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Biomedical subjects

V M Oh

Publications and source records attributed to V M Oh.

At least 37 records · Page 2Linked to original sources
PubMed1990

Cation transport across lymphocyte plasma membranes in euthyroid and thyrotoxic men with and without hypokalaemic periodic paralysis.

1. To study potassium transport in hypokalaemic periodic paralysis in a model of striated muscle cells, we measured specific [3H]ouabain binding (the number of sodium-potassium pumps), sodium-potassium-pump-mediated (ouabain-sensitive) 86Rb+ influx and sodium-potassium-pump-independent (ouabain-resistant) 86Rb+ influx in lymphocytes in vitro. 2. The subjects comprised euthyroid and thyrotoxic men with hypokalaemic periodic paralysis between attacks, men with uncomplicated thyrotoxicosis, and healthy men matched for age and weight. 3. Thyrotoxic patients, both with and without periodic paralysis, had significantly more lymphocyte sodium-potassium pumps than normal, and a significantly greater sodium-potassium-pump-mediated 86Rb+ influx. Anti-thyroid treatment corrected this defect in patients with thyrotoxic periodic paralysis. Euthyroid patients with cryptogenic periodic paralysis had significantly increased sodium-potassium-pump-mediated 86Rb+ influx, but a normal number of sodium-potassium pumps. 4. Only untreated thyrotoxic and euthyroid patients with periodic paralysis showed a significant increase in sodium-potassium-pump-independent 86Rb+ influx (5.2 +/- 2.8 and 4.5 +/- 1.8 respectively, vs control 2.8 +/- 1.0 pmol h-1 10(-6) cells; mean +/- SD; P less than 0.001, P less than 0.005). 5. We conclude that thyrotoxicosis increases the number and activity of sodium-potassium pumps and facilitates, but is probably not necessary for, periodic paralysis. Hypokalaemic periodic paralysis is associated with an increase in sodium-potassium-pump-independent potassium influx.

Adult↗
PubMed1990

Sodium pump numbers and cation transport of lymphocytes in pregnancy-induced hypertension.

Pregnancy-induced hypertension may be linked with sodium pump inhibition and an increase in vascular myocytic tone and, hence, flow impedance. All of the findings of studies on circulating plasma and blood cells are not, however, consistent with this hypothesis. We therefore assessed sodium pump numbers and cation transport in lymphocytes from 23 women with untreated pregnancy-induced hypertension, 28 normotensive pregnant women and 28 healthy non-pregnant women. We measured the maximum 3H-ouabain binding capacity to determine the sodium pump activity and the apparent dissociation constant (the reciprocal of which estimates binding affinity) by Scatchard analysis, ouabain-sensitive (pump-mediated) 86rubidium influx and ouabain-resistant (pump-independent) influx in lymphocytes in vitro. Pregnant women, whether normotensive or hypertensive, had significantly more sodium pump activity and a higher pump-mediated and pump-independent 86rubidium influx than non-pregnant women. Sodium pump activity and the pump-mediated and pump-independent 86rubidium influx all reached normal, non-pregnant levels in normotensive pregnant women 6 weeks after delivery, but remained high in women with pregnancy-induced hypertension. The normotensive and hypertensive pregnant women and non-pregnant women all had similar ouabain binding affinity. The results of our study do not support the circulating sodium pump inhibitor hypothesis in pregnancy-induced hypertension.

Adult↗
PubMed1989

Treatment of allergic adverse drug reactions.

Allergic adverse drug reactions are unpredictable and dose-independent. The cellular events which comprise an allergic reaction cannot be effectively altered until we understand how, for instance, the provoking drug forms an immunoglobulin-like factor which releases chemical mediators of inflammation from effector cells, or how these mediators act on target tissues. Nor do we know how and why different patterns of drug allergy vary over time. The post hoc treatment of reactions is largely empirical and supportive, and depends on the type of reaction and its clinical setting. The treatment of acute severe reactions like analphylaxis include resuscitating the patient, ensuring airway patency, injecting adrenaline i.m., setting up an i.v. infusion of a plasma expander, and injecting an anti-histamine and hydrocortisone. After anaphylaxis the vital signs, the ECG, and respiratory function should be monitored in the intensive care unit; supportive drugs may be needed for 72 hours. Some other systemic disorders induced by allergic drug reactions are well defined, but their treatment is either nonspecific or highly specialised. Because disease and death due to drug allergy are becoming more frequent, clinicians must try to limit them by recording careful drug histories, using radiocontrast agents only when necessary, and prescribing drugs only when benefit will probably exceed risk. Doctors should also advise their patients against the misuse of drugs.

Anaphylaxis↗
PubMed1989

Agranulocytosis and anaemia induced by sulfametopyrazine in a sulfametopyrazine-trimethoprim combination.

