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Biomedical subjects

M Wenk

Publications and source records attributed to M Wenk.

62 records · Page 4Linked to original sources
PubMed1977

Experimental pancreatic carcinogenesis. I. Morphogenesis of pancreatic adenocarcinoma in the Syrian golden hamster induced by N-nitroso-bis(2-hydroxypropyl)amine.

In serial sacrifice experiment, outbred male Syrian golden hamsters were treated once weekly for life with subcutaneous injections of N-nitroso-bis(2-hydroxypropyl) amine (DIPN). The pancreas was examined by high resolution light (1-micro sections) and transmission electron microscopy. Early nonspecific changes in all pancreatic epithelial cellular elements were followed by a progressive proliferation of intra- and interlobular duct cells, with the development of multicentric foci of cystic and papillary cystic adenomas, intraductal carcinomas, and invasive ductal neoplasms. These observations were consistent with multistage morphogenesis of pancreatic adenocarcinoma of ductal origin.

Adenocarcinoma↗
PubMed1976

Partial separation of synaptosomes accumulating 4-aminobutyrate or glutamate by zonal centrifugation on a discontinuous sucrose gradient.

Rat cerebral cortex slices were incubated with 1muM [3H]4-aminobutyrate or [3H]L-glutamine. The subcellular distribution of the accumulated labelled substances were determined by fractionating the nuclei-free homogenates on a 5-step discontinuous sucrose density gradient in a B XIV zonal rotor. The gradient was designed to separate the synaptosomes into 3 subpopulations of increasing density. The patterns of distribution of [3H]4-aminobutyrate and [3H-a1L-glutamate in the three synaptosomal peaks were distinctly different. This indicates the presence of separate types of nerve ending accumulating these two potential neurotransmitters, which are known to be metabolically closely linked through the enzyme glutamate decarboxylase. Recentrifugation of the 3 synaptosomal peaks on flat step gradients in a swingout rotor did not result in any further enrichment in transmitter-specific synaptosomes.

Aminobutyrates↗
PubMedDate not supplied

Influence of intensive physical training on urinary nitrate elimination and plasma endothelin-1 levels in patients with congestive heart failure.

BACKGROUND: Congestive heart failure (CHF) is associated with increased peripheral vascular resistance. Exercise-induced shear stress may release endothelial relaxing factors, such as nitric oxide (NO), and inhibit the production of vasoconstrictors such as endothelin-1 (ET-1) thereby modulating vascular tone. We examined the effect of intensive training on ET-1 plasma concentrations and NO-metabolite elimination in patients with CHF after acute myocardial infarction. METHODS: Seventeen patients with CHF after a myocardial infarction were randomized to an exercise group (n = 9), who performed physical training for 8 weeks, or a control group (n = 8) who received usual care. A physical examination, pulmonary function test, and a maximum exercise test were performed, and 24-hour urinary nitrate elimination and ET-1 in plasma were determined before and at the end of the study period. RESULTS: Maximal oxygen uptake remained unchanged in controls (17.9 +/- 1.4 to 18.1 +/- 1.5 mL/(kg min) but increased in the exercise group (from 20.4 +/- 0.75 to 26.7 +/- 1.4 mL/(kg min). After 8 weeks the urinary nitrate elimination in controls was significantly decreased (1.25 +/- 0.20 to 1.03 +/- 0.22 mmol/24 hours; P < 0.001), while it was unchanged in the exercise group (1.26 +/- 0.23 to 1.39 +/- 0.28; P = 0.71). Plasma ET-1 levels did not change after 8 weeks (7.87 +/- 0.62 versus 7.57 +/- 0.75 and 7.13 +/- 0.6 versus 7.35 +/- 0.7 pg/mL for control and exercise groups, respectively). CONCLUSION: In patients with CHF after acute myocardial infarction nitrate elimination decreases over the subsequent 2 months. This trend was reversed by training. Because nitrate elimination mirrors endogenous NO production, these results suggest that training may positively influence endothelial vasodilator function.

Endothelin-1↗
PubMedDate not supplied

Isoniazid plus sulphadoxine-pyrimethamine can reduce morbidity of HIV-positive patients treated for tuberculosis in Africa: a controlled clinical trial.

An annual 20% excess mortality rate is observed in HIV-seropositive patients after treatment for tuberculosis. An affordable secondary prophylaxis against main opportunistic diseases is needed, i.e. against tuberculosis, toxoplasmosis, pneumocystosis and other infections occurring in this target population. This open prospective randomized study assessed morbidity and mortality in 2 cohorts of HIV-seropositive patients having recently recovered from pulmonary tuberculosis: 134 patients assigned to prophylactic treatment with isoniazid (INH, 300 mg once daily) plus sulphadoxine-pyrimethamine (S, 500 mg/P, 25 mg once weekly), and 129 were controls, comparable for sex, age, weight and HIV-serology. Patients were followed-up for up to 2 years: 192 person-years (PY) in the prophylaxis group and 142 PY in the control group. Four patients developed tuberculosis and 20 patients died in the prophylaxis group, compared to 10 and 23 controls, respectively. Sick days were reported by 22 patients in the prophylaxis group and by 77 patients in the control group. This prophylaxis was associated with a moderate decrease of mortality (log rank test: p = 0.1736), a significant decrease of tuberculosis incidence (log rank test: p = 0. 0234), a highly significant reduction of adverse events and sick days, and a prevention of wasting (p = 0.008) and anaemia (p = 0. 045). No death from toxoplasmosis occurred in the prophylaxis group as compared to 2 possible cases among controls; toxoplasmosis IgG levels declined in treated patients, but increased in controls (p = 0.01). There was no adverse drug reaction due to SP (10,006 doses) or to INH. Compliance with SP intake was good, but moderate as with INH intake. We conclude that a secondary prophylaxis with INH+SP represents a cost-effective measure to improve health conditions of HIV-infected adults in Côte d'Ivoire, following a full treatment course against tuberculosis.

