Mahendr S. Kochar

Matrix study of irbesartan with hydrochlorothiazide in mild-to-moderate hypertension

The purpose of this study was to assess the safety and antihypertensive dose-response effects of irbesartan and hydrochlorothiazide (HCTZ) in patients with mild-to-moderate hypertension. After a 4- to 5-week single-blind placebo lead-in period, 683 patients with seated diastolic blood pressure (SeDBP) between 95 and 110 mm Hg were randomized to receive once-daily dosing with one of 16 different double-blind, fixed combinations of irbesartan (0, 37.5, 100, and 300 mg irbesartan) and HCTZ (0, 6.25, 12.5, and 25 mg HCTZ) for 8 weeks. The primary efficacy variable was the change from baseline in trough SeDBP after 8 weeks of therapy. Data were analyzed by response surface modeling. At Week 8, mean changes from baseline in trough SeDBP (mm Hg) ranged from -3.5 for placebo, -7.1 to -10.2 for the irbesartan monotherapy groups, -5.1 to -8.3 for the HCTZ monotherapy groups, and -8.1 to -15.0 for the combination groups. Irbesartan plus HCTZ produced additive reductions in both SeDBP and seated systolic BP, with at least one combination producing greater BP reduction than either drug alone (P < .001). All treatments were well tolerated; there were no treatment-related serious adverse events. Irbesartan tended to ameliorate the dose-related biochemical abnormalities associated with HCTZ alone. In conclusion, the combination of HCTZ in doses up to 25 mg with irbesartan, in doses up to 300 mg, is safe and produces dose-dependent reductions in BP.

An evaluation of mood states among first-year residents.

To examine the need for preventive and treatment interventions, a prevalence study was conducted to ascertain the rate of depressive symptomatology and other negative mood states among 112 first-year residents The participation rate was 54%. Subjects (N = 61) were administered the Beck Depression Inventory and Profile of Mood States in personal interview sessions. The Profile measures five negative mood states, namely, “tension-anxiety,” “depression-dejection,” “anger-hostility,” “fatigue-inertia,” “confusion-bewilderment,” and one positive state, “vigor-activity.” A 15.5% rate of depression was found, which is lower than a rate of 23 5%, also measured by Becks inventory, among a sample of university undergraduates and 19 9% among an adult sample from the general population. No differences were observed among residency programs or sex on Becks scale; however, significantly higher scores were found for women on the “depression-dejection” dimension of the Profile. The mean scores on all negative mood dimensions of the Profile were below the mean for university undergraduate norms. Neither sleep nor hours worked over the past week were associated with increased Beck scores. These results indicate that sleep deprivation and long work hours did not contribute to depression among the subjects who participated in the study. Female interns, however, appear to be at increased risk of depression, and adequate support systems need to be provided.

Mentors in graduate medical education at the Medical College of Wisconsin.

In 1988, 40 senior faculty members at the Medical College of Wisconsin were surveyed to determine their perceptions of the extent and benefits of mentor relationships between faculty and residents. Seventy-eight percent thought mentor activity was feasible in their own departments; however, only 18% felt that a majority of residents in their departments had a mentor. Seventy-five percent reported having been a mentor, and 90% indicated they had a mentor either currently or previously. All 25 faculty who reported having a mentor felt that this arrangement had assisted them in their career advancement, 88% reported it had enhanced their personal development, and 72% indicated the relationship had helped them deal with stress. The mentor relationship appears to have significant benefits for the medical trainee and should be promoted.

A 52-week comparison of lisinopril, hydrochlorothiazide, and their combination in hypertension.

Lisinopril is a long‐acting converting‐enzyme inhibitor. A 52‐week study was undertaken to compare the antihypertensive efficacy and safety of lisinopril, hydrochlorothiazide (HCTZ), and a combination of the two drugs in 24 patients with a sitting diastolic blood pressure (DBP) of 90 to 120 mm Hg. After a four‐week single‐blind placebo‐washout phase, ten patients received lisinopril, ten received HCTZ, and four received the combination in increasing doses in a double‐blind fashion for the next 12 weeks. The target blood pressure was less than 90 mm Hg DBP and a decrease of at least 10 mm Hg. For the next 12 weeks, the responders continued to receive the same medications; however, the nonresponders from the two groups received the combination, increasing the number of patients receiving both to 13. The DBP was controlled in eight of the ten patients with lisinopril, three of the ten patients with HCTZ, and 11 of 13 (four original and nine nonresponders) with the combination. For the next 28 weeks, 17 patients agreed to continue into a single‐blind phase, during which blood pressure was controlled in six of the seven patients who were treated with lisinopril alone and nine of ten who received the combination. The heart rate rose significantly in the HCTZ‐treated patients during the short‐term treatment and decreased significantly in those treated with lisinopril during the long‐term phase. Side effects were more frequent in patients receiving the combination but were always mild and subsided spontaneously. Lisinopril appeared to be more effective than HCTZ as a step‐1 drug, and the combination was superior to either agent alone.

