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Biomedical subjects

J L Pool

Publications and source records attributed to J L Pool.

At least 37 records · Page 2Linked to original sources
PubMed1992

Antihypertensive and metabolic effects of concomitant administration of terazosin and methyclothiazide for the treatment of essential hypertension.

The efficacy and safety of once-daily 2.5- or 5.0-mg methyclothiazide (MCTZ) added to once-daily 5.0-mg terazosin (TRZ) versus 5.0-mg TRZ alone was evaluated in this double-blind, multicenter study. All patients received TRZ during a 6-week titration period. Hypertensive patients (222) (mean blood pressure of 159/104 mm Hg) were randomized to one of three treatment groups: TRZ alone (N = 76); TRZ+MCTZ-2.5 mg (N = 74); and TRZ+MCTZ-5.0 mg (N = 72) for the 8-week double-blind period. Changes in the supine and standing SBP/DBP from preTRZ period were: TRZ alone (-4.8/-8.1 and -2.6/-6.1 mm Hg); TRZ+MCTZ-2.5 mg (-17.3/-12.4 and -16.0/-11.2 mm Hg); and TRZ+MCTZ-5.0 mg (-20.6/-14.4 and -23.3/-14.6 mm Hg). Blood pressure changes in the combination groups were significantly greater than those in the TRZ alone group. However, there were no statistically significant differences between the TRZ+MCTZ-2.5-mg and TRZ+MCTZ-5.0-mg groups. The combination of TRZ and MCTZ tends to mitigate the adverse effects on serum glucose, uric, potassium and lipids usually associated with thiazide diuretics. Thus, combination treatment that begins with TRZ and adds MCTZ is effective in lowering blood pressure without any significant adverse metabolic effects.

Adrenergic alpha-Antagonists↗
PubMed1992

Lovastatin and coadministered antihypertensive/cardiovascular agents.

Hypertension and hypercholesterolemia frequently coexist and may require concomitant drug treatments. The efficacy and safety profile of lovastatin given in the presence of antihypertensive medication was evaluated using patient subgroups identified in the Expanded Clinical Evaluation of Lovastatin (EXCEL) Study. The EXCEL study examined 8,245 patients with moderate hypercholesterolemia randomly assigned either to a group treated with lovastatin (20-80 mg daily) or to a group given placebo for 48 weeks. After adjustment for patient characteristics, pairwise comparisons were made between patients taking no antihypertensive agents (n = 3,772) and those taking either calcium antagonists (n = 446), selective beta 1-adrenergic receptor blockers (n = 326), nonselective beta-adrenergic receptor blockers (n = 219), potassium-sparing diuretics (n = 187), thiazide diuretics (n = 126), or angiotensin converting enzyme inhibitors (n = 171). The placebo-corrected dose-dependent effect of lovastatin on the percent change from baseline in low-density lipoprotein cholesterol was not attenuated in any subgroup and was slightly enhanced in the calcium antagonist subgroup (-29% to -44%, p = 0.06) when compared with patients taking no antihypertensive agents (-24% to -40%); this difference, however, was only of borderline significance. Patterns of lovastatin-induced increase in high-density lipoprotein cholesterol and decrease in triglycerides were not consistently different among the subgroups. Examination of mean changes in serum transaminases, mean changes in creatine kinase, and the proportion of patients discontinuing therapy for clinical adverse experiences did not indicate the presence of an interaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1991

Expanded clinical evaluation of lovastatin (EXCEL) study results: III. Efficacy in modifying lipoproteins and implications for managing patients with moderate hypercholesterolemia.

In the multicenter, double-blind EXCEL (Expanded Clinical Evaluation of Lovastatin) study the efficacy of lovastatin in modifying plasma lipids and lipoproteins in 8,245 participants with moderate primary hypercholesterolemia was evaluated. Patients were randomly assigned to 48 weeks of treatment with diet and placebo or diet and lovastatin 20 or 40 mg once a day, or 20 or 40 mg twice a day. At all of these dosages, lovastatin produced substantial dose-dependent reductions in low-density-lipoprotein (LDL)-cholesterol levels, averaging 24% (20 mg/day) to 40% (80 mg/day). The magnitude of the effect of this lipoprotein was further reflected by the percentage of patients who achieved National Cholesterol Education Program (NCEP) goals. In the absence of coronary artery disease (CAD) or two other CAD risk factors, the LDL-cholesterol goal of 4.14 mmol/L (160 mg/dL) was attained by 22% of patients in the placebo group and between 81% (20 mg/day) and 96% (80 mg/day) of those treated with lovastatin. For those with CAD or at least two other CAD risk factors, the LDL-cholesterol goal of 3.36 mmol/L (130 mg/dL) was attained by 4% of placebo patients and between 38% (20 mg/day) and 83% (80 mg/day) of those treated with lovastatin. Lovastatin also increased high-density-lipoprotein cholesterol (7-10%) and decreased triglycerides (10-19%) in a dose-dependent manner. Thus, when used as an adjunct to a prudent diet, lovastatin produces favorable changes in the entire lipoprotein profile and is a highly effective agent for managing patients with primary hypercholesterolemia.

