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Biomedical subjects

M Bühler

Publications and source records attributed to M Bühler.

At least 19 recordsLinked to original sources

Mechanism of the antiischemic effect of mibefradil, a selective T calcium channel blocker in dogs: comparison with amlodipine.

Calcium channel blockers are active in variant angina principally by preventing coronary vasospasm. However, a direct antiischemic effect may also occur. In open-chest dogs, an attack of variant angina was mimicked by a 2-min critical coronary stenosis, and the following reversible myocardial ischemia was assessed by measuring the decrease of segmental shortening. We compared the antiischemic mechanism of mibefradil, a T and L calcium channel blocker, with that of amlodipine, a pure L channel blocker. Both drugs showed a similar relationship between the decrease of the rate-pressure product and the antiischemic effect, but only mibefradil reduced heart rate. Amlodipine and mibefradil at the highest doses tested (20 and 70 micrograms/kg/min, respectively) restored 68 +/- 8 and 76 +/- 5% of segmental shortening in the ischemic area, respectively, as compared with preischemic values. Matching blood pressure (by intraaortic balloon) or heart rate (by atrial pacing) to predrug values showed that the antiischemic effect was mainly afterload-dependent for amlodipine and heart rate-dependent for mibefradil. We conclude that in variant angina, in addition to their antivasospastic effects, calcium channel blockers may be antiischemic by a direct myocardial effect associated with a decrease of the rate pressure product. Blockade of the T channel does not seem to participate in the direct antiischemic effect of mibefradil but could explain the decrease of heart rate.

Amlodipine

[35 years fracture documentation by the Working Group for Osteosynthesis Problems (AO)].

35 years of AO-Documentation has clearly demonstrated the possibilities and the effectiveness of fracture documentation. The fracture classification, x-ray documentation and recommended evaluation scores are essential prerequisites for trend analysis and comparison of results. AO offers today the methodology for a decentralized data collection and scientifically planned clinical trials.

Data Collection

Documentation.

In the period from 1. January to 31. December 1992, the new pinless external fixator was applied in eight European and North American clinics as part of a prospective multicentric study run by the AO/ASIF Documentation Centre. The aim of this study was to determine the indications, handling, and clinical results with the new fixator. The new pinless fixator was used 77 times on a total of 75 patients. The main indications were fresh tibial shaft fractures for which immediate definitive treatment was impossible. The majority of cases were secondarily stabilized with an unreamed tibial nail once the local and/or general condition of the patient had improved. In the remaining cases the pinless fixator was used for calcaneal and tibial head traction, segment transport and temporary stabilization in cases of tibial infection. Only after long-term application of the fixator was local infection at the pin site observed. There were no other complications. The new pinless fixator is a valuable addition in the treatment of fresh tibial fractures, in particular, in those cases which cannot be primarily treated due to contributing factors whether local or general.

Adult

[Clinical results with the limited contact DCP plate of titanium--a prospective study of 504 cases].

From the beginning of 1988 to July 1991, ten Swiss and German clinics undertook to document all cases of internal fixation using the titanium LC-DCP as part of a prospective multicenter study. The follow-up period was 14.2 months on average. The clinical results of 504 fixations were convincing. The follow-up rate was 72%. Of these, 95% healed without complication. The most frequent complication was delayed healing which occurred in 2.5% of cases. The infection rate was low (1.1%). A separate comparison of DCP fixations on the tibial shaft in 1984-1988 demonstrated the obvious biological compatibility of the new plate and shows that excellent results can be obtained using plate fixation.

Adult

[Simultaneous measumrement of the renal excretion of 131I-hippuran and 99mTc-MAG3].

This study describes methods of measuring simultaneously the renal excretion of two radiopharmaceuticals and of evaluating their different kinetics. For quantification of the dynamic contributions of scattered radiation in a double-radionuclide study a high-resolution pure germanium detector was used. The geometry of the arrangement was a semi-shielded whole-body counter according to E. Oberhausen. An intra-individual comparison of the renal elimination of 99mTc-MAG3 and 131I-Hippuran shows a systemic difference between both tracers depending on the time after injection, its average being around 11% between the 10th and 20th min. The inter-individual comparison shows deviations from the mean between -29 and +20%.

Adult

[Classification of proximal femoral fractures].

Based on the AO Classification of Fractures, the classification of fractures of the proximal femur will be explained. Especially the sub- and pertrochanteric fractures, as well as the fractures of the femoral neck will be considered. During the period from 1980-1989 26,126 fractures of the proximal femur were documented in the AO/ASIF Documentation Center. These fractures will be discussed regarding following aspects: dispersion of age and fractures, pre-existing systemic illnesses, general and local postoperative complications, choice of implant.

Aged

[Soft tissue infection--osteitis--osteomyelitis].

Statistically the posttraumatic osteitis shows a clear tendency to decrease from 1972-76 in comparison with 1982-86 (AO/ASIF-documentation). The incidence of infection varies considerably according to the different anatomical location of fractures. More recently atypical manifestations became of more importance and ask for differentiated bacteriological examinations. A close postoperative follow-up and exact wound-observations enable an immediate and adequate therapy in case of an infection.

Bacterial Infections

[Nosocomial infections in a university hospital. Results of a prospective study of infections in a medical and surgical ward and a surgical intensive care unit].

