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Biomedical subjects

R R Engel

Publications and source records attributed to R R Engel.

At least 19 recordsLinked to original sources
PubMed1992

Inhibition of glycerol-3-phosphate acyltransferase by analogs of glycerol-3-phosphate.

Analogs of glycerol-3-phosphate were tested as substrates or inhibitors of the glycerol-3-phosphate acyltransferases of mitochondria and microsomes. (rac)-3,4-Dihydroxybutyl-1-phosphonate, (rac)-glyceraldehyde 3-phosphate, (rac)-3-hydroxy-4-oxobutyl-1-phosphonate, (1S,3S)-1,3,4-trihydroxybutyl-1-phosphonate, and (1R,3S)-1,3,4 trihydroxybutyl-1-phosphonate were competitive inhibitors of both mitochondrial and microsomal sn-glycerol-3-phosphate acyltransferase activity. An isosteric analog of dihydroxyacetone phosphate, 4-hydroxy-3-oxobutyl-1-phosphonate, was a much stronger competitive inhibitor of the microsomal than the mitochondrial enzyme. Phenethyl alcohol was a noncompetitive inhibitor of both the microsomal and the mitochondrial acyltransferases. The product of the mitochondrial acyltransferase reaction with (rac)-3,4-dihydroxybutyl-1- phosphonate was almost exclusively (rac)-4-palmitoyloxy-3-hydroxybutyl-1-phosphonate. The microsomal acylation reaction generated both the monoacyl product and (S)-3,4-dipalmitoyloxybutyl-1-phosphonate. The apparent Km for (S)-3,4-dihydroxybutyl-1-phosphonate was 2.50 and 1.38 mM for the mitochondrial and microsomal enzymes, respectively.

Acylation↗
PubMed1992

Double-blind cross-over study of phosphatidylserine vs. placebo in patients with early dementia of the Alzheimer type.

Thirty-three patients with mild primary degenerative dementia according to DSM-III (MMS between 15 and 27) took part in a double-blind cross-over study of phosphatidylserine (Fidia, 300 mg/d) versus placebo. Both treatment phases lasted for 8 weeks with an 8 week washout phase in between and a 4 week washout phase before treatment phase one. Clinical global improvement ratings showed significantly more patients improving under BC-PS than under placebo during treatment phase one. The improvement carried over to the following wash-out and treatment phases. There were no significant improvements in GBS dementia rating scale, psychometric tests or P300-latency. 16-channel EEG mapping findings indicated that the patients initially showed higher power values in all frequency bands (except alpha), when compared to a younger, healthy control group. BC-PS reduced the higher power values compared to placebo, shifting EEG power more towards the normal level.

Aged↗
PubMed1992

Completeness of AIDS reporting in Switzerland: a study based on deaths between December 1987 and June 1990.

OBJECTIVES: To assess completeness and determinants of reporting to the AIDS registry of the Swiss Federal Office of Public Health. DESIGN AND METHODS: Death certificates indicative of AIDS or HIV for deaths occurring between December 1987 and June 1990 were reviewed and compared with reports to the AIDS registry. RESULTS: The completeness of the AIDS registry was 68%. However, almost all cases have now been ascertained, because more than 90% of unreported AIDS cases are detected when death certificates are reviewed. Thus, the ongoing review of death certificates adds to the total case ascertainment. The most important determinant of reporting was the reporting source: specialized AIDS clinics reported 85% of their cases, while all other sources reported only 48%. CONCLUSION: The investigation of the heterogeneity of reporting is important. It can wrongly suggest regional and national differences in the epidemic and lead to a decrease in completeness of reporting over time without actual changes in reporting behavior.

Acquired Immunodeficiency Syndrome↗
PubMed1992

A simple carbon monoxide breath test to estimate erythrocyte turnover.