Cholesterol, HDL↗
PubMed1991

Expanded clinical evaluation of lovastatin (EXCEL) study results: IV. Additional perspectives on the tolerability of lovastatin.

This randomized, double-blind, multicenter, diet-and-placebo-controlled study was designed to clarify the dose-response relationship of lovastatin therapy to lipid-modifying efficacy and drug-related adverse events. Exclusion criteria were minimized so that study patients were representative of the majority of patients with moderate hypercholesterolemia seen in medical practice. After 6 weeks on the American Heart Association Step 1 Diet, a total of 8,245 patients were randomly assigned to 48 weeks of treatment with diet and placebo or lovastatin at dosages of 20 or 40 mg once a day or 20 or 40 mg twice a day. All adverse events were monitored, with particular attention to evaluation of liver and muscle. Liver transaminase elevations suggestive of possible hepatotoxicity, defined as successive elevations in either aspartate transaminase or alanine aminotransferase greater than 3 times the upper limit of normal, occurred in equal numbers of placebo and lovastatin 20 mg/day treated patients (0.1%). The frequencies were higher in lovastatin 40 mg/day and 80 mg/day patient groups (0.9 and 1.5%, respectively). No patient was diagnosed as having clinically symptomatic hepatic dysfunction. Creatinine kinase (CK) elevations above the upper limit of normal occurred frequently in placebo- (29%), as well as lovastatin-treated patients (29-35%), and muscle symptoms were reported with similar frequency in all groups (7-9%). The combination of muscle symptoms with marked CK elevations (greater than 10 times the upper limit of normal) was seen in only five patients: one in a 40 mg/day dose group and four in the 80 mg/day dose group. No patient developed rhabdomyolysis. The incidence of clinical and laboratory adverse events requiring discontinuation was 6% for the placebo group and from 7% (20 mg/day) to 9% (80 mg/day) for lovastatin treatment groups. No new types of adverse experiences related to lovastatin treatment were reported. Lovastatin, as an adjunct to diet for the reduction of elevated LDL cholesterol, was generally very well tolerated.

Alanine Transaminase↗
PubMed1991

Combination antihypertensive therapy with terazosin and other antihypertensive agents: results of clinical trials.

Clinical trials in which the selective alpha 1-adrenergic receptor blocker terazosin was given in combination with other antihypertensive agents are reviewed. Results of a recent study examining the effects of combination terazosin and verapamil therapy on blood pressure and heart rate are also presented. In several studies of the combination of terazosin plus a diuretic (hydrochlorothiazide, methyclothiazide, chlorthalidone, furosemide, amiloride, triamterene, metolazone, or spironolactone), significant decreases in one or more of the blood pressure variables studied were demonstrated (compared with diuretic plus placebo). In a placebo-controlled, double-blind study of terazosin plus atenolol, supine and standing blood pressures decreased significantly from baseline (atenolol monotherapy) after the addition of terazosin but not placebo. In a study of terazosin added to background therapy (including beta-blockers, diuretics, methyldopa, clonidine, captopril, guanethidine, hydralazine, and nifedipine), the addition of terazosin resulted in significant decreases in supine and standing diastolic blood pressures compared with baseline values (background therapy alone). Combination antihypertensive therapy with terazosin and verapamil reduced blood pressure to a significantly greater extent than either agent alone. Preliminary pharmacokinetic results indicate that terazosin did not alter the metabolism of verapamil. No significant abnormal laboratory test results have been reported for patients taking terazosin in combination with other antihypertensive agents; in fact some evidence suggests that terazosin may attenuate adverse lipid, glucose, and potassium changes associated with thiazide diuretics. Adverse experiences associated with terazosin combination therapy are usually mild to moderate. Results from all these studies suggest that terazosin effectively controls mild-to-moderate hypertension when it is used in combination with other antihypertensive agents without cumulative adverse effects.

