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Biomedical subjects

H Howald

Publications and source records attributed to H Howald.

At least 19 recordsLinked to original sources

Prediction of phenotype for acetylation and for debrisoquine hydroxylation by DNA-tests in healthy human volunteers.

The debrisoquine/sparteine-type polymorphism of drug oxidation and the polymorphism for acetylation are two common inherited variations in human drug metabolism. The phenotypes for hydroxylation and acetylation can be predicted be newly developed methods based on mutation-specific amplification of DNA by the polymerase chain reaction (PCR), which also allow for identification of heterozygous carriers of one mutant allele. In the present study, the results of genotyping of 81 healthy European volunteers were compared with the phenotype obtained by the classical biochemical approach using debrisoquine and caffeine as probe drugs. Genotyping correctly predicted all 73 extensive metabolisers (EMs) and 6 out of 8 poor metabolisers (PMs) of debrisoquine. All 48 rapid acetylators and 33 of 35 slow acetylators were predicted. Overall, the DNA analysis result matched the in vivo phenotype in 97.5% of individuals.

Acetylation

Acceptance of isotonic and hypotonic rehydrating beverages by athletes during training.

This study compared the acceptance of two beverages (5% carbohydrate) of distinct osmolarities (hypotonic, 180 mOsm/kg and isotonic, 295 mOsm/kg) during the usual training practice of 97 athletes. A quantitative sensory profile by independent tasters ensured that organoleptic recognition would be unlikely during the tests. Each drink was consumed ad libitum during 3 different training sessions, at home. At each session, a subjective appreciation of hedonic and post-ingestive physiological effects (6 criteria) was obtained by means of a questionnaire. At the end of the experiment, the athletes were asked to express a preference for one of the "six" drinks. More athletes (blindly) chose the isotonic compared to the hypotonic drink (p = 0.03). This difference was not due intrinsically to the drinks, which the subjects were unable to distinguish on any of the criteria, but was related to certain aspects of the consumer's characteristics. Both groups had different drinking practices: the subjects choosing the isotonic beverage drank less before (p = 0.001) and more during (p = 0.013) the exercise. Age, sex, dimensions or type of physical activity (i.e. endurance vs speed/strength disciplines) were unrelated to the preference, except perhaps the duration of habitual exercise (p less than 0.05). We concluded that athletes, although unable to distinguish a hypotonic from an isotonic drink, may have specific habits and/or personal characteristics prompting them to favour one of them.

Adult

[Weaning of young smokers using a transdermal nicotine patch].

To assess efficacy and tolerance of a transdermal nicotine system (TNS) as adjuvant to tobacco withdrawal, 112 young, nicotine-dependent cigarette smokers were treated for nine weeks with TNS (n = 56) or placebo (n = 56). Initial doses of nicotine (21 or 14 mg/24 h) were based on previous smoking habits and stepwise reduced to 7 mg/24 h if abstinence was achieved during medication. After treatment, 39.3% of the TNS users were abstinent versus 19.6% on placebo (p less than 0.05). The craving for cigarettes diminished steadily, but not more significantly on TNS medication. Tenseness, difficulty in concentration and feelings of hunger were consistently and in part significantly lessened in the TNS group. The other withdrawal symptoms were not influenced by TNS treatment. Nine-month follow-up cotinine-verified abstinence rates were 12.5% in the TNS and 3.6% in the placebo group (n. s.). Transient mild or moderate erythema at the application site appeared in 20% of the TNS and 6.3% of the placebo group, and 7.1% of the TNS users dropped out because of severe localized erythema. Other mild, transient, systemic side effects reported by 33.9% of the TNS and 26.8% of the placebo users (n. s.) did not lead to drop-outs.

Administration, Cutaneous

Arterial and endocrine effects of a combination of an angiotensin converting enzyme inhibitor and a vasodilator in normotensive healthy volunteers.

