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Biomedical subjects

W Weber

Publications and source records attributed to W Weber.

At least 235 records · Page 13Linked to original sources

[Pedicled small intestine segment for circular replacement of the extrahepatic bile duct in preserved papillary passage. An animal experiment study].

The effect of a small bowel segment as a extra-hepatic bile duct replacement was examined in 12 pigs followed-up for a period of 420 days. No complications, either during the operation or postoperatively, were observed in any of the animals. The laboratory parameters were within normal range over the entire observation period of 420 days. After 2, 6, and 12 months there was no anastomotic stenosis in the PTC. The intrahepatic biliary tract was not dilated. There was obvious peristalsis of the small bowel transplant towards the papilla of Vater. The autopsy showed that the grafts had healed without any sign of irritation. Histologically the structure of the graft remained undisturbed. There was a clear distinction between the mucosa of the bile duct and that of the small bowel, with no sign of a chronic infection. In the graft as well as in the vascular pedicle the nerve fibres were intact. Liver biopsy showed no pathological changes. In the light of these experiments, a small bowel segment presents a very promising alternative replacement of the extrahepatic biliary tract.

Ampulla of Vater↗

System analysis in multiple dose kinetics: evidence for saturable tubular reabsorption of the organic cation N1-methylnicotinamide in humans.

The renal clearance of N1-methylnicotinamide (NMN) was studied in 8 young women at physiological steady state and at steady state following a combined loading bolus and iv infusion. Urinary NMN concentrations were determined using a new HPLC method, plasma levels by a conventional fluorescence method. At physiological levels net tubular secretion of NMN was evident due to a renal fractional excretion, i.e., a ratio of renal NMN clearance to creatinine clearance, above unity. Increasing plasma concentrations lead to an increase in the fractional excretion, indicating saturation of the underlying tubular reabsorption process. Binding to plasma proteins was excluded by ultra-filtration experiments. Clearances measured at physiological levels were about one half of the maximum renal clearance attained following the infusion. This maximum value was approximately six times the creatinine clearance and may be a useful approximation of the renal plasma flow. System analysis, including a novel method to calculate the net response following a multiple input, was used to determine the pharmacokinetic system parameters.

Absorption↗

[Animal experiment studies of pedicled small intestine transplantation as partial extrahepatic bile duct replacement].

A pedicle graft of the jejunum can in some cases enlarge a bile duct stricture. The enlargement of the patch and its consequences on the liver function are possible problems. In an animal experiment the following questions were sought. 1) Is a partial replacement of the bile duct with a pedicle graft of small bowel possible? 2) Is there an enlargement of the patch in every case and what are the consequences on the biliary tract and on liver function. The experiments were performed on 14 minipigs over a long-term observation period of 450 days. The red and white blood cell count, the GPT, GOT, GPT, bilirubin and alkaline phosphatase and copper were checked monthly. After 2, 6 and 12 months the intra- and extrahepatic biliary tract were visualized via a PTC. After 8 months an angiography of the pedicle graft was performed. 15 months later the animals were killed and the bile duct, the graft and the liver were histologically examined. 1) With a pedicle graft of small bowel a partial replacement of the extrahepatic bile duct is possible. 2) An enlargement of the patch is seen in every case. The enlargement is a consequence of tension at the pedicle. After 15 months no morphological changes were observed at the patch nor were there any irregularities in liver function.

Ampulla of Vater↗

Galanthamine: pharmacokinetics, tissue distribution and cholinesterase inhibition in brain of mice.

Galanthamine was determined in plasma and tissue extracts of mice, after the application of 4, 6 and 8 mg/kg (i.v.), by reverse phase HPLC, with fluorescence detection. A biexponential decline of concentrations in plasma, with a terminal half-life of 43.3 min, was observed after the dose of 4 mg/kg. The volume of distribution (Vss) of 2.17 l/kg was similar to that found in other species, including man. Metabolism to the inactive diastereomer, epigalanthamine, was very limited. There was a rapid accumulation of galanthamine in tissues, which was most pronounced in the kidney (10-fold compared to plasma) and liver (5-fold). In brain, accumulation was similar to other parenchymatous organs (diaphragm, lung) and amounted to 2.10-fold. Red blood cells showed a concentration 1.34-fold greater than plasma. The accumulation of galanthamine in tissue, with the exception of liver and kidney, can be explained by passive distribution according to differences in pH, between intra- and extracellular compartments. Extraction of galanthamine from blood to brain tissue was complete, indicated by a clearance in the range of cerebral blood flow (1.05 ml min-1 g-1). The concentration-time course of galanthamine in brain tissue was parallel to that in plasma during the terminal elimination phase. Measurement of inhibition of acetylcholinesterase (AChE) in the same samples from brain revealed a maximum apparent inhibition of 43% in the homogenate of brain (1:4 w/v in phosphate buffer, 4 mg/kg, 5 min after injection).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Multiple-dose pharmacokinetics of ganglioside GM1 after intravenous and intramuscular administration to healthy volunteers.

