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Biomedical subjects

U Hoffmann

Publications and source records attributed to U Hoffmann.

At least 181 records · Page 10Linked to original sources

Ventilatory effects of hypercapnic end-tidal PCO2 clamps during aerobic exercise of varying intensity.

Nine subjects performed a sequence of sustained and randomised changes between 40 W and 100 W on a cycle ergometer while the end-tidal PO2 was kept close to 17.3 kPa (130 mm Hg) by means of a dynamic forcing technique (reference experiment). In a second series inspiratory CO2 was additionally manipulated so as to hold end-tidal PCO2 (PETCO2) near 6.5 kPa (49 mm Hg; 'CO2-clamp' experiment). By this forcing PETCO2 oscillations were attenuated and more evenly distributed over the frequency range. Ventilation (VT) responded to this manoeuvre with an upward trend that could not be ascribed to a slow CO2-response component, changes in metabolic rate or a dissociation of end-tidal and arterial PCO2. VT differences between reference and CO2-clamp experiments were abolished within a 3-min period following the termination of the external CO2 control. The present results suggest that the CO2-H+ stimulus plays a major role in adjusting ventilation when exercise intensity is decreased. The underlying CO2 effect appears to be neither additive nor bi-directionally symmetrical.

Arteries↗

The frequency histogram--a new method for the evaluation of laser Doppler flux motion.

A digital filter system (DFS) was implemented to describe the frequency components of laser Doppler signals. The DFS calculates a frequency histogram on the basis of the prevalence of a certain frequency band during the sample period. This approach seems to be more suitable for the detection of low-power small-amplitude flux motion components recorded by laser Doppler as compared to the commonly used fast Fourier algorithm. Fourier analysis provides an amplitude-relevant frequency spectrum which may overlook relevant frequency components with small amplitude due to low power or short duration. DFS allows better detection of such signals as demonstrated by the initial clinical results of this study evaluating flux motion on the feet of 4 healthy controls and 10 patients with peripheral arterial occlusive disease. Three frequency components are easily distinguished corresponding to low (3.6 +/- 1.5 cycles/minute) and high (18.6 +/- 4.5 cycles/min) frequency flux motion and the pulsatile waves due to cardiac action.

Aged↗

Flow motion waves with high and low frequency in severe ischaemia before and after percutaneous transluminal angioplasty.

UNLABELLED: STUDY OF OBJECTIVE: The aim was to evaluate skin flux and prevalence of low and high frequency flow motion waves in patients with severe ischaemia due to peripheral arterial occlusive disease before and after percutaneous transluminal angioplasty (PTA) with and without local thrombolysis. DESIGN: Flow motion was recorded by the laser Doppler technique at the dorsum of the foot before, one day, and one month after PTA. The results were separately analysed in patients with successful and unsuccessful treatment. SUBJECTS: 18 patients with rest pain or incipient gangrene were included. Mean pretreatment systolic ankle pressure was 55.8(SD 25.5) mm Hg, and mean transcutaneous PO2 at 43 degrees C was 5.2(9.4) mm Hg. Arteriography revealed relevant stenoses or occlusions of the femoropopliteal and calf arteries. MEASUREMENTS AND RESULTS: Before treatment two patterns of flow motion with characteristic frequency ranges were observed at the foot dorsum and at a probe temperature of 32 degrees C: low frequency (LF) waves with a mean frequency of 2.2(0.5) cycles.min-1 and a mean amplitude of 0.73(0.42) arbitrary units (AU) and high frequency (HF) waves with a mean frequency of 22.6(4.2) cycles.min-1 and a mean amplitude of 0.39(0.33) AU. PTA was successful in 11 of the 18 patients. After successful treatment, prevalence of HF waves decreased from 10/11 to 4/11 cases (p less than 0.001), but remained nearly unchanged after failed procedure. Prevalence of LF waves before and after PTA did not differ significantly. CONCLUSIONS: Our data support the hypothesis that HF waves represent a reaction of skin microcirculation to severe ischaemia. With reference to animal studies it is proposed that HF waves originate from terminal arterioles. They may function as a compensatory mechanism of flow regulation involved in pathophysiology of ischaemia.

Adult↗

Conformational changes in bovine heart myosin as studied by EPR and DSC techniques.