The aim of the present study was to look for possible additive or synergistic effects of the combined oral administration of a single dose of an angiotensin converting enzyme (ACE) inhibitor, benazepril (10 mg) (B), and a long-acting vasodilator, cadralazine (5 mg) (C), on blood pressure, arterial parameters, and active plasma renin. The study was carried out in eight normotensive subjects according to a double-blind, randomized, placebo-controlled, crossover design. Blood pressure (BP), heart rate, humeral artery diameter (D), carotid-femoral pulse-wave velocity (PWV), finger-pulse ratio (FPR), and plasma active renin (PAR) were measured at baseline and every 2 h over 8 h. A significant treatment effect was observed for supine and tilted BP, FPR, PWV, and PAR. The largest decrease in supine systolic and diastolic BP was observed with the combination (10.0 +/- 6.9/7.2 +/- 3.7 mm Hg). Six hours after drug intake, the mean changes in FPR were 0.05 +/- 0.24 (P), -0.06 +/- 0.30 (C), 0.13 +/- 0.32 (B), and 0.28 +/- 0.34 (B + C), and the mean changes in PWV were 0.14 +/- 0.66 m/s (P), 0.09 +/- 0.54 m/s (C), -0.29 +/- 0.50 m/s (B), and -0.55 +/- 0.48 m/s (B + C). PAR was more markedly augmented with the combination of the two drugs (142 +/- 40 pg/ml) than with benazepril alone (90 +/- 62 pg/ml). It was concluded that a single noneffective dose of a vasodilator administered together with an ACE inhibitor in normotensives can lower blood pressure and increase arterial compliance and plasma active renin.

Administration, Oral

Adverse skin reactions to nicotine in a transdermal therapeutic system.

Nicotine in a transdermal therapeutic system (TTS) has been introduced recently to help people to stop smoking. 14 volunteers (10 male, 4 female) with a history of former adverse skin reactions to this device were investigated. Skin tests for contact urticaria and patch tests for contact allergy were done with the individual components of the TTS. Contact sensitization to nicotine was identified in 5 and to the TTS itself in 1 individual. Irritant reactions due to occlusion were present in 9 subjects. The optimal test agent and concentration for elucidating the adverse skin reaction was an aqueous solution of 10% nicotine base. Atopy, as diagnosed by history and skin prick tests to common inhalant allergens, and contact sensitization to standard patch test allergens, were each identified in 6 subjects. Nicotine should be added to the expanding list of transdermally delivered drugs which may elicit contact dermatitis.

Administration, Cutaneous

Fifteen-year changes in exercise, aerobic power, abdominal fat, and serum lipids in runners and controls.

To describe effects of past as well as current exercise, aerobic power, and subcutaneous fat on the serum lipid profile, two groups of former elite athletes (N = 27 runners, N = 9 bobsledders) and a control group of normal men (N = 23) were investigated. Analysis of variance indicated a significant effect of the type of sports activity on HDL cholesterol, apolipoprotein A-I, and triglyceride levels and on the LDL/HDL cholesterol and apolipoprotein B/A-I ratios, with the most favorable values seen in runners and the least favorable values seen in controls. Of the 27 former elite runners, one third (N = 9) had given up or strongly reduced training. This subgroup showed the steepest 15-yr decrease (from 1973 to 1988) in maximum aerobic power and the largest 15-yr increase in subcutaneous fat, and the lipid profile (measured in 1988) corresponded more to the one of bobsledders and controls than to the one of runners who had remained active. Separate correlational analyses of all runners (N = 27) and nonrunners (N = 32) showed that, in both cohorts, i) the 1988 measurements of exercise, aerobic power, and subcutaneous fat were more predictive for the lipid profile in 1988 than the corresponding 1973 values, ii) anthropometric characteristics, especially abdominal fat, had a stronger relation with serum lipid concentrations than exercise and aerobic power, and iii) 15-yr changes in anthropometric characteristics were, but 15-yr changes in exercise and aerobic power were not, associated with triglyceride, lipoprotein, and apolipoprotein levels in 1988.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen

Human muscle structure after exposure to extreme altitude.