Ganglioside GM1 multiple-dose pharmacokinetics were investigated in five healthy male volunteers. Doses of 100 mg were administered either intravenously or intramuscularly for 21 days, and the washout was followed-up for a further 21 days. The highly specific binding of the beta-subunit of cholera toxin was used to quantify ganglioside GM1 levels in plasma, urine, and feces. This dose regime increased the ganglioside GM1 steady-state plasma levels two to three orders of magnitude above the endogenous levels of 0.132 mg/L (coefficient of variation, 8.9%). Large and variable amounts of ganglioside GM1 were found in feces before and during treatment without relation to the dosage. No ganglioside GM1 could be detected in urine at any time. Plasma kinetics were linear with a biexponential disposition. Exogenously administered ganglioside GM1 was confined mainly to the blood volume as indicated by a steady-state volume of distribution of 6.98 +/- 3.57 L and appears to be excreted mainly in the form of metabolites. The total clearance was very slow at 1.61 +/- 0.37 ml/min. Absorption after intramuscular administration was slow (time to reach maximum concentration greater than 12 hours) and yielded steady-state concentrations somewhat lower compared with the intravenous infusion.

Adult↗

Pharmacokinetics of galanthamine in humans and corresponding cholinesterase inhibition.

Measurements were done to determine the plasma concentrations of galanthamine and two of its metabolites, as well as the corresponding inhibition of acetylcholinesterase activity in erythrocytes after applying 5 and 10 mg galanthamine hydrobromide as a constant-rate intravenous infusion for 30 minutes and single oral doses of 10 mg in eight healthy male volunteers. The data obtained revealed first-order pharmacokinetics, complete oral bioavailability, and a mean terminal half-life of 5.68 hours (95% confidence interval, 5.17 to 6.25 hours). Renal clearance accounted for only 25% of the total plasma clearance (CL = 0.34 L.kg-1.hr-1). Only negligible quantities of the putative metabolites, epigalanthamine and galanthaminone, were detected in blood and urine. The inhibition of acetylcholinesterase activity was closely correlated with the pharmacokinetics of galanthamine, a median maximal value of 53% being achieved by applying 10 mg galanthamine intravenously. Analysis of in vitro and ex vivo concentration responses revealed no differences, indicating that no metabolites of galanthamine exert additional inhibition of acetylcholinesterase activity.

Acetylcholinesterase↗

Rapidly fatal subacute sclerosing panencephalitis in a 19-year-old man.

The rare case of a 19-year-old man who suffered a fulminant course of 'subacute' sclerosing panencephalitis (SSPE) leading to death in 6 weeks from the onset of the first symptoms is described. This patient was part of the first reported SSPE cluster in the Netherlands, of which the other 3 patients died 2-6 years after diagnosis was made. In addition, a review of the literature on the rare occurrence of rapidly progressive SSPE was performed.

Adult↗

Anantin--a peptide antagonist of the atrial natriuretic factor (ANF). I. Producing organism, fermentation, isolation and biological activity.

Anantin, a peptide binding to the receptor of the atrial natriuretic factor (ANF) was isolated from a strain of Streptomyces coerulescens. The molecule consists of 17 natural L-amino acids which form a peptidic ring system. It has a MW of 1,871.0. The chemical composition is C90H111N21O24. The compound was found to bind competitively to ANF-receptors from bovine adrenal cortex (Kd = 0.61 microM). Furthermore, it dose-dependently inhibited the ANF-induced intracellular cyclic guanosine monophosphate accumulation in bovine aorta smooth muscle cells. At the same concentration no agonistic effects were detectable in these cells. Thus, anantin is considered to be the first microbially produced antagonist of the cardiac hormone, ANF.

