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Biomedical subjects

H Wenzel

Publications and source records attributed to H Wenzel.

At least 19 recordsLinked to original sources
PubMed2000

Search for new particles decaying to t&tmacr; in p&pmacr; collisions at radicals = 1.8 TeV

We use 106 pb (-1) of data collected with the Collider Detector at Fermilab to search for narrow-width, vector particles decaying to a top and an antitop quark. Model independent upper limits on the cross section for narrow, vector resonances decaying to t&tmacr; are presented. At the 95% confidence level, we exclude the existence of a leptophobic Z' boson in a model of top-color-assisted technicolor with mass M(Z')<480 GeV/c(2) for natural width gamma = 0.012M(Z'), and M(Z')<780 GeV/c(2) for gamma = 0.04M(Z').

Journal Article↗
PubMed2000

Limits on light gravitino production and new processes with large missing transverse energy in p&pmacr; collisions at sqrt

Events collected by the Collider Detector at Fermilab (CDF) with an energetic jet plus large missing transverse energy can be used to search for physics beyond the standard model. We see no deviations from the expected backgrounds and set upper limits on the production of new processes. We consider in addition the production of light gravitinos and set a limit at 95% confidence level on the breaking scale sqrt[F]>/=217 GeV, which excludes gravitino masses smaller than 1.1x10(-5) eV/c(2).

Journal Article↗
PubMed2000

The cost-effectiveness of different management strategies for type I diabetes: a Swiss perspective.

AIMS/HYPOTHESIS: A computer model was developed to determine the health outcomes and economic consequences of different combinations of diabetes interventions in newly diagnosed patients with Type I (insulin-dependent) diabetes in Switzerland. METHODS: We modelled seven complications of diabetes: hypoglycaemia, ketoacidosis, acute myocardial infarction, stroke, lower extremity amputation, nephropathy, and retinopathy. Transition probabilities and costs were taken from published literature. The Swiss health insurance payer perspective was taken. Various combinations of diabetes management strategies, including intensive or conventional insulin therapy and screening and treatment strategies for renal and eye disease were defined. Life expectancy, cumulative incidences of complications, and mean expected total lifetime costs per patient were calculated under six different management strategies. Incremental cost-effectiveness ratios were calculated in terms of costs per life-year gained compared with conventional insulin therapy alone. RESULTS: The addition of screening for microalbuminuria and retinopathy followed by appropriate treatment, if detected, were cost saving, with reduction in cumulative incidence of end stage renal disease and blindness respectively, and, in the case of microalbulminuria screening and treatment, an improvement in life expectancy. Intensive therapy improved life expectancy but increased total lifetime costs. CONCLUSION/INTERPRETATION: Optimal management of Type I diabetic patients, including secondary and tertiary prevention, leads to reduced complications and improved life expectancy, with the increased costs of prevention offset to varying degrees by cost savings due to complications avoided.

Albuminuria↗
PubMed1998

Hydroxamate derivatives of substrate-analogous peptides containing aminomalonic acid are potent inhibitors of matrix metalloproteinases.

Novel peptides containing the sequence -Pro-Leu-Ama(NHOH)- were synthesized and characterized by spectroscopic techniques. Their inhibitory properties towards the activated form of native human gelatinase B (MMP-9) and the catalytic domain of neutrophil collagenase (cdMMP-8) were determined. The most effective inhibitor synthesized exhibits Ki values of 2 x 10(-6) M (cdMMP-8) and 5 x 10(-9) M (MMP-9) thus attaining interesting discrimination between the tested metalloproteinases. A most important feature of this type of inhibitor is its peptide nature making the compounds similar to natural substrates. In spite of the peptide character of the inhibitors synthesized, the P1-P1'-peptide bond shows a high resistance to cleavage by the proteinases.

Humans↗
PubMed1998

Dimer-to-tetramer transformation: loop excision dramatically alters structure and stability of the ROP four alpha-helix bundle protein.

