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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

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

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

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

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

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

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

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

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

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

Thyroid function in preterm infants with respiratory distress syndrome.

Thyroid function was evaluated in premature infants 30 to 35 weeks EGA with severe RDS and was compared to that of healthy control subjects of similar EGA. The infants with RDS had significantly lower serum levels of T3, T4, and FT4I during the first 60, 90, and 30 days, respectively, and had elevated T3UR during the first 10 days. The mean (+/- SD) postdelivery TSH peak was lower in the RDS group (32.8 +/- 9.6 muU/ml) than in the control group (60.9 +/- 21.8 muU/ml; P less than 0.005). After TRH injection the increment in serum TSH was inversely related to the basal FT4I in the control infants but not in the infants with RDS.

Gestational Age

Essential fatty acid deficiency in neonates: inability to reverse deficiency by topical applications of EFA-rich oil.

Correction of essential fatty acid deficiency by transcutaneous absorption of topically applied EFA-rich oil has been reported. We measured serum EFA levels in two groups of neonates receiving fat-free total parenteral nutrition: nine control patients after 16 and 25 days of TPN, and six patients before and 12 days after beginning cutaneous application of 100 mg/kg/day of linoleic acid as sunflower seed oil. Progressive biochemical EFA deficiency occurred in all but one of the control patients. Of the six patients receiving 100 mg/kg/day of linoleic acid, one patient with mild deficiency improved, but progressive EFA deficiency occurred in the other five patients. Serum EFA levels were also measured in four patients following 76 days of TPN and daily application of high doses of topical safflower oil, all of whom had severe biochemical EFA deficiency. The topical application of EFA-rich oil cannot be assumed to be uniformly effective in reversing or preventing EFA deficiency. The transcutaneous absorption of essential fatty acids must be documented by appropriate measurements of EFA in serum lipids.

Administration, Topical

Effect of phototherapy on serum bilirubin levels and red blood cell survival in congenitally jaundiced Gunn rats.

Although phototherapy with blue fluorescent light effectively lowered the serum bilirubin concentration in congenitally jaundiced Gunn rats, no effect on red blood cell surivival as determined by chromium-51 labeling of homologous red blood cells and carboxyhemoglobin concentration was observed. Furthermore, attempts to demonstrate metabolic stress to the red blood cells failed to show increased glucose consumption. No oxidant damage to red cells as reflected by methemoglobin production and Heinz body formation was observed. Thus the anticipated hemolysis secondary to oxidant damage to red blood cells from phototherapy was not found.

Animals

Host heme catabolism in drug-sensitive and drug-resistant malaria.

Chloroquine resistance has arisen in both human and murine forms of malaria. CR Plasmodium berghei in mice does not produce the malaria pigment which is characteristic of the CS form. Determinations of carbon monoxide production (i.e., host heme catabolism) by individual mice revealed that those infected with CS P. berghei produce only one fourth as much carbon monoxide as do CR infected mice at all levels of infection. These observations confirm the idea that malaria pigment is composed of precipitated host cell hemoglobin and suggest that drug resistance is accompanied by a basic alteration in parasite-mediated hemoglobin catabolism.

Animals

Influence of amylase assay technique on renal clearance of amylase-creatinine ratio.

The influence of amylase assay technique on the renal amylase/creatinine clearance measurement was determined by analysis of serum and urine specimens obtained from 10 normal subjects. CAm/CCr averaged 2.19 +/- 0.18% with a saccharogenic technique, 1.52 +/- 0.2% with an iodometric technique, and 0.80 +/- 0.08% with a chromogenic technique. Each of these values differed significantly (P less than 0.05) from the other two. Recovery studies were carried out by adding partially purified human salivary or pancreatic amylase to human newborn serum or urine (which contain minimal endogenous amylase). Equal amylase activity was recovered from serum and urine by the saccharogenic technique whereas recovery from urine was less than 50% of that from serum using the iodometric and chromogenic techniques. The accuracy of the chromogenic technique is markedly improved by the addition of albumin to the urine assay system. Although it appears that only the saccharogenic method provides an accurate estimate of CAm/CCr, each assay technique distinguished the elevated CAm/CCr of patients with pancreatitis from the normal range established for that technique. Accurate clinical interpretation of CAm/CCr measurment requires knowledge of the amylase assay technique used.

Amylases