Suicide and the Stress of Residency Training: A Case Report and Review of the Literature

Suicide rates among physicians have been reported to be twice that of the general adult population. Few data are available, however, regarding suicide among resident physicians. A case study of the suicide of a male intern is discussed. The literature is reviewed to elucidate potential contributory factors including reported causes and manifestations of stress among resident physicians, suicide rates among physicians including house staff with considerations of sex, and common personality characteristics of physicians and medical students. Recommendations are extended which may assist in early recognition and treatment of individuals at risk of impairment and suicide.

Prazosin in hypertension with and without methyldopa

The efficacy of prazosin was assessed in 21 patients with essential hypertension who failed to respond adequately to a combination of methyldopa and hydrochlorothiazide. The patients were divided randomly into two groups; in the first group prazosin was substituted for methyldopa and in the second group prazosin was added to the combination. In group 1, the average blood pressure (BP) fell from 144/102 mmHg (sitting) and 142/105 mmHg (standing) to 136/91 mmHg (sitting) and 129/91 mmHg (standing) after prazosin (17 mg) was substituted for methyldopa. The fall in the diastolic BP was statistically significant (p < 0.01). In group 2, BP fell from 146/101 mmHg (sitting) and 143/103 mmHg (standing) to 126/87 mmHg (sitting) and 118/86 mmHg (standing) when prazosin 14 mg was added to methyldopa and hydrochlorothiazide. The reductions in systolic and diastolic pressures were statistically significant (p < 0.001).

Hemodynamic Effects of Lysine-Vasopressin in Orthostatic Hypotension

Previous investigations have demonstrated that the postural stimulation of arginine vasopressin (AVP) release is reduced in patients with Shy-Drager syndrome. We studied the effects of lypressin nasal spray on hemodynamic parameters in ten patients with chronic orthostatic hypotension. Heart rate, blood pressure, and stroke volume were measured at 0 degrees, 45 degrees and 70 degrees tilt before and one-half hour after two nasal sprays (four United States Pharmacopeia posterior pituitary pressor units, 7.4 micrograms) of lypressin. Lypressin did not significantly alter the effect of tilt on heart rate, stroke volume, and cardiac output but increased the blood pressure and total peripheral resistance. AVP analogues should be tested for treating chronic postural hypotension.

Hypertension control among patients referred by a community blood pressure screening program

Abstract Since 1974 the Milwaukee Blood Pressure Program (MBP) has screened more than 175,000 people for hypertension, 4672 newly identified hypertensives have been referred for treatment to practicing physicians and to a medical school affiliated hypertension clinic on the basis of two elevated blood pressure readings. The mean duration of follow-up has been 20 months for private patients and 14 months for clinic patients. Ninety-two per cent of the referred patients, were subsequently confirmed to have an elevated blood pressure. Approximately 90% of the confirmed hypertensive patients received antihypertensive drugs. Seventy-three per cent of the private patients and 97% of the clinic patients received a diuretic. The antihypertensive drugs were stopped on few occasions by the physician. Lifestyle changes in terms of weight loss and reduction in smoking and drinking were attempted in the clinic. Whereas heavy smoking and alcohol intake could be reduced in some patients, little change in weight was generally observed. Hypertension was controlled in 65% of the private patients and 84% of the clinic patients. The better clinic results may reflect more frequent use of combination antihypertensive therapy and use of the nurse clinicians for reinforcement of the physicians advice in the clinic setting.

Hypertension in obese patients.

Obesity and hypertension often coexist. The waist-hip ratio has been found to be a more accurate predictor of hypertension than either body weight or body mass index. A waist-hip ratio of 0.85 or more in men and 0.75 or more in women is a significant cardiovascular risk factor. Insulin also probably has an important role in the pathogenesis of hypertension in obese patients. Treatment of hypertension in overweight patients begins with weight loss, which is frequently achieved by combining caloric restriction and exercise. Such commonly used drugs as angiotensin-converting enzyme inhibitors, calcium blockers, alpha blockers, and beta blockers are appropriate for medical treatment of these patients.

Lack of Interaction Between Sulindac or Naproxen and Propranolol in Hypertensive Patients

Seventeen patients with hypertension and osteoarthritis participated in a single‐blind crossover study comparing the effects of sulindac 200 mg twice daily, naproxen 500 mg twice daily, and placebo on blood pressure. All patients were treated for hypertension with propranolol monotherapy. Blood pressures were back‐titrated to achieve a baseline diastolic blood pressure of 90 to 100 mm Hg while taking naproxen. There were no significant differences in mean sitting or standing blood pressures among the patients receiving naproxen, sulindac, or placebo treatments. There was no change in pulse, weight, or any of the laboratory measurements at the end of each treatment phase. These results suggest that neither sulindac nor naproxen interferes with propranolol therapy for uncomplicated hypertension.