Adrenergic alpha-Antagonists↗
PubMed1991

Effects of doxazosin on serum lipids: a review of the clinical data and molecular basis for altered lipid metabolism.

The goal of antihypertensive treatment must be not only the reduction of high blood pressure, but also the effective management of elevated cholesterol levels and other risk factors of coronary heart disease (CHD). In controlled clinical trials, doxazosin has been shown to have antihypertensive efficacy comparable with other classes of antihypertensive agents and to lower the levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides while increasing the levels of high-density lipoprotein cholesterol. Doxazosin appears to inhibit the development of CHD on two fronts. First, doxazosin binds to the alpha 1-adrenoreceptor and inhibits the receptor-mediated responses to epinephrine and norepinephrine. Second, doxazosin has direct and indirect effects on lipid metabolism by increasing LDL receptor activity, decreasing intracellular LDL synthesis, reducing the synthesis and secretion of very low-density lipoprotein cholesterol, and stimulating lipoprotein lipase activity. Doxazosin may also inhibit platelet aggregation. Long-term studies will determine how these actions translate into reductions in the morbidity and mortality rates of CHD. First-year results from the Treatment of Mild Hypertension Study (TOMHS) have demonstrated expected reductions in blood pressure for all antihypertensive agents studied. The lipid changes have varied with the type of antihypertensive treatment and have been favorable for doxazosin.

Antihypertensive Agents↗
PubMed1991

Nicardipine as antihypertensive monotherapy: positive effects on quality of life.

The effects of nicardipine and propranolol on patients' quality of life were compared during a double-blind, multicentre, parallel, randomised study of hypertension therapy. After a placebo run-in period, the doses for each patient were successfully titrated to reduce supine diastolic blood pressure to less than 90 mmHg with either nicardipine 60 or 90 mg/day (123 patients) or with propranolol 90-240 mg/day (120 patients). Both drugs demonstrated similar efficacy in reducing systolic and diastolic blood pressure. Total duration of therapy ranged from 6-12 weeks. The Nottingham Health Profile questionnaire was used to assess the effect of each treatment on the patients' quality of life. The overall quality of life score for patients on nicardipine showed a tendency toward improvement, while for those on propranolol, the trend was toward overall worsening. The differences between the two treatment groups were statistically significant for males (P = 0.02). The analysis of the separate components of this evaluation demonstrated that physical mobility was reported to be decreased more for the propranolol-treated patients than for the nicardipine-treated patients (P = 0.02). In contrast to the propranolol-treated patients, the nicardipine-treated patients reported improvements for sleep, social life, work, sex life, and for activities related to hobbies and interests. A second questionnaire was used to assess the effects of the therapies on work productivity. Among those patients who worked for pay, more patients treated with propranolol than those treated with nicardipine rated themselves as less productive at work (P = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Expanded clinical evaluation of lovastatin (EXCEL) study: design and patient characteristics of a double-blind, placebo-controlled study in patients with moderate hypercholesterolemia.

The randomized, double-blind, placebo-controlled trial described in this report was undertaken to clarify the dose-response relation of lovastatin therapy to lipid-modifying efficacy (lipid/lipoprotein modification) and drug-related adverse events in a population with moderately elevated fasting plasma total cholesterol (240 to 300 mg/dl) and low-density lipoprotein cholesterol (greater than or equal to 160 mg/dl). Men or women (postmenopausal or surgically sterile), aged 18 to 70 years, were entered into the trial with minimal exclusion criteria. After 4 to 6 weeks of an American Heart Association phase I diet or a more stringent diet, 8,245 patients from 362 sites were randomized to 1 of 5 parallel diet and drug treatment groups: placebo (n = 1,663) or lovastatin, 20 mg (n = 1,642) and 40 mg (n = 1,645) with the evening meal, and 20 mg (n = 1,646) or 40 mg twice daily (n = 1,649). The regimen of diet and lovastatin (or placebo) was followed for 48 weeks. The 5 treatment groups were similar at baseline. The total cohort had the following characteristics: 59% were men (mean age 56 years); 92% were white; 59% had completed at least 1 year of education beyond high school; 57% had a history of cardiovascular and associated disease; 40% had a history of hypertension; and 29% had coronary artery disease. Health habits were similar among groups, with 18% of patients reporting cigarette smoking, 14% reporting that they consume greater than 1 alcoholic beverage daily and 67% reporting no strenous exercise. Mean lipid/lipoprotein levels were also similar among groups, with the following average levels: total cholesterol (258 mg/dl), low-density lipoprotein cholesterol (180 mg/dl), high-density lipoprotein cholesterol (45 mg/dl) and triglycerides (median = 155 mg/dl). The large size of this trial, its placebo-controlled, double-blind design and the similarity of treatment groups at baseline should allow clear documentation of the long-term effects of lovastatin treatment and generalization of the results to a substantial portion of patients who may be candidates for lipid-modifying therapy.