Carbon monoxide is stoichiometrically released when heme is converted to bilirubin. This report describes and validates a novel technique that permits the estimation of heme turnover and red blood cell survival from the carbon monoxide concentration of end-expiratory breath samples. The end-alveolar Pco of a subject was corrected for environmental carbon monoxide exposure with a simple device that equilibrates with atmospheric carbon monoxide at the same rate as does the subject. The resultant value (endogenous Pco) was tested for its ability to predict heme turnover and red blood cell survival. Red cell survival times of 32 healthy subjects, as calculated from the endogenous Pco, averaged 101 +/- 19 days, a value close to the expected 110-day survival time; 13 patients with clinical evidence of shortened red blood cell survival times had measured erythrocyte life spans ranging from 10 to 59 days. The endogenous Pco of each of seven patients increased after red blood cell transfusion, demonstrating that this technique detected the known rapid turnover of a small fraction of transfused cells. A good correlation (r = 0.91) was observed between heme turnover calculated from endogenous Pco and total fecal biliary pigment output. Carbon monoxide measurements reflect red blood cell destruction in both the marrow and the circulation, therefore yielding shorter life spans than did chromium 51 survival studies. This breath test appears to yield a rapid, semiquantitative assessment of heme turnover and red blood cell survival that is not provided by any other presently available technique. This simple, noninvasive carbon monoxide breath test may find widespread use in the evaluation of anemia and jaundice.

Adult↗
PubMed1991

Fluoxetine versus placebo: a double-blind study with bulimic inpatients undergoing intensive psychotherapy.

In a double-blind trial 40 patients with bulimia nervosa according to DSM III-R criteria were randomly assigned either to a 60 mg fluoxetine group or to a placebo control group. Fluoxetine or placebo was given over a period of 35 days. Parallel to the drug trial, patients participated in an intensive inpatient behavioral psychotherapy program. There were no dropouts at all in the study. Fluoxetine was well tolerated and had only minor adverse effects. In self-ratings and expert ratings concerning attitudes towards eating, eating behavior, and general psychopathology, significant improvements over time were observed in both groups. Using analysis of variance (ANOVA), however, there were no statistically significant "group by time" differences. Results show that the intensive inpatient-care and psychotherapy program was highly effective in changing eating behavior and attitudes as well as general psychopathology. Fluoxetine showed a significant reduction in body weight, especially during the first three weeks of fluoxetine treatment. It was not possible to demonstrate a statistically significant improvement in eating attitudes, eating behavior, and general psychopathology beyond that elicited by intensive inpatient psychotherapy and general inpatient care. These results can possibly be explained by the existence of a "ceiling effect".

Adult↗
PubMed1990

Sensory gating in normals and schizophrenics: a failure to find strong P50 suppression in normals.

In a series of investigations, suppression of the auditory-evoked P50 potential to the second of two paired clicks presented 500 msec apart has been shown to be absent in schizophrenic patients, whereas normals suppress their second response to less than 20% of the first response. The phenomenon has been discussed as a possible trait marker for schizophrenia. The present study with 19 schizophrenics and 23 healthy control subjects was intended as an extended replication of the phenomenon using different stimulus parameters and a slightly different method of measuring P50 amplitudes. Replication was unsuccessful, revealing only weak suppression scores in normal subjects not significantly superior to schizophrenics. Retest sessions yielded generally stronger P50 suppression suggesting that the stability of the measure over time is questionable. The methodological changes are discussed as possible sources of this failure to replicate. It is concluded that the conditions under which P50-suppression occurs should be better clarified in order to facilitate replication.

Acoustic Stimulation↗
PubMed1990

Methodology of 3H-spiperone binding to lymphocytes.

Alterations in lymphocyte binding capacity for the dopamine antagonist 3H-spiperone may be of great interest in psychiatric and neurological disorders: an increase in capacity noted in lymphocytes of schizophrenic patients and their families may well turn out to be a phenotypic vulnerability marker. Since the 3H-spiperone binding assay with lymphocytes does not fulfill common receptor-binding assay criteria and depends more on crucial analytical conditions, shortcomings in binding assay might possibly lead to irreproducible results. A detailed methodological description of the binding assay and subsequent calculations has therefore been given in this paper.