Muscle structural changes during typical mountaineering expeditions to the Himalayas were assessed on muscle biopsies. A significant reduction in muscle fiber size (-20%) and a loss of muscle oxidative capacity (-25%) were observed. The capillary network was not affected by catabolism. It is concluded that the oxygen supply to muscle mitochondria after high altitude exposure is thus improved.

Altitude

Muscle lipofuscin content and satellite cell volume is increased after high altitude exposure in humans.

Muscle ultrastructural changes during a typical expedition to the Himalayas were analyzed by taking muscle biopsies from seven climbers before and after their sojourn at high altitude (over 5000 m for 8 weeks). M. vastus lateralis samples were analyzed morphometrically from electron micrographs. A quantitative evaluation was made of lipofuscin, satellite cells and myonuclei. Significant increases of the volume densities of lipofuscin (+ 235%) and satellite cells (+ 215%) were observed.

Altitude

The use of transdermal nicotine in smoking cessation.

The transdermal administration of nicotine by means of a transdermal nicotine system (TNS) affords a novel way of nicotine replacement to alleviate smoking cessation. The plasma levels of nicotine maintained with the TNS are in the range of the footpoint concentrations observed in smokers. The efficacy of the TNS was investigated in two placebo-controlled double-blind smoking cessation programs with minimal contact and minimal psychological support. A total of 311 smokers were treated for 3 months or 9 weeks. The abstinence rates at the end of the treatment and weaning periods were almost doubled in the TNS groups (36% and 39%) as compared to the placebo groups (23% and 20%) with a significant difference for both studies (p less than 0.05). These data suggest that the TNS can also improve the smoking cessation rates under the conditions of general medical advice, making it suitable for use outside of specialized smoking cessation centers.

Administration, Cutaneous

Eating problems and calorie intake levels in Swiss adolescent athletes.

The purpose of this study was to investigate the incidence of eating disorders (ED), calorie intake levels and body fat measures in Swiss female athletes. Thirty athletic and 34 non-athletic adolescent Swiss females were assessed for tendencies toward eating disorders and weight preoccupation using the Eating Disorders Inventory (EDI). Calorie intakes were calculated from 7-day intake records. Body compositions were determined using skin-fold measures. The athletes were divided into two groups: Those whose activities emphasize leanness (12 gymnasts, means age = 12.5 +/- 1.1 yrs), and those whose activities do not emphasize leanness (18 swimmers, mean age = 12.8 +/- 0.9 yrs). The non-athletic school-girls (mean age = 13.4 +/- 1.2 yrs) served as controls. ANOVA indicated that the gymnasts had lower body fat levels (p less than 0.01) and consumed fewer total calories (p less than 0.05) than swimmers or controls, but all groups consumed similar calories per kg/body weight. Chi square analysis indicated that similar numbers of swimmers (11%), gymnasts (1%) and controls (6%) were exceptionally preoccupied with weight (p greater than 0.05). However, more swimmers (38%) scored high on the body dissatisfaction subscale of the EDI than the gymnasts (1%) or control (9%) (p less than 0.01). In fact, more swimmers scored high on 3 subscales of the EDI compared to the other groups (p less than 0.05). It appears that disturbances in eating behaviors are not limited to sports that emphasize leanness.

Adolescent

Morphological adaptations of human skeletal muscle to chronic hypoxia.

Muscle structural changes during typical mountaineering expeditions to the Himalayas were assessed by taking muscle biopsies from 14 mountaineers before and after their sojourn at high altitude (greater than 5000 m for over 8 weeks). M. vastus lateralis samples were analyzed morphometrically from electron micrographs. A significant reduction (-10%) of muscle cross-sectional area was found on CT scans of the thigh. Morphologically this loss in muscle mass appeared as a decrease in muscle fiber size mainly due to a loss of myofibrillar proteins. A loss of muscle oxidative capacity was also evident, as indicated by a decrease in the volume of muscle mitochondria (-25%). In contrast, the capillary network was mostly spared from catabolism. It is therefore concluded that oxygen availability to muscle mitochondria after prolonged high-altitude exposure in humans is improved due to an unchanged capillary network, supplying a reduced muscle oxidative capacity.

