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Biomedical subjects

B P Hamilton

Publications and source records attributed to B P Hamilton.

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

Diabetes mellitus and hypertension.

Hypertension and diabetes mellitus are chronic medical conditions that frequently coexist. In the United States, it is estimated that 10 million persons suffer from diabetes mellitus, 60 million from hypertension, and 3 million from the combination of the two. There may be a causal relationship between hypertension and diabetes. Obesity may be a precipitating factor for both hypertension and non-insulin-dependent diabetes mellitus. Those with insulin-dependent diabetes mellitus generally become hypertensive only with the onset of nephropathy. Glucose tolerance, insulin resistance, and hyperinsulinemia frequently occur with essential hypertension and may be aggravated by hypertension therapy, especially with diuretics and beta-blockers. Hyperinsulinemia may be an important common factor promoting sodium retention, sympathetic nervous system stimulation, and inhibition of the sodium pump. The Working Group on Hypertension in Diabetes has outlined a flexible modified version of the stepped-care approach to the treatment of hypertension in diabetes. Management is complex because diabetes is associated with autonomic neuropathy, sexual dysfunction, hyperlipidemia, and fluid and electrolyte disorders. All these problems can be exacerbated by antihypertensive treatment. Nonpharmacologic measures, which address weight reduction and sodium restriction, are logical, but aggressive antihypertensive medication is invariably necessary. Diuretics and/or beta-blockers were the mainstay of treatment until the introduction of angiotensin-converting enzyme (ACE) inhibitors and calcium channel blockers. These newer agents have no deleterious effects on carbohydrate metabolism and are generally better tolerated. Antihypertensive therapy may slow the rate of deterioration in diabetic nephropathy. This was first shown with diuretics, beta-blockers, and hydralazine and more recently with ACE inhibitors, which provide effective blood pressure control and a significant drop in albuminuria without affecting the glomerular filtration rate adversely. ACE inhibition may also lead to increased insulin sensitivity and glucose disposal rate. Long-term trials are needed to assess the effects of these new agents on the treatment of hypertension in the diabetic population.

Antihypertensive Agents↗
PubMed1989

Incidence of cardiac arrhythmias associated with mild hypokalemia induced by low-dose diuretic therapy for hypertension.

Nineteen men with mild to moderate hypertension and without a history of cardiac arrhythmias were randomized (double-blind) into groups to receive hydrochlorothiazide (HCTZ) at a dose of 25 mg/day, HCTZ at 50 mg/day, or HCTZ (25 mg) plus triamterene (50 mg) for a six-month period after a three-week (single-blind) placebo period. Serum electrolyte values were determined at baseline and at frequent intervals thereafter. Twenty-four hour ambulatory electrocardiograms were obtained at baseline and just before study termination. Mild hypokalemia (less than 3.5 mEq/L) occurred in approximately half of the patients and was unrelated to treatment group. Serious arrhythmias were infrequent, though some patients had large numbers of extra beats. The incidence of arrhythmia appeared unrelated to serum potassium concentration. We conclude that mild hypokalemia associated with low-dose diuretic therapy for hypertension is not arrhythmogenic.

Adult↗
PubMed1987

Treatment of essential hypertension with PN 200-110 (isradipine).

The safety and antihypertensive efficacy of PN 200-110 (isradipine), a novel calcium antagonist, are discussed in a preliminary report of double-blind, multicenter, controlled, phase III clinical trials for essential hypertension. Patients who qualified for entry after a 3 week placebo-washout period were enrolled in 1 of 5 studies; 2 studies were placebo controlled; 3 studies evaluated PN 200-110 against 1 of 3 active controls: hydrochlorothiazide (HCTZ) propranolol or prazosin. A separate study assessing the effects of PN 200-110 in combination with HCTZ versus propranolol plus HCTZ is also discussed. Compared with placebo, PN 200-110 decreased mean supine systolic and diastolic blood pressures by 20/16 mm Hg versus 4/6 mm Hg. Compared with placebo and active control drugs, PN 200-110 normalized supine diastolic blood pressure to less than or equal to 90 mm Hg in 72% of patients, versus 13% in the placebo group, 74% in the HCTZ group, 45% in the propranolol group and 69% in the prazosin group. In the ability to decrease diastolic blood pressure by greater than or equal to 10 mm Hg, PN 200-110 compared favorably to prazosin (81% vs 81%), and was superior to HCTZ (81% vs 61%) and propranolol (81% vs 36%). In combination with HCTZ, PN 200-110 exerted as great an antihypertensive effect as propranolol plus HCTZ. Long-term therapy with PN 200-110 was also effective. Supine systolic and diastolic blood pressures decreased a mean of 15/13 mm Hg at 3 months, and 18/20 mm Hg at 12 months. PN 200-110 is well tolerated with relatively few adverse effects reported.

