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Biomedical subjects

A M Shepherd

Publications and source records attributed to A M Shepherd.

At least 91 records · Page 5Linked to original sources

Pharmacokinetics of hydralazine, apparent hydralazine and hydralazine pyruvic acid hydrazone in humans.

Hydralazine is an antihypertensive vasodilator agent. Lack of specific assay techniques for its measurement have delayed elucidation of its pharmacokinetic profile. This study compares the plasma profiles of hydralazine, measured both by a specific and by a previously published nonspecific assay and of a major plasma metabolite, hydralazine pyruvic acid hydrazone. After po and iv administration of hydralazine, peak hydralazine levels were lower (7-33%) and plasma half lives were shorter (15-31%) when measured by the specific technique. The mean plasma half life of the pyruvic acid hydrazone was 156 min and mean urinary clearance, 28 ml/min. The plasma profile of hydralazine and of the major metabolite, the pyruvic acid hydrazone, do not appear to correspond to the duration of antihypertensive effect of administered hydralazine.

Acetylation↗

Reduced induction of drug metabolism in the elderly.

Young and elderly subjects were given the hypnotic dichloralphenazone (Welldorm) in a dose of 20 mg/kg nightly for two weeks and the extent of induction of liver microsomal drug metabolism was assessed from alteration in the plasma elimination of quinine and antipyrine (phenazone). With both indices, there was a significant increase in plasma drug clearance in young subjects following dichloralphenazone treatment but no significant alterations occured in the elderly group. These results indicate that, in addition to being less able to metabolize some drugs, elderly patients show a reduced induction response. They may therefore be less likely to become tolerant to those drugs which are inactivated by metabolism.

Adult↗

Drug prescribing patterns in the elderly: a cross-sectional study of in-patients.

A cross-sectional one-day survey of drug prescribing and use in elderly in-patients was carried out in Dundee hospitals. Altogether 873 patients were studied and analyses of prescribing patterns were carried out by patient categories--medical, surgical, geriatric, psychiatric and mentally subnormal--and by major drug groups. While the average number of drugs prescribed per patient on the study day was 3.3, which was not excessive, other results highlighted some possible problems of therapy, viz. the wide range of drugs used within drug groups, the common use of psychotropic drugs, dose regimes which although used in a geriatric population differed little from general adult dosages, and which sometimes involved many administrations per day. Examples were described relating to the use of nitrazepam, phenothiazines and tricyclic antidepressants.

Aged↗

Age as a determinant of sensitivity to warfarin.

1 Parallel human and rat studies were carried out to confirm the previous suggestion of an increased sensitivity to warfarin in old age. 2 The anticoagulant response to warfarin was found to be greater in the elderly groups despite, in the case of the patient study, the elderly subjects being given a smaller weight-related dose. 3 At the same plasma warfarin concentrations there was greater inhibition of vitamin K-dependent clotting factor synthesis in the elderly. There was no difference in the rate of clotting factor degradation in the two age groups. 4 There was no appreciable difference in warfarin pharmacokinetics (plasma half-life, apparent volume of distribution, plasma clearance, plasma protein binding or plasma warfarin alcohol levels) in the two age groups. 5 There appeared to be no major age-related differences in warfarin pharmacokinetics and the increased effect of warfarin in the elderly seemed to result from an increased intrinsic sensitivity to warfarin.

Adult↗

Measurement of cardiac muscle relaxation in hypothyroidism.

The isovolumetric relaxation time of the left ventricle (IRT) in 20 hypothyroid patients (133 +/- (SE of mean) 4 ms) was significantly longer than that in 23 normal subjects (95 +/- 3 ms). During a trial of thyroxine replacement the IRT in 12 hypothyroid patients fell from 143 +/- 4 ms to 107 +/- 4 ms. The IRT seems to be a useful index of end-organ function in hypothyroidism.

Adolescent↗

Haemoglobin and serum iron responses to periodic intravenous iron-dextran infusions during maintenance haemodialysis.

Patients with chronic renal failure who were on maintenance haemodialysis, were given monthly 600 mg iron intravenously as iron-dextran complex to a body replacement total of 5-6 g iron. Those patients who had been on maintenance haemodialysis for a long period and had received numerous blood transfusions failed to show a rise in haemoglobin levels. Those patients who received iron from the commencement of maintenance dialysis, and who had not received blood transfusions, showed a significant increase in haemoglobin concentrations which has been maintained for more than 18 months after iron therapy ceased, despite a concurrent decrease in serum iron concentrations. Pre-treatment and post-treatment levels of serum iron are not of predictive value for the success of iron treatment, neither for the haemoglobin nor the serum iron response. A body replacement dose of iron given intravenously over a year benefits the majority of patients on maintenance haemodialysis and is recommended for the treatment of their anaemia.

Anemia↗

The effect of desferrioxamine on the colorimetric determination of iron in human serum and plasma.

