Biomedical subjects
H R Black
Publications and source records attributed to H R Black.
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.
Long-term experience with descending aortic dissection: the complication-specific approach.
We analyzed long-term results in 71 patients (45 men and 26 women) treated over 17 years for documented descending aortic dissection. Forty-nine patients were treated medically and 22, surgically. Actuarial survival was 65% at 1 year, 57% at 3 years, 50% at 5 years, and 28% at 10 years for the whole group. For the group treated medically, survival was 73%, 63%, 58%, and 25% at 1 year, 3 years, 5 years, and 10 years, respectively, and for the group treated surgically, 47%, 40%, and 28% at 1 year, 3 years, and 5 years, respectively. Ten (20.4%) of the 49 medically treated patients died early (5 of rupture), and 14 (28.6%) died late (8 of dissection). Five medically treated patients crossed over to surgical management for complications of dissection. Among the surgically treated patients, 6 underwent standard graft replacement of the proximal descending aorta, 8 underwent the fenestration procedure (with a standardized retroperitoneal abdominal approach), and 4 underwent the thromboexclusion operation. Specific analysis of fenestration in 14 patients (including some with persistent descending aortic dissection after replacement of the ascending aorta for dissection) found it to be safe and effective. Actuarial survival after fenestration was 77%, 77%, and 53% at 1 year, 3 years, and 5 years, respectively. Thromboexclusion was found effective, and postoperative studies confirmed thrombosis of the descending aorta with preservation of the lowest intercostal arteries. Fifteen of the 21 surviving medically treated patients agreed to return for follow-up imaging. Nine had thrombosis of the false lumen. An interesting radiographic finding was that 4 of the 15 restudied patients had a saccular aneurysm in the aorta at the level of the left subclavian artery. We recommend a complication-specific approach to the management of descending aortic dissection. Uncomplicated dissection is treated medically, whereas complicated dissection is treated surgically, with realized rupture treated by standard graft replacement, limb ischemia treated by fenestration, and enlargement or impending rupture treated by thromboexclusion.
State-of-the-art review: captopril renography--pathophysiological considerations and clinical observations.
Advances in renal angiography and revascularization techniques have renewed interest in developing a better noninvasive screening test for identifying patients with potentially correctable renovascular hypertension. Captopril renography is a promising diagnostic tool in the evaluation of the hypertensive patient. This review highlights the important pathophysiological changes in renal hemodynamics and humoral response attributable to significant renal artery stenosis, and underscores the dramatic effects of angiotensin-converting enzyme inhibition on the renovascular bed. The review also summarizes the available clinical information in captopril renography, and presents consensus recommendations on appropriate patient selection, radionuclide(s) of choice, and suggested diagnostic criteria.
A comparison of the safety of therapeutically equivalent doses of isradipine and diltiazem for treatment of essential hypertension.
We compared the safety of a new dihydropyridine calcium entry blocker, isradipine, with an equipotent dose of diltiazem in 174 mild hypertensives (diastolic blood pressure [DBP] 95 to 105 mm Hg). After appropriate washout and placebo periods, patients were randomly assigned to receive either 1.25 mg isradipine twice daily (Group I) or 40 mg diltiazem thrice daily (Group D). If DBP remained above 90 mm Hg, doses were increased to a maximum of 5 mg isradipine twice daily or 120 mg diltiazem thrice daily. Active therapy was given for a total of 12 weeks. Only 18 patients (nine from each group) did not complete the protocol. The patients were well-matched at baseline with a mean BP of 149/100 mm Hg for those who were randomized to isradipine and completed the protocol and 153/99 mm Hg for the diltiazem group. The responses to each drug were excellent with 72% of the isradipine patients and 73% of the diltiazem group having DBP less than 90 mm Hg at the completion of the study. Of the 156 patients who completed the protocol, only 18 patients (ten in Group I and eight in Group D) failed to respond. Both drugs were well-tolerated. No adverse reactions were reported by 68 percent of the patients in Group I and 65% of those in Group D. The most common side effect was headache (9.0% in Group I and 7.8% in Group D) followed by fatigue (5.2% in Group I and 3.9% in Group D). Age and race did not predict response to either agent but men responded slightly better to diltiazem than women. We conclude that isradipine and diltiazem are equally well tolerated and can be used successfully as a monotherapy to treat hypertension in a wide variety of patients.
Single-dose pharmacokinetics and antibacterial activity of daptomycin, a new lipopeptide antibiotic, in healthy volunteers.
