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Biomedical subjects

R D Cohen

Publications and source records attributed to R D Cohen.

At least 127 records · Page 7Linked to original sources
PubMed1985

The effect of arginine vasopressin on ureagenesis in isolated rat hepatocytes.

The effect of arginine vasopressin (AVP) on ureagenesis was measured in isolated rat hepatocytes with ammonium chloride and L(+)-lactate as substrates. AVP was found to stimulate urea synthesis and the dose-response curve suggests that such an effect is present at concentrations of the hormone as low as 25-50 pmol/l. Both the dose-response curve and the concentrations of NH+4 employed suggest that the effect observed could be of physiological significance.

Animals↗
PubMed1985

Vitamin D metabolites in idiopathic infantile hypercalcaemia.

Metabolites of vitamin D were measured in plasma from 83 patients with idiopathic infantile hypercalcaemia syndrome who were mentally handicapped but had normal calcium values at the time of the study. No significant difference was detected in the mean plasma concentrations of 25-hydroxyvitamin D2, 1,25-dihydroxyvitamin D, 24,25-dihydroxyvitamin D3, or 25,26-dihydroxyvitamin D3 between patients and age matched controls. The mean plasma concentration of 25-hydroxyvitamin D3 was significantly lower in patients than controls but this may be a secondary phenomenon related to less sunlight exposure. In addition, two hypercalcaemic patients with this syndrome were studied during the first year of life, and were found to have normal concentrations of vitamin D metabolites. These findings do not support a role for abnormal vitamin D metabolism in the pathogenesis of this syndrome.

24,25-Dihydroxyvitamin D 3↗
PubMed1985

Does serum angiotensin converting enzyme reflect intensity of alveolitis in sarcoidosis?

Serum angiotensin converting enzyme activity is increased in many patients with pulmonary sarcoidosis and has been proposed as a measure of disease activity. Assay of serum angiotensin converting enzyme, bronchoalveolar lavage, and gallium scans were performed in 27 patients with biopsy proved pulmonary sarcoidosis. There was a positive correlation between serum angiotensin converting enzyme activity and an index of pulmonary gallium uptake assessed by the National Institutes of Health method (r = 0.7, p less than 0.001). There was no significant relationship (r = 0.19) between serum angiotensin converting enzyme activity and bronchoalveolar lavage lymphocytes expressed as a proportion of cells recovered. Increase in the enzyme activity had a sensitivity of 50% as a means of detecting high intensity alveolitis but specificity was only 45%. There was no significant difference in mean angiotensin converting enzyme activity between the following groups: those with positive and those with negative gallium scans; those with bronchoalveolar lavage lymphocyte counts less than or equal to 28% and those with counts greater than 28%. Although there was a significant correlation between the enzyme activity and one component of the alveolitis of sarcoidosis, the data suggest that serum angiotensin converting enzyme activity alone is neither sensitive nor specific enough for high intensity alveolitis.

Female↗
PubMed1984

L(+)-Lactate binding to preparations of rat hepatocyte plasma membranes.

Incubation of rat hepatocyte plasma membranes with L-[14C]lactate resulted in the labeling of protein(s) of apparent molecular weight 40,000 when examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The binding was saturable, irreversible, and inhibited by pyruvate, 2-oxoglutarate, and alpha-cyano-3-hydroxycinnamate, but not by D-lactate. It was markedly enhanced by L-alanine, but not D-alanine or beta-alanine. The binding protein(s) could be solubilized in cholic acid giving a single peak on gel filtration corresponding to a molecular weight of 26,000 and an isoelectric point of 5.1. This peak, when subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis, ran in a position corresponding to an apparent molecular weight of 40,000. When membranes were treated with Triton X-100, lactate binding was retained by the Triton-insoluble fraction. The binding of L-[14C]lactate increased with incubation time, due apparently to the appearance of new binding sites and not to sequestration into vesicles. As many of the characteristics of lactate binding to rat hepatocyte plasma membranes were found to be similar to those of lactate entry into isolated hepatocytes, we speculate that the lactate-binding protein could represent part or whole of a plasma-membrane lactate transporter. Lactate-binding proteins of the same molecular weight were identified in the plasma membranes from rat erythrocytes, cardiac muscle, skeletal muscle, lung, and brain.

