An inpatient trial of the safety and efficacy of losartan compared with placebo and enalapril in patients with essential hypertension.

The antihypertensive activity and safety of losartan, a specific and selective antagonist of angiotensin II (subtype 1) receptors, was evaluated in 100 inpatients with mild to moderate essential hypertension. After a 2-week, single-blind, out patient placebo lead-in period, the last 2 days of which included inpatient monitoring of baseline blood pressure, the patients were assigned randomly to receive once-daily doses of either placebo; 50, 100, or 150 mg losartan; or 10 mg enalapril. Patients were treated double blind for 5 days, followed by a day for the study of drug withdrawal. Beginning with the first dose, the three doses of losartan and enalapril significantly decreased peak and trough systolic and diastolic blood pressures compared with placebo (p < or = 0.05). The area under the blood pressure curve was analyzed as an assessment of total blood pressure change throughout the day. On day 1, total blood pressure reduction with losartan (50-150 mg) was slightly less than with enalapril. By day 5 of double-blind treatment, the reduction in blood pressure in these groups was similar, suggesting that losartan has a slower onset of action than enalapril. No rebound hypertension was observed after study-drug discontinuation. Losartan was well tolerated in this trial, with an adverse event profile similar to placebo and enalapril.

Antihypertensive efficacy of the angiotensin II AT1-receptor antagonist losartan: results of a randomized, double-blind, placebo-controlled, parallel-group trial using 24-hour blood pressure monitoring. Ambulatory Blood Pressure Monitoring Study Group.

The antihypertensive efficacy of once- and twice-daily losartan was evaluated in a randomized, double-blind, placebo-controlled, parallel-group trial using ambulatory 24-h blood pressure monitoring in 122 patients with mild to moderate essential hypertension. Data are reported for 112 patients who completed the active treatment phase. Losartan exerted a sustained 24-h antihypertensive effect at all doses studied (50 or 100 mg once daily, or 50 mg twice daily). Losartan demonstrated a smooth, gradual onset of action, did not affect normal circadian variations on blood pressure, and had no significant effect on heart rate. An additive antihypertensive effect was obtained by adding low-dose hydrochlorothiazide to losartan monotherapy at all doses of losartan studied. Losartan was well tolerated during the study with a frequency of adverse events comparable with placebo. No major adverse events were recorded. The results of this study indicate that losartan is an effective and well-tolerated antihypertensive agent that provides 24-h blood pressure-lowering efficacy from a single daily dose of 50 mg.

What medical schools and universities can learn from one another.

Colleges and universities devoted to undergraduate education and non-medical graduate education (hereafter called "universities") have much to teach medical schools and much to learn from them. Universities and medical schools differ significantly in their sources of revenue, cultures of promotion and tenure, academic values, and decision-making processes. Yet from the experience of universities, medical schools can learn innovative techniques of curriculum assessment and teaching, how to handle diversity issues, and ways to expand the definition of scholarship. In turn, medical schools can help teach universities the importance of fiscal and regulatory accountability, the benefits of interdisciplinary efforts, the practical benefits of problem-based learning, and techniques for adjusting to rapid change. The authors, all with medical school faculty backgrounds, developed the views reported in this article when they were Fellows in a leadership training program sponsored by the American Council on Education (ACE). They urge their colleagues to reach out beyond their specialties and departments and learn from higher education institutions that are grappling with problems analogous to those faced by medical schools.

Losartan potassium lowers blood pressure measured by ambulatory blood pressure monitoring.

