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H Wenzel

Publications and source records attributed to H Wenzel.

At least 19 recordsLinked to original sources
PubMed2006

[Costs of diabetes mellitus type 2 and self measurement of blood glucose in Germany].

UNLABELLED: It is extremely difficult to assess the prevalence and the total costs of diabetes mellitus for the German health care system. The last sound assessment of the total costs is based on the CODE-2 study, although this study reflects the situation in 1998. METHODS: In this paper we assess again the total costs of diabetes mellitus type 2 and self measurement of blood glucose (SMBG) for the German healthcare system, based on the analysis of a recently published retrospective, multicentre trial dealing with the impact of SMBG on long-term patient outcomes. RESULTS: Overall, yearly costs for the treatment of diabetes mellitus type 2 and its complications amount to Euro 3 196,-per patient. This equals 4.6% to 8.2% of the German healthcare expenditure, in relation to the estimated prevalence of the disease in Germany. The cost difference between the cohorts with and without SMBG was not essential (Euro 290,-higher costs in the cohort with SMBG). CONCLUSIONS: From a public health standpoint, prevention of diabetes mellitus or at least prevention of its complications by optimising glucose metabolism should be given highest priority in times of limited resources for healthcare. SMBG is perhaps a valuable tool to achieve this target.

Blood Glucose Self-Monitoring↗
PubMed2001

Structure-based design and synthesis of potent matrix metalloproteinase inhibitors derived from a 6H-1,3,4-thiadiazine scaffold.

We describe a new generation of heterocyclic nonpeptide matrix metalloproteinase (MMP) inhibitors derived from a 6H-1,3,4-thiadiazine scaffold. A screening effort was utilized to identify some chiral 6-methyl-1,3,4-thiadiazines that are weak inhibitors of the catalytic domain of human neutrophil collagenase (cdMMP-8). Further optimization of the lead compounds revealed general design principles that involve the placement of a phenyl or thienyl group at position 5 of the thiadiazine ring, to improve unprimed side affinity; the incorporation of an amino group at position 2 of the thiadiazine ring as the chelating agent for the catalytic zinc; the placement of a N-sulfonamide-substituted amino acid residue at the amino group, to improve primed side affinity; and the attachment of diverse functional groups at position 4 or 5 of the phenyl or thienyl group at the unprimed side, to improve selectivity. The new compounds were assayed against eight different matrix metalloproteinases, MMP-1, cdMMP-2, cdMMP-8, MMP-9, cdMMP-12, cdMMP-13, cdMMP-14, and the ectodomain of MMP-14, respectively. A unique combination of the above-described modifications produced the selective inhibitor (2R)-N-[5-(4-bromophenyl)-6H-1,3,4-thiadiazin-2-yl]-2-[(phenylsulfonyl)amino]propanamide with high affinity for MMP-9 (K(i) = 40 nM). X-ray crystallographic data obtained for cdMMP-8 cocrystallized with N-allyl-5-(4-chlorophenyl)-6H-1,3,4-thiadiazin-2-amine hydrobromide gave detailed design information on binding interactions for thiadiazine-based MMP inhibitors.

Binding Sites↗
PubMed2001

Novel heterocyclic inhibitors of matrix metalloproteinases: three 6H-1,3,4-thiadiazines.

The title compounds, (2S)-N-[5-(4-chlorophenyl)-2,3-dihydro-6H-1,3,4-thiadiazin-2-ylidene]-2-[(phenylsulfonyl)amino]propanamide, C18H17ClN4O3S2, (I), (2R)-N-[5-(4-fluorophenyl)-6H-1,3,4-thiadiazin-2-yl]-2-[(phenylsulfonyl)amino]propanamide, C18H17FN4O3S2, (II), and (2S)-N-[5-(5-chloro-2-thienyl)-6H-1,3,4-thiadiazin-2-yl]-2-[(phenylsulfonyl)amino]propanamide, C16H15ClN4O3S3, (III), are potent inhibitors of matrix metalloproteinases. In all three compounds, the thiadiazine ring adopts a screw-boat conformation. The molecules of compound (I) show a short intramolecular N(Ala)-H...N(exo) hydrogen bond [N...N 2.661 (3) A] and are linked into a chain along the c axis by N(endo)-H...S(endo) and N(endo)-H...O(Ala) hydrogen bonds [N...S 3.236 (3) and N...O 3.375 (3) A] between neighbouring molecules. In compound (II), the molecules are connected antiparallel into a chain along the a axis by N(exo)-H...O(Ala) and N(Ala)-H...N(endo) hydrogen bonds [N...O 2.907 (6) and N...N 2.911 (6) A]. The molecules of compound (III) are dimerized antiparallel through N(exo)-H...N(endo) hydrogen bonds [N...N 2.956 (7) and 2.983 (7) A]. The different hydrogen-bonding patterns can be explained by an amido-imino tautomerism (prototropic shift) shown by different bond lengths within the 6H-1,3,4-thiadiazine moiety.

Crystallography, X-Ray↗
PubMed2001

Environmental accounting--a decision support tool in WWTP operation and management.

