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Biomedical subjects

W Weimar

Publications and source records attributed to W Weimar.

At least 181 records · Page 10Linked to original sources
PubMed1996

Intragraft IL-4 mRNA expression is associated with down-regulation of liver graft rejection.

The mechanism underlying spontaneously resolving allograft rejection following clinical liver transplantation is unidentified. In this process, immunoregulatory T helper (Th)-2 cytokines like IL-4, often identified with down-regulation of the Th1-dependent (IL-2) cell-mediated response, might play a significant but unknown role. For this reason, we analyzed mRNA expression by reverse transcriptase-polymerase chain reaction (RT-PCR) in 57 biopsies derived from 19 recipients. Specimens included biopsies without evidence of rejection (n = 36), biopsies with histological evidence of rejection (n = 10) not followed by clinical signs of graft rejection, and biopsies with histological rejection that were accompanied with clinical rejection (n = 11), defined by rising serum bilirubin and aspartate amino transaminase (ASAT) levels. Intragraft IL-4 mRNA expression significantly correlated with spontaneously resolving rejections. In 70% (7/10) of these biopsies, IL-4 mRNA was detectable, while only 19% (7/36) of the biopsies without signs of rejection (p < 0.01; Fisher's exact test) and 18% (2/11) of the rejection biopsies concurrent with graft dysfunction expressed the IL-4 gene (p = 0.03). In contrast, IL-2 mRNA expression was not detectable in biopsies derived from the spontaneously resolving rejections. None (0/10) of these samples expressed the IL-2 gene, which was not significantly different from the proportion of biopsies transcribing the IL-2 gene in the absence of rejection (11%, 4/36). IL-2 mRNA expression was found more often in biopsies associated with graft dysfunction (36%, 4/11). These results show that IL-4, in contrast to IL-2 mRNA expression, is associated with spontaneously resolving liver rejection. This suggests that Th2 cells down-regulate the Th1-dependent cell-mediated immune response after clinical liver transplantation.

Aspartate Aminotransferases↗
PubMed1995

A double-blind, placebo-controlled study of monoclonal anti-interleukin-2 receptor antibody (BT563) administration to prevent acute rejection after kidney transplantation.

In a double-blind, randomized, placebo-controlled trial, BT563, a murine IgG1 anti-IL-2R antibody, was given as a rejection prophylaxis after kidney transplantation. Drug-related side effects were not observed. During the 10-day course of BT563, no rejections (0/27) were found, whereas a rejection episode occurred in 7 patients (7/29) (P = 0.01) during placebo treatment. Within the first 4 postoperative weeks, freedom from rejection in the BT563 group and in the placebo group was 96% vs. 76% (P = 0.05). Due to rejection in the placebo group, 2 grafts were lost. At 3 months, an overall rejection incidence in the BT563 and placebo group was found of 3/27 (11%) vs. 8/29 (28%) patients (P = 0.18). Infectious complications were distributed equally between the 2 groups. CMV disease, found in 3 placebo-treated patients, occurred after rejection treatment (2/3). Within the BT563 group, 1 patient lost his graft due to renal artery thrombosis, 2 grafts were lost as a result of technical failure, and 2 patients had a squamous cell carcinoma that could be treated curatively. We conclude that the use of the anti-IL-2R mAb BT563 effectively prevents rejection after kidney transplantation without increasing infectious complications.

Acute Disease↗
PubMed1995

Effects of 24R,25-dihydroxyvitamin D3 in combination with 1 alpha-hydroxyvitamin D3 in predialysis renal insufficiency: biochemistry and histomorphometry of cancellous bone.

