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Biomedical subjects

K Wagner

Publications and source records attributed to K Wagner.

At least 181 records · Page 10Linked to original sources
PubMed1995

A multicenter, randomized, double-blind, placebo-controlled, two-year trial to study the effect of nitrendipine on chronic renal transplant function.

The ongoing multicenter, randomized, double-blind, placebo-controlled trial investigates the effect of nitrendipine on kidney function after renal transplantation. Renal transplant recipients (6th-12th postoperative week, serum creatinine < 3 mg/dl) were divided into a normotensive (diastolic blood pressure < 90 mmHg) and a hypertensive group (diastolic blood pressure > or = 90, < 115 mmHg). Normotensive patients are randomly treated for 104 weeks with nitrendipine 2 x 5 mg daily or placebo, hypertensive patients with 2 x 10 mg - 2 x 20 mg nitrendipine daily or placebo and in case of inefficacy with additional antihypertensive drugs. Primary end point of the study is the renal transplant function. The trial was started in June 1990. One hundred and eight patients were included into the normotensive and 138 patients into the hypertensive group. Renal allograft function, cyclosporine trough levels and the donor characteristics were not different between the normotensive and hypertensive groups at entry into the study. After 12 months there was no significant change of renal transplant function in both groups. Cyclosporine trough levels were also similar in the normotensive and hypertensive group after 12 months. As expected, blood pressure decreased significantly after 12 months from 150 +/- 17/95 +/- 11 mmHg to 141 +/- 16/90 +/- 9 mmHg in the hypertensive group (p < 0.01). In contrast, in the normotensive group blood pressure increased significantly from 128 +/- 12/80 +/- 6 mmHg to 135 +/- 15/86 +/- 8 mmHg (p < 0.001). No normotensive but 4 hypertensive patients developed graft failure during the first 12 months of the study.

Adolescent↗
PubMed1994

[The effect of obesity on outcome of kidney transplantation].

BACKGROUND AND AIM: Obesity is a risk factor for postoperative complications in surgery. In a retrospective study we investigated the course of body weight during the waiting period and the first postoperative year and the influence of obesity on graft function. PATIENTS AND METHOD: The medical records of 334 adult patients undergoing cadaveric kidney transplantation between 1986 and 1992 were reviewed. Immunosuppression was performed with cyclosporine and prednisone. For all patients the Broca index was calculated with the relative body weight by the formula: body weight/Broca index x 100 (% BI). Obesity was defined as relative body weight > or = 120% BI. RESULTS: At the time of the indication for kidney transplantation 15.3% of the patients were obese. Only 12 of these 51 obese patients reduced their body weight below 120% BI until transplantation, whereas 25 patients increased weight in excess of 120% BI. Thus the number of obese patients raised to 19.2% by the time of transplantation. The graft survival in the obese group was significantly lower than in the nonobese group. This difference appeared already in the first half year after transplantation being constant in the following time. The resulting 1-year graft survival was 82.8% and 91.4% respectively (p < 0.05). During the first year 59 patients more became obese, the percentage of obese raised up to 36.0%. One year after transplantation there was no longer significant difference of graft survival rate in the further follow-up between obese and nonobese patients. CONCLUSION: Our findings show, that obesity is an important risk factor for early graft loss. Therefore all participating physicians assume a great responsibility for the pre-operative treatment during the waiting time.

Adult↗
PubMed1994

Neutralizing monoclonal antibodies define two different functional sites in human interleukin-4.

Human interleukin-4 (IL-4) is a small four-helix-bundle protein which is essential for organizing defense reactions against macroparasites, in particular helminths. Human IL-4 also appears to exert a pathophysiological role during various IgE-mediated allergic diseases. Seven different monoclonal antibodies neutralizing the activity of human IL-4 were studied in order to identify functionally important epitopes. A collection of 41 purified IL-4 variants was used to analyse how defined amino acid replacements affect binding affinity for each individual mAb. Specific amino acid positions could be assigned to four different epitopes. mAbs recognizing epitopes on helix A and/or C interfered with IL-4 receptor binding and thus inhibited IL-4 function. However, other mAbs also inhibiting IL-4 function recognized an epitope on helix D of IL-4 and did not inhibit IL-4 binding to the receptor protein. One mAb, recognizing N-terminal and C-terminal residues, partially competed for binding to the receptor. The results of these mAb epitope analyses confirm and extend previous data on the functional consequences of the amino acid replacements which showed that amino acid residues in helices A and C of IL-4 provide a binding site for the cloned IL-4 receptor and that a signalling site in helix D interacts with a further receptor protein.