Three separate single-dose studies were performed to define the disposition and pharmacokinetics of daptomycin in healthy volunteers. Daptomycin was administered as a single 14C-labeled dose (1.0 mg/kg of body weight) and as single doses between 0.5 and 6.0 mg/kg. All doses were intravenous. Antibacterial activity was determined from doses of 2.0, 3.0, 4.0, and 6.0 mg/kg against two strains of Staphylococcus aureus (one methicillin resistant) and one Enterococcus strain. After administration of 14C-labeled daptomycin, recovery of 14C in urine and feces accounted for 83% of the administered dose, with the greatest fraction (78%) appearing in the urine. Specific analysis for daptomycin in both urine and plasma indicated that metabolic products were present in urine, but total 14C in plasma consisted of daptomycin only. Doses between 0.5 and 6 mg/kg were linear, with a limited total body clearance (0.13 to 0.21 ml/min/kg) and a small volume of distribution (0.10 to 0.15 liter/kg). The small volume of distribution may be a factor of the high plasma protein binding (90 to 95%). Renal clearance made up 34 to 54% of total body clearance. Daptomycin demonstrated in vivo antibacterial activity against all three test strains, with the greatest activity observed against methicillin-resistant S. aureus. The predicted MIC for all three strains was approximately 13 micrograms/ml, corresponding to total (bound plus unbound) drug. On the basis of the drug's pharmacokinetics and antibacterial activity, doses of 4 to 6 mg/kg/day, possibly in divided doses, are predicted to be effective.
Captopril renal scintigraphy--a way to distinguish functional from anatomic renal artery stenosis.
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Cough and ACE inhibitors.
To assess the prevalence of cough as a side effect of angiotensin-converting enzyme inhibitor antihypertensive therapy, we reviewed 300 consecutive patient charts from a private practice and 200 consecutive patient charts from a university-based referral center for hypertension. Incidence of definite angiotensin-converting enzyme inhibitor-induced cough in the private practice was 25% and in the university practice, 7%, with an additional 6% of university-practice patients reporting a possible angiotensin-converting enzyme-inhibitor induced cough. This incidence is considerably greater than listed in the Physicians' Desk Reference. Reasons for the variability in incidence as reported in the literature are explored. Clinicians must be aware of this potentially disturbing side effect of angiotensin-converting enzyme inhibitors to avoid expensive and unnecessary diagnostic evaluations.
The limited echocardiogram: a modification of standard echocardiography for use in the routine evaluation of patients with systemic hypertension.
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Metabolic considerations in the choice of therapy for the patient with hypertension.
The objective of treating patients with hypertension is not simply to reduce blood pressure but rather to prevent the associated morbidity and mortality. Recent assessments of clinical trials have shown that while the risk of stroke is consistently lower with antihypertensive therapy, the same degree of success has not been demonstrated for coronary artery disease (CAD). Although there are many explanations of why we have not done as well in preventing CAD, one possibility is that the therapy used in clinical trials, primarily thiazide diuretics and beta-adrenoreceptor blockers, has increased the patient's risk of developing coronary atherosclerosis or lethal arrhythmias. Four classes of antihypertensive agents are recommended for initial therapy--thiazide diuretics, beta-adrenoreceptor blockers, angiotensin-converting enzyme (ACE) inhibitors, and calcium entry blockers. The metabolic effects of thiazide diuretics include electrolyte disturbances (hypokalemia, hypomagnesemia, and hyponatremia), dyslipidemia (increased triglycerides), abnormalities of glucose metabolism (hyperglycemia, hyperinsulinemia, and peripheral insulin resistance), and hyperuricemia. beta-Adrenoreceptor blockers have many of the same metabolic adverse reactions. beta-Adrenoreceptor blockers without intrinsic sympathomimetic activity (ISA) also cause dyslipidemias (lowered high-density lipoprotein cholesterol and increased triglycerides) and abnormalities of glucose metabolism (hyperglycemia, hyperinsulinemia, and peripheral insulin resistance). beta-Adrenoreceptor blockers with ISA and third-generation beta-blockers with selective partial agonist activity (celiprolol and dilevalol) do not cause dyslipidemia and to date do not appear to induce abnormalities in glucose metabolism. ACE inhibitors may decrease triglycerides and increase high-density lipoprotein cholesterol, and captopril may improve insulin sensitivity. Calcium entry blockers are metabolically neutral.(ABSTRACT TRUNCATED AT 250 WORDS)
Captopril renography in the diagnosis of renal artery stenosis and the prediction of improvement with revascularization. The Yale Vascular Center experience.