Adult↗
PubMed1990

Alpha 1-adrenoreceptor blockade and the molecular basis of lipid metabolism alterations.

For the past 40 years, adrenoreceptors have been studied as the biomolecular mediators of tissue response to catecholamines. An expanded role of alpha-adrenoreceptors in the regulation of risk factors for coronary heart disease (CHD) has recently emerged. Hypercholesterolaemia, hypertension, and cigarette smoking are the major risk factors and their interactions are associated with increased mortality. Control of hypertension alone has failed to reduce the risk of CHD. Conversely, reduction of elevated total cholesterol and low density lipoprotein (LDL)-cholesterol has been shown to lower the risk of CHD. As a result, multiple risk factor approaches to the management of patients have evolved in attempts to reduce deaths from CHD. Selective alpha 1-adrenoreceptor antagonists appear to have a dual function in CHD risk management since they control elevated blood pressure by peripheral vasodilatation and reduce atherogenic lipids by several mechanisms. With selective alpha 1-blockade, the number of LDL-cholesterol receptors is up-regulated and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG Co-A reductase) activity is suppressed causing reductions in total cholesterol, LDL-cholesterol, and apoprotein B levels. Effects on intermediary metabolism reduce synthesis of very low density lipoprotein (VLDL) which contributes to a reduction of total triglyceride levels and, to a lesser extent, to a reduction of total cholesterol levels. Increased lipoprotein lipase activity leads to reduced total triglyceride and VLDL levels and to increased high density lipoprotein (HDL)-cholesterol levels. As demonstrated by the initial prospective data from Phase I of the Treatment of Mild Hypertension Study (TOMHS), both reduction of raised blood pressure and beneficial lipid modifications are sustained (1 year) with selective alpha 1-blockade. The prospective benefits on morbidity and mortality from CHD of such favourable changes in these two major risk factors remain to be quantified.

Adrenergic alpha-Antagonists↗
PubMed1990

The expert system approach to predicting protein structure.

Prediction of protein structure is an open-ended problem. Since an approach from first principles cannot be taken in reasonable computer time, short-cuts using further data are necessary. Such data include information about the specific protein in question, and information in databases which are about proteins in general. Is it possible to write a general, flexible 'superalgorithm' which would suit most circumstances? If so, it would seem likely to overcome one of the most understated but nonetheless greatest difficulties associated with molecular modelling and computer-aided drug design--reproducibility. To this end, a 'polymorphic programming environment' has been developed which represents both an expert system and a high-level language for theoretical chemists and molecular biologists. This language is GLOBAL (Ball et al., 1990). In a series of earlier studies, and more recently by means of GLOBAL itself, the nature of reproducibility and its rather surprising limits have been explored, and in general the current status and future potential of protein modelling have been examined.

Expert Systems↗
PubMed1989

Review of the effects of doxazosin, a new selective alpha 1-adrenergic inhibitor, on lipoproteins in patients with essential hypertension.

Control of high blood pressure has failed to reduce the risk of atherosclerotic coronary heart disease (CHD). Hypercholesterolemia, which is common among hypertensive patients, cigarette smoking, and hypertension are the major risk factors for CHD. To minimize CHD risk, elevated blood pressure and atherogenic lipid levels should be lowered, but various antihypertensive agents appear to adversely affect lipid levels, actually precluding the CHD risk reduction expected from blood pressure control. Doxazosin, a once-daily, long-acting, alpha 1-adrenergic inhibitor, not only is effective therapy for essential hypertension but also has a favorable impact on lipids. During controlled studies of doxazosin's antihypertensive efficacy, the following blood lipid levels were measured: total cholesterol, total triglycerides, high-density lipoprotein (HDL) cholesterol (including HDL2 and HDL3), low-density lipoprotein (LDL) cholesterol, very low-density lipoprotein cholesterol, and apoproteins (apos) AI and B. Results showed total cholesterol (-0.8 to -8.9 percent), total triglycerides (-5.0 to -17.4 percent), and LDL (-9.0 to -16.9 percent) were reduced. The positive prognostic indicators, HDL (+0.7 to +13.0 percent) and HDL:total cholesterol ratio (+3.1 to +26.3 percent), were increased. Apo B decreased, but apo AI remained unchanged. In these hypertension studies, doxazosin has favorably reduced two major CHD risk factors. As part of a new, long-term, controlled, multicenter trial, the prospective benefits of these risk factor reductions on CHD morbidity and mortality will be quantified for doxazosin and other antihypertensive agents.