OBJECTIVES: To determine the blood pressure lowering effect and safety of losartan potassium 50 mg once or twice daily, or 100 mg once daily, using 24-h ambulatory blood pressure monitoring and conventional trough clinic blood pressure. DESIGN: Multicenter, double-blind, randomized, parallel, placebo-controlled trial. SETTING: Nine sites in university hospitals and urban centers in the United States. PATIENTS: 122 mild to moderate hypertensive adult non-black men and women, 21 years of age and older, who were within 30% of their ideal body weight. INTERVENTION: Qualification required a mean 24-h ambulatory blood pressure measurement of > or = 85 mmHg and a sitting diastolic blood pressure of 95-115 mmHg. Subjects were then randomized to placebo or losartan potassium in three different dose regimens. CLINIC BLOOD PRESSURE EVALUATIONS: Trough blood pressure was measured by trained observers using standardized methods, and ambulatory blood pressure measurements were obtained for 26 h using a SpaceLabs Model 90207 monitor. RESULTS: All doses of losartan potassium significantly decreased mean systolic 24-h ambulatory blood pressure (range -9.4 to -14.2 mmHg; P < or = 0.01) and mean diastolic 24-h ambulatory blood pressure (range -5.6 to -9.0 mmHg; P < or = 0.01) compared with placebo. All decreases were significantly different from placebo. The 24-h blood pressure profiles revealed a smooth, sustained antihypertensive effect of losartan potassium at all doses. Similar reductions in blood pressure were observed using trough clinic measurements. There were no significant differences in overall clinical adverse experiences between treatment groups. There were no significant changes in heart rate, body weight, electrocardiograms or mean laboratory measurements. CONCLUSIONS: Losartan potassium, the first of a new class of potent and specific AT1-selective, non-peptide, angiotensin II antagonists, significantly reduces mean 24-h ambulatory blood pressure and trough clinic sitting blood pressure, and is well tolerated.

Failure of the community-based Vita-Stat automated blood pressure device to accurately measure blood pressure.

OBJECTIVE: To evaluate the Vita-Stat automated blood pressure computer (a patient-operated blood pressure measuring device available in the community) to determine its value as an instrument to monitor blood pressure in the ambulatory patient. DESIGN: Comparative study using the Vita-Stat vs a gold standard, the mercury sphygmomanometer. SETTING: Three local grocery stores. PARTICIPANTS: Sixty-three passersby who agreed to answer questions and to sit for several measurements of blood pressure. INTERVENTIONS: Simultaneous measurement of blood pressure with each subject wearing a Vita-Stat cuff on the left arm and a mercury sphygmomanometer cuff on the right arm. Two pressures were measured sequentially in the same manner. MAIN OUTCOME MEASURES: The reproducibility, accuracy, sensitivity, and specificity of the Vita-Stat computer compared with the gold standard. RESULTS: In sequential measurements, the Vita-Stat readings of both systolic and diastolic blood pressure correlated less well with each other than did the mercury readings (intramachine differences). The Vita-Stat readings also correlated poorly with the mercury readings of systolic and diastolic blood pressure (intermachine differences). The variability in readings recorded by the Vita-Stat were striking, with differences of up to 60 mm Hg from the mercury readings. More than half (63.2%) of the subjects had Vita-Stat readings that were more than 5 mm Hg different from the mercury readings. Vita-Stat systolic readings were usually lower than mercury readings and also varied by as much as 60 mm Hg below in one patient to 58 mm Hg above the mercury reading in another. The sensitivity of the Vita-Stat in correctly diagnosing hypertension was 0.26; the negative predictive value was 0.45. CONCLUSIONS: Our data suggest that the Vita-Stat is not only inconsistent but inaccurate in measuring blood pressure in the ambulatory patient and is, therefore, not appropriate to use as a monitoring device.

Blood pressure effects of the angiotensin II receptor blocker, losartan.