The results of an 11-month pilot study of surveillance of nosocomial infections are reported. Prospective surveillance was performed by daily examination of the microbiology reports and daily visits by the infection control nurse to the ward for the review of charts and Kardex of all patients for detection of "infection clues". Work sheets were used to collect all data during the daily rounds. Infection rates were calculated by dividing the the total number of hospital-acquired infections by the total number of discharges during the surveillance period. Active surveillance was performed for 6 months in the surgical intensive care unit (SCIU), 5 months in the surgical ward (SW) and 9 months in the medical ward (MW). Of 1527 patients discharged from these wards, nosocomial infections developed in 158 patients (10.4%). The overall infection rate was 14% (214 nosocomial infections). The infection rate varied greatly from ward to ward due to different patient populations, invasive procedures and severity of underlying diseases. Incidence infection rates were 42.5% for the SICU, 19.6% for the SW and 4.1% for the MW. The major sites affected were surgical wounds (42%), urinary tract (23%), respiratory tract (19%) and bloodstream (8%). The major etiologic agents associated with these nosocomial infections were E. coli, Pseudomonas aeruginosa, enterococci and Staphylococcus aureus. Conclusions drawn from the results of surveillance are discussed. The major benefits of an effective surveillance program for nosocomial infections are (a) estimates of the endemic levels of nosocomial infection, (b) identification of the nosocomial pathogens commonly encountered within a given institution, (c) identification of risk factors and (d) prompt recognition of epidemics. These data provide the necessary basis for an effective infection control program.

Cross Infection

On the kinetics and mechanism of enoate reductase.

Enoate reductases from Clostridium spec. La 1 and Clostridium kluyveri show a rather broad substrate specificity i.e. many alpha,beta-unsaturated carboxylates are reduced in a NADH-dependent reaction. The relative rates for different substrates are different for both reductases. The Km value of NADH for the reductase from C. spec. La 1 is about 12 muM. The transhydrogenase activity (reduction of N-acetylpyridine adenine dinucleotide) with NADH shows a maximum at pH 8 which is about 2 units higher than that for the reduction of enoates. Results of initial rate studies can be best explained by a Bi Bi ping pong mechanism. No back reaction and no proton exchange from 2(-3)H-labelled acylates could be demonstrated. NAD+ is a mixed-type inhibitor. The product inhibition constant Ki = 0.84mM and the dissociation constant for the dead-end inhibition complex 4.8mM. Aliphatic acylates show no measurable inhibition when they are applied in concentrations at the 100-fold Km values of the corresponding enoates. Measurable inhibitions can be observed with phenyl group-containing acylates. 3-Phenylpropionate (38mM) shows about 86% inhibition. Fumarate which is not a substrate inhibits the reduction of enoates by NADH as well as by reduced methylviologen. However, the reduction of NAD+ by reduced methylviologen as well that of acetylpyridine adenine dinucleotide by NADH is not inhibited by fumarate. On the other hand inhibitors such as morin or dicoumarol which probably bind to the flavin domain do not impair the reduction of enoates by reduced methylviologen however, all reductions with NADH are inhibited. These results are indicative for three binding domains: one for NADH which can be blocked by dicoumarol or morin, another for enoates which can be occupied by fumarate and a third one for reduced methylviologen. Enoate reductase splits off exclusively the (4S)-hydrogen atom from NADH. There is no direct hydrogen transfer from NADH to the products. Depending on the substrate concentration the isotope effect of the reduction of (E)-2-methyl-2-butenoate with (4S)-[4(-3)H]NADH varies from 6.8 to 1.3. The presence of NAD+ decreases the isotope effect.

Aerobiosis

Rhein as an electron acceptor for various flavoproteins and for electron transport particles.

Rhein (4,5-dihydroxyanthraquinone-2-carboxylic acid) which has been previously employed as an inhibitor for electron transport particles, NADH dehydrogenase, and other flavoproteins is reducible under physiological conditions. Soluble hydrogenase from Alcaligenes eutrophus H 16, several flavoproteins, and electron transport particles from baker's yeast and from beef heart were found to catalyse NADH oxidation with 9 micrometers to 2mM rhein as the electron acceptor. Dithionite or enzymatically reduced rhein (lambda max = 408 nm) is immediately reoxidized to rhein lambda max = 437 nm) by oxygen. Cyclovoltagrams reveal the midpoint redox potentials --0.240 V, -0.270 V, -0.280 V, -0.335 V at pH 6.0, 7.0, 7.7, 9.2, respectively. Due to its redox behaviour, caution should be exercised using rhein as a flavin-site-directed inhibitor for biological electron transfer systems.

Alcaligenes

[Sleeping behavior between the ages of 2 and 18. Longitudinal study].

Sleeping behavior was investigated in 320 Swiss children 2 to 18 years of age. The data were based on the First Zurich Longitudinal Study (1954-1980). The incidence of resistant behaviour at bedtime increased from 8 to 40% between age 2 and 10. Evening wakefulness was observed in 20% of the 2- to 7-year-old children, and in 40-50% of the older children. The incidence of night waking decreased from 40-50% in the preschool period to 20% at age 12.20% of the 2 to 4-year-old children and only 1% of the 12-year-old children woke up every night. Evening wakefulness and night waking were observed in some children over periods of several years. Up to age 5 the incidence of "bad dreaming" was 60%, subsequently it decreased to about 25%. Somnambulism was observed in 5% of the children. None of the described sleeping behaviors showed sex differences.

Adolescent