Animals↗
PubMed1984

The mechanism of inhibition of ureogenesis by acidosis.

In perfused rat liver a decrease of cytosol pH, determined with pH-sensitive microelectrodes, from 7.2 to 6.85 is associated with a 50% fall in ureogenesis from ammonium chloride. In isolated rat hepatocytes the fall in ureogenesis due to acidosis is associated with decrease in the mitochondrial and cytosolic concentration of citrulline. Limitation of carbamoyl phosphate synthesis and thus citrulline supply could be responsible for the inhibition of ureogenesis observed.

Acidosis↗
PubMed1984

Idiopathic infantile hypercalcaemia--a continuing enigma.

Seventy six children with documented Fanconi-type idiopathic infantile hypercalcaemia were studied and compared with 41 with the Williams-Beuren syndrome. Clinical comparison showed, as expected, very close similarities but also considerable differences, particularly in the severity of feeding problems and the degree of failure to thrive. The estimated incidence of idiopathic infantile hypercalcaemia alone has remained constant for the past 20 years, at approximately 18 cases per year in the United Kingdom (1 per 47 000 total live births). Long term morbidity in these children is mainly due to mental handicap and arteriopathy, but hypertension (29%), kyphoscoliosis (19%), hyperacusis (75%), and obesity (50%) may be added complications. In one child, hypercalcaemia recurred during adolescence but this seems to be excessively rare. More detailed investigation before treatment is required to discover the aetiology of hypercalcaemia in this condition.

Aortic Valve Stenosis↗
PubMed1984

Incidence of metabolic bone disease in rheumatoid arthritis and osteoarthritis.

Bone biopsy specimens from the iliac crest were obtained during surgical operations from 45 patients with rheumatoid arthritis (RA) and 41 with osteoarthritis (OA). Control material was obtained from 20 cases of sudden death due to cardiovascular disease. By both conventional histology and image analysis techniques about a quarter of all patients showed some osteoporosis. This was equally common among the OA and RA patients. It was more common among those with transparent skin and those taking corticosteroids. The only case showing mild osteomalacia suffered from OA. No gross differences were apparent between the groups in relation to plasma biochemical studies, diet, or exposure to sunlight. These results are in striking contrast to the high incidence of osteomalacia in RA reported from the west of England; moreover they do not confirm reports of hypercalcaemia among rheumatoid subjects. We conclude that the differences regarding osteomalacia are due to selection of cases. We find no evidence that osteomalacia is specifically associated with RA.

Aged↗
PubMed1984

Pulmonary disposition of moxalactam.

Moxalactam is a new synthetic oxa-beta-lactam antibiotic with a broad spectrum of activity against Gram-positive and Gram-negative aerobic and anaerobic bacteria. It has proven clinical efficacy in pneumonia caused by a variety of infecting organisms. Therapeutic concentrations of moxalactam are achieved in most body tissues and fluids, including pleural fluid and sputum. However, assessment of the adequacy of lung tissue levels in pneumonia requires the sampling of material at an alveolar level. We performed bronchoalveolar lavage (BAL) in 13 patients one hour after they had been given moxalactam intravenously in doses ranging from 250 mg to 2 g. Absolute alveolar drug levels ranged from less than 1 to 6 micrograms/ml, and serum levels from 8 to 50 micrograms/ml. When expressed per micromole of creatinine, there was a significant relationship (r = 0.85; p less than 0.01) between serum and alveolar moxalactam levels in those patients in whom the drug concentration could be quantified accurately in BAL fluid.

Adult↗
PubMed1983

Health-related experimental learning for college undergraduates.

Guided service experience commonly enriches medical education at the doctoral and postdoctoral levels but rarely has been offered to premedical students. Internships in health agencies were individually arranged for 198 self-selected college undergraduates in 101 different settings which emphasized the social, economic, and interpersonal factors in health care. Students served as nursing aides, clinical assistants, and health educators and in other nontechnical roles; each wrote an analytical report based upon a study plan and firsthand observations. The expectations of both students and host institutions were usually exceeded. Benefits included help in career decisions, exercise in self-directed learning, and demonstration of noncognitive qualities desired in professional work. The authors conclude that undergraduate students are competent to deal with sensitive ethical and social issues in patient care and to provide needed health services of high quality.

