8 mmol um/day. Sodium excretion increased from 57.4 +/- 3.7 via .8 +/- 4.6 (P < 0.001) to 322.5 +/- 10.2 mmol/24 h (P < 0.001) at the end of each sodium diet. Urinary urodilatin excretion increased from 24.8 +/- 3.0 via 35.5 +/- 9.0 (P = 0.07) to 49.0 = mol/min (P < 0.01). At the end of each diet, urodilatin was infused for 2 h at 20 ng.kg body wt-1.min-1. Natriuresis increased after low- (4.1 to 52.9 mmol/h, P < 0.001), normal (6.9 to 44.9 mmol/h, P < 0.05), and high-sodium diet (20.1 to 102.9 mmol/h, P < 0.001). Diuresis increased from 174 to 709 (P < 0.001), 395 to 1,026 (P < 0.05), and 266 to 1,339 ml/h < 0.001). The present results indicate that endogenous urodilatin plays an important role in sodium homeostasis and that renal response to exogenous urodilatin is modulated by sodium balance.

Adaptation, Physiological↗
PubMed1996

Retention of cytokine-inducing substances inside high-flux dialyzers.

Reprocessing of dialyzers is often performed with nonsterile solutions possibly contaminated with bacterial-derived cytokine-inducing substances. We investigated the retention of cytokine-inducing substances inside the dialyzer during reprocessing in a closed loop in vitro hemodialysis system using a polyamide high flux membrane. After the first in vitro circulation of human whole blood, rinse of the blood compartment (BC) and reverse ultrafiltration (RUF) was performed with either cytokine-inducing substance-free saline or saline contaminated with filtrates from Pseudomonas cultures (6 ng/ml LAL-reactive material); subsequently, dialyzers were stored in 2% formaldehyde. Dialyzers were rinsed with approximately 15 liters pyrogen-free saline before the second circulation using blood from the same donor; the effluates were free of cytokine-inducing substances and formaldehyde. Before and after the blood circulations, peripheral blood mononuclear cells (PBMC) were separated and total production of IL-1 alpha and IL-1 beta was determined after overnight incubation. In noncirculated PBMC as well as in PBMC separated after whole blood circulation with pyrogen-free processed dialyzers, production of IL-1 beta was not detectable. After contaminated rinse of the BC, production of IL-1 beta could be observed (1,600 +/- 1,100 pg/ml, mean +/- SEM). When pyrogen-free RUF was performed after contaminated BC rinse, IL-1 beta production averaged 163 +/- 92 pg/ml when using reused dialyzers, but 1,820 +/- 880 pg/ml when using new dialyzers. After reuse with pyrogen-free BC-rinse and contaminated RUF no IL-1 beta synthesis was observed; however, when pyrogen-free BC-rinse and contaminated RUF was applied to new dialyzers, IL-1 beta synthesis averaged 1,620 +/- 1,200 pg/ml. We conclude that cytokine-inducing substances are retained inside the dialyzer, probably by adsorption to the membrane as well as to the protein layer covering the membrane and are still biologically active after sterilisation. Cytokine-inducing substances adsorbed to the protein layer can be partially removed by RUF. Finally, the protein layer on the membrane appears to reduce the convective transfer of cytokine-inducing substances from the dialysate into the blood compartment.

Bacteriological Techniques↗
PubMed1996

Long-term performance of hemofilters in continuous hemofiltration.

We measured the filter performance of six polyamide hemofilters with a running time exceeding 72 h applied for continuous hemofiltration in intensive care patients. The sieving coefficients for urea and creatinine were close to unity and remained constant. The sieving coefficient of polyfructosan (mean molecular weight 3 kD) was around 0.75 and did not change with running time. The hydraulic permeability remained also unchanged. The relationships between blood pressure and blood flow and between blood flow and filtration rate remained linear, and the gradient did not change with time. We conclude that a daily routine change of polyamide hemofilters applied in continuous arteriovenous hemofiltration and presumably in continuous venovenous hemofiltration is not necessary within the first 72 h of treatment, unless a major decrease in the filtration rate occurs.

Acute Kidney Injury↗
PubMed1996

Recurrence of membranoproliferative glomerulonephritis after renal transplantation in a patient with chronic hepatitis C.