We report a case of prolonged fever, agranulocytosis, and anaemia associated with the long acting sulphametopyrazine-trimethoprim combination (Kelfiprim). A woman of 23 years took an overdose of 13 tablets over five days for presumed cystitis. One day after the last dose the patient developed fever and a generalised rash. The fever persisted and her previously normal leukocyte count decreased to 1.8 x 10(9)/1. After treatment with paracetamol the fever settled briefly, and then recurred for another 16 days. A later peripheral blood leukocyte count of 0.77 x 10(9)/1, haemoglobin of 10.8 g/dl, and a hypocellular bone marrow with depressed granulopoiesis and haemopoiesis suggested marrow suppression induced by sulfametopyrazine. Since the IgM antibody against the Epstein-Barr virus capsid antigen was detected, the adverse drug reaction might have been aggravated by this virus. The case highlights the risk of severe haematological adverse reactions associated with sulphonamide treatment, and argues for the use of trimethoprim alone for uncomplicated cystitis.

Adult↗
PubMed1989

Metabolic effects of antihypertensive drugs.

Metabolic changes in essential hypertension may complicate the primary disease, or drug and nondrug intervention, or both. These changes include disturbances in renal function, the metabolism of urate, glucose and lipids, and in cation transport across plasma membranes. Some of these disorders may be worsened by the chronic administration of antihypertensive drugs like diuretics, beta-adrenoceptor antagonists, and the angiotensin converting enzyme inhibitors. Recent randomised controlled trials of antihypertensive drugs showed that the apparently adequate control of hypertension with a thiazide or beta-antagonist does not consistently prevent cerebrovascular and cardiac deaths and morbidity, and that beta-antagonists protect only nonsmoking men against cardiac death. One explanation is that blood pressure may not have been lowered enough. By contrast, cardiac deaths may be increased in patients whose diastolic pressure is reduced below 85-90 mmHg. The adverse metabolic effects of antihypertensive drugs may in part offset their protective benefits. However, population evidence does not support the general avoidance of thiazides or beta-antagonists in mild hypertension. Where possible drug treatment should be tailored to individuals according to their general condition, age, and any concurrent disease or medication.

Antihypertensive Agents↗
PubMed1987

Enhancement of specific [3H]ouabain binding and ouabain sensitive 86rubidium influx in intact human lymphocytes by a dialysable factor in human and fetal calf serum.

We have measured specific [3H]ouabain binding and ouabain sensitive 86rubidium influx in intact human lymphocytes incubated for up to 7 days in media containing different concentrations of fetal calf serum and human serum. Incubation for periods of up to 7 days with fetal calf serum and human serum produced increases in both specific [3H]ouabain binding and ouabain sensitive 86rubidium influx that were dependent on concentration and time. Neither specific [3H]ouabain binding nor ouabain sensitive 86rubidium influx was altered when dialysed serum was used, suggesting that both fetal calf serum and human serum contain a dialysable factor or factors which stimulate specific [3H]ouabain binding and ouabain sensitive 86rubidium influx in intact human lymphocytes. To further elucidate the mechanisms underlying these changes we also measured the activity of two other enzymes of the lymphocyte plasma membrane, 5'-nucleotidase and gamma-glutamyltransferase, the uptake of [3H]thymidine by the intact cells, and the effects of cycloheximide, puromycin, and anisomycin, inhibitors of protein synthesis. The activity of 5'-nucleotidase was increased after incubation of the lymphocytes in fetal calf serum for 72 h, but the activity of gamma-glutamyltransferase was not changed, suggesting some selectivity of the stimulatory effect. Measurements of [3H]thymidine uptake by the lymphocytes showed that the major part of the observed changes in specific [3H]ouabain binding and ouabain sensitive 86rubidium influx was not attributable to transformation of the lymphocytes to lymphoblasts. All three inhibitors of protein synthesis prevented the increase in specific [3H]ouabain binding due to fetal calf serum.

5'-Nucleotidase↗
PubMed1986

Reversible inhibition of leucocyte sodium pumps by a circulating serum factor in essential hypertension.

To test whether leucocyte sodium pumps function abnormally in patients with essential hypertension specific tritium-ouabain binding (number of pumps) and ouabain sensitive uptake of rubidium-86 (86Rb+) (transport activity) were measured in mononuclear leucocytes from 37 untreated hypertensive patients and 85 normotensive subjects. Ouabain binding was lower and transport activity per binding site higher in the hypertensive patients before incubation (p less than 0.001), but both variables were normal after incubation for 72 hours with fetal calf serum. To determine whether a circulating inhibitor of sodium pumps was present in patients with hypertension ouabain binding and 86Rb+ uptake were measured in normal leucocytes before and after incubation for 72 hours with serum from 13 untreated hypertensive patients and 18 normotensive subjects. Ouabain binding was lower after incubation of cells with serum from hypertensive patients than after incubation with normal serum both before (p less than 0.01) and after (p less than 0.001) dialysis of the serum. The results suggest that in hypertension a circulating serum inhibitor of the sodium pump causes a chronic but reversible reduction in the number of pumps.

