Cerebrovascular reactivity after cessation of menopausal hormone treatment.

OBJECTIVE: Women who are currently using menopausal hormone therapy (MHT) have higher cerebrovascular reactivity when compared with postmenopausal women who are not taking MHT; however, the effect of cessation of MHT on cerebrovascular reactivity is not known. Given that MHT can have structural and activational effects on vascular function, this study was performed to characterize cerebrovascular reactivity following cessation of MHT in women at low risk for cerebrovascular disease. METHODS: Cerebrovascular reactivity was measured in a subset of women from the Kronos Early Estrogen Prevention Study (KEEPS) 3 years after cessation of the study drug (oral conjugated equine estrogen, transdermal 17ß-estradiol, or placebo [PLA]). RESULTS: Age, body mass index, and blood pressure were comparable among groups. At rest, the middle cerebral artery velocity (MCAv), cerebrovascular conductance index, mean arterial pressure, and cerebral pulsatility index did not differ among groups. Slope-based summary measures of cerebrovascular reactivity did not differ significantly among groups. However, utilizing repeated-measures modeling, there was a significant upward shift in MCAv responses (p = 0.029) in the combined MHT group compared with the PLA group. CONCLUSION: MHT has a marginal sustained effect on cerebrovascular reactivity when measured 3 years after cessation of hormone treatment.

Macro- and microvascular function in habitually exercising systemic lupus erythematosus patients.

OBJECTIVES: Vascular dysfunction is commonly observed in systemic lupus erythematosus (SLE) patients and may explain the accelerated cardiovascular disease (CVD) risk. It is unknown whether physical activity influences vascular function in SLE patients. We aimed to determine whether habitually exercising SLE patients also demonstrate a reduction in vascular function. METHOD: This study involved 41 young and middle-aged adults, including 15 healthy controls, 12 sedentary SLE patients, and 14 physically active SLE patients. RESULTS: Flow-mediated dilation (FMD), a measure of macrovascular function, was lower (3.6 ± 1.3 vs. 8.1 ± 1.2%; p < 0.05) and inflammatory markers [C-reactive protein (CRP), interleukin (IL)-12, and tumour necrosis factor (TNF)-α] were higher in sedentary SLE patients than in age-matched healthy controls (p < 0.05). Importantly, FMD and inflammatory markers were not different between physically active SLE patients and healthy controls. There were no group differences in skin reactive hyperaemia (RH) or minimal vascular resistance, both measures of microvascular function. Physically active SLE patients had lower intercellular adhesion molecule (ICAM)-1 concentrations and SLE disease activity scores than their sedentary peers. FMD was inversely associated with IL-6 and IL-10 (both p < 0.05). CONCLUSIONS: Significant SLE-associated macrovascular dysfunction was absent in physically active SLE patients. Additionally, vascular function was associated with inflammatory markers, suggesting that the favourable influence of physical activity may be mediated by its effect on inflammation.

The effect of acute beta-adrenoceptor blockade on examination performance.

Simple tests of verbal reasoning and mental arithmetic, taken under mildly stressful conditions, have been shown to give a reproducible test of intellectual function within groups of normal subjects. Using these tests, in two separate examinations, a double-blind cross-over study was performed on 35 medical students to assess the effects of acute beta-adrenoceptor blockade with propranolol on intellectual function. With placebo treatment, students recorded an average total score of 231.3 marks, with average scores of 108.9 marks on the mental arithmetic paper and 122.4 marks on the verbal reasoning paper. Treatment with propranolol was associated with an improvement in total score of 9.2 +/- 3.9 marks (P less than 0.05), an improvement in mental arithmetic score of 5.6 +/- 2.3 marks (P less than 0.05) and an improvement in verbal reasoning score of 3.6 +/- 2.4 marks (NS). Eighteen out of the 35 students said that they were mildly anxious before one examination and 13 students said they were anxious before both examinations. Those students who admitted anxiety seemed to benefit the most, in terms of improved examination performance, from treatment with propranolol.

Effect of angiotensin converting-enzyme inhibition on potassium-mediated aldosterone secretion in essential hypertension.

1. Eight patients with essential hypertension were challenged with an infusion of 32 mmol of potassium chloride in saline before and after control of their blood pressure by the angiotensin converting-enzyme (ACE) inhibitor enalapril. 2. The potassium infusion was associated with similar increases in plasma aldosterone before and during enalapril treatment, although absolute aldosterone levels were lower after enalapril treatment despite higher plasma potassium levels. 3. The handling of the potassium load was altered by ACE inhibition. The area under the curve of a plot of the increase in plasma potassium above baseline against time was greater during enalapril treatment than during treatment with placebo. 4. These observations contrast with data obtained in the dog and demonstrate that in patients with essential hypertension stimulation of aldosterone secretion by potassium is not abolished by chronic suppression of plasma angiotensin II; and although plasma aldosterone remains at a lower level, the homoeostasis of plasma potassium is only mildly impaired.

Dihydrocodeine in renal failure: further evidence for an important role of the kidney in the handling of opioid drugs.

The pharmacokinetics of a single oral dose of dihydrocodeine were studied in nine patients with chronic renal failure treated by haemodialysis and nine subjects with normal renal function. In the patients the mean peak plasma dihydrocodeine concentration occurred later and the area under the curve was greater than in the normal subjects. Furthermore, the drug was still detectable after 24 hours in all the patients but only three of the normal subjects. These data, together with those obtained from previously published clinical case reports, contradict the traditional view that the body's ability to cope with opioid drugs is not altered in renal failure.

Effect of dialysate buffer on potassium removal during haemodialysis.

There is a linear relationship between potassium removal during haemodialysis and plasma potassium (Kp). Kp falls rapidly during the first hour of dialysis but very little during the last two hours of a five hour dialysis. There is a fairly constant movement of potassium from the intracellular to extracellular space throughout dialysis. Total potassium removal is best predicted by pre-dialysis Kp, but change in Kp is related to the impact of dialysis on acid-base status. The choice of acetate or bicarbonate buffered dialysate does not effect potassium removal during dialysis.

The effects of a chronic infusion of arginine vasopressin in salt-restricted, water-deprived man.

The effects of a 48 h infusion of arginine vasopressin (AVP) were measured in five separate studies on four normal salt-restricted physicians, in whom fluid retention was prevented. The infusion was associated with an increase in renal sodium excretion which continued during the 24 h after the infusion had been discontinued. During the infusion plasma renin activity (PRA), plasma aldosterone and noradrenaline, and packed cell volume (PCV) fell; glomerular filtration rate, assessed by endogenous creatinine clearance, increased. The findings are best explained by a vasopressin-induced increase in plasma volume, which in the absence of fluid retention is likely to have been due to a redistribution of body water.

Hydralazine and prazosin in the treatment of hypertension.

We report the results of an observer blind crossover trial in 31 patients with essential hypertension comparing the hypotensive effect of four doses of prazosin and of hydralazine used as the third step of triple therapy and additional data on the efficacy of low dose combinations of these two drugs. Both drugs had an appreciable antihypertensive effect, 1 mg of prazosin being equivalent to 12.5 mg of hydralazine. Increasing the dose of prazosin from 4 to 8 mg twice daily and hydralazine from 50 to 100 mg twice daily did not consistently reduce blood pressure. The combination of the two drugs at low doses resulted in the blood pressure of more patients being controlled (diastolic blood pressure 90 mm Hg or below) than when either drug was used alone at high dose. The symptoms reported by patients were similar for both drugs. The combination did not lead to an increased reporting frequency. The trial demonstrates one of the problems of a crossover study, namely a treatment/period interaction.