Blood Pressure↗
PubMed1987

Red blood cell Na+,K+-ATPase in men with newly diagnosed or previously treated essential hypertension.

Alterations of cellular function of Na+,K+-adenosine triphosphatase (ATPase; Na+-K+ pump) have been implicated in the pathophysiology of essential hypertension. Therefore, this aspect of red blood cell (RBC) Na metabolism was studied in black men with newly diagnosed, untreated essential hypertension (NEH) and a normotensive control group. RBC Na content, Na+-K+ pump number (ouabain binding sites), and pump activity were measured. No statistically significant differences were found between the two groups for any of these three parameters. However, a group of previously treated essential hypertensive subjects (PEH) who had been withdrawn from therapy in the preceding 6 weeks were also studied. This group differed significantly from the NEH subjects in regard to all RBC Na+-K+ pump parameters. Their RBC Na content (10.27 +/- 3.23 vs 7.77 +/- 2.52 mmol Na/LRBC; p = 0.006) was higher, and their Na+-K+ pump activity (166 +/- 50 vs 221 +/- 87 nmol inorganic phosphate/mg membrane protein/hr; p = 0.03) and Na+-K+ pump number (213 +/- 40 vs 284 +/- 85 binding sites/RBC; p = 0.001) were lower compared with those in NEH subjects. Although the PEH subjects were older and somewhat less hypertensive than their NEH counterparts, these factors were not found to influence the Na+-K+ pump parameters. These results indicate that chronic diuretic therapy of patients with essential hypertension is associated with a reduced number of RBC Na+-K+ pumps. Since RBCs are not considered target cells for diuretics, the effects of these drugs on RBC electrolyte metabolism may occur at the time of erythropoiesis by the production of RBCs with fewer Na+-K+ pumps.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Detection of primary aldosteronism by the 6-hour integrated aldosterone/renin ratio.

An outpatient diagnostic procedure measuring the 6-hour integrated plasma concentration of aldosterone and plasma renin activity was used to detect primary aldosteronism in 12 patients with low renin hypertension, including six with mild hypertension and normal urinary excretion and spot plasma levels of aldosterone. The ratio of integrated plasma concentration of aldosterone to plasma renin activity in the 12 patients (mean, 339; range, 116-700; p less than 0.0001) did not overlap with that measured in 105 normotensive controls (mean, 27.8; range, 5-97) or in 87 subjects with essential hypertension (mean, 29.2; range, 4-67). Eight patients had surgically proven adenomas (3 of which measured less than 5 mm) with normalization of blood pressure following adrenalectomy. The four remaining patients had bilateral hyperplasia. The 6-hour integrated plasma concentration of aldosterone to plasma renin activity ratio was found to be a useful new outpatient diagnostic tool for evaluation of primary hyperaldosteronism.

Adenoma↗
PubMed1985

Relationships among endogenous digitalis-like factors in essential hypertension.

Elements of a hypothesis that relate endogenous digitalis-like factors to both natriuretic hormone and hypertension are briefly reviewed. The stimulus for secretion of these factors appears to involve a tendency toward a state of extracellular fluid volume expansion as a consequence of an inherited or an acquired defect in renal function. Several studies implicate the brain and, in particular, the hypothalamus in the control of the secretion. The digitalis-like factors are thought to act by partial inhibition of active sodium transport, thereby promoting increased intracellular levels of Na+ and Ca2+ in a variety of cell types. In the kidney, inhibition of sodium transport leads to a compensatory natriuresis to correct the tendency for volume overload. In smooth muscle, the inhibition of sodium transport will indirectly increase intracellular calcium levels. The increased availability of Ca2+ will elevate muscle tone and increase peripheral vascular resistance. Also presented are criteria that may be used to characterize digitalis-like activity in samples and extracts obtained from purification procedures. Finally, we review our measurements of the 6-h integrated plasma levels of digitalis-like factors and other hormones for normotensive subjects and patients with essential hypertension. The data indicate the presence of two classes of digitalis-like factors with potentially different roles in electrolyte metabolism and hypertension.