The effect of a range of concentrations of desferrioxamine on a colorimetric determination of serum, or plasma, iron concentration is described. The method of iron estimation used was an autoanalyzer method using tripyridyltriazine as chromogen. There was found to be a small, reproducible diminution in the serum iron estimation in the presence of desferrioxamine. This was independent of the concentration of desferrioxamine. High serum concentrations of iron can be measured reproducibly in the presence of desferrioxamine after dilution of the serum with saline.

Autoanalysis↗

Staff and student perceptions of a student health service.

Results of a survey at one English university suggest that, of the various student personnel services provided by that institution, the Student Health Service was the best known and most used by the students. Both students and academic staff attributed greater importance to that particular service than to any other. Ways in which these two groups of university members justified such special provision are presented and discussed.

Attitude to Health↗

Further studies of gastric hypersecretion in chronic renal failure.

The effect of medical treatment has been studied in four patients with end-stage renal failure who suffered from severe spontaneous gastric hypersecretion, associated with very low levels of intraduodenal pH in two cases. Atropine decreased the overnight gastric acid output, but the residual acid secretion and duodenal content of acid remained dangerously high in one of the patients. Secretin inhibited the basal gastric secretion of acid in all cases and converted the pH of the duodenal contents to alkaline. While atropine cannot be used to control the gastric hypersecretion, secretin may prove to be valuable in the therapeutic management of the gastric hypersecretion of patients with chronic renal failure.

Bicarbonates↗

The chemical composition of the egg shells of the potato cyst-nematode, Heterodera rostochiensis Woll.

1. Eggs of the potato cyst-nematode (Heterodera rostochiensis Woll.) were isolated by sieving a suspension of crushed cysts. Eggs were broken open by ultrasonic vibration and the egg shells separated from the released larvae by centrifuging in a potassium tartrate density gradient. About 1 mg. of dried egg shells was obtained from 1000 cysts. 2. The major constituent of the egg shells was protein (59%, calculated from nitrogen content). About 80% of the egg shells went into solution on acid hydrolysis. Of the 18 amino acids determined with the Technicon Auto-Analyser, proline was most abundant and, with aspartic acid, glycine and serine, made up about 64% by weight of the total amino acids. The small amounts of aromatic and sulphur-containing amino acids, and the presence of hydroxy-proline, indicate a collagen-like protein. 3. The egg shells gave a positive van Wisselingh colour test for chitin, and glucosamine was detected in their acid hydrolysate by chromatography. The glucosamine content of the egg shells, determined by the Elson-Morgan colorimetric method, was 7%, corresponding to about 9% chitin. 4. Dried egg shells contained about 7% of lipid, 6% of carbohydrate and 3% of ash. Polyphenols (3% by weight of the egg shells) were detected in the acid hydrolysates. 5. Neither the collagen nor the chitin showed evidence of crystallinity when examined by X-ray diffraction.

Amino Acids↗

Testicular LH receptors during aging in Fisher 344 rats.

Levels of serum LH, prolactin, testosterone, progesterone and 17-OH progesterone and the testicular concentration and total content of LH receptors were measured in 4-, 11-, 18-, and 27-month-old Fisher 344 rats. All 27-month-old rats had Leydig cell tumors. At first, testicular LH receptor levels decreased with age, but with the appearance of the testicular tumors, these levels increased dramatically. Serum prolactin levels fluctuated with age, but were significantly decreased in 27-month-old rats, as were serum LH levels. Serum testosterone levels decreased steadily with age, while the testosterone-LH receptor ratio remained constant until the appearance of the testicular tumors, after which the ratio decreased precipitously. Serum progesterone levels remained constant throughout the life of Fisher 344 rats until the appearance of testicular tumors, when they increased dramatically. Serum 17-OH progesterone levels were increased significantly at 11 and 27 months as compared to four months of age, but levels at 18 months were similar to those seen in the 4-month-old animals. Therefore, in aged Fisher 344 rats with spontaneous Leydig cell tumors, there is an alteration in the testicular testosterone synthesizing pathway at a step after progesterone.

17-alpha-Hydroxyprogesterone↗

Age and blood pressure determine vasodepressor response to sodium nitroprusside.

Twenty-two patients, aged 33-72 years, with uncomplicated essential hypertension were given sequential incremental intravenous infusions of sodium nitroprusside, each of 10 min duration, to examine the determinants of the vasodepressor response. Changes in mean arterial pressure (delta MAP), heart rate (delta HR), and plasma norepinephrine (delta nc) were determined at the end of each infusion period. The slopes of the dose-response curves obtained were directly proportional to predrug blood pressure (p less than 0.0001) and inversely proportional to baroreflex sensitivity as measured by the slope of the delta HR vs. delta MAP relationship (p = 0.0007). Baroreflex sensitivity was in turn inversely proportional to, and approximately equally dependent on, predrug blood pressure and age (p = 0.0116). Thus, the slopes of the dose-response curves were determined by both predrug blood pressure and patient age. The relationship was such that predrug blood pressure accounted for approximately 75% of the variability in the slope of the dose-response curve, and age for only 25%. This suggests that the age-related reduction in baroreflex sensitivity is mechanistically different from the hypertension-related reduction and is of less importance in modifying homeostatic responses to vasodilation.

Adult↗