Amino Acid Sequence↗
PubMed1994

Transfected Chinese hamster ovary cells as a model system for cytokine immunocytochemistry and in situ hybridisation.

The presence of cytokine producing cells is most easily revealed by techniques measuring the secreted cytokines in culture supernatants or body fluids. However, these techniques only measure the bulk cytokine release by a given, often mixed cell population. To demonstrate cytokine production at the single cell level, immunocytochemistry (ICC) and in situ hybridisation (ISH) are now widely used techniques. To establish these techniques, an easily accessible model system is needed which permits the evaluation of different ICC and ISH protocols. It can be used to demonstrate the specificity of the antibodies and may serve as a positive control for samples of unknown cytokine content. Here we propose the use of Chinese hamster ovary (CHO) cells transfected to express one specific cytokine as such a model system. Its usefulness is demonstrated by the characterisation of six monoclonal antibodies to human interleukin-4 and the establishment of two in situ hybridisation protocols.

Animals↗
PubMed1994

Effect of sepsis on mucosal protein synthesis in different parts of the gastrointestinal tract in rats.

1. In a previous study we found that the protein synthesis rate was increased by 50-60% in the mucosa of the jejunum and ileum during sepsis in rats. It is not known if sepsis affects protein turnover in other parts of the gastrointestinal tract as well. 2. In the present study, the influence of sepsis on mucosal protein synthesis in different parts of the gastrointestinal tract, from the stomach to the rectum, was determined in rats. 3. Sepsis was induced by caecal ligation and puncture; control rats underwent sham-operation. Protein synthesis rate was measured in vivo after administration of a flooding dose of [14C]leucine. 4. Basal mucosal protein synthesis rates were lower in the colon than in the rest of the gastrointestinal tract. Sixteen hours after caecal ligation and puncture, the protein synthesis rates were increased by 40-85% in the mucosa of the small and large intestine and the rectum, whereas in the gastric mucosa, the protein synthesis rate was reduced by approximately 40%. 5. The results suggest that mucosal protein synthesis rates differ in the various regions of the gastrointestinal tract, and that the metabolic response to sepsis is different in the stomach than in the rest of the gastrointestinal tract. The finding of a reduced protein synthesis rate in the gastric mucosa may partly explain the tendency to gastric stress ulcers and bleeding seen clinically in sepsis.

Animals↗
PubMed1994

Quantitative cerebrospinal fluid acid-base balance in acute respiratory alkalosis.

Data on canine cisternal cerebrospinal fluid (CSF) ions in acute respiratory alkalosis are limited and fragmentary. We hypothesized that with the fall in arterial PCO2 (PaCO2) and in the face of normal osmoregulation, CSF [Na+] remains relatively constant and CSF [Na+-Cl-] narrows to account in part for the fall in CSF [HCO3-]. We therefore measured blood and CSF acid-base variables and ions of two groups of pentobarbital-anesthetized, mechanically ventilated dogs (n = 10 in each group). In the control group, PaCO2 was kept constant and changes in serum and CSF ions were minimal. In Group II (acute respiratory alkalosis), both PaCO2 and cisternal CSF PCO2 decreased by 10 mm Hg. Five hours after induction of respiratory alkalosis, mean CSF [HCO3-] decreased significantly by 4.4 +/- 1.2 mEq/L (mean +/- SD). The fall in CSF [HCO3-] was similar to changes in CSF strong ion difference (SID = Na(+)+K(+)+Ca(2+)+Mg(2+)-CL(-)-lactate), which decreased 4.4 +/- 1.9 mEq/L. Concentrations of the four major CSF cations did not change significantly. Cisternal CSF lactate rose significantly by 1.2 +/- 0.9 mEq/L, accounting for 25% of the change in CSF [HCO3-]. The remaining (75%) change in CSF [HCO3-] was accounted for by changes in CSF [Cl-].

Acid-Base Equilibrium↗
PubMed1994

A sporadic form of hereditary neuropathy with liability to pressure palsies: clinical, electrodiagnostic, and molecular genetic findings.