Aldosterone↗
PubMed1984

Serum thyroid hormone changes during whole body hyperthermia.

In order to elucidate changes in thyroid hormone metabolism during acute heat stress, we measured sequentially serum thyroxine (T4), triiothyronine (T3), and reverse T3 (rT3) levels in 5 patients with neoplasia during treatment with whole body hyperthermia. The core temperature was raised from 37.0 degrees C to 42.0 degrees C over a 2-hour period, maintained at 42.0 degrees C for 2 hours, and then cooled to 37.0 degrees C over 2 hours. This short period of severe hyperthermia produced a fivefold rise in rT3 and a fall in T3 levels to one half of baseline levels. T4 and free T4 levels increased slightly, but thyrotropin (measured in two patients) did not change. These changes in T3 and rT3 levels were detectable at the fourth hour after onset of hyperthermia, were maximal at 24 and 48 hours, and in one patient were uncorrected after 4 days. We conclude that this reciprocal change in T3 and rT3 levels is a response to stress and may represent in part adaptation to a high environmental temperature by the suppression of theromengic T3. Whole body hyperthermia of short duration for cancer therapy produces profound changes in the peripheral degradation of thyroxine, which last for several days. This must be considered in the management of patients receiving hyperthermia, and the technique itself may prove to be a useful model for the study of adaptation to heat stress.

Humans↗
PubMed1984

Improvement in depressed cardiac function in hypertensive patients during pindolol treatment.

To assess changes in left ventricular function during antihypertensive treatment using pindolol, a beta-adrenocepter blocking drug with potent intrinsic sympathomimetic activity, serial echocardiographic measurements were obtained in 70 hypertensive patients before and during 15 weeks of treatment with pindolol. For analysis, the patients were separated into three groups on the basis of their baseline left ventricular fractional shortening (Group I, 35 patients with normal fractional shortening of 28 percent or more; Group II, 16 patients with abnormal fractional shortening of 21 to 27 percent; and Group III, 19 patients with markedly abnormal fractional shortening of 20 percent or less). More than half of the patients in Group I and Group II had decreases in mean blood pressure of 10 percent or more in response to pindolol, but only one fourth of Group III patients had similar responses (p less than 0.05). Patients with normal pretreatment fractional shortening had a mild decrease in fractional shortening during pindolol treatment, whereas patients with either abnormal or markedly abnormal fractional shortening had an increase in fractional shortening. This increase in fractional shortening suggests the possibility that the partial agonist or intrinsic sympathomimetic activity of pindolol may play a role in preserving left ventricular function in patients with borderline or impaired function.

Adult↗
PubMed1984

Withdrawal phenomena in subjects with essential hypertension on clonidine or tiamenidine.

The incidence and pathogenesis of withdrawal phenomena with the centrally acting drugs clonidine (CLON) and tiamenidine (TIAM) were evaluated. Thirty subjects with hypertension on hydrochlorothiazide (HCTZ) were randomized to TIAM or CLON. Blood pressure and integrated plasma catecholamine levels fell equally in response to both drugs. On withdrawal, blood pressure and pulse rose in both groups with no difference between them. Three subjects had symptoms of withdrawal, four had blood pressure overshoot above pretreatment levels of 10 mm Hg or more, and eight had a rise in blood pressure of 30 mm Hg systolic or 20 mm Hg diastolic. There was no difference between TIAM and CLON in these effects. There was a direct correlation between blood pressure rise and increase in integrated plasma norepinephrine levels. We conclude that the incidence of withdrawal phenomena in subjects on TIAM or CLON is infrequent and that there is a direct relationship between the rise in blood pressure and the loss of suppression of catecholamines by these drugs.

Adult↗
PubMed1983

Intrinsic sympathomimetic activity of pindolol. Evidence for interaction with pretreatment sympathetic tone.