BACKGROUND: Losartan potassium, the first nonpeptide selective blocker of angiotensin II at the AT1 receptor, has been shown to exhibit clinical antihypertensive effects. The aim of the present study was to characterize the efficacy and duration of action of losartan by ambulatory blood pressure monitoring. METHODS: The study was performed in nonblack hypertensive patients whose baseline untreated clinical diastolic blood pressures were 95 mm Hg or higher and whose average 24-hour ambulatory diastolic blood pressures were 85 mm Hg or higher. Patients were randomized, double-blind, into four treatment groups: placebo (n = 32) or losartan, 50 mg once daily (n = 29), 100 mg once daily (n = 30), or 50 mg twice daily (n = 31). Clinical and 24-hour ambulatory blood pressures were measured at baseline (off treatment for at least 4 weeks) and after 4 weeks of treatment. RESULTS: By clinical sphygmomanometer measurements at the end of the 24-hour or 12-hour dosing intervals (trough), all three losartan dosages were significantly more effective than placebo at decreasing systolic and diastolic blood pressures. By average 24-hour ambulatory systolic/diastolic blood pressure measurements, the decreases produced were 0.0/0.2 mm Hg for placebo and 9.2/6.9, 9.9/6.4, and 13.2/8.5 mm Hg, respectively, for losartan, 50 mg once daily, 100 mg once daily, and 50 mg twice daily. All drug effects were different from placebo (P < .01). The effects of losartan, 50 mg twice daily, were not significantly different from those of losartan, 100 mg once daily, but, as expected, the effects were greater than those of losartan, 50 mg once daily (P < .05). Addition of hydrochlorothiazide, 12.5 mg/d, during an additional 2-week treatment period in patients whose clinical diastolic blood pressure remained at 85 mm Hg or higher while receiving monotherapy produced additional and clinically meaningful blood pressure decrements that were similar in all four treatment groups. There was no clinically important difference in the incidence of adverse events among the losartan-treated and placebo groups [corrected]. CONCLUSION: Ambulatory blood pressure monitoring, which virtually eliminated antihypertensive placebo responses, demonstrated clear 24-hour efficacy for losartan, 50 mg once daily, as well as for higher doses of 100 mg once daily and 50 mg twice daily. This AT1 receptor blocker had antihypertensive effects that appeared additive when combined with low-dose diuretic therapy. Losartan was generally well tolerated.

The hypotensive action of captopril and enalapril is not prostacyclin dependent.

Angiotensin converting enzyme inhibitors have been proposed to have a prostaglandin-dependent component to their hypotensive action. The aim of this study was to assess whether the structurally dissimilar angiotensin converting enzyme inhibitors captopril and enalapril stimulate the synthesis of prostacyclin, whether their hypotensive action is blunted by indomethacin, and whether these biochemical or physiologic parameters differ for the two drugs, in white subjects with essential hypertension. Twelve patients were enrolled and 11 finished the study. The study consisted of a double blind, randomized, double-crossover design. All patients received either placebo or 50 mg indomethacin twice a day for 3 weeks; after 1 week of placebo or indomethacin either 50 mg captopril or 10 mg enalapril twice a day was added and continued for 2 weeks. Each patient received every possible combination. Neither captopril nor enalapril stimulated prostacyclin production as determined by measurement of the urinary excretion rate of its main enzymatic metabolite, 2,3-dinor-6-keto-prostaglandin-F1 alpha. Although indomethacin reduced the urinary excretion of the enzymatic metabolite of prostacyclin by more than 50%, it did not influence the hypotensive effect of captopril or enalapril. We conclude that neither captopril nor enalapril have a significant prostacyclin-dependent component to their hypotensive action.

Cytosolic calcium and insulin resistance in elderly patients with essential hypertension.

We evaluated insulin sensitivity in normotensive (blood pressure, BP, less than 135/85 mm Hg) and hypertensive (BP greater than 160/90 mm Hg) elderly subjects over 65 years old who were stratified as normal weight (body mass index, BMI, less than 27) and obese (BMI greater than 27). Obese hypertensive individuals demonstrated marked hyperinsulinemia (P less than .01) and significantly reduced (P less than .05) submaximally stimulated adipocyte 2-deoxyglucose (2-DOG) uptake (abdominal wall fat biopsy). Normal weight hypertensive subjects also demonstrated higher levels of insulinemia and lower insulin-stimulated 2-DOG uptake than nonobese controls. Adipocyte [Ca2+]i levels were elevated in all elderly subjects compared to young individuals (P less than .01). Basal and maximally stimulated 2-DOG uptake were similar in all groups. One month of therapy with a calcium channel blocker, 10 mg nitrendipine twice daily, reduced blood pressure in the hypertensive subjects, reduced plasma insulin to control values during an oral glucose tolerance test in obese hypertensive individuals (P less than .01), and restored adipocyte 2-DOG uptake at submaximally effective insulin concentration to control values in normal weight and obese hypertensive subjects. In summary, older hypertensive, and particularly older obese hypertensive, patients manifest significant insulin resistance accompanied by elevated levels of [Ca2+]i in their adipocytes.

Epidemiology of hypertension in the elderly.