The various emissions to water, air and soil from the municipal wastewater treatment plant of Avedore Wastewater Service Company are accounted for and quantified in terms of the environmental impacts to which they contribute: global warming, acidification, eutrophication, space demand for controlled deposition of residues, as well as persistent toxicity, human toxicity and eco-toxicity. The impacts are expressed on the same scale, namely as fraction of the total per capita loads in a national scenario 1990, also called the person equivalent or PE1990. This provides a compact and informative overview of the environmental impacts and allows for a holistic prioritisation in the operation and management of the plant. The accounting shows that the resulting emissions per person in the catchment area of the plant correspond to 0.5-5.0% of the average Danish PE1990 for the impacts in question.

Acid Rain↗
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

Search for a fourth-generation quark more massive than the Z0 boson in p&pmacr; collisions at radicals = 1.8 TeV

We present the results of a search for pair production of a fourth-generation charge -1 / 3 quark (b(')) in sqrt[s] = 1.8 TeV p&pmacr; collisions using 88 pb(-1) of data obtained with the Collider Detector at Fermilab. We assume that both quarks decay via the flavor-changing neutral current process b(')-->bZ(0) and that the b(') mass is greater than m(Z)+m(b). We studied the decay mode b(')b(');-->Z(0)Z(0)b&bmacr; where one Z0 decays into e(+)e(-) or &mgr;(+)&mgr;(-) and the other decays hadronically, giving a signature of two leptons plus jets. An upper limit on the sigma(p&pmacr;-->b(')b(');)x[B(b(')-->bZ(0))](2) is established as a function of the b(') mass. We exclude at 95% confidence level a b(') quark with mass between 100 and 199 GeV/c(2) for B(b(')-->bZ(0)) = 100%.

Journal Article↗
PubMed2000

Transverse momentum and total cross section of e(+)e(-) pairs in the Z-boson region from p&pmacr; collisions at sqrt

The transverse momentum and total cross section of e(+)e(-) pairs in the Z-boson region of 66<M(ee)<116 GeV/c(2) from p&pmacr; collisions at sqrt[s] = 1.8 TeV are measured using 110 pb(-1) of collisions taken by the Collider Detector at Fermilab during 1992-1995. The total cross section is measured to be 248+/-11 pb. The differential transverse momentum cross section is compared with calculations that match quantum chromodynamics perturbation theory at high transverse momentum with the gluon resummation formalism at low transverse momentum.

Journal Article↗
PubMed2000

Measurement of the helicity of W bosons in top quark decays

We use the transverse momentum spectrum of leptons in the decay chain t-->bW with W-->lnu to measure the helicity of the W bosons in the top quark rest frame. Our measurement uses a t&tmacr; sample isolated in 106+/-4 pb(-1) of data collected in p&pmacr; collisions at sqrt[s] = 1.8 TeV with the CDF detector at the Fermilab Tevatron. Assuming a standard V-A weak decay, we find that the fraction of W's with zero helicity in the top rest frame is F0 = 0.91+/-0. 37(stat)+/-0.13(syst), consistent with the standard model prediction of F0 = 0.70 for a top mass of 175 GeV/c(2).

Journal Article↗
PubMed2000

Observation of diffractive b-quark production at the fermilab tevatron

We report a measurement of the fraction of b quarks produced diffractively in &pmacr;p collisions at sqrt[s] = 1.8 TeV. Diffraction is identified by the absence of particles in a forward pseudorapidity region. From events with an electron of transverse momentum 9.5<p(e)(T)<20 GeV/ c within the pseudorapidity region |eta|<1.1, the ratio of diffractive to total b-quark production rates is found to be R(&bmacr;b) = [0.62+/-0.19(stat)+/-0.16(syst)]%. This result is comparable in magnitude to corresponding ratios for W and dijet production but significantly lower than expectations based on factorization.

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↗
PubMed2000

Outline of a diabetes disease management model: principles and applications.

A complex interactive computer model was developed to determine the health outcomes and economic consequences of different diabetes interventions for user-defined observation periods. The interventions include intensive or conventional insulin therapy, different oral hypoglycaemic medications, different screening and treatment strategies for micro-vascular complications, different treatment strategies for end-stage complications, or multi-factorial interventions. The analyses can be performed on different sub-groups of type 1 and 2 diabetic patients, defined in terms of age, gender, baseline risk factors and pre-existing complications. The model performs real-time simulations. Full on-screen documentation of the model structure, logic, calculations and data sources is available to maximize the model's transparency. Economic and clinical data used in the disease management model are editable by the user, allowing the input of new data as they become available, the creation of country-specific, HMO-specific, or provider-specific versions of the model, and the exploration of new hypotheses ('what-if' analyses). The approach used allows maximum flexibility, adaptability, and transparency within the model structure. For the user-defined patient cohorts and intervention strategies the diabetes disease management model compares life expectancy, expected incidence and prevalence of complications as well as expected life-time (or shorter) treatment cost. Diabetes and complication management strategies can be compared in different patient populations in a variety of realistic clinical settings. The model allows extrapolation of results obtained from relatively short-term clinical trials to longer-term medical outcomes, and from trial populations to real-life populations providing a tangible yardstick to judge the quality of diabetes care. The model was used to evaluate diabetes care options in Germany, France, Switzerland, UK and US.

Computer Simulation↗
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↗