Compliance of physicians and patients with a consensus protocol for treatment of advanced breast cancer.

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.

[Mitral valve and mitral ring movement in mitral stenosis. An ultrasonic study with different valve models (author's transl)]. / Mitralklappen- und Mitralringbewegung bei Mitralstenose anhand von verschiedenen Klappenmodellen

We constructed three different mitral valve models in order to investigate the different mechanisms which account for the concordant opening and closing movement of the posterior compared to the anterior mitral valve in mitral stenosis. Three different types of movements are possible: a dorso-anterior movement of the mitral ring, opening and closure of the valve itself and a rotation of the entire valve apparatus. Our in-vitro studies showed that the best explanation for the concordant diastolic movement of the posterior valve is given by the assumption that during the early diastolic opening phase of the valves the whole stenotic valve apparatus is rotated upward, i.e. towards the transducer. This rotation, has a higher amplitude compared to the residual downward-oriented opening movement of the posterior valve.

[Cyclic AMP and plasma renin activity in renal vein blood after amitryptiline, theophylline, furosemide and beta adrenergic blocking substances (author's transl)]. / Zyklisches AMP und Reninaktivität im Nierenvenenplasma nach Amitryptilin, Theophyllin, Furosemid und beta-adrenergen Rezeptorantagonisten

The influence of amitryptiline, theophylline and furosemide on the concentration of cyclic-AMP and plasma renin activity (PRA) was investigated in renal vein plasma. Additionally, the stimulating effect of furosemide on the PRA after application of the beta-adrenergic receptor antagonists propranolol and practolol and the cyclic AMP concentration in the plasma were measured. All drugs were given intravenously. After amitryptiline cyclic-AMP concentration increased about 1.5-fold compared with the basal value,PRA was not altered. After theophylline cyclic-AMP concentration increased about 1.2-fold, PRA 2.0-fold compared with the basal value, PRA was not altered. After theophylline cyclic-AMP concentration increased about 1.2-fold, PRA 2.0-fold coa increased within 7 min and no further increase was observed till the 15th min. After practolol cyclic-AMP concentration and PRA decreased about 20% compared with the basal value within 10 min. The stimulating effect of subsequently applied furosemide on PRA was not altered, but the cyclic-AMP concentration was not changed in this time by furosemide. After propranolol cyclic-AMP concentration and PRA decreased about 20% compared with the basal value. The cyclic-AMP concentration was not influenced by the following furosemide application, in agreement with the findings after practolol, however, PRA could be stimulated only in 36% of these patients under beta-receptor blockade. Our results show that changes of the concentrations of cyclic-AMP and of PRA are independent of each other. An elevated intracellular cyclic-AMP level due to the inhibition of phosphodiesterase is as a single factor unable to stimulate renin release. Our results give no evidence of a direct involvement of the adenylcyclase-system in the mechanism of renin release. The effect of propranolol and practolol on the basal value of PRA and cyclic-AMP is equal. The different influence of 10 mg propranolol and 20 mg practolol on the stimulating effect of 40 mg furosemide on the PRA can be interpreted as a dosage problem.

[Treatment of essential hypertension with propranolol (author's transl)]. / Die Behandlung der essentiellen Hypertonie mit Propranolol

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.

[The influence of propranolol, practolol and theophylline on the plasma renin activity (author's transl)]. / Beeinflussung der Plasmareninaktivität durch Propranolol, Practolol und Theophyllin

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.

[Plasma aldosterone and plasma renin activity in patients with essential and renal hypertension under acute stimulation with saline depletion and acute suppression with saline infusion]. / Das verhalten des plasmaaldosterons und der plasmareninaktivität bei primaärer und renaler hypertonie unter stimulations- und suppressionsbedingungen

Plasma aldosterone, plasma renin activity, sodium and potassium in the plasma and the urine were determinated under acute stimulation with saline-depletion (furosemide) and under acute suppression with saline infusion in 40 patients with primary hypertension stage I, 19 patients with primary hypertension stages II and III, and 11 patients with renal hypertension (chronic glomerulonephritis and chronic pyelonephritis). The majority of the patients with primary hypertension stage I showed a good stimulation of the plasma aldosterone and the plasma renin activity under acute salt depletion. Three out of the 40 patients with primary hypertension stage I, and 13 of the 19 patients with primary hypertension stages II and III did not show any stimulation of the renin secretion ("low renin hypertension"). In all these patients the plasma aldosterone stimulation remained intact. With infusion of saline all the groups showed suppression of the plasma aldosterone and the plasma renin activity. A good stimulation of the plasma renin activity, demonstrates that in our experiments the renin-angiotensin system cannot be responsible for the increase in aldosterone secretion under salt depletion. Most likely the increase of the plasma aldosterone, in spite of the fixed renin activity, is stimulated by the sodium depletion due to diuretics. In all patients with primary hypertension we did not find an inadequate reaction of the aldosterone secretion under saline infusion. The patients with renal hypertension showed a minimal stimulation and suppression of the plasma renin activity. The plasma aldosterone secretion increased only slightly under sodium depletion and the decrease under saline infusion was statistically not significant. Thus we conclude that these patients show an inadequate reaction of the plasma aldosterone and renin secretion under salt infusion and depletion.

[Ultrasonic cardiographic studies of heart size in atrial septal defect, combined mitral and aortic valve disease]. / Ultraschallkardiographische Untersuchungen der HerzgröBe bei Vorhofseptumdefekt, kombinierten Mitral- und Aortenvitien

27 patients with following diagnoses were examined by ultrasound: ASD; Aortic valve disease; Mitral valve disease with predominant insufficiency; Mitral stenosis; right heart failure; patients without evidence of cardiac disease. The right ventricular dimension (RVD Index) was assessed representing the distance between the right ventricular epicardial echoes and echoes from the right side of the interventricular septum divided by the patient's body surface area, analogue measurements were done to obtain the left ventricular dimension (LVD Index). The ratio from LVD to RVD was calculated. The motion of the interventricular septum was classified as Normal, Abnormal A and Abnormal B, according to known criteria. Three groups of patients could be differentiated: Patients without cardiac disease; Patients with right ventricular enlargement and ASD; Patients with left ventricular enlargement with aortic and mitral valve disease. In patients with cardiac enlargement, echocardiography provides better information concerning the ratio of the left ventricular to the right ventricular diameter compared to a routine chest X ray.