Adrenergic alpha-Antagonists↗
PubMed1989

Cyclic therapy of osteoporosis with neutral phosphate and brief, high-dose pulses of etidronate.

We have designed a cyclic regimen for the treatment of osteoporosis based on the activate, depress, free, and repeat (ADFR) concept. Osteoclastic bone resorption is activated by 7 days of oral neutral phosphate and inhibited with a brief pulse (5 days) of etidronate disodium at a high dose (20 mg/kg body weight). Patients next take calcium supplements for 48 days before resuming phosphate to enter the next cycle. Osteoporotic women increased the bone mineral density of the lumbar spine at 6 months by 7.2 +/- 5.2% (mean +/- SD, N = 14) and at 12 months by 8.2 +/- 4.0% (N = 8). Control observations in regularly exercising postmenopausal women (N = 30) showed no significant change in spine mineral density after 20 months (0.5 +/- 3.2%), confirming the stability of the measurement technique. The two patients who responded poorly to the cyclic regimen each showed a blunted rise in serum PTH during oral phosphate administration, suggesting that the rise in PTH induced by oral phosphate may be an important component of this cyclic regimen. This preliminary study does not identify which component or components of the regimen are responsible for the increase in bone mass but provides positive encouragement for randomized studies designed to determine the optimum dosage, duration, and timing of each component of the regimen.

Adult↗
PubMed1989

Spectrum of dysautonomia in mitral valvular prolapse.

PURPOSE: Symptoms suggesting altered autonomic regulation of cardiovascular function have been noted in some patients with mitral valvular prolapse (MVP) but may also occur in patients with other disorders. We evaluated cardiovascular responses to autonomic stimuli in 118 patients with symptoms of dysautonomia, 78 of whom had MVP, and 40 of whom did not, to determine if unique patterns of these responses distinguished patients in one symptomatic subgroup from another. SUBJECTS AND METHODS: The responses of patients to standing, quantitated Valsalva maneuver, facial immersion in ice water, and administration of isoproterenol, phenylephrine, and tyramine were compared with those in 12 asymptomatic patients with MVP and 23 normal volunteers. RESULTS: Constitutional, cardiovascular, and neuropsychiatric symptoms occurred with similar frequency in the two symptomatic patient groups. The most common pattern of abnormal responses in symptomatic patients with or without MVP was (1) an increased heart rate and elevated plasma norepinephrine levels while supine and then while standing quietly for five minutes, (2) an exaggerated increase in heart rate during phase II of Valsalva, (3) a diminished bradycardic response during phase IV of Valsalva, and (4) an exaggerated heart rate response to administration of isoproterenol. The increased heart rate during Valsalva, but not the exaggerated sensitivity to isoproterenol, was correlated with the magnitude of the chronotropic response to standing only in symptomatic patients with MVP. Exaggerated hypertensive overshoot during phase IV of Valsalva was observed in only a few symptomatic patients. No consistent pattern of these abnormalities, however, was noted in any of the patient subgroups. Hemodynamic responses to autonomic stimuli in asymptomatic MVP patients were generally indistinguishable from those observed in normal subjects. CONCLUSION: These findings suggest that abnormal cardiovascular responses to autonomic stimuli may occur in any patient with symptoms of dysautonomia regardless of the presence or absence of MVP and that the pattern of these abnormal responses may be diverse. It is therefore important to characterize the pattern of altered autonomic regulation of cardiovascular function in each patient when considering mechanistic implications or making therapeutic decisions about these patients.

Adolescent↗
PubMed1988

Clinical experience and rationale for angiotensin-converting enzyme inhibition with lisinopril as the initial treatment for hypertension in older patients.

