Anti-arthritic propionic acid derivatives and 17-oxosteroid measurements--a direct interference.

Many drugs interfere with the assay of urinary 17-oxo and oxogenic steroids. Some propionic acid derivatives, in particular, tiaprofenic acid, have now been shown to affect this assay. Care should be taken when interpreting results in patients on these drugs.

Enterohepatic circulation of vitamin D: a reappraisal of the hypothesis.

Vitamin-D metabolites in bile were investigated after oral and intravenous doses of radioactively labelled vitamin D had been given to six patients with T-tube biliary drainage after cholecystectomy. The vitamin was mainly excreted as highly polar inactivation products and less than 4% of the metabolites in bile were present as 25-hydroxyvitamin D or its glucuronide conjugate. There was insufficient vitamin D or 25-hydroxyvitamin D in bile for the reabsorption of these metabolites to make a significant contribution to normal vitamin-D status. Therefore interference with an enterohepatic circulation of vitamin-D metabolites cannot be a cause of vitamin-D deficiency.

Wegener's granulomatosis complicated by diabetes insipidus.

We report a case of Wegener's granulomatosis complicated by cranial diabetes insipidus in which no evidence of local sinus erosion or intracranial granuloma was found. Unlike previously reported cases, the diabetes insipidus has not resolved despite successful treatment of the vasculitis. The patient is also unusual in that she had a prolonged 9-month prodromal period of seronegative polyarthritis before the appearance of typical systemic vasculitis and granuloma formation.

Clinical trials of intra-articular aspirin in rheumatoid arthritis.

The effect of the intra-articular injection of acetylsalicylic acid in patients with rheumatoid arthritis was compared with that of hydrocortisone acetate and with that of saline in blind, controlled, clinical trials. All three preparations were effective in relieving pain and improving the range of motion, and no significant differences were demonstrated. The results suggest a need for the re-appraisal of the value of intra-articular administration of synthetic corticosteroids.

Vitamin D metabolism in acute and chronic cholestasis.

To study the effects of acute and chronic cholestasis on vitamin D metabolism we investigated six cases of acute extrahepatic obstructive jaundice and eight cases of primary biliary cirrhosis (PBC) (three supplemented with vitamin D). Plasma 25-hydroxyvitamin D (25OHD) was low in the patients with PBC unsupplemented with vitamin D but normal in obstructive jaundice. None of the patients with PBC showed radiological or histological evidence of osteomalacia. In PBC, dietary intake of vitamin D was low but response to ultra-violet irradiation of the skin was normal even in those with a considerably raised serum bilirubin. Patients with PBC or obstructive jaundice had low levels of 25 hydroxyvitamin D binding protein which correlated with the serum albumin. The half-life of intravenously injected (3)H vitamin D(3) ((3)HD(3)) and the subsequent production of (3)H 25OHD were normal in all the patients with obstructive jaundice and in most with PBC. The two patients with PBC who produced less (3)H 25OHD than expected were receiving vitamin D supplements. The urinary tritium ((3)H) excretion after the injection of (3)HD(3) correlated with the serum bilirubin. After the injection of (3)H 25OHD(3) the urinary excretion of (3)H was minimal and did not correlate with the serum bilirubin, suggesting that the radioactivity appearing in the urine after the (3)H vitamin D(3) injection was associated with vitamin D metabolites other than 25OHD. Factors contributing to the low plasma 25OHD in primary biliary cirrhosis may be a low dietary intake of vitamin D, inadequate exposure to ultra-violet light, and a tendency to urinary wastage of vitamin D metabolites.

Abnormal vitamin D metabolism in cirrhosis.

Vitamin D metabolism was investigated in 10 patients with cirrhosis. Mean plasma 25 hydroxycholecalciferol (25 OHD) centration in alcoholic cirrhosis was lower than in controls but the difference was not significant. In three patients restudied after the summer, plasma 25 OHD had risen. In contrast to the finding in normal subjects, the half-life of intravenously administered 3H cholecalciferol was short in cirrhotics and showed no correlation with plasma 25 OHD. Furthermore, the appearance of 3H 25 OHD from 3H cholecalciferol was reduced compared to the control group four hours after injection. Increased rate of metabolism of cholecalciferol and deficient production of 25 ohd contribute to vitamin D deficiency in liver disease.

Multiple endocrine adenomatosis (Type I) and familial hyperparathyroidism.

Hyperparathyroidism is the commonest presenting feature in multiple endocrine adenomatosis Type I (MEA Type I), the other manifestations may be delayed for many years or appear only in relatives. A family now diagnosed as MEA Type I, who was previously thought, in 1965, to have familial hyperparathyroidism due to chief cell hyperplasia is now described. The importance is stressed of family surveillance and long-term follow-up in all cases of primary hyperparathyroidism. Those tests that are essential in the long-term surveillance of the patients and their first degree relatives are discussed.

Concentrations of flurbiprofen in serum and synovial fluid from patients with active rheumatoid disease: some preliminary observations.

In 3 patients with active rheumatoid disease, concentrations of flurbiprofen of approximately 2 microgram per ml were achieved in synovial fluid 3 hours after a single oral dose of flurbiprofen (100 mg). The highest concentrations were seen between 3 and 9 hours after administration of the dose. The concentration of flurbiprofen in synovial fluid seemed to fall more slowly than in the circulation, but more extensive data would be needed to confirm this. In all 3 patients the drug was absorbed rapidly into the circulation, the highest serum concentrations of 7 microgram to 9 microgram per ml being seen in the first blood sample withdrawn 1.5 hours after administration of the dose. Serum concentrations fell with a mean apparent half-life of approximately 3 hours.

1-alphahydroxycholecalciferol in chronic renal failure. Studies of the effect or oral doses.

Four patients with advanced chronic renal failure and osteodystrophy were treated with 1-alphahydroxycholecalciferol, a synthetic vitamin D analogue, in a daily oral dose of 1.5 to 2.0 mug, for periods up to 1 year. They showed increased calcium absorption, positive calcium and phosphorus balances, moderate increases in serum calcium levels, marked reductions in serum alkaline phosphatase levels, a decrease in serum immunoreactive parathyroid hormone levels, and radiologic and histologic improvement in bone disease. One patient with proximal myopathy showed improvement in muscular strength. 1-Alphahydroxycholecalciferol appears to be effective therapy for renal osteodystrophy.