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Biomedical subjects

T Morgan

Publications and source records attributed to T Morgan.

At least 37 records · Page 2Linked to original sources

Enalapril & nifedipine in essential hypertension; synergism of the hypotensive effects in combination.

Twelve male hypertensive patients who had required enalapril and nifedipine to control their blood pressure were entered into a study of modified 2 x 2 factorial design (3 week study periods) to determine the effect of each drug separately and in combination. Factorial analysis indicated that enalapril alone (20 mg/d) lowered supine blood pressure by 10 +/- 2/8 +/- 1 mmHg, nifedipine alone (30 mg/d) lowered supine blood pressure by 11 +/- 2/8 +/- 1 mmHg and there was a positive interactive effect of 10 +/- 3/7 +/- 2 mmHg (P less than 0.001) such that the combination lowered supine blood pressure by 32 +/- 3/24 +/- 2 mmHg. The effects of the individual drugs were both significant (P less than 0.001) but did not differ from each other. Enalapril and nifedipine are both effective antihypertensive drugs and in some hypertensive patients their effects appear to be synergistic.

Aged

Effect of atrial peptide on collecting duct function.

1. The effects of synthetic rat atrial natriuretic peptides (ANP) on diffusional 22Na+, 36Cl- and tritiated water (THO) permeability of in vitro microperfused rat papillary collecting ducts and the effect in vivo of ANP on stop-flow sodium concentrations in the terminal segment of rabbit nephrons were studied. 2. The addition of 4 x 10(-8) or 4 x 10(-7) mol/l ANP to the medium or perfusion solution did not alter diffusional 22Na+ or 36Cl- permeability of microperfused rat papillary collecting ducts. 3. The basal diffusional THO permeability of papillary collecting ducts was not altered when 4 x 10(-7) mol/l ANP was present in the medium and did not inhibit the increment in diffusional THO permeability induced by vasopressin or reduce the permeability to water in a duct previously stimulated by vasopressin. 4. The administration of ANP (2 micrograms/kg bodyweight) to rabbits in water diuresis did not alter systemic blood pressure but induced a marked natriuresis and increases in urine flow and potassium excretion. This natriuresis was not associated with alterations in stop-flow sodium reabsorptive capacity or sodium permeability of the collecting tubules and ducts. 5. Previously reported in vivo clearance data suggest that ANP causes, at least in part, a natriuresis by altering sodium transport in the medullary collecting ducts. In this study, however, a direct effect could not be demonstrated and it is possible that the medulla needs to be functioning in its normal environment for such effects to be demonstrated.

Animals

Interaction in hypertensive man between sodium intake, converting enzyme inhibitor (enalapril), plasma renin and blood pressure control.

Sixteen patients with hypertension entered a study in which the effects of enalapril were compared with sodium restriction, with the two in combination and with placebo using a balanced randomized double-crossover design. Each patient had four treatment phases of two weeks, duration which comprised a 2 x 2 factorial design as well as an initial period on sodium restriction and enalapril placebo. All patients received a reduced sodium diet and sodium intake was altered by slow Na tablets. Increasing sodium intake raised blood pressure similarly whether patients were receiving enalapril or its placebo. Enalapril lowered blood pressure to a similar extent in patients on either a low and high sodium intake. The combination of a low sodium intake and enalapril was additive and there was no interactive effect between the two therapies whether assessed by a linear or a logarithmic method. Plasma renin was increased by enalapril and lowered by increased sodium intake. These effects were additive and there was no interactive effect. Neither the initial plasma renin nor the rise in renin predicted which patients would respond to enalapril. Enalapril was an effective antihypertensive agent and its blood pressure-lowering effect and that of sodium restriction were additive.

Aged

Significance of isolated antibody to hepatitis B core antigen determined by immune response to hepatitis B vaccination.

The immune response to hepatitis B vaccine was studied in 14 individuals with isolated, high-titer antibody to hepatitis B core antigen (anti-HBc) and examined as an indicator of this serologic pattern's significance. Four subjects demonstrated a low-titer antibody to hepatitis B surface antigen (anti-HBs) on repeated testing, and three in this subgroup had anamnestic responses (anti-HBs, 82 to 140 ratio units) after vaccination. Compared with 22 seronegative controls, the remaining ten had significantly higher anti-HBs response rates (78% vs 22%, P = .003) and median anti-HBs titers (4 vs 0 ratio units, P = .008) two weeks after vaccination. One of ten subjects had an anamnestic response, while another exhibited no response. The general pattern of anti-HBs responsiveness observed in those subjects with isolated, high-titer anti-HBc was intermediate between seronegative and anti-HBs-positive groups and may indicate a state of waning immunity after natural infection. Hepatitis B vaccination with follow-up anti-HBs testing should be done for those patients with isolated, high-titer anti-HBc to help exclude chronic infection and boost protective immunity.

Adult

The effect of perindopril on blood pressure in humans on different sodium intakes.

Perindopril is a new inhibitor of converting enzyme activity with a prolonged half-life. Thirty-two patients with essential hypertension and a diastolic blood pressure greater than 95 mm Hg were stratified into two groups according to their 24 h urine sodium excretion. They were randomized in a double-blind fashion to placebo or perindopril and a dose titration made in steps of 2, 4, 6, and 8 mg given once daily at weekly intervals. The goal diastolic blood pressure was 90 mm Hg. Goal blood pressure was achieved in 11 of 16 patients on perindopril and 3 of 6 patients on placebo. Perindopril caused a fall in BP of 22/11 (supine) and 27/14 (erect) mm Hg while the placebo group had falls of 3/2 (supine) and 3/0 (erect) mm Hg. Most of the blood pressure fall occurred in the first week of therapy with 2 mg/day. Side effects were few and occurred mainly in the placebo phase. There was no alteration in urine protein, white cell count, plasma urea, or creatinine. The fall in blood pressure achieved at the end of the titration or with 2 mg did not differ between the two groups. There was no correlation between blood pressure response and 24 h urine sodium or plasma renin activity. These results indicate that perindopril is an effective antihypertensive drug that appears to work equally well in patients on high or low sodium intake.