To enhance diagnosis and predict improvement in blood pressure control following surgery or renal angioplasty in patients with hypertension and renal artery stenosis (RAS), we employed captopril renography in 113 clinically selected patients, all of whom had renal angiography to verify the diagnosis. Criteria for normal captopril renograms were established from an initial cohort of 23 hypertensive patients with normal angiograms who had been judged to be at high risk for RAS using the same clinical criteria. Renal revascularization or nephrectomy was performed in 45 patients and the success of the procedure was determined in the 40 patients for whom 3-month follow-up was available. In these 113 patients, 58 (51%) had RAS. Captopril renography was 91% sensitive and 87% specific in identifying or excluding RAS. Diagnostic utility was preserved in those patients with renal insufficiency (serum creatinine equal to or greater than 1.5 mg/dL) (n = 46). Scintigraphic abnormalities induced by captopril were strongly associated with cure or improvement in blood pressure control following revascularization or nephrectomy (16 of 19), while the lack of captopril-induced change was associated with failure of such intervention (17 of 21) (P = .0001). We conclude that captopril renography is sensitive and specific for the diagnosis of RAS in a clinically selected high-risk group of hypertensives, and that the test accurately predicts the success or failure of therapeutic intervention.
Report of the Working Party Group for Patient Selection and Preparation.
Captopril renography is a valuable test in the diagnosis of patients with renal artery stenosis. We examined the criteria for selecting patients for this procedure and the best methods for preparing the patient for renography.
A simplified diagnostic approach to pheochromocytoma. A review of the literature and report of one institution's experience.
Pheochromocytoma is an unusual but potentially devastating tumor. Although a high index of suspicion is necessary, the likelihood of a pheochromocytoma is lower in the absence of the typical symptoms and findings. Nonetheless, screening must be broadened to include patients with a lower risk of the disease, such as those with resistant or labile hypertension who are minimally symptomatic. Extensive diagnostic evaluations should be reserved for those whose clinical or laboratory findings are more suggestive. Symptoms in a group of patients in whom a pheochromocytoma was seriously considered but excluded overlap symptoms in patients with a pheochromocytoma. Certain symptoms are useful: flushing to suggest a non-pheochromocytoma illness; visual symptoms, flank pain, and pallor to suggest that a pheochromocytoma is more likely. Combinations of symptoms can be of value: 2 or more symptoms from the triad of headache, palpitations, and diaphoresis were present in the majority of pheochromocytoma patients, but in a smaller number of non-pheochromocytoma patients. The presence of the entire triad is more specific, but less sensitive. New hypertension, or hypertension associated with unexplained orthostatic hypotension, are suggestive of an underlying pheochromocytoma. Twenty-four-hour urine studies are consistently abnormal in patients with a pheochromocytoma, but are also elevated in a significant proportion of non-pheochromocytoma patients. Values greater then 1.5-2-fold above the upper limit of normal are very suggestive that a pheochromocytoma is present, and warrant a more intensive subsequent evaluation. Imaging studies are reliable in the diagnosis of pheochromocytoma, and can help to confirm or exclude the disease. Patients with a higher clinical likelihood and any elevated urinary testing, or with a lower clinical likelihood and persistently and/or significantly elevated urinary testing, should have imaging studies performed. This combination of clinical screening, 24-hour urinary testing, and imaging studies is a useful and reliable approach to patients suspected of harboring a pheochromocytoma.
Prevalence of postural hypotension at baseline in the Systolic Hypertension in the Elderly Program (SHEP) cohort.
OBJECTIVE: The objective of this study was to examine the prevalence and correlates of postural hypotension (defined as a drop in systolic blood pressure of greater than or equal to 20 mm Hg) in a cohort of elderly persons with isolated systolic hypertension (ISH). DESIGN: Baseline cross-sectional analysis of the 4,736 persons randomized in the Systolic Hypertension in the Elderly Program (SHEP). SETTING: A randomized multi-center double-blind outpatient clinical trial of the impact of treating ISH. PARTICIPANTS: Men and women age greater than or equal to 60 years with the systolic blood pressure (SBP) greater than or equal to 160 mm Hg and diastolic blood pressure (DBP) less than 90 mm Hg. MEASURES: Medical histories were obtained using interviewer-administered, standardized clinical history forms. At entry into the study, seated and standing BP was measured by certified BP technicians using a random zero sphygmomanometer. Postural hypotension (PH) was assessed at 1 and 3 minutes after the participant arose from a seated position. MAIN RESULTS: PH was found in 10.4% of participants at 1 minute and in 12.0% of participants at 3 minutes. 5.3% of participants demonstrated PH at both time intervals while 17.3% demonstrated PH at either or both of the time intervals. Factors significantly (P less than 0.05) associated with the presence of PH were higher mean SBP and a lower mean body mass index. CONCLUSIONS: Somewhat different persons were defined as having PH based upon the 1 minute and 3 minute standing measures of BP, and prevalence estimates of PH can vary depending on whether one or more intervals of measurement are used. Cross-sectional data analysis indicated that PH, in healthy community-dwelling older persons with ISH, may not be associated with a history of disorders or problems usually thought to be related to PH. However, prospective data are needed to determine the prognostic significance of PH, and whether one or multiple measurements carry more significance.
