Evaluation of patients with local reactions to insulin with skin tests and in vitro techniques.

To better understand the part played by IgE and IgG antibody in the production of dermal reactions to insulin and the usefulness of skin tests in the evaluation of these reactions, we studied 21 diabetic patients referred for evaluation of large local insulin reactions, 46 diabetic patients without local insulin reactions, and 22 healthy nondiabetic controls. Study subjects were skin tested with 15 different insulins, and the results were evaluated over 48 h. All control subjects and 41 of 46 diabetic patients without local reactions were skin-test negative to insulin. The 11% of diabetic patients who reacted had positive wheal-and-flare reactions at 20 min to animal-species insulin but negative skin tests to human insulin. Study revealed two subgroups of patients with histories of local reactions. Ten (48%) of these patients had negative skin tests to insulin. Five of this subgroup remained skin-test negative to quantities of less than or equal to 8 U insulin/skin test. Eleven (52%) of the patients formed a subgroup with positive insulin skin tests; most of these patients were skin-test positive to human insulin and to beef, pork, or both insulins as well. Although the group mean insulin-specific IgE values of this latter subgroup were significantly higher than those of any other study group, overlap of these individual IgE values did not allow separation of specific individuals with positive skin tests from those of patients on insulin without dermal reactions.(ABSTRACT TRUNCATED AT 250 WORDS)

Antihypertensive and metabolic effects of single and combined atenolol regimens.

The antihypertensive and metabolic effects of placebo (PL), a fixed combination of hydrochlorothiazide (25 mg) and triamterene (50 mg) (HCTZ/TRI), atenolol (25 mg) (Atc-25), atenolol (50 mg) (Ate-50) and their combination with HCTZ/TRI given once daily, were tested on 256 patients with mild-to-moderate essential-hypertension. After 3 weeks of PL monotherapy, 43 patients were randomized to PL (group 1), 41 patients to HCTZ/TRI (group 2), 44 patients to Ate-25 (group 3), 42 patients to Ate-50 (group 4), 43 patients to Ate-25/HCTZ/TRI (group 5), and 43 patients to Ate-50/HCTZ/TRI (group 6) in a double-blind parallel design study and were followed for 4 weeks. At the end of week 7, those patients who were randomized to groups 5 and 6 were allowed to continue for an additional 12 weeks, if their arterial pressure was satisfactorily controlled. Complete blood counts, blood chemistries, urinalyses, and electrocardiograms were done initially and during the study. Monotherapy with HCTZ/TRI, Ate-25, and Ate-50 had significant and equal antihypertensive effects compared with placebo. (P less than .01). However, the combination of Ate-25/HCTZ/TRI and Ate-50/HCTZ/TRI resulted in further reduction of arterial pressure with the effect being greatest with Ate-50/HCTZ/TRI (P less than .001). Patient groups 3 through 6 had also slower heart rates compared with groups 1 and 2 (P less than .01). Mild, but statistically significant, increases in BUN, glucose, triglycerides, and uric acid were noted in groups 2, 5, and 6 (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Transdermal clonidine as an adjunct to sustained-release diltiazem in the treatment of mild-to-moderate hypertension.

An open-label study was conducted to evaluate the clinical safety and efficacy of transdermal clonidine as an adjunct to sustained-release (SR) diltiazem (90 mg twice daily) in mild-to-moderate hypertension. Ninety patients with a mean baseline sitting blood pressure of 154/102 mmHg were given 90 mg of diltiazem SR twice daily and transdermal placebo. After four weeks of therapy, 21 patients (23%) had trough sitting diastolic blood pressures (DBP) less than 90 mmHg and were withdrawn. Of the remaining 69 patients (DBP greater than or equal to 90 mmHg), 60 (mean blood pressure 149/98 mmHg) continued to receive 90 mg of diltiazem SR twice daily, to which was added transdermal clonidine, titrated as needed (3.5 cm2, 7.0 cm2, or 10.5 cm2) to achieve blood pressure control. During titration, 58 patients achieved DBP less than 90 mmHg, with a mean blood pressure of 133/84 mmHg. Of these patients, 54 completed an eight-week maintenance period, during which their mean blood pressure was 137/84 mmHg. No significant decrease in pulse or change from baseline in lipid profiles (high-density lipoprotein, low-density lipoprotein, apolipoprotein A-I, apolipoprotein B) was observed with combination therapy. The most frequently reported side effect during maintenance therapy was mild skin irritation at the transdermal application site. One patient was withdrawn because of contact dermatitis. Compliance with the oral twice-daily regimen was variable, with 83% of patients failing to take diltiazem SR at the prescribed dosing intervals 80% to 100% of the time. Transdermal clonidine was worn as directed by 97% of patients. It is concluded that transdermal clonidine in combination with diltiazem SR is safe and effective in the treatment of mild-to-moderate hypertension.

Comparison of the efficacy and tolerability of an angiotensin converting enzyme inhibitor (lisinopril) versus a calcium channel antagonist (diltiazem SR) in the treatment of moderate to severe hypertension.

