1. To compare the bioavailability and the elimination of propranolol in seven untreated coeliac patients and six normal subjects, plasma concentrations were measured after oral and intravenous propranolol. The bioavailability and clearance of propranolol were similar in both groups. 2. With the use of a perfusion technique, propranolol absorption in the proximal jejunum was found to be decreased by 71% in five untreated coeliac patients, compared with the absorption in four normal subjects. 3. These results indicate that propranolol absorption is decreased in the proximal jejunum in untreated coeliac disease but overall absorption in the small bowel is not impaired.
1. After intravenous administration to 19 subjects, aged 18–95 years, plasma diazepam concentrations were measured over 160 h. Plasma protein binding of diazepam was also measured in each subject. 2. The terminal plasma half-life of diazepam ranged from 15.0 to 125 h and was positively correlated with age ( r = 0.797). Total plasma diazepam clearance was not correlated with age ( r = −0.017). 3. The free fraction of diazepam ranged from 0.0137 to 0.0386 and was significantly correlated with age ( r = +0.863). Free diazepam clearance, which ranged from 432 to 1870 ml/min, was also correlated with age ( r = −0.717). 4. It is concluded that the increased sensitivity of the elderly to diazepam is, at least in part, due to pharmacokinetic factors.
1. A method is described for the quantitative assay of human endogenous pyrogen in saline and plasma which is valid in the presence of exogenous pyrogens. 2. The value of the assay is demonstrated by a study of the relation between endotoxin concentration and endogenous pyrogen production by human leucocytes in vitro.
1. Endogenous pyrogen (EP) was detected in tumour extracts from four patients with renal carcinoma and fever. No EP was detected in extracts of tumours from six afebrile patients or in extracts of normal kidney. 2. Tumour slices from one febrile patient released EP into a nutrient incubation medium; this process was suppressed by the presence of cycloheximide. Tumour slices from an afebrile patient did not release EP on incubation. 3. Leucocytes from the peripheral blood of two febrile patients with renal carcinoma did not yield EP on incubation in saline. 4. The production of EP by leucocytes ‘activated’ by 2 h incubation with a Proteus endotoxin was not inhibited by cycloheximide. 5. It is suggested that fever associated with renal carcinoma is caused by the release of EP within the tumour.
1. Steady-state fever has been produced in normal volunteers by an intravenous priming injection followed by a sustaining infusion of leucocyte pyrogen. During this fever, volumes of up to 550 g blood were withdrawn, and separated into cells and plasma. 2. No febrile responses were observed when on subsequent days the cells or the plasma was re-infused. 3. These findings are compatible with the hypothesis that the inability to detect a circulating pyrogen in patients with inflammatory fever, reflects the difficulty of obtaining sufficiently large volumes of blood. 4. Transfusion of blood is unlikely to be a useful means of establishing whether circulating endogenous pyrogen is concerned in naturally occurring fever.