Eighty-six hypertensive patients were treated with pindolol, a beta-adrenergic blocking drug with intrinsic sympathomimetic activity. To evaluate the interactions between beta-blockade, intrinsic sympathomimetic activity, and the level of pretreatment sympathetic activity, blood pressure, heart rate, and forced expiratory volume in one second (FEV1) were examined before and during a 15-week treatment program. The response of patients with a relatively higher pretreatment sympathetic tone reflected by a resting heart rate equal to or greater than 80 beats per minute (Group I) was compared with the response of patients with a lower pretreatment heart rate (less than 80 beats per minute) (Group II). Decreases in mean blood pressure were similar in the two groups. In patients in Group I, the net effect of pindolol was a modest decrease in heart rate and FEV1, supporting the concept that when sympathetic tone is relatively high, the beta-blocking effect is dominant. In contrast, patients in Group II showed little change in heart rate or FEV1 during pindolol treatment, reflecting a balance between the intrinsic sympathomimetic activity and beta-blocking effects of pindolol. Thus, the intrinsic sympathomimetic activity of pindolol is physiologically evident, and relative impact is dependent on the pretreatment level of sympathetic tone.

Clinical Trials as Topic↗
PubMed1983

Plasma norepinephrine and epinephrine responses to glucagon in patients with suspected pheochromocytomas.

Plasma norepinephrine and epinephrine levels were measured before and after glucagon administration in 28 patients suspected of having a pheochromocytoma: three patients were subsequently found to have tumors. The norepinephrine response predicted the presence or absence of a tumor in 27 of the 28 patients. Epinephrine levels doubled, on the average, in patients who did not have pheochromocytomas, and were not useful in distinguishing the patients with or without tumors. A comparison of the response to glucagon and a placebo indicated that changes in plasma catecholamine levels were hormone-related and not the result of side-effects accompanying injection. The glucagon provocation test, with measurement of plasma norepinephrine and epinephrine levels, may be a useful adjunctive tool for evaluating patients suspected of having a pheochromocytoma when performed according to a standardized protocol and interpreted in relation to appropriate controls.

Adolescent↗
PubMed1983

Cardiac arrhythmias after abrupt clonidine withdrawal.

Abrupt clonidine withdrawal may be associated with sharp marked increases in catecholamine levels, heart rate, and blood pressure, which may induce nausea, vomiting, and palpitations. Relatively little information is available on the incidence of cardiac arrhythmias in this setting. With continuous ambulatory ECG recordings, we determined the incidence of arrhythmias in seven male hypertensive patients (without active heart disease) after abrupt clonidine withdrawal. Serious ventricular arrhythmias, including brief ventricular tachycardia, developed in two patients who had greater increases in mean systolic blood pressure (28 +/- 3 vs 10 +/- 8 mm Hg) and double product (552 +/- 681 vs 333 +/- 195) than the others. The differences were not significant. Ventricular arrhythmias were not related to age, dose, withdrawal symptoms, initial blood pressure, urinary norepinephrine levels, or ECG abnormalities. We conclude that serious ventricular arrhythmias may be relatively common but unpredictable during clonidine withdrawal, even in patients with no clinically apparent heart disease. The triggering of ventricular arrhythmias should be added to the list of components of clonidine withdrawal syndrome.

Adult↗
PubMed1983

Effect of the administration of zinc sulfate on hypogonadism and impotence in patients with chronic stable hepatic cirrhosis.

Zinc sulfate was administered in a double-blind manner for 6-8 months to cirrhotic outpatients with impotence and/or hypogonadism. Seven placebo and six zinc-treated patients showed mild symptomatic improvement; however, there was no significant clinical difference between the two groups. Serum zinc levels rose significantly in the zinc-treated group but urinary gonadotropin and serum testosterone levels did not change in either group. Zinc sulfate does not appear to be an effective treatment for sexual dysfunction associated with alcohol-induced hepatic cirrhosis.

Adult↗
PubMed1982

Pulmonary function in hypertensive patients treated with pindolol: a report of two studies.