The ROP loop excision mutant RM6 shows dramatic changes in structure and stability in comparison to the wild-type protein. Removal of the five amino acids (Asp30, Ala31, Asp32, Glu33, Gln34) from the loop results in a complete reorganization of the protein as evidenced by single crystal X-ray analysis and thermodynamic unfolding studies. The homodimeric four-alpha-helix motif of the wild-type structure is given up. Instead a homotetrameric four-alpha-helix structure with extended, loop-free helical monomers is formed. This intriguing structural change is associated with the acquisition of hyperthermophilic stability. This is evident in the shift in transition temperature from 71 degreesC characteristic of the wild-type protein to 101 degreesC for RM6. Accordingly the Gibbs energy of unfolding is increased from 71.7 kJ (mol of dimer)-1 to 195.1 kJ (mol of tetramer)-1. The tetramer-to-monomer transition proceeds highly cooperatively involving an enthalpy change of DeltaH=1073+/-30 kJ (mol of tetramer)-1 and a heat capacity change at the transition temperature of DeltaDNCp=14.9(+/-)3% kJ (mol of tetramerxK)-1. The two-state nature of the unfolding reaction is reflected in coinciding calorimetric and van't Hoff enthalpy values.

Amino Acid Sequence↗
PubMed1995

Selective kallikrein inhibitors alter human neutrophil elastase release during extracorporeal circulation.

Cardiopulmonary bypass causes hemorrhagic complications and initiates a biochemical and cellular "whole body inflammatory response." This study investigates whether a variety of selective inhibitors of the contact pathway of intrinsic coagulation modulate complement and neutrophil activation during simulated extracorporeal circulation. After 60 min of recirculation in the presence of the slow tight-binding boronic acid inhibitor, Bz-Pro-Phe-boroArg-OH (10.7 microM), complete inhibition of kallikrein-C1-inhibitor complex formation and marked inhibition of C1-C1-inhibitor complex formation and the release of human neutrophil elastase were observed. Arg15-aprotinin (3.1 microM), Ala357,Arg358 alpha 1-antitrypsin (2.6 microM), and soybean trypsin inhibitor (48.0 microM) either completely or partially inhibited the generation of kallikrein-C1-inhibitor complexes but were less effective inhibitors of human neutrophil elastase release. The second-order rate constants for the inhibition of kallikrein in purified systems are consistent with the order of effectiveness of the inhibitors in blocking human neutrophil elastase release in heparinized blood. Our results suggest that low-molecular-weight selective inhibitors of kallikrein may be effective agents in the attenuation of the contact-mediated inflammatory response in cardiopulmonary bypass.

Amino Acid Sequence↗
PubMed1993

Is screening and intervention for microalbuminuria worthwhile in patients with insulin dependent diabetes?

OBJECTIVE: To analyse the cost-benefit of screening for and antihypertensive treatment of early renal disease indicated by microalbuminuria in patients with insulin dependent diabetes mellitus. DESIGN: Previously published data were used to estimate transition probabilities for each step from normoalbuminuria until death. The effect of intervention on urinary albumin excretion rate by antihypertensive treatment was arbitrarily set at three different levels. All direct costs (screening, antihypertensive treatment, treatment of end stage renal failure) were included in the cost-benefit analysis by using real discount rates of 2.5% and 6%. SETTING: Computer simulation. SUBJECTS: Simulated cohort of 8000 patients. MAIN OUTCOME MEASURES: Mortality, incidence of diabetic nephropathy, incidence of end stage renal failure, and costs versus savings. RESULTS: Assuming treatment effects of 33% and 67% median life expectancy increased by four to 14 years, respectively, and the need for dialysis or transplantation decreased by 21% to 63%. Costs and savings would balance if the annual rate of increase of albuminuria was decreased from 20% to 18% a year. CONCLUSIONS: Screening and intervention programmes are likely to have life saving effects and lead to considerable economic savings.