We report a patient who had episodes of recurrent peripheral nerve pressure palsies. Electrodiagnostically, we found a clear decrease of nerve conduction velocity in affected and unaffected nerves. All the patient's relatives showed entirely normal clinical and electrodiagnostic findings. Histopathologically, there were extensive irregularities of the myelin sheaths with numerous tomaculous swellings. DNA analysis revealed a deletion for probes flanking the PMP-22 gene at the maternal chromosome 17 in our patient. His mother showed a normal gene dosage for all markers deleted in our patient, indicating a new mutation.

Adult↗
PubMed1994

Teicoplanin pharmacokinetics and dosage recommendations in chronic hemodialysis patients and in patients undergoing continuous veno-venous hemodialysis.

Multiple-dose pharmacokinetics of teicoplanin, a glycopeptide antibiotic against gram-positive infections, were studied in 9 chronic hemodialysis (HD) patients and in 7 patients with an acute renal failure (ARF) treated by continuous veno-venous hemodialysis (CVVHD). After a loading dose of 800 mg i.v. the 400 mg maintenance doses were administered according to a target trough concentration of 5-15 mg/l. Using the Bayesian estimation method implemented in the computer program Abbottbase Pharmacokinetic System (PKS), we defined an open three-compartment kinetic model for teicoplanin and calculated the individual pharmacokinetics. The mean terminal elimination half-life was 176 +/- 41.3 h in the HD group and 99 +/- 22.3 h in the CVVHD group (p < 0.005). The total body clearance (CL) was 4 +/- 1.2 ml/min and 9.2 +/- 1.7 ml/min in the HD and CVVHD patients respectively (p < 0.001). The mean reduction of the serum levels during a HD session was 9.1% in the patients dialysed with a F8 filter and 20.2% with a high-flux F60 filter (p < 0.001). The resulting extraction rate was 10 +/- 3.6% (F8) which is similar to the unbound fraction. The elimination of teicoplanin during CVVHD therapy strongly depended on the ultrafiltration rate (UFR) (r = 0.923, p < 0.05). An UFR of 15.6 l/24 h resulted in a removal of 32%/24 h of a 400 mg dose and an UFR of 6.2 l/24 h in 9.5%/24 h respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1993

Regulation of human IgE response in hu-PBL-SCID mice.

The human IgE response was investigated in hu-PBL-SCID mice created by ip injection of human PBL into C.B.17 scid/scid (scid) mice. With 30-100 x 10(6) PBL/mouse, 80 to 90% of the animals responded with human IgE serum levels of 3-1000 ng/ml after 2 weeks. PBL from all donors analyzed (total number > 20) responded with IgE production. The half-lives of human IgE, IgM, and IgG in scid mice were determined to test the possibility of a passive transfer of the immunoglobulins in contrast to de novo synthesis. The values found were 88, 128, and 126 hr, respectively. In general, immunoglobulin production of all isotypes continuously increased over a period of 7-9 weeks after PBL injection, indicating de novo synthesis had taken place. The kinetics of the IgE response exhibited two phases: An initial burst of IgE production occurred between Days 12 and 22. This burst reached levels of 25-70 ng/ml IgE. After a rapid decline to about 50% of the peak value there was a sustained, slow, increase of IgE production for several weeks, excluding a passive transfer for IgE. About half of the donors lacked the initial burst of IgE production and only exhibited a slowly rising IgE production that is indistinguishable from the slow phase of the former donor population. The levels reached in this second phase of IgE production were 20-40 ng/ml after 6-7 weeks. This kinetics may reflect the presence of two different B cell populations, of which only one is present in all donors. The initial IgE burst was only partially dependent on the presence of human IL-4, reflected by a partial inhibition of this response by a neutralizing monoclonal anti-IL-4 antibody. The IgE response in scid mice seems to consist therefore of an IL-4-independent and an IL-4-dependent part, indicating the response to be partially driven by preswitched B cells. Injection of exogenous recombinant human IL-4 (rhIL-4) was not suitable due to the short half-life of rhIL-4 in scid mice of 12 min. Attempts to supply a constant source of rhIL-4 by injection of IL-4-producing Chinese hamster ovary cells failed because of toxic effects produced by these cells. The human IgE production in the scid mice was suppressed by interferon-alpha (BD) to 60-80% compared to that of untreated mice. The suppression was not isotype specific, however, because production of IgG and IgM was inhibited to similar extents.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