Binding, Competitive↗
PubMed1990

Effects of single doses of alpidem, lorazepam, and placebo on memory and attention in healthy young and elderly volunteers.

The aim of the present study was to compare the effects of alpidem, a new imidazopyridine derivative with benzodiazepine-like anxiolytic effects, with those of lorazepam and placebo on memory and attention in two age groups of healthy volunteers. The study design was that of a randomized double-blind crossover trial with 12 young (18-30 years old) and 12 elderly (65-80) subjects. At weekly intervals, each subject was administered single oral doses of 25 mg alpidem, 50 mg alpidem, 1 mg lorazepam, and placebo in a randomized sequence. Computerized memory and attention tests were performed 90 minutes before and 320 minutes after drug administration. Lorazepam and alpidem 50 mg produced memory impairments: for verbal memory tests the difference against placebo was highly significant for both drugs, while for visual memory this impairment was significant for lorazepam only. No memory effects were seen with 25 mg alpidem. There were no significant drug effects on attention, suggesting a specific amnestic effect not explained by general sedation. Performance of the elderly subjects was much lower than that of the younger ones in both memory and attention tasks. It was not possible to observe any interaction effects between drug and age.

Adolescent↗
PubMed1990

Cognitive determinants of the postimperative negative variation.

This study examined cognitive determinants of the postimperative negative variation (PINV), a slow brain potential observable after the onset of an imperative stimulus in a forewarned reaction time task. Controllability of the aversive imperative stimulus by a motor reaction and predictability of the contingency were varied in a factorial design. The exogenous portion of the slow negative wave was assessed in a passive listening condition using tones of the same quality as the imperative stimuli, but presented without forewarning. Results show that PINV not only occurs when control is absent but also during unpredictably gained control. Similarly, unpredictable lack of control yields a more negative potential than continual helplessness. Negativity elicited by the aversive tone alone was not significantly different from PINV during predictable lack of control. The order of conditions, which was manipulated between groups, did not affect amplitudes. It was concluded that contingency change is a crucial cognitive determinant of the PINV, whereas the effect of lack of control is difficult to differentiate from the sensory influence of the acoustic stimulation.

Adult↗
PubMed1989

CO production by feces and urine.

Virtually all CO production in humans and animals is thought to result from the catabolism of heme, and endogenous CO production (VCO) is used as a measure of heme turnover. Using a rebreathing technique, we found that previously fed mice had an apparent VCO that was 40% greater than that of mice that had been fasted before the study. This unexpected result was shown to reflect an excess CO production by the excreta (feces, urine, or both) of fed mice relative to the excreta of fasted mice. Incubation of feces and urine of humans, rats, and mice demonstrated CO release that was not inhibited by autoclaving or acidification to pH 1. CO release from excreta was markedly reduced, however, under anaerobic conditions, and fed and fasted animals excreted CO at the same rate when their excreta were maintained in an anaerobic state. We conclude that feces and urine can release CO via nonenzymatic, oxidative reactions and, under some circumstances, this source of CO can influence measurements of VCO.

Animals↗
PubMed1988

Selected aspects of AIDS among homosexual men.

This report is a brief summary of important points concerning AIDS and homosexual men. We present the current overall figures of the cumulative AIDS incidence for Switzerland, the United States and the world and similar figures for homosexual men in Switzerland, the United States and Europe. A brief history of the epidemic is included with focus on the role of homosexual men. The main risk factors for acquiring HIV infection among homosexual men, including large numbers of sexual partners, receptive and intercourse and rectal douching, are mentioned with emphasis on results from "The San Francisco Men's Health Study". The development of education and prevention programs is outlined along with the role in these areas of The Swiss AIDS Foundation and Swiss Federal Office of Public Health. Decreases in high risk sexual practices and decrease in seroconversion rates are also discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Cognitive deficits in aging and therapeutic evaluation of encephalotropic substances.

