Pyrexia, anaemia and acute renal failure secondary to omeprazole.

We present the case of a 77-year-old woman who initially presented with pyrexia of unknown origin, anaemia and mild renal impairment. When her omeprazole was stopped she improved rapidly. When omeprazole was re-started she developed fever and acute renal failure, which again settled quickly on discontinuation of omeprazole. This case demonstrates how drugs can cause severe multisystem disorders that may appear to be infective or inflammatory.

In vivo regulation of human cardiac beta-adrenoceptors by a partial agonist as compared with a full antagonist: selective differences in coupling to adenylate cyclase.

Chronic therapy with the beta 1-selective adrenoceptor partial agonist xamoterol is not associated with the tolerance observed with other beta-adrenoceptor agonists. A possible explanation is that xamoterol therapy does not desensitise human cardiac beta-adrenoceptors in vivo. beta-Adrenoceptor density and adenylate cyclase activities were determined in right atrial appendages obtained from 40 patients randomised in a double-blind fashion to receive either xamoterol or atenolol for at least 5 weeks before coronary artery bypass surgery. There was no significant difference in total or subtype beta-adrenoceptor densities, but basal and isoproterenol stimulated adenylate cyclase activity were significantly greater in the atenolol-treated group, as was the intrinsic activity of the beta 2-adrenoceptor partial agonist procaterol, suggesting that chronic therapy with xamoterol does not downregulate human cardiac beta-adrenoceptors in vivo. Coupling of beta-adrenoceptors to adenylate cyclase, predominantly mediated by the beta 2 subtype, is enhanced, however, after therapy with atenolol relative to therapy with xamoterol.

Subtype selective regulation of coupling of rat cardiac beta adrenoceptors to adenylate cyclase.

There is now evidence from human studies to suggest that cardiac beta-adrenoceptor density and coupling to adenylate cyclase may be regulated in a subtype selective fashion. An animal model was used to investigate this further. Rats were infused for 6 days with the non-selective full agonist isoprenaline (n = 6) or the beta 1-selective partial agonist xamoterol (n = 6) with sham operated rats (n = 6) for control. beta-Adrenoceptor subtype density and coupling to adenylate cyclase were determined in left ventricular membranes. Isoprenaline infusion downregulated both beta 1- (30%) and beta 2- (63%) adrenoceptor subtypes with associated reduction in adenylate cyclase stimulation through both subtypes. Xamoterol did not downregulate either subtype, but selectively uncoupled beta 1-adrenoceptors. beta 1- and total beta-adrenoceptor-mediated stimulation of adenylate cyclase was reduced less by xamoterol than isoprenaline. We conclude that coupling of rat cardiac beta-adrenoceptors can be regulated in a subtype selective fashion and that the partial agonist xamoterol does not desensitise beta-adrenoceptor mediated stimulation of adenylate cyclase to the same extent as the full agonist isoprenaline.

Cardiac failure secondary to hypocalcaemia of nutritional osteomalacia.

A 41-year-old Asian woman presented with mild congestive cardiac failure, initially controlled with a small dose of diuretic. Subsequently there was a marked deterioration in her condition with severe cardiac failure resistant to treatment. At this time biochemistry revealed a hyperphosphataemic variety of osteomalacia. Her cardiac failure improved promptly on correcting the hypocalcemia. Although hypocalcaemia is a recognised cause of cardiac failure it has not been described in privational osteomalacia.

Blood filled cyst of the papillary muscle of the mitral valve producing severe left ventricular outflow tract obstruction.

A 46 year old man was found to have left ventricular outflow obstruction caused by a blood-filled cyst attached to the anterior papillary muscle of the mitral valve. It was successfully excised.

Dialysis arthropathy: complication of long term treatment with haemodialysis.

Twenty eight patients who had received haemodialysis for more than 10 years were reviewed to establish the incidence of joint problems. Only six patients had no joint symptoms, one had avascular necrosis, one had had recent septic arthritis, and four had hyperparathyroidism. The remaining 16 patients had no evidence of hyperparathyroidism yet had an arthropathy causing pain and stiffness in many joints, particularly the shoulders. Ten of these 16 patients had a recurrent carpal tunnel syndrome requiring repeated surgical decompressions, which resulted in only partial improvement. Of the eight patients who had received dialysis for more than 15 years, seven had this "dialysis arthropathy" and six had recurrent carpal tunnel syndrome. Dialysis arthropathy is a common and often severe and disabling complication of long term treatment with haemodialysis. The cause is not known, but amyloid was found in a synovial biopsy specimen from one patient.