Albuminuria↗
PubMed1990

Antihypertensive treatment in Germany, subjected to a cost-effectiveness analysis.

German physicians are increasingly adopting national and international recommendations on the promotion of non-pharmacological treatment of elevated blood pressure. This reflects a greater sensibility to the advantages and disadvantages of antihypertensive drugs versus dietary means. Furthermore, the rapid growth of health expenditure is a central issue in many policy decisions. Increasingly, the use of cost-effectiveness analysis (CEA) and cost-benefit analysis (CBA) is being advocated as a possible means of making the medical care system more efficient. We report an analysis of the value of treating hypertension in Germany-West.

Aged↗
PubMed1989

[Extracorporeal shockwave lithotripsy of bile duct stones].

Extracorporeal lithotripsy (EL) was undertaken in 50 patients (mean age 73.7 years; range 29-90 years) with extrahepatic and, in five, with intrahepatic gallstones, the usual endoscopic methods having been unsuccessful in removing the stones. Occasionally stone fragments were passed spontaneously, but in most they had to be removed endoscopically, in 48 (96%) with extrahepatic and in three (60%) with intrahepatic stones. Biliary tract or gallbladder infections occurred after the lithotripsy and associated local litholysis in seven of the 48 with extrahepatic (14%) and three of the five (60%) with intrahepatic stones. There was one hospital death. The results indicate that EL has definite advantages over surgical treatment in these patients, who are usually elderly and in whom surgical intervention is more risky.

Adult↗
PubMed1989

[Effect of omega-3-fatty acids on biliary lipids and lithogenicity].

Until now no studies are available about the influences of omega-3-fatty acids on biliary lipids in men. The effects of 1.5 g omega-3-fatty acids per day on biliary lipid concentration and composition were studied in 13 male healthy persons over six weeks. Biliary cholesterol concentration decreased from 5.4 +/- 0.53 mol% to 3.7 +/- 0.30 mol% (25%) statistically significant. Phospholipids and bile acids remained unchanged. Cholesterol saturation index (CSI) was lowered from 1.13 +/- 0.12 to 0.85 +/- 0.06 (p less than 0.05). Bile acid composition and conjugation rates were unchanged. No significant side effects could be observed. Substitution of omega-3-fatty acids induced in healthy male persons a decrease of biliary cholesterol and lithogenicity.

Adult↗
PubMed1989

[Changes in biliary lithogenicity caused by 4 weeks' weight reduction].

In 2 of 12 patients (16.6%) cholesterol monohydrate crystals occurred in duodenal bile samples after a 4 weeks fasting period (452 kcal/day). Cholesterol monohydrate crystals could be observed until recently mainly in patients with cholesterol gallstones. Therefore, this finding indicates increased biliary lithogenicity despite a non statistical decrease in CSI from 1.35 +/- 0.35 to 1.19 +/- 0.64. Presumably the increased lithogenicity may be caused by an increased glycoprotein concentration and an improvement in gallbladder contractility. Short time fasting obviously will be a risk factor for the development of gallstones, if weight and metabolic normalisation cannot be achieved.

Adult↗
PubMed1988

[Dietary modification of bile lipids].

The average incidence of gallstones in european countries is about 25%. Excessive secretion of cholesterol into the bile can predispose to saturation and gallstone-formation. Obesity, overnutrition, diets rich in refined carbohydrates, diets high in cholesterol intake and poor in dietary fibre, lipid lowering drugs, age and female sex hormones are recognized causing increased cholesterol secretion into the bile. These metabolic consequences may predispose to a higher incidence of cholesterol gallstone than in normal persons. Taking all the results of the literature together patients with gallstones should be encouraged to take a low cholesterol, low calorie, low refined carbohydrate and high polyunsaturated fat diet rich in bran und vegetable fibre. Obese patients should reduce their body weight. These dietary recommendations should be given for patients with gallstones during bile acid therapy and after successful dissolution in order to prevent gallstone recurrence.

Bile↗