Ro 31-1118, a new cardioselective β-adrenoceptor antagonist

Summary Five patients with mild hypertension were given single oral doses of Ro 31-1118 (10, 20, 40, and 80 mg) and placebo in a randomized, double-blind, within-patient study. Plasma concentrations of Ro 31-1118 and supine, standing, exercise, and post-exercise heart rates and blood pressures were measured before and at regular intervals after drug administration.The pharmacokinetic data were consistent with a one-compartment model with first-order absorption and a variable time lag. Peak plasma concentrations and area under curve were linearly related to dose, whereas time to peak concentration, half-time, clearance and apparent volume of distribution were dose-independent.There was a reduction in exercise and post-exercise heart rate of approximately 10% after 10 mg and 20 mg Ro 31-1118, and of approximately 15% after 40 mg and 80 mg. At all doses standing systolic blood pressure was reduced by approximately 5%. A similar fall was seen in exercise and post-exercise systolic blood pressures. There was no substantial effect of Ro 31-1118 on supine or standing heart rates nor on diastolic blood pressure. No adverse effects were reported.It is concluded that Ro 31-1118 has linear pharmacokinetics over the dose range 10–80 mg, and has a weak antihypertensive effect when administered in single doses to patients with mild hypertension.     

Who is not reassured following benign diagnosis of breast symptoms?

Many women fail to be reassured about their breast symptom following benign diagnosis. Identification of the factors contributing to this continued anxiety is important in order that appropriate intervention can be incorporated into the care of women undergoing diagnosis. In this study, we measured levels of anxiety, depression, stress, perceived personal risk of breast cancer, fear of breast cancer treatment and general health anxiety along with clinical and demographic variables in women undergoing investigation of breast symptoms. We then assessed if these factors were associated with reassurance about the breast symptom immediately following benign diagnosis. METHODS: Women attending a specialist 'one-stop' breast clinic completed a questionnaire in the clinic prior to diagnosis and a reassurance measure post-benign breast symptom diagnosis. RESULTS: Post-diagnosis, 67% of women were reassured however, 33% were not reassured about their breast symptom despite a benign diagnosis. Women who were not reassured were more likely to be educated only to high school level and have presenting symptoms of a change in breast shape/dimpling of the breast. There was a trend for women who were not reassured to have breast pain and be diagnosed with a benign breast cyst. Examination of the psychological variables showed that women who were not reassured compared to reassured women had higher levels of health anxiety, perceived stress, fear of breast cancer treatment and general anxiety. Logistic regression analysis entering all the predictors suggests that level of education was the strongest predictor of lack of reassurance following benign diagnosis. CONCLUSION: This study found that a significant proportion of women who undergo investigation and receive a benign diagnosis of their breast symptom experience uncertainty. Our finding that women who were not reassured were more likely to be educated only to high school level suggests that this group may benefit from additional information about breast symptoms and benign diagnosis. Additionally, our results indicate that women with high levels of anxiety, perceived stress and general worry about their health may need further reassurance in the immediate diagnosis phase. Further research focussing on how reassurance is interpreted in the context of women's perceptions about breast symptoms and breast disease is important so that appropriate support can be offered for women undergoing diagnosis of breast symptoms.