Aged

Effect of atrial natriuretic peptide on collecting duct function evaluated by stop-flow in rabbits.

1. The effect of a low dose of a synthetic atrial natriuretic peptide (ANP), rat atriopeptin II (23 amino acids), on stop-flow sodium concentrations was examined in rabbits in water diuresis. 2. Atrial natriuretic peptide (2 micrograms/kg body weight) was injected intravenously as a bolus either before or after the commencement of stop-flow. 3. Atrial natriuretic peptide induced a significant natriuresis within 2 min of injection. This natriuresis was associated with smaller increases in urine volume and potassium excretion. Atrial natriuretic peptide did not alter blood pressure. 4. Atrial natriuretic peptide did not significantly alter stop-flow sodium concentrations. 5. These findings indicate that ANP does not directly alter sodium transport across medullary collecting ducts. 6. It is proposed that ANP acts via a mediator to alter sodium movement across terminal segments of the nephron.

Animals

Effect of carvedilol and metoprolol on blood pressure, blood flow, and vascular resistance.

Carvedilol and metoprolol were given for 4 weeks in a double-blind study to patients with essential hypertension. The effects on blood pressure were measured and hemodynamic alterations were assessed by forearm venous plethysmography before and after chronic administration, and 2 h after an acute dose before and during chronic therapy. Carvedilol (50 mg/day) reduced supine and erect blood pressure, and pulse rate similar to the reduction with metoprolol (100 mg b.i.d.). There was a tendency for forearm blood flow to rise and for forearm resistance to fall with both drugs. When administered acutely, there was no fall in pulse rate with carvedilol compared to the fall with metoprolol when on placebo or active therapy. The blood pressure fall with acute administration was similar with both drugs when not on treatment, but when on chronic therapy, there was no fall with metoprolol but a marked fall with carvedilol. In this circumstance, vascular resistance rose with metoprolol but not with carvedilol. No effect of either drug on a modified cold presser test was observed. Both drugs were well tolerated and there were no significant side effects except for an excessive fall in blood pressure in one patient on carvedilol. Plasma renin activity (PRA) fell with both drugs and there was a tendency for both plasma potassium and plasma uric acid to rise. Carvedilol was well tolerated and reduced blood pressure successfully.

Adrenergic beta-Antagonists

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

Improved laboratory efficiency and diagnostic accuracy with new double-lumen-protected swab for for endometrial specimens.

Intrauterine specimens were obtained from 22 patients with endometritis and 24 control patients following cesarean section by using both a new protected swab and a standard anaerobic swab. The protected swab improved the value of the direct smear and Gram stain, resulted in fewer false-positive cultures, better defined endometrial flora in patients with endometritis, and permitted major savings in laboratory personnel time and materials.

Bacteria

The effect of labetalol in the treatment of severe drug-resistant hypertension.

Twenty-two hypertensive patients from a large clinic, who were resistant to conventional therapy, were entered into this study. Most patients previously had received beta-blocking drugs, thiazide diuretics, alpha-methyl-dopa, or vasodilator drugs (hydrallazine or prazosin) which failed to control their blood pressure. The therapy with vasodilator drugs was discontinued, and the therapy with labetalol (a drug with both alpha-blocking and beta-blocking effect) was commenced. Subsequently, as the blood pressure came under control, other drugs that the patients were taking were also withdrawn. In 13 of the 22 patients, labetalol enabled the blood pressure to be controlled at acceptable levels. In six patients, the response was not considered to be sufficient to justify continuation of labetalol therapy. In three patients, the drug was withdrawn because of postural hypotension in one patient, intractable diarrhoea in another, and an allergic-type skin rash in the third. In certain patients, postural changes in blood pressure were observed, but this rarely produced symptoms. It is suggested that, if blood pressure control is not achieved with a thiazide diuretic and a beta-blocking drug, then labetalol should be introduced and the beta-blocking drug should be withdrawn.

Aged

A study of the interaction of catecholamines and antidiuretic hormone on water permeability and the cyclic AMP system in isolated papillae of the rat.

The diffusional water permeability of collecting ducts in vitro and the cyclic A.M.P. content of isolated papillae were measured after exposure to different concentrations of antidiuretic hormone, isoproterenol and noradrenalin. Antidiuretic hormone 25 mu units/ml. caused a 25% increase in diffusional water permeability. This response was not affected by isoproterenol (10(-6) M) or noradrenalin (2 x 10(-6) M). Antidiuretic hormone 100 mu unit ml-1 caused a 50% increase in diffusional water permeability which likewise was not altered by isoproterenol or noradrenalin. Isoproterenol (10(-6) M) and noradrenalin (2 x 10(-6) M) had no significant effect on basal levels of diffusional water permeability. Isoproterenol had no significant effect on the tissue concentration of cyclic A.M.P. concentration induced by antidiuretic hormone. Noradrenalin (2 x 10(-6) and 10(-4)) had no significant effect on basal cyclic A.M.P. concentration. However, noradrenalin inhibited the stimulation of cyclic A.M.P. induced by antidiuretic hormone. This effect was inhibited by phentolamine. This study suggests that catecholamines do not alter water handling by a direct action on the water permeability of the kidney but probably exert their action through an effect of A.D.H. release.

Animals

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