Hypertension is a major health problem for patients over 65 years of age. Control of elevated blood pressure reduces cardiovascular morbidity and mortality rates among older hypertensive patients. Increased total peripheral vascular resistance is the primary hemodynamic abnormality in these patients. Initially, diuretics were used alone to lower total peripheral vascular resistance, and thus blood pressure, in older patients. The antihypertensive efficacy of angiotensin-converting enzyme inhibitors has been questioned in this age group, in which low-renin hypertension is common. The latter condition might be thought to favor blood pressure control with diuretics and impair the response to angiotensin-converting enzyme inhibitor therapy. However, recent studies with lisinopril, a new long-acting, nonsulfhydryl angiotensin-converting enzyme inhibitor, indicate that reductions in systolic and diastolic blood pressure in older hypertensive patients receiving either angiotensin-converting enzyme inhibitor or hydrochlorothiazide monotherapy were not significantly different. These data demonstrate that angiotensin-converting enzyme inhibitor monotherapy can effectively lower blood pressure in older hypertensive patients.

Adult↗
PubMed1988

Isolated renal artery dissection secondary to medial degeneration.

Renal artery aneurysms can have variable presentations, often resulting in a therapeutic dilemma to the clinician. We review the causes, clinical features, pathological conditions and treatment options for this problem. We report a case of a thrombus in 1 of 2 left renal arteries, which resulted in uncontrollable hypertension. At nephrectomy the angiographically normal vessel had medial degeneration, demonstrating the diffuse nature of this disease. Conservative renal-sparing management should be considered whenever possible.

Adult↗
PubMed1988

The impact of renal fusion and ectopia on aortic surgery.

This article is concerned with observations in 17 patients with renal fusion and ectopic abnormalities: horseshoe kidney in 13 patients, crossed ectopia with fusion in two, pancake kidney in one, and pelvic kidney in one. Three patients had occlusive disease, one may have had renal artery occlusion, and 13 had aneurysms--three thoracoabdominal and 10 infrarenal. Rupture of aneurysm had occurred in one patient at each level and six patients had had one or more previous attempts at aneurysmal removal. Diagnosis and evaluation were made with the aid of intravenous pyelography, retrograde pyelography, CT scanning, and at operation (three patients). Three patients had two normally located right and left renal arteries. Twelve patients had one to three additional aberrant arteries arising from the aorta and iliac arteries. One patient's renal blood supply arose from multiple aberrant arteries. Ureters crossed the midline in two patients. Treatment of occlusive disease consisted of endarterectomy in one patient and percutaneous transluminal angioplasty in two. Aneurysms were treated by graft replacement with retroperitoneal exposure in seven patients and transabdominal exposure in six. One patient was treated medically. Renal isthmus division was employed in only two patients and involved accessory arteries were reattached to the grafts in all cases. Death from myocardial infarction occurred in two patients (12%). Eleven patients subjected to operation were alive 6 months to 14 years later.

Aged↗
PubMed1988

Effect of doxazosin monotherapy on blood pressure and plasma lipids in patients with essential hypertension.

The efficacy and safety of doxazosin (DOX) for the treatment of hypertension was investigated. A multicenter, double-blind, placebo-controlled, parallel design was employed. A 4-week placebo runin period was followed by a 9-week double-blind period during which patients were randomly assigned to placebo or 2, 4, or 8 mg doxazosin. Blood pressures (BP) and heart rates (HR) were measured 24 hours postdose. The mean changes in standing BP (mmHg) were -6.2/-6.9 (2-mg regimen), -5.7/-5.8 (4-mg regimen), -8.5/-7.7 (8-mg regimen) for DOX patients and 0.7/-2.9 for placebo patients. The mean changes in supine BP (mmHg) were -3.2/-4.7 (2-mg regimen), -4.0/-5.1 (4-mg regimen), -4.6/-5.6 (8-mg regimen) for DOX patients and -0.5/-3.3 for placebo patients. There was no evidence of a dose-response relationship for DOX; however, DOX serum levels were linearly related to the dose. Responder rate for the combined DOX patients was 38% (32/84) and for the placebo patients 27% (8/30). HR (24 hours postdose) was not modified by DOX. Patients in the 8-mg regimen had a significantly higher gain in mean body weight (+ 1.3 +/- 0.3 kg; P less than 0.05) compared to the 2-mg regimen, 4-mg regimen, and placebo groups. Plasma norepinephrine was not significantly modified by DOX. DOX had a favorable effect on plasma lipids. DOX lowered LDL cholesterol (P less than 0.05), total cholesterol, and apoprotein B and increased HDL/(LDL + VLDL) ratio (0.05 less than or equal to P less than 0.1) compared to placebo. Dropout rate and treatment-related side effects were equally distributed among the DOX and placebo groups. No patients had the dose of medication reduced because of side effects. Three DOX patients were withdrawn because of postural dizziness.

Blood Pressure↗