Several aspects relevant for the evaluation of encephalotropic substances are presented. A) Memory improving pharmacological effects found in animal studies are often lacking in human studies. B) Global clinical measures of therapeutic success differenciate well between verum and placebo. In contrast to psychological tests, however, objectivity and reliability of global measures is low. C) Diagnosing dementia requires laboratory screening, psychiatric judgment and psychological testing. Psychological theories about age-related decline of different cognitive abilities and psychiatric DSM-III criteria of dementia are however not congruent. One reason for this discrepancy is that psychological theories seldom consider the very old, where dementia is present in sufficient degree. We were able to demonstrate this in a pilot study with 51 residents of a home for the aged, whose average age was 81 years. The subtest Similarities (WAIS), a measure of conceptual ability usually considered to be stable throughout the aging process, showed a marked decline after age 75 in accordance with the psychiatric criterion of dementia, impairment of abstract thinking.

Aged↗
PubMed1988

Perception of waking and sleeping: possible implications for the evaluation of insomnia.

Perception of awakening, its connection to electroencephalogram (EEG), and its significance for morning recall were studied in insomniacs and normals. Fourteen insomniacs and 14 age- and sex-matched controls kept a sleep log for 1 week and slept once in the laboratory (standard polygraphy). In addition, actual perception of awakening was measured by a behavioral device. Results suggest that physiological arousal is necessary, but not sufficient, for perception of awakening. Many arousals that are not perceived occur during the first REM-NREM cycle. Insomniacs nearly exclusively perceive those arousals occurring after consolidated sleep (at least 15 min) and at the beginning of interrupted sleep intervals. It is suggested that insomniacs perceive these intervals as continuous wakefulness and have difficulty in perceiving short-lasting sleep, whereas controls often do not perceive wakefulness at all. The latter may be a sleep-protecting mechanism. Number and correlation suggest that recalled awakenings are exactly those perceived. The connection between physiological and experimental subjective data is discussed.

Adult↗
PubMed1986

Psychophysiological differentiation of two types of anxiety and its pharmacological modification by minor tranquillizer and beta-receptor-blocker.

To evaluate the influence of beta-blockers and/or minor tranquillizers on autonomic reactions during brief stress, 48 healthy subjects were randomised into 4 groups: A = 4 mg Pindolol, B = 1.5 mg Cloxazolam, C = Placebo, D = 4 mg Pindolol + 1.5 mg Cloxazolam. Subjects underwent four stress situations: Counting, noise, mental arithmetic and ergometry, each lasting 4 min with rest periods of 8 min in between. Electromyogram, finger pulse amplitude, heart rate, pulse wave velocity and electrodermal activity were recorded simultaneously on-line. Analysis of variance showed that the two drugs had significant main effects in different systems: Pindolol reduced heart rate, mainly during mental arithmetic and ergometry, Cloxazolam reduced electrodermal activity, mainly during noise. It can be concluded that different structured situations with a varying amount and type of anxiety induce different autonomic reactions; these reactions can be differentially modified by the drugs applied.

Adult↗
PubMed1985

Tin protoporphyrin inhibits carbon monoxide production in adult mice.

We studied the effect of tin protoporphyrin, a potent inhibitor of heme oxygenase (EC 1.14.99.3), on carbon monoxide (CO) production in mature mice. Measurements of CO production provide a sensitive, noninvasive means of quantitating heme catabolism. CO accumulation in the gas space of closed chambers was decreased by about 25% for mice treated with two 50 nmol/g doses of tin protoporphyrin as compared to saline-treated controls. Calculated rates of CO production were 0.28 +/- 0.07 and 0.40 +/- 0.05 nmol X g-1 X h-1 for mice injected with tin protoporphyrin and saline, respectively (p less than 0.01). When hemin (125 nmol/g) was administered to simulate hemolysis, CO production increased markedly in both saline- and tin protoporphyrin-treated mice. However, the rate of CO production in tin protoporphyrin-treated mice was only 44% that of saline-treated animals (p less than 0.0001). These studies demonstrate that tin protoporphyrin inhibits heme catabolism in both the basal- and heme-loaded states and confirm that this inhibition is at the heme oxygenase step in the heme to bilirubin pathway.

Animals↗