Epidemiological studies confirm that hypertension, particularly systolic hypertension, is a major cardiovascular and cerebrovascular risk factor in the elderly. Clinical trials convincingly demonstrate the benefits of treating both diastolic hypertension in persons up to age 80 years, and isolated systolic hypertension in persons over age 60. The European Working Party on Hypertension in the Elderly (EWPHE) trial showed that reducing elevated blood pressure resulted in a 27% reduction in overall cardiovascular mortality, as well as significant reductions in severe congestive heart failure, strokes and deaths from myocardial infarction. The Systolic Hypertension in the Elderly Program (SHEP) also reported a 36% reduction in the incidence of stroke and decreases in cardiovascular events, including myocardial infarctions, when hypertension was treated. Additional EWPHE data suggest that the optimal level of systolic blood pressure control is between 146 and 158mm Hg, while patients in the SHEP trial with isolated systolic hypertension derived benefits at an average treated systolic blood pressure of 143mm Hg. Elderly study populations comply well with antihypertensive treatment, and blood pressure can be safely lowered with simple drug regimens. Nonpharmacological treatment is recommended for initial treatment of mild diastolic hypertension and isolated systolic hypertension, and as adjuvant treatment with medication. Since all antihypertensive agents can lower blood pressure in the elderly, therapy should be chosen based on its potential for side effects, drug interactions and effects on concomitant disease states.

Short-term effects of estrogen and progestin on blood pressure of normotensive postmenopausal women.

Blood pressure rises in women with increasing age, possibly related to the decrease in production of female hormones that accompanies menopause. Although estrogen or progestin administration alone consistently does not lower blood pressure in postmenopausal women, possible interactions of these two hormones in affecting blood pressure are not well understood. We studied 12 surgically postmenopausal, normotensive women, aged 51 +/- 2 years (SEM). Treatment for each subject consisted of 1 week each of placebo, estrogen (conjugated equine estrogens, 2.5 mg/day), progestin (medroxyprogesterone acetate, 60 mg/day), and combined estrogen and progestin, given in varied order. At the end of each week, auscultatory blood pressures were measured while patients were seated. Neither estrogen nor progestin alone either increased or decreased blood pressure significantly, whereas combined estrogen and progestin lowered systolic, diastolic, and mean blood pressures 6 to 7 mm Hg (P less than .05). Treatment order was unrelated to the change in blood pressure values. The authors suggest that administering progestin with estrogen may be more effective in lowering blood pressure than either hormone alone in postmenopausal women.

The antihypertensive efficacy of hydrochlorothiazide is not prostacyclin dependent.

We tested the hypothesis that vascular prostacyclin synthesis is stimulated by hydrochlorothiazide and could account for some of the drug's antihypertensive effect. We studied 13 patients with mild essential hypertension in a randomized, double-blind design to assess the effects of indomethacin on hydrochlorothiazide's ability to lower blood pressure, alter body weight, stimulate plasma renin activity, and modulate vascular prostacyclin biosynthesis as assessed by the urinary excretion of the major enzymatically produced metabolite of prostacyclin, 2,3-dinor-6-keto-prostaglandin F1 alpha (PGF1 alpha), measured by GC/MS. Administration of hydrochlorothiazide, 50 mg daily for 2 weeks, was associated with a significant decrease in both systolic and diastolic blood pressure in both supine (systolic, 148 +/- 3 to 136 +/- 3 mm Hg; diastolic, 97 +/- 2 to 94 +/- 3 mm Hg) and upright (systolic, 151 +/- 4 to 131 +/- 2 mm Hg; diastolic, 103 +/- 2 to 97 +/- 3 mm Hg) positions. Hydrochlorothiazide administration resulted in a 1 kg weight loss and stimulation of plasma renin activity from 1.7 +/- 0.4 to 5.3 +/- 1.1 ng angiotensin I/ml/hr. However, the urinary excretion of 2,3-dinor-6-keto-PGF1 alpha was unchanged after administration of hydrochlorothiazide (86 +/- 13/ng/gm creatinine during placebo, 74 +/- 13 ng/gm during week 1 of hydrochlorothiazide, and 70 +/- 9 ng/gm during week 2 of the drug). Administration of indomethacin, 50 mg twice a day, resulted in greater than 60% inhibition of 2,3-dinor-6-keto-PGF1 alpha excretion but did not affect the antihypertensive response to hydrochlorothiazide. Indomethacin did not oppose the diuretic effect of hydrochlorothiazide as assessed by weight loss but did attenuate the rise in plasma renin activity. Our data demonstrate that the blood pressure-lowering effect of a thiazide diuretic does not require enhanced prostacyclin synthesis and the cyclooxygenase inhibitor indomethacin does not antagonize the antihypertensive efficacy of hydrochlorothiazide.

