A B S T R A C T Mevinolin reduces cholesterol synthesis by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase. The safety and effectiveness of this agent was evaluated in a double-blind, placebo-controlled study in One subject (12.5 mg) was withdrawn because of abdominal pain and diarrhea. These results suggest that if long-term safety can be demonstrated, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase are likely to prove useful in the treatment of hypercholesterolemia. INTRODUCTION Elevated serum cholesterol is a major factor in the development of atherosclerosis and coronary heart disease (1, 2). There is a substantial and currently unsatisfied need for safe, well tolerated therapy capable of effecting large reductions in serum cholesterol.

SummarySerum thyroid hormone concentrations were measured before and during 10 days' treatment with atenolol (200 mg/day), acebutolol (400 mg/day), oxprenolol (160 mg/day) and propranolol (160 mg/day) in 24 hyperthyroid patients. During propranolol treatment serum triiodothyronine (T3) concentrations fell significantly (P < 0 05) but there was no change in thyroid hormone concentrations in the other groups although all patients reported a symptomatic improvement.

Serum thyroid hormone concentrations were measured before and during 6 months treatment with propranolol (160 mg/day) in eight patients with T3 (triiodothyronine) toxicosis. Serum total T3 concentrations showed a significant (p less than 0.01) and sustained fall to approximately 80% of pre-treatment values. Six of the patients, however, remained clinically and biochemically hyperthyroid and our data do not support the use of propranolol as sole therapy in T3 toxicosis.

1. The absorption of 6U of soluble human insulin following subcutaneous injection into the anterior abdominal wall, thigh and into the thigh following admixture with aprotinin was assessed in normal subjects. The plasma immunoreactive insulin profiles were determined during a 6 h post injection period in subjects receiving concomitantly somatostatin to suppress endogenous insulin secretion. 2. Subcutaneous injection of human insulin into the anterior abdominal wall compared with the thigh led to significantly higher incremental insulin levels between 30 and 50 min (P less than 0.05) followed by lower values at 240‐300 min (P less than 0.05). The absorption of soluble human insulin from a subcutaneous depot is faster from the anterior abdominal wall compared with the thigh associated with a faster clearance from plasma. 3. Injection into the thigh of insulin admixed with aprotinin resulted in higher plasma insulin levels at 10 min (P less than 0.001) and 20 min (P less than 0.05) compared with insulin given alone. Similarly, the insulin level was significantly higher with the admixture between 10 and 20 min (P less than 0.05) compared with insulin into the anterior abdominal wall. 4. Admixture of insulin with aprotinin therefore leads to an acceleration of the early phase of absorption from subcutaneous tissue due to a local hyperaemic effect.

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