Acclimatization

Effect of chronic hypoxia on muscle enzyme activities.

Biopsies from the vastus lateralis muscle of seven participants in the Swiss expedition to Mt. Everest and Lhotse in 1986 were taken before departure to and after return from high altitude, and used for measurements of maximal activities of 12 reference enzymes of anaerobic and aerobic-oxidative metabolic pathways. The results indicated that strenuous exercise at high altitude induced increases in enzyme activities of glycolysis and decreases in enzyme activities of terminal substrate oxidation (the citric acid cycle, fatty acid oxidation, ketone body utilization, respiratory chain). The decreases in enzyme activities of aerobic-oxidative metabolism were related to similar decrements in mitochondrial volume density, which suggests that the enzymic changes resulted from a loss of mitochondrial structure rather than from qualitative changes of the mitochondrial population. These changes indicated that strenuous exercise may intensify the stress of high-altitude exposure and, thus, induce an aerobic to anaerobic shift of muscle energy metabolism.

Acclimatization

Oxygen transport system before and after exposure to chronic hypoxia.

Maximal VO2 on the treadmill (VO2max) and on the bicycle ergometer (VO2peak), maximal cardiac output (Qmax), by a CO2 rebreathing method, maximal heart rate (HRmax), blood hemoglobin concentration (Hb), and hematocrit (Hct) were measured on six subjects before (B) and 3 weeks after (A) prolonged exposure to chronic hypoxia. It was observed that after high-altitude exposure VO2max, VO2peak, and Qmax were lower (P less than 005) than before [A: 4.13 +/- 0.67; 3.28 +/- 0.41 and 16.89 +/- 2.49 (l/min +/- SD); B: 4.39 +/- 0.39; 3.53 +/- 0.34 and 21.81 +/- 1.27, respectively], whereas Hb and Hct were larger (A: 162 +/- 8 g/l and 0.46 +/- 0.02; B: 142 +/- 7 and 0.41 +/- 0.02) and HRmax was unchanged (178 +/- 7 vs 175 +/- 9 bts/min). Thus, the calculated stroke volume of the heart and the Hb flow at VO2 peak were lower in A than in B (95 +/- 15 vs 124 +/- 7 ml and 2,723 +/- 307 vs 3,129 +/- 196 g/min) (P less than 0.05, respectively), whereas the arteriovenous O2 difference was greater in A than in B (195 +/- 16 vs 162 +/- 19 ml O2/l; P less than 0.05). At any given submaximal work load, VO2 and HR were the same in B and in A, whereas Q was lower in A by approximately 2-3 l/min. However, because of the increased Hb, leading to a higher arterial O2 content, at any work load the O2 flow remained unchanged.

Acclimatization

[Risk of arthrosis of the upper ankle joint in long distance runners: controlled follow-up of former elite athletes].

To study the potential influence of long-term, high-intensity physical training on premature osteoarthrosis of the ankle joint, we re-examined former members of the Swiss National team from 1973 in retrospective cohort study in 1988. Twenty-seven track and field long-distance runners and orienteers (mean age 42 [95% confidence interval 41-43] years), 9 bobsledders (42 [39-46] years) and a control group of 23 healthy normal men (35 [33-36] years) were investigated. Physiological and exercise characteristics of all subjects had been recorded in 1973, and in 1988 these measurements were repeated together with a rheumatological and radiological examination of the ankle joint. A four-point scale of radiological joint state was used, taking into account the degree of subchondral sclerosis, osteophyte formation and joint space narrowing. In univariate analysis, the long-distance runners, and among them especially the orienteers (n = 10), showed significantly (both p less than 0.05) more radiological signs of degenerative ankle disease than controls. After adjustment for age, this difference disappeared. Age was itself significantly and positively related to radiological degenerative ankle disease (r less than 0.38; p less than 0.01). Orienteers reported significantly more frequently (60 vs 12%; p less than 0,01) functional instability of the ankle joint than track and field runners. Functional and mechanical (clinical) instability were interrelated in our material (r = 0.33; p less than 0.05) but neither of them was significantly related to radiological signs of degenerative ankle disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Long-term effects of physical training on aerobic capacity: controlled study of former elite athletes.

