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Biomedical subjects

S Carney

Publications and source records attributed to S Carney.

13 recordsLinked to original sources

Treatment of mild hypertension in elderly males.

1. Males, born between 1900 and 1925, with mild hypertension have been treated for periods varying from 300 to 2000 days. 2. The life and death status of all patients (except two) was known on 1st November 1978. 3. A group of patients with mild hypertension receiving treatment based on a thiazide diuretic had a greater mortality than the other drug-treated group. 4. The increased mortality was caused by an increased number of myocardial infarcts. 5. Elderly male patients with mild hypertension probably have preexisting vascular disease and therapy should not automatically be started. If therapy is started, beta-adrenoreceptor-blocking drugs may be a preferred therapy.

Adrenergic beta-Antagonists

The evidence that salt is an important aetiological agent, if not the cause, of hypertension.

1. Salt intake and the incidence of hypertension correlate between populations. 2. Salt intake within a population may correlate with the incidence of hypertension. 3. Disorders that lead to retention of salt cause hypertension. 4. Modest salt restriction reduces blood pressure in many patients. 5. Reducing salt balance and preventing the compensatory rise in angiotensin II controls blood pressure in most patients. 6. Salt is the probable cause of the epidemic of hypertension in the Western world; this could be prevented by salt restriction.

Aldosterone

Hypertension treated by salt restriction.

31 patients with a diastolic blood-pressure between 95 and 109 mm Hg have been treated for two years with a regimen involving a moderate restriction of salt in the diet. The results are compared with those in a control group and in a drug-treated group. Salt restriction has reduced the diastolic blood-pressure by 7.3+/-1.6 mm Hg, a result similar to that in patients treated with antihypertensive drugs. In the untreated group the diastolic blood-pressure rose by 1.8+/-1.1 mm Hg. Most patients did not achieve the desired amount of salt restriction and a stricter adherence to the diet might have caused further falls in blood-pressure. Excessive salt intake is probably a major cause of the epidemic of hypertension in "civilised" countries and a reduction in salt intake may help to control the epidemic. In persons with a diastolic blood-pressure between 90 and 105 mm Hg salt restriction should be tried before drugs.

Blood Pressure

Treatment of mild hypertension.

1. A total of 206 patients, elderly males with hypertension (diastolic blood pressure 95--110 mmHg) were followed for periods varying from 1 to 5 years, 107 patients with diastolic blood pressure less than 95 mmHg were followed over the same period, and 101 patients with diastolic blood pressure greater than or equal to 110 mmHg were also followed. 2. The mortality of each group and the effect of therapy for hypertension on mortality has been compared. 3. The incidence of myocardial infarct in the group treated with thiazide diuretics is greater than in the other groups. 4. It would appear unlikely that therapy will improve the prognosis in elderly people with mild hypertension.

Benzothiadiazines

Molecular exclusion electrophoresis of human serum lipoproteins: patterns in control and ischaemic heart-disease populations.

1. Electrophoresis of pre-stained lipoproteins on acrylamide-gel gradients has been carried out on serum from populations of control subjects and patients with ischaemic heart disease. The technique resolves components intermediate in position and, by inference, in size, between very-low-density and low-density lipoproteins. 2. These central band components were found in 37% of a control population but the incidence varied with age and sex, being lowest in young males and highest in elderly males. 3. The incidence of central band components in patients with ischaemic heart disease was 64% (males) and 71% (females), and the difference between these figures and those for matched control subjects was highly significant. The intensity of central band components in the group with ischaemic heart disease was significantly greater than in the control group. 4. The presence and intensity of central bands show positive correlation with serum cholesterol and triglyceride values, but many patients showing the phenomenon have normal lipid values. Of patients with ischaemic heart disease 31% showed central band components and had normal lipid values.

Adolescent

Optimal dose of a thiazide diuretic.

In essential hypertension, 25 mg and 100 mg of chlorthalidone per day reduced blood pressure to a similar extent. The larger amount (100 mg per day of chlorthalidone) caused a greater reduction in extracellular volume and a larger rise in plasma renin activity and serum uric acid levels. Hypokalaemia was common with 100 mg per day of chlorthalidone, but was rarely seen in patients who took 25 mg per day, and neither dose caused total body potassium depletion. In the management of hypertension, 25 mg of chlorthalidone is the preferred dose as it produces most of the antihypertensive effects with only minor biochemical changes.

Chlorthalidone

A study in vitro of the concentrating defect associated with hypokalaemia and hypercalcaemia.