Adult↗
PubMed1986

Adrenal phaeochromocytoma and neurofibromatosis presenting with hypotension.

We report a case of adrenal phaeochromocytoma with the stigmata of neurofibromatosis, who presented with acute hypotension. The patient later had episodes of hypertension alternating with hypotension, associated with electrocardiographic changes simulating myocardial infarction, and finally a completed stroke. The circumstances illustrate the problem of early recognition of the protean clinical effects of an excess of circulating adrenal medullary hormones. They also emphasise the need to consider phaeochromocytoma as a differential diagnosis of apparent clinical shock.

Adrenal Gland Neoplasms↗
PubMed1985

Effects of long-acting propranolol on blood pressure and heart rate in hypertensive Chinese.

In a double-blind, balanced and randomised study we used treadmill exercise to assess the effects of long-acting propranolol (LA propranolol) 160 or 320 mg or placebo, given once daily for 4 weeks, on heart rate (HR) and blood pressure (BP) in 15 Chinese subjects with mild primary hypertension (PHT). We used 24 h ECG monitoring to assess drug effects on HR. Another 18 patients were similarly assessed without exercise. Steady-state plasma propranolol concentrations after LA propranolol 160 and 320 mg were comparable to those after ordinary propranolol 80 and 160 mg daily measured in 11 and 12 separate patients. LA propranolol 160 and 320 mg reduced HR and BP before and during vigorous exercise. LA propranolol 160 and 320 mg reduced HR for 17.6 and 21.4 h of the day, and 320 mg significantly reduced the mean 24 h HR, and the mean maximum HR. The drug effects on BP and HR, and the average plasma propranolol levels after LA propranolol were similar to those reported in European subjects.

Adult↗
PubMed1984

Measurement of specific [3H]-ouabain binding to different types of human leucocytes.

We have studied the specific binding of [3H]-ouabain to intact mononuclear leucocytes (82% lymphocytes) and polymorphonuclear leucocytes. In both types of cells [3H]-ouabain binding was saturable, confined to a single site of high affinity, slow to reach equilibrium, slow to reverse, temperature-dependent, competitively antagonized by potassium, and facilitated by the presence of divalent cations. The equilibrium dissociation constants were 2.4 +/- 0.7 nmol/l (polymorphs) and 2.4 +/- 0.4 nmol/l (mononuclear cells) (NS). The values of maximal specific ouabain binding, measured by Scatchard analysis of concentration vs binding curves (Bmax), were 33.9 +/- 6.0 fmol/10(6) cells (polymorphs) and 59.3 +/- 11.6 fmol/10(6) cells (mononuclear cells) (P less than 0.02). The corresponding numbers of sites per cell were 20415 +/- 3616 and 35712 +/- 6986 respectively (P less than 0.02). When the numbers of binding sites were expressed per square micron of cell surface area the difference between the two cell types was proportionately greater (83 and 186 sites per micron 2 respectively). We conclude that the [3H]-ouabain binding sites on mononuclear and polymorphonuclear leucocytes are similar in nature, but different in both number and density on the cell surface. Measurements of Bmax in mixed cell populations should therefore take account of cell type as well as cell size and number.

Binding, Competitive↗
PubMed1980

Clinical pharmacology of beta-adrenoceptor antagonism in angina pectoris: an overview.

Beta antagonists competitively block beta 1-adrenoceptors that mediate both the rate and force of myocardial contraction. Their precise mechanism of anti-anginal action is uncertain. A reduction in oxygen demand may relative pain and improve effort tolerance. Alternatively inhibition of the adrenergic drive to contraction may offset the increased ventricular wall tension due to incomplete relaxation. Partial agonist activity in a beta-antagonist does not influence efficacy nor protect against airflow obstruction. Membrane stabilising activity is clinically trivial. Cardioselectivity makes airflow obstruction less likely at low but not at high blood concentrations of drug. Alpha-receptor antagonism may also prevent broncho-constriction; it has not been assessed in coronary vasospasm. The dosage and choice of drugs are based on pharmaco-kinetic and dynamic data in animals and man. The major side-effects of beta-blockade are heart failure and airflow obstruction. Cardiotoxicity from overdosage may be treated with isoprenaline, dopamine or glucagon while beta 2-agonists will reverse bronchoconstriction. Since beta-antagonists raise-peripheral vascular impedance, reduction of preload with nitrates enhances their antianginal efficacy. Combining a beta-antagonist with nifedipine seems especially useful. Beta-blockade is worth trying in angina with normal coronary arteries. In acute coronary insufficiency beta-blockade reduces both the work-load on the heart and the somatic features of anxiety, so preparing patients for investigations, like coronary arteriography, aimed at definitive treatment.