Pulmonary function was measured serially in two separate randomized trials of pindolol in the treatment of essential hypertension. Patients with overt obstructive airways disease were excluded. In study 1, 131 hypertensive patients were randomized to placebo (31) and 15 mg (33), 30 mg (33), and 60 mg (34) of pindolol. Pulmonary function was measured before and at weeks 8 and 15 of active medication. Bronchospasm--a 20% increase in forced expiratory volume in 1 second (FEV1) after isoprenaline--developed in three patients on active treatment and one on placebo. In eight patients on pindolol and one on placebo, bronchospasm ceased. Compared to placebo, no deterioration in pulmonary function occurred with pindolol and in three tests--maximum voluntary ventilation (MVV) (L/min), MVV%, midexpiratory flow rate (MEFR) (L/min)--significant improvement occurred. In study 2, 14 hypertensive patients were randomized to pindolol (mean dose 50 mg/day), 15 to propranolol (mean 360 mg/day), and 14 to chlorthalidone (mean 107 mg/day). Pulmonary function was measured after 3 weeks of placebo and again after 6 weeks of active treatment. While propranolol produced slight deterioration in pulmonary function, pindolol and chlorthalidone produced slight but significant improvement (p less than 0.05) with maximum MEFR (L/sec). Pulmonary function tests measured after isoprenaline were significantly worse in patients on propranolol compared to those on placebo, but were unchanged in patients on pindolol or chlorthalidone. The conclusions are: (1) Pindolol in antihypertensive doses does not produce airways obstruction and some improvement in pulmonary function may occur. (2) In comparable doses, pindolol has a positive effect on pulmonary function and propranolol a negative effect which, when summated, is statistically significant. (3) Propranolol, but not pindolol, appears to block the bronchodilator effects of isoprenaline. The lack of pulmonary function impairment may be due to intrinsic sympathomimetic activity properties of pindolol.

Chlorthalidone↗
PubMed1982

Pindolol and systolic time intervals in patients with hypertension.

Two studies of systolic time intervals (STIs) in patients with mild to moderate hypertension (HBP) revealed that no mean change in systolic intervals occurred with pindolol therapy, although some patients had significant alterations in their STIs. Pindolol responders with normal pretreatment preejection period to left ventricular ejection time (PEP/LVET) ratios had a significant increase in this ratio following pindolol therapy, whereas those with abnormal pretreatment PEP/LVET ratios had improvement in this ratio on administration of the drug. Patients on propranolol showed no change in PEP/LVET ratio. Propranolol administration slowed heart rate and lengthened Q-S2, S1-S2, and LVET, however, without altering the Q-S2 and LVET index, indicating that the changes were caused by the effect of propranolol on the heart rate alone. Chlorthalidone in high doses significantly reduced the Q-S2 index and the S1-S2 index, indicating that these changes were not caused by alteration of the heart rate. The second study suggests that STIs may provide a predictive clue for clinical response to pindolol. Patients with normal cardiac function (group I) are more likely to respond to pindolol than are those with abnormal cardiac function (group II). Directionally opposite changes in STIs in the two subgroups suggest different mechanisms for changing cardiac function. Pindolol's dual role as a beta-blocking agent with intrinsic sympathomimetic activity is proposed as a possible explanation, beta-blocking effects predominating in group I and sympathomimetic activity balancing the beta effect in group II.

Adult↗
PubMed1982

Age-related probability of development of hereditary medullary thyroid carcinoma.

Hereditary medullary thyroid carcinoma is inherited as an autosomal dominant trait; at birth each child of an affected parent has a 50% chance of developing the disease. Measurement of plasma calcitonin concentrations after provocative calcium or pentagastrin stimulation has proved useful in the early diagnosis of this disease. To determine the age-related risk of conversion from a negative to a positive provocative test, 445 members of 11 kindreds were studied with sequential tests. Of 159 family members with a 50% risk at birth of developing medullary thyroid carcinoma 38 converted from a negative to a positive test result (mean age of conversion was 15 years). By means of methods previously described for determining the age-related probability for developing Huntington chorea, we present a method for determining the probability of development of medullary thyroid carcinoma. An individual at risk whose test result was negative had the following probability of converting to a positive test result at a later date: age (years)/probability, 0/0.5; 5/0.49; 10/0.41; 15/0.25; 20/0.16; 25/0.10, 30/0.05; and 35/0. We conclude that hereditary medullary thyroid carcinoma is regularly detectable in the pediatric age group and that screening should begin by age 5 years and be continued at regular intervals until age 35.

Adolescent↗