The diffusional water permeabilities of collecting ducts in the presence and absence of antidiuretic hormone have been measured in isolated papillae from normal, hypokalaemic and hypercalcaemic rats. In a similar in vitro situation the effect of antidiuretic hormone on the papillary content of cyclic AMP has been measured. The diffusional water permeability of collecting ducts in the absence of antidiuretic hormone did not differ significantly in papillae taken from the different groups of rats. The diffusional water permeability in the presence of ADH was 7.4 +/- 0.2 (S.E.M.) mum s-1 in collecting ducts taken from normal rats. In collecting ducts taken from hypokalaemic or hypercalcaemic rats the corresponding values were 5.9 +/- 0.3 and 5.8 +/- 0.5 mum s-1 respectively. This significant decrease (P less than 0.01) in the response to antidiuretic hormone would shift the point at which distal tubule fluid first attains isotonicity with the interstitium. If this shifts from cortex to medulla a greater amount of water enters the interstitium of the medulla and produces an impairment of maximal urinary concentrating ability and this defect could explain most of the observed results in hypokalaemic and hypercalcaemic. Cyclic AMP content of the tissue after the addition of ADH was reduced in papillae taken from hypokalaemic rats. This reduced activation of adenyl cyclase could be the mechanism responsible for the impaired response in water permeability but it is also possible that there is interference, with the chain of reactions mediating permeability changes, at a separate site.

Animals

The effect of lithium on the permeability response induced in the collecting duct by antidiuretic hormone.

The diffusional and osmotic water permeability of collecting ducts in isolated papillae of rats' kidneys were measured in papillae taken from normal and lithium pretreated rats. The diffusional water permeability of collecting ducts in papillae from normal rats in the absence of ADH was 4.1 +/- 0.2 (S.E.M.) (n = 18) muM s-1 increasing to 7.2 +/- 0.6 mum s-1 with ADH. Values obtained with lithium (10 mM) in the medium, perfusate or both and in papillae taken from lithium pretreated rats did not differ significantly from the above. The cyclic AMP content of the papillae taken from normal rats was 83 +/- 6 pm mg protein in the absence of ADH and increased to 196 +/- 12 (n = 13) with 500 mu units ml-1 ADH. Lithium 10 mM in the medium did not alter this response. Papillae from lithium pretreated rats had a similar basal level of cyclic AMP but the increment in a lithium (10 mM) medium after ADH was significantly less. These results indicate that the impaired water handling of lithium treated rats is probably not due to a failure of the membrane to increase its permeability to water after ADH. Though lithium does alter the production of cyclic AMP this is not believed to be important regarding any alteration in water permeability. We believe it is probable that lithium interferes with sodium chloride transport at some more proximal nephron segment thereby producing the syndrome of polyuria.

Animals

Sodium restriction and thiazide diuretics in the treatment of hypertension.

In a group of hypertensive patients it has been shown that moderate sodium chloride restriction has a hypotensive effect that is similar to that produced by thiazide diuretics. Blood pressure changed in relation to body weight in individual patients, and appeared to correlate with their sodium balance. The more a patient was depleted of sodium, the lower was the blood pressure. The serum potassium level fell with the use of thiazide diuretics, but in this group of patients there was little change in total body potassium content. The fall in serum potassium level appeared to relate to a shift into the cells due to the accompanying alkalosis. Potassium supplementation appeared to have had little effect and was unnecessary for most patients who were given diuretics for hypertension. Amiloride corrected the alkalosis and restored the serum potassium level to normal.

Amiloride

Changes in plasma renin activity and blood pressure after acute and chronic administration of beta-adrenergic receptor-blocking drugs.

1. Prindolol and propranolol chronically cause a fall in mean blood pressure and mean plasma renin activity, but no correlation was observed between the two variables. 2. The response of blood pressure to prindolol and propranolol was not predicted by the basal plasma renin activity. 3. Propranolol administered acutely caused the plasma renin activity to fall with no acute change in blood pressure, whereas prindolol caused the blood pressure to fall with no change in plasma renin activity. 4. The effects of beta-adrenergic-blocking drugs on plasma renin activity and blood pressure can be dissociated and it is unlikely that their hypotensive action is mediated through the renin-angiotensin system. 5. Basal plasma renin activity does not identify the patients who will respond to beta-adrenergic-blocking drugs.

Adult

The interrelationships between antidiuretic hormone, adenyl cyclase, tissue cyclic AMP and diffusional water permeability.

1. Physiological concentrations of antidiuretic hormone increase diffusional water permeability but not measurable cyclic AMP content in the isolated papilla of the rat's kidney. 2. Theophylline (6 mM) increases diffusional water permeability and cyclic AMP content in the isolated papilla of the rat's kidney. 3. The increase in water permeability is detected with 5 muunits.ml-1 of ADH and is maximal with 50 muunits.ml-1. The same maximum was achieved with 6 mM theophylline. 4. Cyclic AMP and dibutyryl cyclic AMP both increase water permeability, but to a lesser extent than theophylline or ADH. 5. In the presence of theophylline, ADH causes a dose related generation of tissue cyclic AMP up to a dose of 2,000,000 muunits.ml-1. 6. Adenyl cyclase is increasingly activated by ADH up to doses of 2,000,000 muunits.ml-1. 7. These results suggest that while ADH activates the adenyl cyclase system and changes water permeability there are sufficient disparities to cast doubt on an exclusive role for cyclic AMP as the second messenger.

Adenylyl Cyclases