A randomized, placebo-controlled, double-blind crossover investigation in 12 patients with non-asthmatic chronic obstructive lung disease and co-existing stable angina pectoris was done to compare two beta 1-selective adrenoceptor blocking agents, atenolol 100 mg and bisoprolol 20 mg. Systolic and diastolic blood pressures (SBP, DBP), heart rate (HR) as well as airway resistance (AWR, and less frequently forced expiratory volume in 1 s (FEV1) and intrathoracic gas volume (ITGV) were measured in the sitting position before and at various times up to 24 h after drug intake. During the first 4 h both beta-blockers produced a significant reduction in HR in comparison to placebo (p less than 0.01). Atenolol 100 mg significantly increased AWR relative to placebo and bisoprolol (p less than 0.05). After 24 h, a significant reduction in HR (p less than 0.01) could only be demonstrated after bisoprolol, whereas atenolol alone led to a significant elevation in AWR relative to placebo and bisoprolol (p less than 0.05) at that time. It is concluded that bisoprolol appears to have a high degree of beta 1-selectivity, thus providing a wide split between beta 1- and beta 2-adrenoceptor blockade. Bisoprolol in its therapeutic dose range is expected to be relatively safe as regards bronchoconstriction in patients suffering both from hypertension and/or angina pectoris and chronic obstructive lung disease.
In a 4-week randomized, double-blind study, 87 patients with essential hypertension received either 10 mg bisoprolol (B) or 100 mg metoprolol (M) once daily (o.d.). The effects of the beta blockers on systolic blood pressure, heart rate and rate-pressure product during exercise, 24 h (E2) and 3 h (E3) after administration (p.a.) were compared with the values obtained in the baseline exercise test (E1). 24 hours p.a. the effects of B were significantly stronger than of M (E1-E2: B vs M; P less than 0.01) whereas 3 h p.a. no significant differences were detectable between B and M. The residual effects 24 h p.a. in relation to the effects 3 h p.a. (E1-E2/E1-E3) were significantly greater with B (86-93%) than with M (53-66%). In contrast to the findings with 100 mg M o.d., 10 mg bisoprolol o.d. guarantees a persistent reduction in exercise blood pressure and heart rate throughout the entire dosage interval of 24 h.
A 32-year-old man presenting with typical features of Cushing's syndrome showed baseline cortisol and ACTH values indicating ACTH-dependent disease. Dynamic function tests (dexamethasone, corticotropin releasing hormone (CRH), desmopressin), were suggestive of paraneoplastic ectopic ACTH production. However, inferior petrosal sinus (IPS) ACTH sampling demonstrated a maximum baseline central (363 pmol/l)-peripheral (19 pmol/l) ACTH gradient of 19.1 for the right IPS, conventionally suggestive of Cushing's disease. However, again, IPS ACTH level did not increase after CRH stimulation. Magnetic resonance imaging, while showing no evidence of an intrasellar tumour, revealed an 1.5 x 1.0 cm mass in the left sphenoid sinus which was initially interpreted as most probably being a mucosal polyp. After neurosurgical removal of the tumour, transient secondary adrenal insufficiency was present. The structure and immunostaining characteristics of the tumour demonstrated an ACTH cell adenoma of the pituitary. Ectopic ACTH-secreting pituitary adenomas may cause significant difficulties in differential diagnosis, localisation and appropriate therapy. Thus, although these tumours are rare, they should be included in the list of possible causes of ACTH-dependent Cushing's syndrome.
Earlier studies suggest that cardiovascular responses in the laboratory and in the field are likely to be related when the laboratory tasks involve active coping, when the field measure is taken continuously, and when there is allowance for the effects of autocorrelation and physical activity on the ambulant cardiovascular measure. These studies lead to the hypothesis that the hyperreactivity common to the laboratory and to the field has a beta-adrenergic basis. We examined the heart rate variability of 16 hyperreactive and 16 hyporeactive subjects over an 8-hour period while they were receiving either a placebo or a cardio-selective beta-blocking drug (Bisoprolol) in a double-blind crossover design. Subjects were classified on the basis of their heart rate and systolic blood pressure responses to a complex self-paced, reaction-time task. Response in the field was assessed from the standard deviation of the raw heart rate series, after allowance for the serial dependency in the data using autoregressive methods and, when allowance was made for physical activity, assessed from the muscle activity of the thigh. As predicted, on placebo hyperreactive subjects had markedly more variable heart rates, particularly when allowance was made for physical activity. Although not confirmed by a significant interaction effect, this difference largely disappeared under beta-blockade.
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