Adrenal Cortex↗

[The use of pulse oximetry in the compartment syndrome].

After conservative therapy of a left-sided radius fracture a 14-year-old patient developed a compartment syndrome; within 24 h, that required immediate surgical intervention. Despite palpable peripheral pulsation of the radial and ulnar arteries, it was not possible to measure the arterial oxygen saturation by pulse oximetry on the forefinger and fifth finger of the left hand, so that a compartment syndrome due to a disorder of perfusion could be diagnosed. After fasciotomy, it became possible to measure the oxygen saturation by pulse oximetry as well as plethysmographic visualization of the pulse curve. In this case pulse oximetry confirmed the indication for surgical intervention and immediately demonstrated its success.

Adolescent↗

[Sensitivity of preoperative diagnosis in mesenteric vascular occlusion].

In a consecutive series the sensitivity of the preoperative diagnostic in acute mesenteric vascular occlusion was investigated prosprectively in 62 patients. 22 patients had an arterial thrombosis, 20 patients a venous thrombosis, 13 patients had an embolism, six patients a non-occlusive disease and one patient suffered from a dissection of the aorta. All but three patients (95.2%) had a leukocytosis with an average of 18,700/nl. The serum lactate was increased in 88.7% of the patients. The percutaneous ultrasonography was without any pathological findings in 45% of the patients. The x-ray of the abdomen shows signs of an ileus in more than half of the patients. The angiography had a sensitivity of 74%.

Aged↗

Multiple peaks and low bioavailability of furosemide correlate with the volume of fluid ingested.

Two different single dose cross-over bioavailability studies were performed comparing a new oral furosemide preparation (test preparation = preparation A) with a marketed standard with a marketed standard preparation (reference preparation = preparation B). Test and reference preparation contained 40 mg of furosemide each. Into both studies, 18 healthy male volunteers were included; 4 volunteers participated in both studies. In study 1, the volunteers ingested the tested preparations together with 300 ml of an electrolyte solution in order to substitute volume and electrolyte deficits. Additional 200 ml were given 30 min post dose, 500 ml during the next 30 min and 1000 ml during the second hour after drug intake. In study 2, the tested preparations were ingested together with 200 ml of water without any additional volume substitution. The plasma concentration curves of study 1 showed a double peaking with a first maximum of furosemide levels at 1 h and a second peak at 3 h and 4 h, respectively, on average. The concentration-time curves of study 2 showed a single peak 1 h p.a. in the mean for both preparations. The relative bioavailability of preparation A was about 67% in study 1 compared to study 2. Preparation B showed a relative bioavailability of 59% in study 1 compared to study 2.

Adult↗

The secreted form of the epidermal growth factor receptor. Characterization and crystallization of the receptor-ligand complex.

A protein composed of the external domain of the epidermal growth factor (EGF) receptor is secreted by A431 human tumor cells. The soluble receptor protein was isolated in bulk quantities from cell culture supernatants. It has an intact ligand binding site, exists in a 93-kDa monomeric form, and does not undergo oligomerization upon ligand binding; thus the receptor dimerization reported for the EGF holoreceptor appears not to be a function of its external domain. The unique system of a physiological soluble receptor was utilized for a crystallization study. Crystals were obtained but only in the presence of the ligand. They contained (in equimolar amounts) receptor as well as EGF. The crystals belong to the tetragonal space group P4(3)2(1)2 or P4(1)2(1)2 with unit cell dimensions a = b = 118 A, c = 202 A. The packing density parameter was 3.55 A3/dalton, indicating the asymmetric unit to consist of one receptor-ligand complex.

Cell Line↗

[Activities of the Swiss Cancer League in the campaign against cancer].

The Swiss Cancer League ist the head organization of 19 cantonal and regional cancer leagues with a total of over 60,000 members. Its goal is cancer control on a medical-scientific basis. The League is working toward this goal by funding of research, information and social service. The funding of research is done through grant applications similar to the rules of the Swiss National Fund. Basic and applied research are equally supported. Information is increasingly transmitted through national campaigns (melanoma prevention, cancer and nutrition, European Code). Social services are decentralized and taken care of by the cantonal and regional leagues. The principal revenues derive from private donations (bequests, card sales etc.).

Health Education↗