The effect of combined administration of 24R,25-dihydroxyvitamin D3 (24,25-(OH)2D3) and 1 alpha-hydroxyvitamin D3 (1 alpha-(OH)D3) was studied in 24 non-dialyzed patients with chronic renal insufficiency (CRI), matched pairwise as to age, sex, and creatinine clearance (Cr.cl). Low Ca intake had been supplemented beforehand. Then, 1 alpha-(OH)D3 (mean dose 0.55 micrograms daily) was given orally to all patients for 3 months (T0 to T3). Subsequently, patients were assigned randomly to 6 months further treatment either with 1 alpha-(OH)D3 alone (Group A) or with 1 alpha-(OH)D3 plus a high dosage of 24,25-(OH)2D3 (50 micrograms orally, twice weekly) (Group B). Histomorphometry was performed at T0, T3, and T9. In both groups iPTH was equally suppressed, into the lower normal range. Whereas in Group A, serum Ca rose steadily and Cr.cl declined, in Group B both parameters levelled off between T6 and T9. At T9, in Group A the elevated resorption and osteoid indices had normalized markedly, but osteoblasts (Ob.Pm) and mineralizing boundaries (M.Bd) were depressed considerably between T3 and T9. In contrast, in Group B, preservation of Ob.Pm and improved mineralizing activity were observed (M.Bd at T9 > T3 > T0). Resorption indices hardly changed. In the patients with high Ob.Pm at T0, cancellous bone area increased significantly. This was not observed in Group A. Thus, in Group B, osteoblast recruitment appeared maintained and M.Bd appeared normalized. Decline of remodeling toward an adynamic state with an increased risk of hypercalcemia appeared prevented.

24,25-Dihydroxyvitamin D 3↗
PubMed1995

Stimulation of immune-competent cells in vitro by human cardiac valve-derived endothelial cells.

Both fresh and cryopreserved human cardiac valve allografts are transplanted without matching donor and recipient for blood group or human leukocyte antigens (HLA) and without the usual immunosuppressive therapy that follows organ transplantation. Calcification occurs in almost all transplanted valves, and in children acute valve failure is frequently seen. We hypothesized that failure of the human valve allografts could have an immunologic basis. This hypothesis was tested in a functional way by performing lymphocyte stimulation assays using fresh and cryopreserved valve pieces and endothelial cells derived from valve leaflets as stimulator. Human peripheral blood lymphocytes, both matched and mismatched for HLA antigens, were used as responder cells. The results were expressed as the stimulation index. Fresh valve pieces induced a significantly higher stimulation index (median, 9; range, 4 to 117) compared with the cryopreserved pieces (median, 2; range, 0 to 9; p = 0.002 by Wilcoxon test). The stimulation index was significantly reduced when lymphocytes matched for HLA-DR with the valve pieces were used (median, 1; range, 0 to 5) as compared with the HLA-DR-mismatched combination (median, 4; range, 2 to 117; p = 0.006, Wilcoxon test). Valve leaflet-derived endothelial cells were able to induce a median stimulation index of 8 (range, 3 to 15) when incubated with lymphocytes mismatched for HLA-A, -B, and -DR. In conclusion, stimulation of immune-competent cells in vitro is induced by both fresh and cryopreserved human valve pieces and by endothelial cells derived from fresh valve leaflets. The immune response can be reduced by using cryopreserved valves or by matching valve donor and responder lymphocytes for HLA-DR.(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic Valve↗
PubMed1995

Pharmacodynamics of prophylactic antirejection therapy with an anti interleukin-2 receptor monoclonal antibody (BT563) after heart and kidney transplantation.