We studied 15-yr changes in physical training, subcutaneous fat, and maximal oxygen consumption (VO2 max) in male former elite athletes (27 long-distance runners and 9 bobsledders) and in a control group of 23 normal men. In 1973, elite athletes all trained vigorously, whereas in 1988 there was a great interindividual variation in physical training. In the lowest tertile of runners' training activity in 1988 (n = 9), the rate of decline in VO2max during the 15 yr was 1.11 +/- 0.15 (SE) ml.kg-1.min-1.yr-1, or 16% per decade, whereas the most active quintile of runners (n = 5) tended to increase VO2max (NS). The remaining 13 runners showed a rate of decline in VO2max of 0.54 +/- 0.14 ml.kg-1.min-1.yr-1, or 7% per decade. The rates of decline were 0.22 +/- 0.12 and 0.56 +/- 0.10 ml.kg-1.min-1.yr-1, or 5 and 11% per decade, in bobsledders and controls, respectively. When normalized for lean body mass instead of body weight, VO2max showed a reduced variability in the rate of decline, with values ranging from 0.00 +/- 0.27 (most active runners) to 0.69 +/- 0.15 ml.kg lean body mass-1.min-1.yr-1 (least active runners). In multiple linear regression analysis, 15-yr changes in mileage, running pace, and truncal fat together explained 51% of variance in the 15-yr change of VO2max normalized for body weight in runners and 41% in all study men. In runners, change in truncal fat was dependent on changes in both mileage and running pace. In the presence of physical training and anthropometric variables in the regression equation, the 15-yr decrease in maximum heart rate was only modestly predictive of the change in VO2max.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue

Neurosonographic assessment of twin pairs in the perinatal period.

Twins have higher rates of perinatal mortality, prematurity and its complications, low birth weight, intrauterine growth retardation, congenital anomalies and long-term developmental morbidity. In 31 twin pairs we evaluated the incidence and severity of peri-intraventricular hemorrhage (PIVH) and post-hemorrhagic ventricular dilatation. On ultrasonography minor PIVH (grades I and II) was observed in 26% of A twins and 25% of B twins (p less than 0.5). Major PIVH (grades III and IV) was less common, occurring in 3% of A twins and 6% of B twins (p less than 0.5). Ventriculomegaly, mostly regressive was equally distributed between the two groups of babies. From these results it can be concluded that with efficient antenatal care and skillful perinatal management of twin pregnancy, the incidence of major perinatal neurological complications such as PIVH and ventriculomegaly are not higher in the second-born twin.

Cerebral Hemorrhage

[Muscle structure and aerobic performance capacity in recruit training school].

The aerobic performance capacity (VO2 max) and muscle ultrastructural composition was analyzed in 18 subjects undergoing basic training in the Swiss army. Three groups were selected based on their sports activity. Group S contained subjects that had a previous systematic background in sports activities and trained regularly at least three times per week. A second group consisted of subjects that had no previous training and were subjected to an additional, individually adjusted endurance exercise (three times per week) for the first 8 weeks of their service period (group T). The control group (C) had no previous training and followed only the regular military duties. VO2 max was found to be significantly higher in group S at the beginning of the military service. However, VO2 max did not change significantly during the service period in any of the groups, Muscle mitochondria showed a significant change (+19%) only in group T. Heart rate recordings indicated that despite "strenuous" military activity, heart rates rarely reached levels sufficient for an increase in aerobic performance capacity.

Adult