Biomedical subjects
Publications and source records attributed to E Grossman.
A number of therapeutic agents, foods, chemicals, and poisons have been associated with the development or exacerbation of hypertension. This review discusses those identified in recent years.
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Two hundred and sixteen non hospitalized patients with skin tags (ST) were studied for the presence of diabetes mellitus (DM) and obesity. Overt DM was found in 57 (26.3%) patients and impaired glucose tolerance test was found in 17 (7.9%) patients. Sixteen new cases of DM were found among this group. All the diabetic patients in the study population had non-insulin dependent DM. Sixty-two (28.7%) of the patients were obese. No correlation was found between the localization, size, colour and number of the ST and the presence of DM. Our study indicates that ST are not associated with increased incidence of obesity compared to the general population. On the other hand, ST are associated with impaired carbohydrate metabolism, and may serve as means for identifying patients at increasing risk of having DM.
The serotonergic antagonist ketanserin (K) was compared to nifedipine (N) in a five-center international study on hypertensive patients over the age of 50 years. After a 4-week placebo run-in period, patients were randomly assigned to receive for 3 months either ketanserin (40 mg b.i.d. after 2 weeks of 20 mg b.i.d.) or nifedipine (20 mg N retard b.i.d.). After 1 month, monotherapy patients whose blood pressure was not sufficiently reduced received a diuretic in combination therapy. At the end of the active treatment period, patients who had remained on monotherapy received placebo until hypertension returned or for a maximum of 2 months. One hundred and seventeen patients were entered in the study, 58 on K and 59 on N. More patients switched to combination with a diuretic in the K group (14 patients) than in the N group (6 patients). The overall reduction in blood pressure was similar for K and N. Total response rate was high (96%) for the two drugs. Blood pressure was reduced both at peak and trough drug levels. No orthostatic reactions were observed, and no rebound hypertension occurred at discontinuation of therapy. Ketanserin monotherapy slightly decreased heart rate (-1 beats/min). whereas N produced a significant increase (+6 beats/min). Body weight significantly increased with K (+1.1 kg) and was unchanged with N. More patients complained of adverse reactions during N monotherapy (47%) than during K monotherapy (34%). Flushing and leg edema were more frequent with N.
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Renovascular hypertension superimposed on essential hypertension, a condition encountered in the elderly, was studied. An experimental animal model consisting of a two-kidney one-clip Goldblatt preparation in the spontaneous hypertensive (SHR) rat, that would simulate this condition, was designed. A 0.25 mm silver clip was placed on the left renal artery of SHR male rats. The same procedure performed on WKY rats served as control. All experiments were performed on low, normal, and rich sodium diet. Systolic blood pressure (BP) was measured by tail-cuff method. Plasma renin concentration (PRC) was determined before and after clipping of the renal artery. Results were as follows: Mean systolic BP increased significantly in clipped rats fed with normal and rich sodium diets. SHR showed an increase from 144 +/- 3 (mean + s.e.m.) to 168 +/- 3 mmHg, and WKY rats showed an increase from 120 +/- 2 to 139 +/- 5 mmHg. There was a two- to threefold rise in PRC. A low-salt diet given prior to clipping prevented the appearance of renovascular hypertension despite a significant rise in PRC. We concluded that renal artery narrowing plays a significant role in the rise of BP in the basically essential type of hypertension.
Exercise testing has emerged as an important method for improved evaluation of the cardiovascular system. However, juvenile patients presenting resting borderline hypertension have not been extensively studied. Therefore, this study evaluated the response to exercise in this group of patients. Nine hundred men aged 16 to 29 years performed a multistage near-maximal exercise test. The control group consisted of 338 age- and weight-matched, asymptomatic, healthy, normotensive individuals. Mean physical working capacity (+/- SD) was 129 +/- 28 W (82 +/- 18% of the normal according to our standardization) in the hypertension group, and 153 +/- 29 W (102 +/- 18%) in the control group (P less than 0.001). Mean systolic blood pressures at termination of exercise were 181 +/- 25 and 164 +/- 25 mm Hg in the hypertensive and the control groups, respectively; the mean diastolic values at termination of exercise were 49 +/- 32 and 32 +/- 29 mm Hg, respectively. The magnitude of the changes in blood pressure from rest to near-maximal values was smaller in the borderline-hypertensive individuals demonstrate a clear hypertensive pattern of reaction to physical activity, thus emphasizing the importance of exercise testing as part of the routine workup of such patients. The relationship between borderline hypertension and the risk of myocardial events has been established, and early hygienic or even pharmacological measures are necessary.
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A multicentre study was undertaken to determine whether side effects induced by hypotensive drugs could be reduced by replacement with low dose captopril. There were 100 patients on combinations of drugs, including diuretics, beta-blocking agents, methyldopa, clonidine and vasodilators. A questionnarie to obtain information on quality of life was completed by the patients. Each patient had major drugs, possibly responsible for side effects, withdrawn. Captopril was added at an initial dose of 12.5 up to 25 mg b.i.d. and titrated to a maximum of 50 mg t.i.d., until the blood pressure was equal to or lower than the level on entry into the study. Blood pressure was measured every two weeks and questionnaries were completed a number of times during the treatment period and scored at random, not in chronological order. A marked drop in blood pressure was obtained: mean systolic blood pressure went down from 173.4 +/- 2 to 154.5 +/- 2 mm Hg and diastolic blood pressure dropped from 104.5 +/- 11 to 9l.5 +/- 12 mm Hg. Neither tachycardia nor orthostasis was observed. Side effects, including inability to concentrate, nightmares, dizziness and sexual dysfunction, were reduced in 36% of the patients. Captopril itself produced no significant additional adverse reactions. It is concluded that captopril is a safe and effective drug, which can replace antihypertensive drugs that have deleterious side effects.