A mouse monoclonal antibody (BT563) directed to the alpha-chain of the IL-2 receptor was administrated immediately after transplantation in a dose of 10 mg/day prophylactically to 30 heart transplant recipients (HTx) and 40 renal transplant recipients (RTx) to induce immunosuppression. Plasma levels increased to a plateau level of 5300 ng/ml in HTx and 5900 ng/ml in RTx. BT563 plasma disappearance curves gives a mean T1/2 of respectively 39 h (range 14-112 h) and 42 h (range 8-122 h) for HTx and RTx respectively. The CD25 marker (IL-2R) on the peripheral blood lymphocytes disappeared within hours after the first gift and returned to normal within 0-20 days after the last gift. In HTx more often CD25+ cells were found in the presence of BT563 and more rejections occurred shortly after discontinuation of BT563 compared to the RTx group. Rejectors and non-rejectors within the HTX group did not differ with respect to the period of depletion of CD25 positive cells in the peripheral blood. In 56% of the patients a substantial IgM antibody response was detected. This response was similar for HTx and RTx and not related to rejection. The frequency of IgG responses was low in both HTx (13%) and RTx (21%) patients and the IgG response was not related with graft rejection or with antirejection treatment. Peripheral monitoring showed that mAb plasma levels, antimurine antibody responses and number of CD25 positive cells were not related with the clinical results. The mAb BT563 proved to be safe with respect to the generation of antimurine antibodies and, when given in combination with CsA, is a therapy with a potential for high efficacy.

Animals↗
PubMed1995

Fever and rigors as sole symptoms of azathioprine hypersensitivity.

The case history of a haemodialysis patient with fever and rigors is presented. This diagnostic problem turned out to be a hypersensitivity reaction to azathioprine, with identical complaints recurring after a rechallenge with azathioprine, findings which resolved on discontinuation of this drug. The more extended indications for use of azathioprine warrant attention to the possibility of side-effects like drug fever.

Azathioprine↗
PubMed1995

Acute dialytic support for the critically ill: intermittent hemodialysis versus continuous arteriovenous hemodiafiltration.

There is still debate about whether continuous renal replacement therapy is superior to intermittent hemodialysis (IHD) as dialytic support for the critically ill patient with acute renal failure, mainly because of lack of comparative data. We sought to address this issue by reviewing the medical records of such patients admitted to a single surgical intensive care unit treated with either continuous arteriovenous hemodiafiltration (CAVHD) or IHD between January 1, 1986, and August 31, 1993. Of 94 consecutive patients who received dialytic support for severe acute renal failure, 34 (36%) patients were treated with IHD and 60 (64%) patients with CAVHD. The patients were comparable in terms of age or gender and represented a similar case mix. Patients treated with CAVHD were more severely ill as manifested by a lower mean arterial pressure (75 +/- 3 vs. 86 +/- 5 mm Hg; p < 0.05), higher Apache II score (26.5 +/- 0.5 vs. 22.2 +/- 0.3; p < 0.05), and a higher number of organ system failures (3.4 +/ 0.2 vs. 2.6 +/- 0.3; p < 0.05). Despite greater illness severity and a higher probability of death (55 +/- 2.6 vs. 33 +/- 2.5%; p < 0.0001), in those treated with CAVHD, no difference in outcome was observed between groups: CAVHD 26/60 (43%) vs. IHD 20/34 (59%; NS). The mean Apache II score of patients treated with CAVHD who survived was similar to that of patients treated with IHD who died (24.5 +/- 0.3 vs. 24.2 +/- 0.4; NS).(ABSTRACT TRUNCATED AT 250 WORDS)

APACHE↗
PubMed1995

High-risk surgical acute renal failure treated by continuous arteriovenous hemodiafiltration: metabolic control and outcome in sixty patients.

The outcome and metabolic control was studied in 60 critically ill patients with acute renal failure (ARF) treated by continuous arteriovenous hemodiafiltration (CAVHD) in a single surgical intensive care unit. Mean age (+/- SEM) was 60 +/- 2 years with a male predominance (80%). The majority of patients required mechanical ventilation (83%) and/or vasopressor support (70%) and suffered from multiorgan failure [mean number of organ system failures 3.3 +/- 0.3 (range 1-6)]. CAVHD resulted in a rapid decline of serum urea and creatinine levels during the first 72 h (urea 47.4 +/- 2.3 to 30.3 +/- 1.4 mmol/l, p < 0.05, and creatinine 572 +/- 27 to 361 +/- 23 mumol/l, p < 0.05); thereafter, controlled steady-state levels were achieved with serum urea levels kept below 30 mmol/l with full protein alimentation and often despite hypotension, surgery and septicemia. Significant electrolyte derangements could be easily corrected and maintained within normal limits. Bicarbonate homeostasis could be restored within 48 h in patients with severe metabolic acidosis (HCO3- < 20 mmol/l) with use of bicarbonate as a buffering anion (17 +/- 0.5 to 23.2 +/- 0.6, p < 0.05). CAVHD allowed rapid removal of excess body and lung water (up to 5 liters/day) without hemodynamic instability. Despite a mean pretreatment APACHE II score of 26.5, 26 patients (43%) survived until discharge from the intensive care unit, of whom 23 (38%) survived to leave hospital. Requirement of mechanical ventilation or vasopressor support, higher APACHE II scores and septicemia were all associated with a poor prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)