One hundred and ten patients (mean age 50.6 years) with moderate to severe essential hypertension (DBP between 105 and 116 mmHg) were randomised to eight weeks of double-blind treatment with lisinopril (n = 56) or diltiazem SR (n = 54). Fourteen patients withdrew from therapy; six patients withdrew because of adverse events (lisinopril, n = 3; diltiazem SR, n = 1) and lack of BP control (lisinopril, n = 1; diltiazem SR, n = 1). Both monotherapies were titrated upward (lisinopril 20-40 mg daily, diltiazem SR 120-180 mg twice daily) to achieve an office DBP < 90 mmHg. Hydrochlorothiazide (HCTZ; 25 mg daily) was added to monotherapy after week 4 if patients did not reach the BP goal (i.e. non-responders). After four weeks of therapy, 72% of patients (74 of 103) were nonresponders. At eight weeks of therapy, 66 patients (lisinopril, n = 32; diltiazem SR, n = 34) had received HCTZ. At week 8, 53% of lisinopril and 36% of diltiazem SR patients met the response criteria. Mean office DBP decreased from baseline -18.1 +/- 8.6 mmHg for lisinopril patients and -15.9 +/- 10.1 mmHg for diltiazem SR patients at week 8. Lisinopril was as effective as diltiazem in reducing systolic and diastolic office BP at week 4 (p > 0.1). Likewise, at weeks 4 and 8, no statistically significant differences were detected between treatments (p > 0.05) for systolic and diastolic ambulatory BP averaged over 24 hours. Both treatments were well tolerated and showed important antihypertensive efficacy in patients with moderate to severe BP elevation.

A clinical trial evaluating the 24-hour effects of bisoprolol/hydrochlorothiazide 5 mg/6.25 mg combination in patients with mild to moderate hypertension.

This study used 24-h ambulatory blood pressure (BP) monitoring to investigate the effectiveness of a novel low-dose combination of bisoprolol/hydrochlorothiazide in adult patients with mild to moderate essential hypertension. Thirty-six patients with stable mild to moderate hypertension (sitting diastolic BP 95-114 mmHg) after a placebo run-in phase received oral bisoprolol/hydrochlorothiazide 5 mg/6.25 mg once daily for 4 weeks in a single-blind regimen. At office visits, BP and pulse were measured with statistically significant reductions (p < 0.01) recorded after 2 and 4 weeks of treatment. Twenty-four-h ambulatory BP monitoring at the completion of therapy revealed significant reductions (p < 0.01) in both systolic and diastolic 24-h, daytime, and nighttime BP, compared with the end of the placebo treatment phase. Systolic and diastolic load were also reduced (p < 0.01). The combination was well tolerated, and overall quality-of-life questionnaire scores indicated an improvement after bisoprolol/hydrochlorothiazide therapy (p = 0.02). No clinically significant changes from baseline in laboratory parameters were observed; in particular, serum potassium was unchanged. This is the first study to demonstrate the 24-h effectiveness of the bisoprolol/hydrochlorothiazide 5 mg/6.25 mg combination, using 24-h ambulatory BP monitoring. In addition, antihypertensive therapy with low doses of bisoprolol/hydrochlorothiazide in combination may improve tolerability.

Postmenopausal osteoporosis: treatment with low-dose sodium fluoride and estrogen.

Eleven menopausal patients were treated for 12 to 18 months with low-dose sodium fluoride and calcium. Six patients also received estrogen replacement. A significant increase in spine or hip bone mineral density measured by dual photon absorptiometry was observed in all patients. The estrogen-treated group had the greatest increase in bone density. Addition of estrogen seems to supplement bone gain and allow sodium fluoride to be administered in lower doses, which are easily tolerated and yet effective.

Hypertension and primary hyperparathyroidism: a five-year case review.

All cases of surgically proven and cured primary hyperparathyroidism, over a five-year period, were reviewed for the presence of hypertension, renal and/or prerenal azotemia, nephrolithiasis, nephrocalcinosis, and patient symptom status. In this group of 23 patients, the prevalence of hypertension was greater than 78% (18 patients), which is statistically significant. Approximately 28% (5 patients) of the 18 hypertensive patients had some degree of azotemia and/or elevated serum creatinine. Most of the 23 patients were symptomatic, over the age of 50, female, and without nephrolithiasis or nephrocalcinosis. The possible etiologic mechanisms of calcium-mediated hypertension are discussed, and the important association of hypertension with primary hyperparathyroidism is emphasized.

Primary hyperparathyroidism and pregnancy.

The incidence of pregnancy with primary hyperparathyroidism (PHPT) is probably underestimated, possibly because of the lack of routine prenatal serum calcium screening and possibly because the combination of pregnancy and mild asymptomatic PHPT is less than disastrous. This is the first reported case in which serum calcium and parathyroid hormone levels were measured periodically during a successful gestation in an asymptomatic and untreated patient with provisional primary hyperparathyroidism.