Lack of efficacy of hydergine in patients with Alzheimer's disease.

BACKGROUND: There is no effective pharmacologic treatment for Alzheimer's disease, the most common dementing illness in the United States. Hydergine, a combination of ergoloid mesylates, is the only approved medication for Alzheimer's disease, but despite widespread use its efficacy remains to be established. We conducted a clinical trial of Hydergine-LC, a newer preparation of ergoloid mesylates in the form of a liquid in a capsule (LC) that may have greater bioavailability, to determine its value in patients with Alzheimer's disease. METHODS AND RESULTS: Eighty older adults with probable Alzheimer's disease participated in this double-blind, placebo-controlled trial of Hydergine-LC for 24 weeks. The recommended dose of 1 mg orally three times daily was used. Cognition and behavior were evaluated before and after the trial, and the patients were monitored for adverse effects. The medication was safe and well tolerated. The Hydergine-LC group did not perform better after treatment than the placebo group on any test, and its performance was worse (P less than 0.01 and P less than 0.02, respectively) on one cognitive measure (Wechsler Adult Intelligence Scale Digit Symbol Substitution Task) and on one behavioral scale (the Geriatric Evaluation by Relatives Rating Instrument). CONCLUSIONS: Hydergine-LC appears to be ineffective as a treatment for Alzheimer's disease.

Perspective on hypertension in the elderly.

More than half of elderly men and women have hypertension, leading to a significant risk of increased morbidity and mortality. The cause of hypertension in this age group is unknown. Left ventricular hypertrophy is frequently present, often associated with diastolic dysfunction. Systolic hypertension in the elderly increases the risk of cardiovascular disease, but there are no good data to show that the treatment of isolated systolic hypertension reduces the morbidity or mortality. Good evidence indicates that antihypertensive treatment in this group decreases cardiovascular morbidity and mortality up to age 80, so most elderly hypertensive patients should be treated. An empiric trial of nonpharmacologic therapy can be initiated in those with mild hypertension and no cardiovascular disease, but most patients will require drug therapy. Most elderly hypertensive patients have accompanying illnesses for which they may or may not be taking medications. Some antihypertensive drugs exacerbate coexisting diseases while others augment treatment regimens. Similarly, drugs may interact in a beneficial or adverse way. Finally, drug metabolism is altered by age, leading to problems with toxicity or diminished efficacy. The choice of medication should be based on all such considerations, including the cost and convenience of the drugs available.

Hydralazine does not stimulate prostacyclin biosynthesis in hypertensive patients.

The hypothesis that vascular prostacyclin synthesis is stimulated by the oral administration of hydralazine and may account for part of its vascular effect was tested. Eight white patients with mild essential hypertension were studied in a randomized, double-blind design to assess the effects of indomethacin on hydralazine's ability to lower blood pressure, elevate pulse, and alter the vascular prostacyclin biosynthesis as assessed by the urinary excretion of the major enzymatically produced metabolite of prostacyclin, 2,3-dinor-6-keto-prostaglandin F1 alpha (PGF1 alpha) measured by gas chromatography-mass spectrometry. Administration of hydralazine at either 50 mg bid or 100 mg bid for a week, doses commonly administered in clinical settings, was not associated with a statistically significant fall in mean blood pressure, although there was a tendency towards a decrease but did result in an increase in heart rate. Administration of indomethacin had no effect on the hemodynamic parameters secondary to hydralazine. Administration of indomethacin resulted in a slight but significant weight gain compared to placebo, but the addition of hydralazine did not result in a further increase in weight. Neither dose of hydralazine resulted in an increase in the urinary excretion of 2,3-dinor-6-keto-PGF1 alpha. The excretion rate was 85 +/- 16 ng/g of creatinine during placebo, 88 +/- 16 ng/g of creatinine during hydralazine, 50 mg bid, and 65 +/- 8 ng/g of creatinine during hydralazine, 100 mg bid. Administration of indomethacin, 50 mg bid, resulted in a significant decrease in 2,3-dinor-6-keto-PGF1 alpha from 65 +/- 6 ng/g to 37 +/- 8 ng/g of creatinine.(ABSTRACT TRUNCATED AT 250 WORDS)

Research consent forms: continued unreadability and increasing length.