APACHE↗
PubMed1995

Heme synthesis in chronic renal failure: the effects of hemodialysis, peritoneal dialysis and erythropoietin treatment.

UNLABELLED: Increased plasma porphyrins have been described in patients with chronic renal failure (CRF). We measured plasma levels of porphyrins and the activity in erythrocytes of porphobilinogen deaminase (PBG-D), one of the key enzymes in heme biosynthesis, in CRF patients not yet on dialysis and in patients on intermittent hemodialysis (IHD) or chronic ambulatory peritoneal dialysis (CAPD), some of whom were being treated with recombinant human erythropoietin (rHuEPO). In addition, the amount of immuno-detectable PBG-D (Ig PBG-D) per 100 units standard PBG-D activity (Ig PBG-D/100 U) and the total amount of Ig PBG-D, using polyclonal antibodies, were determined in erythrocytes of all patients and controls to detect changes in biodegradation of this enzyme. Plasma porphyrins were increased in CRF patients not yet on dialysis and even higher in both patient groups on dialysis compared with controls. Plasma porphyrins were higher in patients on IHD than in patients on CAPD. The activity of PBG-D was increased and Ig PBG-D/100 U was decreased in patients on IHD compared with CRF patients not yet on dialysis and patients on CAPD. Reticulocyte counts were also greater in patients on IHD than in CRF patients not yet on dialysis and patients on CAPD. Ig PBG-D was increased in both groups of patients on dialysis and treated with rHuEPO compared with patients not treated with rHuEPO. IN CONCLUSION: (1) in patients on IHD, an increased production of porphyrins is, at least partly, caused by an increased PBG-D activity, and (2) an increased PBG-D activity and a decrease in Ig PBG-D/100 U in patients on IHD could be explained by the presence of a (relatively) young erythroid cell population in which a larger part of PBG-D has not yet been degraded.

Adult↗
PubMed1995

Effect of atrial natriuretic peptide on renal and vascular permeability in diabetes mellitus.

Synthetic human atrial natriuretic peptide (ANP) (102-126) 0.01 microgram/kg per minute or vehicle was intravenously infused for 2 h in 10 patients with insulin-dependent diabetes mellitus and microalbuminuria (albumin excretion, 20 to 200 micrograms/min) and in 10 healthy subjects. In the diabetic group, the immunoglobulin G clearance was higher, but both size index and charge index as calculated from albumin and immunoglobulin clearances were equal compared with normal values. The fractional clearances of small dextrans (< 3.6 nm) were lower in diabetics, which was compatible with a depressed hydraulic permeability (Kf). During ANP infusion, the excretion of albumin and immunoglobulin G increased in the diabetic subjects (189 +/- 12 to 521 +/- 84 and 7.1 +/- 3.5 to 21 +/- 8.1 micrograms/min, respectively; both P < 0.05) only. In the diabetics, the clearance of dextrans > 54 A increased and our calculations indicated an increase in "shut-flow" (omega o). The transcapillary escape rate of albumin, which was elevated in the diabetics at baseline, increased in the diabetic group only. Thus, ANP uncovers altered size selectivity of the filtration barrier in a phase that is otherwise characterized by charge-selective changes only. Moreover, the increased susceptibility of the glomerular capillaries in diabetics to ANP seems to be part of a more generalized capillary abnormality, because ANP also increases the transcapillary escape of albumin.