Thermal behavior of intact and LC-2 deficient myosin obtained from bovine heart was studied using EPR and DSC techniques. The reactive thiol sites (Cys 704) of myosin was labelled with 4-maleimidopiperidine-nitroxyl, and the measurements were taken in X-band in the conventional and saturation transfer EPR time domains. DSC scans were made from 5 degrees up to 60 degrees C with 0.25 degree C/min scan rate. Bovine heart myosin was isolated by standard methods. The LC-2 deficient myosin was prepared by cleaving myosin with alpha-chymotrypsin (400:1 molar ratio) for 1.5 min at 25 degrees. Our basic finding was a conformational change in LC-2 deficient myosin detected at 18 degrees C. It was not observed in intact myosin suggesting that the dissociation of the regulatory light chain resulted in a local structural change in the neighbourhood of the attached label in the 20 kD domain. The rotational correlation time of the label and the microwave saturation behavior of myosin at 25 degrees C exhibited no significant differences after removal of the LC-2 light chain. However, the mobility of the same label was significantly diminished in skeletal muscle. Studying the melting behavior of myosin, six endothermic peaks were detected at 19; 41.3; 43.3; 45.5; 48.5; and 54.3 degrees C (enthalpies: 708.4; 399; 773.8; 1089; 1612.8; and 3304.8 kJ/mol). They were assigned to the segment containing the essential thiols: HMM S-2, HMM S-1 (50kD and 20kD plus 27kD) and LMM. Removal of the LC-2 light chain was associated with the disappearance of the 18 degrees transition showing again a structural change in LC-2 deficient myosin which extended to a larger region.

Adenosine Diphosphate↗

Diameters of lymphatic capillaries in patients with different forms of primary lymphedema.

Fluorescence microlymphography was performed near the medial ankle in 12 healthy controls, 12 patients with congenital and 12 with sporadic lymphedema of the lower extremities. Diameters of lymphatic capillaries were determined on the videoscreen by playback of the tape recordings using a morphometric technique. In the patients with congenital disease (Nonne-Milroy) aplasia of microlymphatics was diagnosed in 8 instances, ectasia in 4. Patients with sporadic lymphedema and manifestation after puberty exhibited initial lymphatics of normal caliber. In controls mean capillary diameter was 56.3 +/- 9.0 microns, in congenital disease with ectasia 99.3 +/- 9.0 microns (difference significant at the p less than 0.005 level) and in the sporadic form 49.7 +/- 7.7 microns. Congenital lymphedema may be subdivided into a form with aplastic and ectatic microvessels which possibly show different responses to therapy.

Adolescent↗

[Determination of the release of drugs from transdermal therapeutic systems. Presentation of a new release system].

A relatively simple release model for transdermal therapeutic systems (TTS) is described. The TTS is separated from the elution solvent by a semipermeable membrane. The elution solvent passes an elution channel with a flow rate of 3-9 ml/h. For the quantitative determination of the drug HPLC or UV spectrometry are used. Depending on the active drug and the design of the TTS, different releasing kinetics are observed. While diclofenac follows approximately a zero order kinetic, the respective kinetic for mepindolol roughly follows a diffusion controlled square root of t-order.

Administration, Cutaneous↗

Subacute effects of propranolol and B 24/76 on isoproterenol-induced rat heart hypertrophy in correlation with blood pressure.

We compared the potential beta-receptor blocker, B 24/76 i.e. 1-(2,4-dichlorophenoxy)-3[2-3,4-dimethoxyphenyl)ethanolamino]-prop an-2-ol, which is characterized by beta 1-adrenoceptor blocking and beta 2-adrenoceptor stimulating properties with propranolol. The studies were performed using an experimental model of isoproterenol-induced heart hypertrophy in rats. A correlation of the blood pressure was neither found in the development nor in the attempt to suppress the development of heart hypertrophy with the two beta-receptor blockers. Both beta-blockers influenced the development of hypertrophy to a different, but not reproducible extent. It was possible to suppress the increased ornithine decarboxylase activity with both beta-blockers in hypertrophied hearts, but there was no effect on the heart mass. Neither propranolol nor B 24/76 could stop the changes in the characteristic myosin isoenzyme pattern of the hypertrophied rat heart. Thus, the investigations did not provide any evidence that the beta-receptor blockers propranolol and B 24/76 have the potency to prevent isoproterenol from producing heart hypertrophy.

Animals↗

Hereditary angioedema and aortitis.

A 28-year-old male with hereditary angioedema died of an extensive stroke. Autopsy revealed cicatricial aortitis with narrowing of the coronary ostia, myocardial infarctions, and a left ventricular mural thrombus. There was neither acute inflammation of the aorta nor systemic vasculitis. A possible association of the aortitis with the hereditary angioedema is discussed.

