The source and significance of raised serum enzymes in rheumatoid arthritis.

Hepatobiliary dysfunction in rheumatoid arthritis has been suggested on the basis of raised serum activity of alkaline phosphatase, 5-nucleotidase, lactic dehydrogenase and gamma-glutamyl transferase, but a specific pathological lesion has not been demonstrated and serum transaminases and bilirubin are almost invariably normal. This paper reports a series of studies designed to determine the tissues of origin of the enzymes and offers an alternative interpretation of the enzymological findings. The results suggest that only alkaline phosphatase originates from the liver, while lactic dehydrogenase and 5-nucleotidase originate from synovial fluid polymorphs and synovial lining cells, respectively. Serum alkaline phosphatase may be induced by inflammatory mediators such as interleukin-1 because it correlates with the acute phase response. Serum lactic dehydrogenase is an integrated measure of polymorph lysis in all joints and offers a marker of joint inflammation more specific than measures such as the ESR. Levels of serum 5-nucleotidase provide information about the activity of the synovium. Finally, because hepatic necrosis does not normally occur, the transaminases may be used to monitor drug toxicity.

Corticosteroid replacement therapy: twice or thrice daily?

Although glucocorticoid replacement is conventionally administered twice daily, the pharmacokinetics of hydrocortisone would predict very low levels of plasma cortisol by mid-afternoon. This study compared plasma cortisol day profiles in 7 hypoadrenal patients while on twice daily and thrice daily hydrocortisone replacement. The twice daily regimen was associated with very low levels of cortisol at 16.00 and 18.00 h. This was eliminated by administering the same total dose in a thrice daily regimen. Furthermore, estimates of 'well-being' by visual analogue scale correlated significantly with simultaneous plasma cortisol levels and 5 of the patients expressed a preference for the thrice daily regimen. The findings suggest that thrice daily glucocorticoid replacement therapy should be adopted routinely.

Plasma arginine in cancer of the gastrointestinal tract: effect of surgical treatment.

The concentration of 21 amino acids was measured in the venous plasma of 41 patients with cancer of the gastrointestinal tract who had lost weight, 12 patients who had lost a similar amount of weight from non-malignant, non-septic conditions (benign weight loss), 12 patients with cancer of the gastrointestinal tract who had not lost weight and 21 control patients. Sixteen patients with localised tumours were restudied eight and 12 weeks after successful removal of the primary growth. Six patients with pyloric stenosis (benign weight loss) were similarly studied for comparison after corrective surgery. The concentration of the amino acid arginine was significantly greater in patients with cancer both with weight loss (71.2 +/- 4.1 mumol/l mean +/- SEM) and without weight loss (66.8 +/- 4.1 mumol/l) when compared both with patients with benign weight loss (34.6 +/- 3.2 mumol/l) and with control patients (48.2 +/- 3.5 mumol/l) (p less than 0.05). In patients with cancer subjected to surgery the concentration of arginine (76.4 +/- 7.5 mumol/l) fell to normal levels eight weeks after operation and remained normal 12 weeks after surgery (48.6 +/- 4.4 mumol/l) (p less than 0.05). This was in contrast with the rise in plasma arginine in patients with pyloric stenosis after surgery, suggesting that the raised level of arginine was due to the presence of the primary tumour.

Alteration of pituitary-thyroid function in patients with chronic renal failure treated by haemodialysis or continuous ambulatory peritoneal dialysis.

Pituitary-thyroid function was investigated in 60 patients with chronic renal failure and 18 normal subjects. Serum triiodothyronine and free thyroxine levels were lower in patients treated by either haemodialysis or continuous ambulatory peritoneal dialysis compared with the normal subjects. Serum thyroxine and free thyroxine index were significantly lower in the haemodialysis-treated patients than in the normal subjects. There were no differences in serum thyroxine and free thyroxine index between the continuous ambulatory peritoneal dialysis-treated and normal groups. Serum thyrotrophin was not raised in any of the groups but the serum thyrotrophin response to thyrotrophin-releasing hormone was blunted in both groups of patients. Basal serum prolactin and growth hormone were raised in both groups of patients but there was no significant difference between them. This study confirmed that pituitary-thyroid function is abnormal in patients receiving haemodialysis and established that a similar pattern of abnormalities occurs in patients undergoing continuous ambulatory peritoneal dialysis.

The incorporation of ammonia nitrogen into albumin in man: the effects of diet, uremia and growth hormone.

15 N-ammonium chloride was given orally to 17 individuals in 20 studies. Retention of 15N by those with normal renal function was inversely proportional to the protein intake; enrichment of albumin with 15N increased during protein restriction. Protein restriction appeared to be a more potent stimulus to the synthetic use of ammonia than a large pool of urea nitrogen. Both retention of isotope and enrichment of albumin decreased when a high protein diet was given. Enrichment of albumin with 15N in response to 10 or 20 mg of growth hormone daily was similar to that in healthy individuals on a 20 g protein diet for 3 weeks. The relevance of these findings to the nutritional potential of recycled urea nitrogen is discussed.