Adult↗
PubMed1995

Use of APACHE II classification to evaluate outcome and response to therapy in acute renal failure patients in a surgical intensive care unit.

The study objective was to determine the applicability of the acute physiology and chronic health evaluation (APACHE) II score in surgical patients with acute renal failure (ARF) requiring dialytic support, and to assess its utility in evaluating data from this specific disease group. This was a retrospective, partly prospective follow-up study of patients who developed ARF during their course of stay on the surgical intensive care unit (ICU) of a Dutch university hospital from January 1, 1986, to January 31, 1994. A total of 111 patients were identified, of whom 104 patients were considered eligible for this study. Data for the individual APACHE II scores were calculated from the most deranged values during the initial 24 h of ICU admission (APACHE II1) and on the day dialytic support was instituted (APACHE II2). The ratio between the two APACHE II scores was also calculated for each patient (AP2/AP1 ratio). Receiver operating characteristic curves (ROC) were constructed. Other variables evaluated included age, sex, serum creatinine, diagnostic category, time from ICU admission to start of dialytic support, and the type of dialytic support. Of these 104 patients (median age 64; range 23-85 years), 51 (50%) survived to leave the ICU, of whom 47 (46%) survived to leave hospital. The APACHE II2 score (27.0 +/- 4.4 vs. 22.4 +/- 3.5; p < 0.001) and AP2/AP1 ratio (1.12 +/- 0.09 vs. 0.97 +/- 0.06; p < 0.001) were significantly higher for nonsurvivors as compared to survivors. The ROC curve was most discriminative for the AP2/AP1 ratio (area under the curve 0.92) and to a lesser extent for the APACHE II2 score (area under the curve 0.78). Estimated risk of death with the APACHE II equation did not improve predictive power. Multivariate analysis of various variables revealed the AP2/AP1 ratio as the single most important factor predicting death (odds ratio 13.8, p < 0.001). Adjusting for the AP2/AP1 ratio, no impact on outcome was observed for age, diagnostic category, time from ICU admission to start of dialytic support, and the type of dialytic support. Above a value of 1.0 of the AP2/AP1 ratio, logistic regression revealed a sharp increase in death probability with increasing AP2/AP1 ratio. APACHE II, when used at the time of initiation of dialytic support, proved to be a valid way in our surgical ICU to stratify ARF patients by the severity of their illness. Moreover, use of the AP2/AP1 ratio further improved the usefulness of this severity index and may help to identify patients who have little chance of survival. Predicting death with the APACHE II equation did not improve predictive power.

APACHE↗
PubMed1995

Optimising glomerular filtration rate and effective renal plasma flow measurements using a simple pharmacokinetic model.

We applied an open one compartment pharmacokinetic model for the determination of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) based on a rapid intravenous loading dose followed by a constant infusion of 125I-iothalamate and 131I-orthoiodohippurate in order to ensure constant plasma levels of the two clearance markers. The loading dose was based on the assumption that the volume of distribution of the two markers equals the extracellular volume (25% of the body weight). The infusion rate as calculated after the clearance of thalamate was estimated from body weight, age, sex and serum creatinine using Cockcrofts formula. The clearance of hippurate was assumed to be four times that of thalamate. We studied the reliability of this model in 212 patients with insulin dependent diabetes mellitus (IDDM; n = 74), nephrotic syndrome (NS; n = 18) and heart (HTX; n = 69) or kidney (KTX; n = 51) transplants. A steady state concentration was obtained in all patient groups, even when GFR was markedly depressed. In patients with diabetes, we observed more variance between plasma and urinary clearances of thalamate, which could be due to inaccuracies in urine sampling. In these patients, GFR should be measured using a method that is not dependent on urine collection. Also, the estimation of GFR by means of Cockcrofts equation seems to underestimate GFR in diabetic subjects.

Glomerular Filtration Rate↗