Adult↗

VO2 kinetics in subjects differing in aerobic capacity: investigation by spectral analysis.

The power-VO2 transfer functions of 38 subjects differing in aerobic capacity have been determined on the basis of breath-by-breath total oxygen uptake (VO2,t) measurements during light cycle ergometer exercise (lactic acid concentrations below 2 mmol.l-1). At constant pedalling frequency (1 Hz) pseudorandom binary sequences (PRBS) of workload were used as the testing signal. The VO2,t response was analysed by autocorrelating the ergometer power input and crosscorrelating the power input and VO2,t output. From the spectra of these functions the amplitude ratios and phase relationships were computed for the first six harmonics of the PRBS fundamental (14 mrad X s-1). We found that differences in aerobic capacity are associated with significant differences in the amplitude plots of the VO2 transfer function.

Adult↗

Action of intragastric ethanol on pancreatic exocrine secretion in relation to the interdigestive gastrointestinal motility in humans.

On different days, fasted volunteers were given either 100 ml of ethanol (40% v/v), glucose (isocaloric to ethanol) or distilled water intragastrically; the instillations always starting during the first observed duodenal phase I of the interdigestive migrating complex (IMC). Both ethanol and glucose produced a fed pattern of motility but only glucose significantly (P less than 0.05) delayed the reappearance of a new duodenal phase III of the IMC when compared to water. Ethanol and glucose significantly increased the 1-h duodenal bicarbonate output 7- and 16-fold, respectively. Glucose, but not ethanol, stimulated the duodenal amylase output when compared to water. Glucose, but not ethanol, caused a significant rise in plasma gastrin concentration; plasma secretin levels not being altered by both substances. We conclude that in non-alcoholic humans, an intragastric administration of ethanol in a concentration present in whisky and in an amount that is consumed in ordinary social drinking has a weak stimulatory action on pancreatic bicarbonate secretion and that this action is not mediated by release of secretin.

Adult↗

Myosin isoenzymes in normal and hypertrophied human hearts.

Distinct myosin isoforms were identified from the ventricles and atria of foetal, normal and hypertrophied human hearts. Ventricle and atrium myosins cannot be differentiated by their sedimentation behaviour in the analytical ultracentrifuge, they vary, however, with regard to the Ca2+-dependent ATPase and also the activation parameters in measurements of the enzyme activity in dependence on temperature. In agreement with other authors we observed a foetal light chain in the ventricular tissue of the latter half of gestation, when myosin was characterized by SDS-polyacrylamide gel electrophoresis and isoelectric focusing. Using pyrophosphate gel electrophoresis an additional foetal isomyosin was observed besides the typical ventricular myosin HV-3, which migrates faster. Two distinct myosin isoforms designated as HA-3 and HA-1 occur in the atrium of the normal human heart. It was found that besides their own isoenzymes normal atria also contain ventricular isomyosin, whose relative proportion is markedly increased in the hypertrophic atrium. In contrast, we usually observed only one isoenzyme in the normal ventricle. Moreover, in case of myocardial infarction a dramatic transformation of myosin heavy chain composition with a shift to an atrial myosin type took place in the ventricle.

Adult↗

Effects of a 7-day head-down tilt (-6 degrees) on the dynamics of oxygen uptake and heart rate adjustment in upright exercise.

Oxygen uptake (VO2) kinetics and heart rate (HR) kinetics were studied in six healthy male students before and on days 1,3 and 5 after a continuous 7-d antiorthostatic bedrest (-6 degrees). The exercise test protocol consisted of pseudorandom binary sequences (PRBS) of workload (W) performed on a bicycle ergometer in the upright position (20 W - 80 W, 15 bits, 30 s per bit; the sequence was repeated three times). Amplitude ratio and phase of the W-VO2 and W-HR relations were computed at six harmonic frequencies in the range 0.014 - 0.084 rad X s-1. After bedrest the VO2 kinetics was found to be impaired at the harmonic frequencies greater than 0.056 rad X s-1. Additionally, the mean heart rate during the PRBS cycles was increased (108 +/- 15 as compared to 92 +/- 10 min-1). There were no significant effects on HR kinetics and on the static W-VO2 relation. During an endurance training program both VO2 and HR changes were restored to the pre-bedrest levels. It is concluded that the impairment of VO2 kinetics can be attributed mainly to muscular factors.

Adult↗