Consent forms are often long and incomprehensible. The authors studied 88 consecutive research consent forms generated at the Denver Veterans Administration Medical Center, evaluating the reading levels of the forms using the Fry Readability Scale and recording the numbers of lines of text. The mean grade reading level required for comprehension was 13.4 years of schooling. Twenty-two percent of all text passages scored were at the postgraduate level of readability. This difficult readability level has not improved since the forms were last tested in 1982. The mean length of the forms was 84.6 lines. Also found was a 58% increase in the length of forms since 1982, a factor known to impair comprehension. These factors, poor readability and increasing length, may make many consent forms incomprehensible. It is recommended that investigators be brief, use plain English, and write consent forms at appropriate reading levels, and receive training on how to obtain valid consent.

The natural history of medication compliance in a drug trial: limitations of pill counts.

To assess medication compliance over time, we prospectively performed pill counts among 121 ambulatory hypertensive subjects for less than or equal to 12 months. Prescribed regimens consisted of pinacidil or hydralazine administered four times a day and of secondary drugs administered up to twice daily. Surreptitious pill counts occurred every 1 to 12 weeks. Among a middle-aged subject group that had been selected for high rates of compliance, we observed mean compliance rates that approximated 100%. We noted marked intrasubject and intersubject variability for any one medication, between medications, and over time. From baseline blood pressures (+/- SE) of 155.5 +/- 1.9/97.3 +/- 1.0 mm Hg, subsequent mean blood pressures varied by compliance subgroup: "hypocompliers" (less than 80%), 151.3/91.0 mm Hg; "hypercompliers" (greater than or equal to 120%), 147.6/91.4 mm Hg; and "eucompliers" (80% to 119%), 143.3/88.5 mm Hg (systolic blood pressure: F1,52 = -220.9, NS; diastolic blood pressure: F1,52 = -121.4, NS). We concluded that weekly pill counts indicated marked intersubject and intrasubject variability, obscured by long-term averages; that compliance lapses appeared to be random; and that excessive medication-taking was the most consistent with "pill dumping."

Epidemiologic aspects of elderly hypertensive patients and the results of treatment with nitrendipine.

Throughout the developed world, populations are growing older. Blood pressure, especially systolic blood pressure, increases with aging, and this increase leads to increased risks of cardiovascular morbidity and mortality. Clinical trials demonstrate that treatment of hypertension in the elderly reduces overall cardiovascular mortality, cardiac mortality, nonfatal cardiovascular events, congestive heart failure, progression to severe hypertension, and strokes. Drug treatment has been well tolerated, but diuretic therapy has been known to increase plasma glucose, uric acid, and creatinine. Therapeutic trials of nonpharmacologic treatment may be indicated in those with mild elevation in blood pressure and no serious end organ disease. However, most people up to age 80 will require drug treatment. Many drugs are effective in the elderly, but, some like beta-blockers, may not be as effective as in younger patients. Controlled clinical trials demonstrate that nitrendipine, a calcium channel blocking drug, significantly reduced mean systolic and diastolic blood pressure in older hypertensive patients, (successfully controlling pressure in a high percentage) and was well tolerated. Drug effects persist for 12 h or more. The drug decreased the exercise-induced rise in the rate-pressure product. Although there is a temporary increase in heart rate, this returns to baseline after a short time. Side effects include headache, flushing, dizziness, edema, and palpitations. Therefore, nitrendipine offers a reasonable and useful alternative to many other drugs in the treatment of combined systolic and diastolic hypertension in the elderly.

Use of fluoxetine, a selective serotonin-uptake inhibitor, in the treatment of obesity: a dose-response study (with a commentary by Michael Weintraub).