AIDS-Related Opportunistic Infections↗
PubMedDate not supplied

Rapid prediction of individual dosage requirements for lignocaine.

The mean and standard deviation of lignocaine (lidocaine) pharmacokinetic parameters in a patient population were determined on the basis of 327 serum concentration measurements obtained in 42 patients treated for ventricular arrhythmias. The application of a Bayesian forecasting method, which uses the estimates of the population parameters and 1 or 2 serum concentration measurements as feedback information, was tested retrospectively in 17 of the 42 patients (group I, 32 levels), and prospectively in 10 additional patients (group II, 20 levels). With 1 individual feedback concentration, sampled 2 to 4 hours after the start of lignocaine infusion, serum concentrations at 12 and 24 hours could be accurately predicted. The prediction error (measured minus predicted concentration) ranged between -1.2 and +1.6 (mean -0.03) mg/L in group I, and from -0.7 to +1.5 mg/L (mean +0.13) mg/L in group II; the correlation coefficient of measured and predicted levels were 0.92 and 0.86, respectively. In contrast, a prediction of lignocaine concentrations in these patients using only population parameters without feedback was poor: range of the prediction error = -3.1 to +3.0 mg/L (mean = +0.001 mg/L, r = 0.63, groups I and II, n = 52). The results demonstrate that with the Bayesian forecasting technique, accurate assessment of individual dosage requirements can be obtained within a few hours after starting lignocaine therapy.

Adult↗
PubMedDate not supplied

Serum level monitoring of antibacterial drugs. A review.

Serum concentration measurements of antibacterial agents are increasingly used to optimise drug dosage regimens. However, this approach is only justified for drugs with a low therapeutic index and poor predictability of serum concentrations, such as the aminoglycosides, chloramphenicol and vancomycin, whereas the penicillins and cephalosporins can safely be applied well above their minimum inhibitory concentrations. Wide interpatient variation in distribution and elimination are the main reasons for the unpredictability of aminoglycoside serum concentrations. It has been shown that in patients with normal creatinine clearance, the apparent elimination half-life of gentamicin varies from 0.4 to 7.6 hours. The pharmacokinetics of the aminoglycosides are most adequately described by a 3-compartment open model where the slow terminal half-life reflects elimination from the deep tissue compartment. The accumulation of the aminoglycosides in this compartment, which includes the kidneys and inner ear, is probably an important factor in their potential toxicity in these organs. Careful serum level monitoring may reduce, but cannot totally avoid, the risk of side effects. However, maintenance of effective drug levels appears to be at least an equally important goal of aminoglycoside serum level monitoring. Chloramphenicol is also a potentially toxic antibacterial agent. Its therapeutic range is usually considered to be 15 to 25 mg/L. The most important side effects are the 'grey baby syndrome' and bone marrow toxicity. Chloramphenicol is metabolised to several microbiologically inactive products. It also shows wide interpatient variability of its pharmacokinetics, especially in young children, and serum levels should therefore be followed in these patients. Vancomycin, a highly effective agent for staphylococcal and enterococcal infections, may also exhibit nephrotoxic and ototoxic side effects. A well-defined therapeutic range has not yet been established but in view of its minimum inhibitory concentrations it seems reasonable to maintain vancomycin serum concentrations between 15 and 50 mg/L. Since this drug is excreted unchanged in the urine, serum levels should particularly be monitored in patients with impaired renal function. The advances in routine therapeutic drug monitoring are directly related to rapid developments in technologies associated with the quantification of these agents. Microbiological plate diffusion assays are now often replaced by more specific immunoassays (radioimmunoassay, enzyme immunoassay, and fluorescence immunoassay) and chromatographic techniques.

Aminoglycosides↗
PubMedDate not supplied

Ingested asbestos and intestinal carcinogenesis in F344 rats.

The effect of oral exposure to amosite or chrysotile on azoxymethane-induced intestinal carcinogenesis was investigated in male F344 rats. In two separate experiments, F344 rats, 6 weeks of age, were given ten weekly subcutaneous injections of azoxymethane, and intragastric administration of amosite or chrysotile three times weekly during this period. In experiment 1, rats were sacrificed at 34 weeks. The incidence rates and mean number of intestinal tumors per rat were similar in all groups. However, a slightly higher incidence, not significant, of metastatic intestinal carcinomas was seen in rats exposed to asbestos. In the second experiment, rats were allowed to live out their life span. The incidence of intestinal tumors was similar in the rats receiving amosite with azoxymethane and azoxymethane alone. Thirty-two percent of the rats receiving amosite alone had colon tumors; these tumors are usually rare in F344 rats. It was concluded that the experimental evidence suggested but did not prove that oral asbestos exposure in F344 rats may have increased the incidence of intestinal tumors occurring naturally.

Animals↗