Systolic Hypertension in the Elderly Program (SHEP). Part 6: Baseline physical examination findings.
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Simplified captopril renography in diagnosis and treatment of renal artery stenosis.
To improve the diagnosis and forecast the response to surgery or renal angioplasty in patients with hypertension and renal artery stenosis, we employed a simplified captopril renography protocol in conjunction with renal arteriography in 94 clinically selected patients. Fifty hypertensive patients (group 1) with a high clinical likelihood of renovascular hypertension were evaluated using a simplified captopril renography protocol and renal angiography on the arterial side. Criteria for normal captopril renal scintigrams were established based on this original cohort and validated in an additional 44 clinically comparable patients (group 2). Renal revascularization or nephrectomy was performed in 39 patients, and success of the procedure was determined in the 34 patients for whom 3-month follow-up was available. In the 94 patients, 44 (47%) had renal artery stenosis. Simplified captopril renography was 91% sensitive and 94% specific in identifying or excluding renal artery stenosis in the combined group, with no difference in the diagnostic utility between groups 1 and 2, or in those with renal insufficiency (n = 38) or those with bilateral disease (n = 17). Scintigraphic abnormalities induced by captopril were strongly associated with cure or improvement in blood pressure control following revascularization or nephrectomy (15 of 18), while the lack of captopril-induced changes was associated with failure of such intervention (13 of 16) (p = 0.0004). We conclude that simplified captopril renography is highly sensitive and specific in the diagnosis of renal artery stenosis in a clinically selected high-risk population and that the test accurately predicts the success or failure of therapeutic intervention.
Drug treatment of hypertension in patients with diabetes mellitus.
Patients with diabetes mellitus have an increased prevalence of hypertension and its vascular consequences, including coronary and cerebrovascular disease. Drug treatment of hypertension in diabetic subjects is fraught with potential difficulties, including the altered efficacy of medications, the increased risk of side effects, and the possibility of worsening glycemic control and increasing serum lipid levels. Despite these difficulties, treatment is an important part of reducing morbidity and mortality from vascular events. Antihypertensive therapy may also have the potential to prevent or retard the development of diabetic nephropathy. In this article, we discuss the efficacy and metabolic and nonmetabolic side effects of the various classes of antihypertensive agents in patients with diabetes mellitus and suggest a stepped-care approach to the drug treatment of patients with hypertension and diabetes.
Resistant hypertension in a tertiary care clinic.
STUDY OBJECTIVE: --To determine the prevalence of resistant hypertension in a tertiary care facility, the frequency of its various causes, and the results of treatment. DESIGN: --Review of clinic records of all patients seen for the first time between January 1, 1986, and December 31, 1988. METHODS: --Patients meeting criteria for resistant hypertension were examined for appropriateness of their medical regimen, presence of secondary causes of hypertension, noncompliance, interfering substances, drug interactions, office resistance (elevated blood pressure in the office only while receiving treatment), and other potential causes of resistance. RESULTS: --Of the 436 charts reviewed, 91 were those of patients who met criteria for resistant hypertension and were seen more than once. The most common cause was a suboptimal medical regimen (39 patients), followed by medication intolerance (13 patients), previously undiagnosed secondary hypertension (10 patients), noncompliance (nine patients), psychiatric causes (seven patients), office resistance (two patients), an interfering substance (two patients), and drug interaction (one patient). Blood pressure control, defined as diastolic blood pressure of 90 mm Hg or less and systolic blood pressure of 140 mm Hg or less for patients aged 50 years or less (less than or equal to 150 mm Hg for those aged 51 to 60 years and less than or equal to 160 mm Hg for those aged greater than 60 years), was achieved in 48 (53%) of those 91 patients. Another 10 had significant improvement in their blood pressure (greater than or equal to 15% decrease in diastolic blood pressure). Of patients whose blood pressure was controlled after they had been on a suboptimal regimen, the two most frequently used therapeutic strategies were to add (50%) or modify (24%) diuretic therapy or to add (50%) or increase the dose of (12%) a newer drug, either a calcium entry blocker or angiotensin-converting enzyme inhibitor. CONCLUSION: --We conclude that resistant hypertension is common in a tertiary care facility and that a suboptimal regimen is the most common reason. Furthermore, in the majority of these patients, the elevated blood pressures can be controlled or significantly improved.