Pharmacologic measures which increase serotonergic activity in the brain decrease food consumption and lead to decreased weight in animals. Fluoxetine, an inhibitor of serotonin reuptake, decreases food intake in animals and is associated with weight loss in depressed and otherwise healthy obese patients. To determine the most effective daily fixed dose which causes weight loss in nondepressed obese patients, fluoxetine (10, 20, 40 or 60 mg) or placebo was administered once daily for 8 weeks to 655 patients consisting primarily of women (mean age 40 years, mean weight 95 kg). Diet and activity were not controlled. The placebo-treated patients lost 0.6 +/- 2.3 kg. With the 60-mg fluoxetine dose, patients lost an average of 4.0 +/- 3.9 kg (P less than 0.001), with intermediate responses at the lower doses. Weight loss was proportional to the initial body mass index (weight/height squared). There were no statistically significant differences between any fluoxetine treatment group and placebo for discontinuations from the study. There were statistically significant dose-dependent increases in reports of asthenia, somnolence and sweating. Thus, fluoxetine 60 mg daily appears to be potentially effective for use in weight reduction.

Treatment of hypertension in the elderly with a new calcium channel blocking drug, nitrendipine.

PURPOSE: Treatment of hypertension in the elderly decreases cardiovascular morbidity and mortality. We hypothesized that nitrendipine would be efficacious in the treatment of hypertension in the elderly. We evaluated potential differences between nitrendipine and the commonly used drug hydrochlorothiazide (HCTZ). PATIENTS AND METHODS: The study was conducted as a double-blind randomized clinical trial of nitrendipine or HCTZ. Thirty hypertensive subjects over age 60 with a median sitting blood pressure greater than or equal to 95 mm of Hg were recruited into the study. A diastolic blood pressure with treatment of less than 95 mm Hg with a 5 mm Hg or greater decrease from baseline was considered a successful response. RESULTS: Nitrendipine decreased mean (+/- SEM) blood pressure from 163 +/- 3/102 +/- 1 to 142 +/- 2/89 +/- 2 mm Hg, and HCTZ decreased it from 164 +/- 4/102 +/- 1 to 143 +/- 5/91 +/- 2 mm Hg. A greater proportion of patients had a successful response with nitrendipine (81 percent) than with HCTZ (64 percent). The antihypertensive effect of nitrendipine twice daily appeared to be sustained for 24 hours. Blood pressure response to exercise was attenuated with both drugs. HCTZ caused gout, leg pains, muscle aches, hypokalemia, increased uric acid levels, and increased total cholesterol and triglyceride levels. Nitrendipine caused edema and tachycardia. CONCLUSION: Nitrendipine significantly reduces blood pressure with few side effects and no adverse metabolic effects, and offers a reasonable alternative for treating hypertension in the elderly.

Propranolol increases prostacyclin synthesis in patients with essential hypertension.

We tested the hypothesis that vascular prostacyclin synthesis is increased by propranolol and could account for some of the drug's antihypertensive effect. We studied 10 white patients with mild essential hypertension in a randomized, double-blind design to assess the effects of indomethacin with or without the addition of propranolol on blood pressure and vascular prostacyclin biosynthesis, as assessed by the urinary excretion of the major enzymatically produced metabolite of prostacyclin, 2,3-dinor-6-keto-prostaglandin F1 alpha (PGF1 alpha), F1 alpha (PGF1 alpha), measured by gas chromatography-mass spectrometry. Seven patients responded to propranolol with a lowering of mean arterial blood pressure in both supine and upright postures. The fall in mean arterial blood pressure (-14.1 +/- 2.1 mm Hg sitting; -17.4 +/- 1.7 mm Hg supine) with propranolol alone was significantly greater than that produced when propranolol was given to patients receiving indomethacin (-7.8 +/- 1.9 mm Hg sitting; -7.7 +/- 3.0 mm Hg supine). Our drug-responsive patients demonstrated a significantly lower excretion rate of 2,3-dinor-6-keto-PGF1 alpha than was found in an age and sex-matched group of normal volunteers. With propranolol treatment, drug-responsive patients showed a significant increase in the excretion of 2,3-dinor-6-keto-PGF1 alpha, such that the mean excretion was not significantly different from that in normal volunteers. Indomethacin caused a significant rise in mean arterial blood pressure and a significant fall in 2,3-dinor-6-keto-PGF1 alpha excretion, and it blocked the rise in urinary 2,3-dinor-6-keto-PGF1 alpha associated with propranolol therapy.(ABSTRACT TRUNCATED AT 250 WORDS)