The stimulating effect of theophylline on the plasma renin activity (PRA) under beta-receptor blockade by propranolol or practolol was investigated in 27 patients with essential hypertension of degree I-II. After propranolol and also practolol PRA decreased about thirty per cent of the basal value, increased however by the factor of 2 to 3 after application of theophylline, in spite of the blockade of the beta-receptors indicated by a slight decrease of systolic blood pressure and heart rate. The effect of propranolol and practolol on the basal PRA was not different. Our results show the possibility, to stimulate renin secretion despite blockade of beta receptors by propranolol or practolol, respectively.

In a multicenter study we used a consensus protocol including more than five subsequent therapeutic steps for treatment of patients with advanced breast cancer. A total of 335 evaluable patients from 27 participating hospitals were allocated to a low- or high-risk group, receiving different therapies during the initial phase of treatment. About half of these patients were treated without protocol violations (compliers). The protocol non-compliers were divided into three groups: those receiving more intensive therapy than recommended, those with similarly intensive, and those with less intensive therapy. The reasons for protocol violations were analysed. The intensity of the therapy given actually was correlated with the survival of subgroups. Median survival times were significantly longer in 208 low-risk than in 127 high-risk patients (P less than 0.0001), marginally longer in 165 compliers than in 170 non-compliers (P less than 0.04), significantly longer in low-risk compliers than in low-risk non-compliers (P = 0.002), and significantly shorter in high-risk compliers than in high-risk non-compliers (P = 0.007). Survival of all subgroups of low-risk non-compliers was the same regardless of the actual therapies given. The survival of high-risk patients who received less intensive therapy was significantly longer than that of high-risk compliers (P = 0.015). After six cycles of successful chemotherapy there was no difference, either in time to progression or in survival, between patients who had received either maintenance therapy or no therapy. We postulate that the groups of low-risk and high-risk patients comprised patients with different prognoses. Among low-risk patients, survival of the subgroup with poor prognosis (low-risk non-compliers) was not influenced by therapy. Among high-risk patients, a subgroup with poor prognosis may have been overtreated by using standard chemotherapies as recommended in our consensus protocol.

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Effect of long-term administration of propranolol was studied in 90 unselected patients with essential hypertension. At a dose of 180 and 360 mg daily it dropped the blood pressure to at least 155/95 mm Hg in 31 patients (34.4%). Those who responded to propranolol had lower systolic and diastolic blood pre-treatment pressures than those who failed, were younger by an average of eight years, and in no case had decreased plasma-renin activity and demonstrated greater plasma-renin activity after furosemide. After a titration phase with increasing doses of propranolol those who responded were treated in a crossed double-blind test with propranolol or placebo. There was a significant difference in systolic blood pressure (standing and lying) and diastolic pressure (standing) between the two. There was also a highly significant difference in heart rate. During chronic beta blockade the basal and stimulated plasma-renin activity fell. But percentage stimulation of renin secretion was fully maintained. However, aldosterone response was decreased. Serum potassium rose slightly but significantly, cAMP 24-hour urine excretion fell significantly. Electrolyte excretion did not differ between the two treatment periods.

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