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Comprehensive one-day renal function tests in 20 patients with a history of analgesic abuse showed varying degrees of chronic renal failure in all. There was no evidence of a selective defect in proximal tubular function, while a defective concentrating mechanism, usually considered necessary for the diagnosis of analgesic-induced renal damage, could be demonstrated in only 16 patients. A urinary acidification defect associated with a concentrating defect was found in nine cases and was thought to reflect specific collecting duct dysfunction. Urinary ammonium excretion was reduced in 13 subjects, owing to a reduced number of functioning nephrons or inadequate acidification, or both. Low citrate excretion was frequently encountered, and this, as well as defective urinary acidification, may play some part in predisposing patients with analgesic nephropathy to intrarenal calcification and progressive renal failure.

In a retrospective study to compare the drug consumption during pregnancy of mothers of infants with congenital abnormalities and of those without, over 97% of 1,369 mothers took prescribed drugs and 65% self-administered drugs. Significantly more mothers of infants with congenital abnormalities took aspirin, antacids, dextroamphetamine, phenobarbitone, sodium amytal, other barbiturates, cough medicines, iron, sulphonamides, and nicotinamide than mothers in the control group. However, most mothers taking analgesics, antacids, appetite suppressants, barbiturates, cough medicines, iron, sulphonamides, and vitamins produced normal infants. Any teratogenic effect of these drugs is therefore one of low potency. On the other hand, deficiencies such as those of ascorbic acid and folic acid may have a teratogenic effect. There is need for caution in presuming teratogenic effects on the basis of the associations shown here. During pregnancy, however, it would appear wise to avoid the administration of any drug which carries a suspicion of teratogenicity unless that drug is specifically indicated, and self-medication with common household remedies such as aspirin and antacids should be avoided. These recommendations would also apply to any woman of childbearing age in whom conception is likely.

Pain may be attacked in the rheumatic diseases (1) centrally, with drugs ranging in efficiency from those which are potentially addictive and under the Dangerous Drugs Act (e.g., pethidine) and are therefore rarely used, down to simple analgesics such as paracetamol; (2) peripherally, by local action, whether it be by applications of heat or cold, by injections of local anaesthetics or anti-inflammatory agents, or by surgery; (3) peripherally, by anti-inflammatory non-analgesic agents taken systemically, such as the corticosteroids; and (4) peripherally, by anti-inflammatory-analgesic-antipyretic agents taken systemically, such as aspirin.The exact sites of action of the pyrazoles, indomethacin, the anthranilic compounds, and other anti-inflammatory-analgesic-antipyretic drugs are as yet uncertain, but along with these methods of attacking the pain-producing areas help must also be given to the distressed mind behind the joints. Faith in the future, cheerfulness, freedom from depression, and the development of a philosophy to deal with the uncertainties of the disease are essential. It has been said that you don't have to be a doctor to treat uncomplicated lobar pneumonia: anybody with a bottle of penicillin in his hands holds the cure. It is the incurable diseases that are really worth treating, and that make demands on the physician. To quote Tuker: "My last word is this. Whoever has the care of a sorely stricken arthritic must encourage him to fulfil himself intellectually and spiritually, and to achieve-no matter what, but to achieve, so that he may nightly lay himself down on his bed of pain looking forward happily to the morrow's task, mind centred upon it, no matter what it is; sticking in stamps, research into anything you like, dabbling with pastel or water colours, writing chatty letters to friends. Anything at all, but let it be for him the most pressing thing of the day, and let him believe that you think it is. Help him and let him live, live fully."This is perhaps the best analgesic of all.

Of 14 patients with analgesic nephropathy 11 were followed up for 9 to 88 (mean 36) months after withdrawal of analgesics containing phenacetin. Ten of these 11 are still alive and have improving, static, or very slowly declining renal function. Analgesic withdrawal is therefore worth achieving even in the presence of advanced renal failure. Careful prolonged follow-up is required to prevent or detect relapse and to deal with the complications of prolonged renal failure, particularly bone disease and acidosis. Early diagnosis is life-saving in this condition. Attention is drawn to the diagnostic value of sterile pyuria, but the best screening test for the condition is careful interrogation of all patients with chronic renal disease of unknown aetiology; analgesic intake is rarely denied if asked for specifically.

A double-blind cross-over study of ketoprofen (Orudis) 150 mg daily and ibuprofen (Brufen) 1,200 mg daily was carried out in 35 outpatients with rheumatoid arthritis. Results suggest that analgesic and anti-inflammatory activity of ketoprofen is superior to that of ibuprofen. Significantly greater pain relief (P < 0·05) and reduction in joint circumference (P < 0·01) was obtained with ketoprofen than with ibuprofen. Side effects of the drugs were comparable and not serious.

Pain threshold was measured in 106 patients with rheumatoid arthritis, 50 with ankylosing spondylitis, and 50 normal controls using Keele's algometer. In rheumatoid arthritis patients with a low pain threshold had more severe pain for a greater part of the day and required more tablets for pain relief. In ankylosing spondylitis the pain threshold was higher and was not related to pain or analgesic requirements. There was no evidence that pain threshold affected the course or outcome of rheumatoid arthritis in any way.

Benorylate (4-acetamidophenyl 2-acetoxybenzoate) is a new esterified aspirin preparation whose antirheumatic properties are reported to be as good as those of aspirin. Gastrointestinal blood loss, measured with (51)Cr-labelled red cells, during benorylate therapy was compared with that during therapy with soluble aspirin in 15 subjects, a simplified crossover procedure being used. Mean blood loss during benorylate therapy was 1.7 ml/day which was significantly less than that during therapy with soluble aspirin (5.1 ml/day; P

In a clinical trial of two antirheumatic agents two methods of collection of side effects were used, one with and the other without a check list of possible symptoms. Findings suggested that the use of a check list interfered with the collection of side effects. Known side effects of aspirin-tinnitus, deafness, and gastrointestinal disturbance-were more efficiently shown and symptoms not included in the check list were more likely to be reported when a check list was not used.

Two studies on 41 patients with osteoarthrosis of the hip or knee have shown fenoprofen—a compound with analgesic and anti-inflammatory properties—to be an effective addition to the drug treatment of these conditions. It was found to be superior to paracetamol but no statistically significant difference was shown in a comparison with phenylbutazone.

Since phenacetin was withdrawn from Askit Powders and Beecham's Powders in 1966 these preparations have declined in importance as a cause of analgesic nephropathy in Western Scotland. In most patients with analgesic nephropathy who persist in abuse of compound analgesics renal function continues to decline. The deterioration, however, is less rapid among those taking aspirin and caffeine mixtures than in those taking preparations which also contain phenacetin.

The competence of the laryngeal-closure reflex was assessed in a group of patients having ketamine anaesthesia and found to be depressed. All patients in a control group of conscious volunteers had a competent reflex. The possible dangers of ketamine anaesthesia without endotracheal intubation are discussed.

Three patients with analgesic nephropathy are reported who, in addition to the accepted features of this syndrome, had dilatation of one or both upper urinary tracts due to ureteric or periureteric fibrosis without intraluminal obstruction. We attribute this lesion to analgesic abuse and suggest that any patient with unexplained ureteric fibrosis should be questioned about analgesic consumption. This association also suggests a possible role for analgesic abuse in the pathogenesis of retroperitoneal fibrosis.