The effect of nisoldipine, a new calcium antagonist, on rats with renovascular hypertension was evaluated. Eight one-kidney, one clip hypertensive rats (1K, 1C rats) given nisoldipine 10 mg/kg for 4 weeks were compared with eight 1K, 1C hypertensive control rats. Fifteen other rats underwent sham-operation (right nephrectomy, no clip), of which eight received nisoldipine in the same dosage. A significant decrease in systolic blood pressure (BP) was achieved in the nisoldipine groups: from 154 +/- 4 to 107 +/- 7.5 mmHg in the 1K, 1C group (P less than 0.005) and from 117 +/- 4.2 to 89 +/- 5.4 mmHg in the sham-operated rats (P less than 0.01). The significant decrease in BP was maintained for only 6 days, but did not rise markedly throughout the entire study. Four 1K, 1C control rats died before term, two after 14 days and two after 20 days. There was no significant change in the pulse rate. Sugar and cholesterol levels in the nisoldipine groups remained constant. Nisoldipine caused a natriuresis without kaluresis in both groups: sodium excretion in the 1K, 1C rats increased from 0.25 +/- 0.05 to 2.32 +/- 0.2 mmol/day, and from 0.34 +/- 0.1 to 1.85 +/- 0.15 mmol/day in the sham-operated rats. A slight decrease in aldosterone levels in the 1K, 1C rats was observed. It appears that the combination of both natriuretic and vasodilatory effects during nisoldipine treatment results in a favourable hypotensive response in 1K, 1C hypertensive rats.
Six patients with angiographically proven renal artery stenosis were given a low salt diet, consisting of 10 mEq sodium per day for 4-6 days. Five patients showed a remarkable decrease in blood pressure (BP), from 169 +/- 12/107 +/- 4 to 131 +/- 12/84 +/- 5 mmHg, despite a rise in renin level. The decrease in BP was paralleled by a decrease in urinary sodium excretion. Restoration of the regular diet caused immediate elevation of blood pressure. We conclude that severe sodium restriction can reduce blood pressure in patients with renovascular hypertension.
A 71-year-old hypertensive patient experienced a severe hypertensive crisis. His blood pressure was 300/200 mm Hg three days after nifedipine therapy was discontinued. He had been taking nifedipine together with methyldopa. During five months on the combined treatment, his blood pressure had not risen higher than 170/100 mm Hg. A severe hypertensive crisis following abrupt nifedipine withdrawal has not been previously reported, to our knowledge. We recommend that caution be used when abrupt cessation of nifedipine therapy is considered in the treatment of hypertension.
Long-acting nifedipine tablets were given to 47 severely and moderately hypertensive patients with renal insufficiency, cardiovascular, cerebrovascular, and peripheral vascular disease, diabetes mellitus, asthma, and systemic lupus erythematosus. Nifedipine substituted vasodilators (n = 22), was added to beta blockers and thiazides (n = 14), and was used alone (n = 11). In all three groups blood pressure was significantly reduced without aggravation of angina pectoris, intermittent claudication, cerebrovascular disease, or renal failure. Side effects were mild and transient. We found nifedipine tablets convenient and safe, as well as efficacious in patients with serious conditions.
Twelve patients with pheochromocytoma have shown unusual clinical and laboratory presentation. These include three patients with cardiac manifestations (sick sinus syndrome, obstructive cardiomyopathy and ischemic ECG changes). Two patients with gastrointestinal problems (acute abdomen due to ischemic bowel and constipation). One child with sudden blindness and one, non diabetic patient with polyuria. Laboratory findings included four patients with diabetes mellitus, four patients with hypercalcemia two of them with concomitant hyperreninemia and one patient with hypokalemia. Awareness of the illness leads to the discovery of unusual cases and even a most severely sick patient can make a complete recovery.
Nifedipine long acting tablets were substituted for converting enzyme inhibitors in eight patients with renovascular hypertension. A significant drop in blood pressure was observed. Nifedipine was shown to be as effective (in lowering blood pressure) as a drug that acts directly on the renin angiotensin system. These data offer support for previously reported findings that the action of angiotensin II is calcium mediated.
Enalapril, an angiotensin converting enzyme (ACE) inhibitor, was given to 12 patients with renovascular hypertension: To five of them as a single drug after discontinuing other medications, and to seven patients as a substitute for one of their previous medications. The drug proved effective in controlling hypertension in all patients. Flushing and palpitations occurred in two of them, one of whom also showed a rise in creatinine and mild hyperkalemia. Two patients who had developed side effects while on captopril (renal deterioration in one, and severe rash in the other) tolerated enalapril well. Enalapril effectively reduced the blood pressure in the one patient with bilateral renal artery stenosis without causing renal failure.