Adrenergic alpha-Antagonists↗
PubMed1979

Relationship between bronchial effects and plasma practolol concentration in man.

A double-blind, balanced and randomised study in 8 healthy volunteers examined the effects of relatively high versus low single doses of practolol on heart rate and ventilation at rest and during standardised exercise. Practolol 1 and 4 mg/kg, a typically non-selective drug propranolol 0.2 mg/kg, and placebo were given intravenously at weekly intervals. Cardiac beta-adrenoceptor blockade was measured by the reduction in exercise heart rate greater than 160 beats/min, and bronchial beta-adrenoceptor blockade by the reduction in exercise peak expiratory flow rate (PEFR) up to 4 h after each treatment. Results were assessed by analysis of co-variance. All three active treatments reduced exercise heart rate markedly, practolol 4 mg/kg causing most reduction. Exercise PEFR was significantly reduced by propranolol 0.2 mg/kg compared with both practolol 1 mg/kg and placebo at all times of measurement, and by practolol 4 mg/kg compared with practolol 1 mg/kg and placebo at most times. Mean plasma concentrations after practolol 4 mg/kg were 3.5 to 4.5 times higher than after 1 mg/kg. Practolol may lose its 'cardioselectivity' and cause airflow obstruction at relatively high plasma concentrations above about 2 microgram/ml.

Adult↗
PubMed1979

Influence of ciclazindol on monoamine uptake and CNS function in normal subjects.

The potential antidepressant drug ciclazindol inhibited dopamine uptake into human platelets without affecting 5-hydroxytryptamine uptake as compared with a control. It inhibited the tyramine pressor response less than desipramine after single 50-mg oral doses in 6 healthy volunteers under double-blind conditions. Compared with tandamine in a double-blind placebo-controlled study in nine healthy subjects, ciclazindol 50 mg orally caused no significant anticholinergic effects but reduced appetite according to an analysis of variance. Nonparametric analysis did not confirm the anorectic effect. Previous studies had shown that ciclazindol increased glucose uptake into isolated human skeletal muscle independently of insulin. Overall, ciclazindol resembles the antiobesity drug mazindol in molecular structure and pharmacological effects in man. Interactions with sympathomimetic amines and adrenergic neurone-blocking drugs cannot be excluded on the basis of these studies.

Adult↗
PubMed1978

Studies of cardioselectivity and partial agonist activity in beta-adrenoceptor blockade comparing effects on heart rate and peak expiratory flow rate during exercise.

1 The effects of beta-adrenoceptor antagonists given in single doses by oral or intravenous routes were examined in two double-blind controlled studies performed in healthy volunteers. Heart rate and peak expiratory flow rate (PEFR) were measured at rest and during standardized exercise. 2 Propranolol 80 mg and metoprolol 100 mg orally tended to reduce, and propranolol and metoprolol 0.2 mg/kg intravenously did reduce the physiological increase in PEFR during exercise; oxprenolol 80 mg orally and 0.2 mg/kg intravenously did not. Practolol 200 mg orally reduced this increase, but practolol 1 mg/kg intravenously did not. 3 In a third study of similar design, pindolol 0.05 mg/kg intravenously did not affect exercise-induced increase in PEFR. 4 Heart rate during exercise was reduced to a comparable extent at different times by all the active treatments. 5 Oxprenolol and pindolol share with practolol the property of partial agonist activity, which might contribute to their apparent lack of effect on airways resistance. A further possibility is that alpha-adrenoceptor blockade helps to maintain exercise-induced increase in PEFR.

Adrenergic beta-Antagonists↗
PubMed1977

The different effects of sodium bicarbonate and aluminium hydroxide on the absorption of indomethacin in man.

The influence of oral sodium bicarbonate and aluminium hydroxide on the absorption of indomethacin has been studied in normal volunteers. While sodium bicarbonate appeared to increase indomethacin absorption, aluminium hydroxide markedly reduced both the rate and extent of absorption. The buccal absorption of indomethacin over the pH range 5-9 was also studied in normal volunteers, and showed that the percentage absorption increased markedly as the pH was reduced. The clinical importance both of pH-partition and of adsorption are discussed in the context of antacid interactions. It is concluded that caution must be exercised when prescribing an antacid with other orally-administered drugs.

Absorption↗