Education, Medical, Undergraduate↗
PubMed1982

Near-fatal bronchospasm in an asthmatic patient following ingestion of flurbiprofen. A case report.

Aspirin and other inhibitors of prostaglandin synthetase are known to precipitate bronchospasm in sensitive individuals. We describe a 42-year-old patient with mild asthma who had a near-fatal attack of bronchospasm and required intermittent positive pressure ventilation and resuscitation following ingestion of a single tablet of flurbiprofen (Froben; Boots). When prescribing such agents, an appropriate history should be taken, and when asthma or hypersensitivity to related drugs is suspected, oral challenge with a small test dose and administration of the first dose under supervision are essential.

Adult↗
PubMed1982

The techniques and uses of intracellular pH measurements.

Weak-acid, 31P-nuclear magnetic resonance (NMR) and microelectrode techniques for measuring intracellular pH (pHi) are compared by demonstration of their use in rat liver. The ultimate test of suitability of these methods is the confidence with which they can be used to clarify aspects of metabolic regulation, translocation of substances across biological membranes, and the control of cell pH itself. Though resting pHi in perfused liver is fairly similar with all three techniques, substantial quantitative differences between values obtained with 31P NMR and microelectrodes are revealed after addition of fructose to the perfused liver preparation. The use and limitations of weak-acid methods in determining the mechanism of inhibition of gluconeogenesis from lactate by acidosis and in determining the pH responsiveness of the lactate transporter in the hepatocyte plasma membrane are demonstrated. Microelectrode-derived values of pHi are probably referable to the bulk phase of the cytosol, whereas values from the other two methods are more complex in their interpretation. Microelectrode and NMR methods have the great advantage of being non-destructive, and continuous records may be obtained.

Animals↗
PubMed1982

Evidence for a lactate transporter in the plasma membrane of the rat hepatocyte.

1. The rate of uptake in 15 s of L- and D-lactate was studied in isolated hepatocyte preparations from starved rats. 2. Observations were also made of the effect of different concentrations of unlabelled L- and D-lactate on L-[14C]- and D-[14C]-lactate uptake. 3. Lactate uptake into hepatocytes appears to occur by two processes, one saturable and at least partially stereospecific, the other non-saturable, at least up to 28 mmol/l, and probably representing simple non-carrier assisted diffusion. 4. The 15 s uptake of lactate is inhibited by alpha-cyano-3-hydroxycinnamate and by rho-chloromercuriphenylsulphonate but not by the general anion transporter inhibitor 4-acetamido-4'-isothiocyanostilbene-2,2'-disulphonic acid, ouabain or the structural analogue DL-rho-hydroxyphenyl-lactate. 5. Transporter-mediated lactate entry into liver cells is enhanced by lowered extracellular pH. 6. It is suggested that the contribution of the diffusion component of lactate entry into the cell may be exaggerated by the artifactual nature of the isolated hepatocyte preparation, and that under some circumstances in vivo, lactate transport into hepatocytes could determine the rate of lactate removal from blood.

Animals↗
PubMed1982

Metabolic inter-relationships of intracellular pH measured by double-barrelled micro-electrodes in perfused rat liver.

1. Intracellular pH (pHi) was measured under differing conditions in the functionally isolated, perfused rat liver using double-barrelled recessed-tip micro-electrodes. 2. Under normal acid-base conditions mean hepatic pHi was 7.18. 3. Over the range studied, hepatic pHi was negatively and linearly related to the logarithm of perfusate PCO2. 4. Measurement of pHi together with measurement of pHe and intracellular and extracellular lactate concentrations suggested a non-equilibrium distribution of lactate and lactic acid across the hepatic cell membrane requiring an active transport process for entry of lactate to the cell. 5. Upon addition of D-fructose (10 mM) to the perfusate there was a rapid fall in pHi of between 0.2 and 0.54 units, which was substantially greater than observed in earlier similar experiments in which 31P-nuclear magnetic resonance was used to measure pHi. Reasons for this discrepancy are considered.

Animals↗