Chronic hepatitis C (HCV) infection may be associated with membranoproliferative glomerulonephritis (MPGN) with or without concomitant cryoglobulinemia. We report on a patient with end-stage renal disease caused by MPGN I in association with replicative HCV infection. Two years after successful renal transplantation, this patient developed nephrotic syndrome caused by recurrence of MPGN I in the renal transplant. The recurrence of renal disease after transplantation in this patient with chronic replicative HCV further elucidates the role of the viral infection in the pathogenesis of MPGN and suggests anti-viral treatment as, e.g., with interferon.

Adult↗
PubMed1996

Relationship between human leukocyte antigen determinants and courses of hepatitis B virus infection in Caucasian patients with end-stage renal disease.

BACKGROUND: Divergent results have been reported with regard to the relationship between the course of hepatitis B virus (HBV) infection and the human leukocyte antigen (HLA) determinants. The aim of the present study was to investigate the phenotype frequencies of HLA class-I and -II alleles in Caucasians with and without HBV infection. METHODS: Fifty-eight patients with persistent HBV infection (group 1), 119 patients with resolved HBV infection (group 2), and 106 patients neither infected by HBV nor vaccinated against HBV (group 3) were analyzed. All patients had end-stage renal disease. HLA class-I antigens were serologically determined. For HLA class-II typing we performed DRB1, DQA1, and DQB1 genotyping using a polymerase chain reaction-sequence-specific oligonucleotide procedure. RESULTS: Compared with group 2, group 1 showed increased frequencies of HLA-B8, DR3 (P < 0.05), A30, DQA1*0501 (P < 0.01), and a decreased frequency of HLA-B12 (P < 0.05). Decreased frequencies of HLA-B27, B40, DR13, and DQ1*0604 (P < 0.05) and an increased frequency of HLA-B35 (P < 0.05) were found in groups 1 and 2 compared with controls (group 3). None of the differences detected in the phenotype frequencies of HLA alleles were statistically significant after correction. CONCLUSIONS: We conclude that the susceptibility to HBV infection and the different courses of HBV infection are not strongly related to HLA status in Caucasians.

Adult↗
PubMed1996

Induction of interleukin-1 and interleukin-1 receptor antagonist during contaminated in-vitro dialysis with whole blood.

BACKGROUND: Previous studies on the permeability of cellulosic and synthetic dialysers for bacterial-derived cytokine-inducing substances gave conflicting results. We tried to study this issue as close to the in-vivo situation as possible. METHODS: An in-vitro dialysis circuit with whole human blood present in the blood compartment of cuprophane (Cup), polysulphone (PS), and polyamide (PA) dialysers was employed; sterile filtrates derived from Pseudomonas aeruginosa cultures were added to the dialysate. We studied the induction of interleukin-1 beta (IL-1 beta) by plasma samples taken from the blood compartment as well as the induction of IL-1 beta and interleukin-1 receptor antagonist (IL-1Ra) in mononuclear cells separated from whole blood after circulation by radioimmunoassay and polymerase chain reaction. RESULTS: Plasma samples from the blood side of all dialysers induced IL-1 beta from non-circulated mononuclear cells after addition of pseudomonas filtrates to the dialysate; the maximal amount of IL-1 beta induced by samples from the blood compartment was 4.8 +/- 1.2 ng/ml for Cup, 1.9 +/- 0.5 ng/ml for PS, and 2.0 +/- 0.6 ng/ml for PA. Mononuclear cells separated after contaminated dialysis will all types of dialysers expressed increased mRNA levels for IL-1 beta and IL-1Ra. Production of IL-1Ra by cells separated after contaminated dialysis was determined after Cup and PS dialysis; there was increased production of IL-1Ra by these cells (Cup, 10.3 +/- 4.2; PS, 7.3 +/- 2.5 ng/ml) compared to cells separated after sterile dialysis (Cup, 5.6 +/- 2.1, P < 0.05; PS, 4.5 +/- 1.1 ng/ml, n.s.) or from non-circulated blood (Cup experiments, 4.7 +/- 1.5, P < 0.05; PS experiments, 4.1 +/- 1.2 ng/ml, n.s.). CONCLUSIONS: These data suggest penetration of cytokine-inducing substances through both cellulosic and synthetic dialysers. Differences between dialysers may exist regarding extent and time course of penetration. The detection of cytokine mRNA as well as the measurement of IL-1Ra synthesis is a more sensitive marker for the transfer of cytokine-inducing substances through dialyser membranes than the measurement of IL-1 beta protein synthesis.

Base Sequence↗