In a multicentre, randomised trial of prednisolone in acute polyneuropathy of undetermined aetiology (Guillain-Barré syndrome), 21 patients were treated with prednisolone (60 mg daily for one week, 40 mg daily for four days, and then 30 mg daily for three days) and 19 did not have steroid treatment. Patients were graded on a six-point scale by one of two neurologists who had no knowledge of the treatment schedule. Reassessment at one, three, and twelve months consistently showed greater improvement in the control than the prednisolone group but the only statistically significant result was in the improvement at three months among patients entered to the trial within a week of onset of illness. The 6 control patients had improved by 2.5 +/- 0.43 grades by three months from entry to the trial whereas the 10 prednisolone patients had only improved by 0.9 +/- 0.46 grades (P less than 0.05). There was 1 death related to the polyneuropathy in each group, and 1 suicide in a control patient during convalescence. 6 prednisolone patients were left with considerable disability compared with 1 control patient. There were 3 relapses in the prednisolone group, but none in the control group. The results indicate that steroid treatment is not beneficial and can be detrimental in acute neuropathy of undetermined aetiology.

A controlled study of the effects of the potent vitamin-D metabolite, 1, 25-dihydroxycholecalciferol (1,25[OH]2D3), and vitamin D3 was done in 18 non-dialysed patients with chronic renal failure (C.R.F.). Patients with a creatinine clearance below 35 ml/min and mild renal osteodystrophy were selected. After 6 months' observation of the spontaneous course the patients were randomly allocated to 6 months' oral treatment with either 1, 25 (OH)2D3 or vitamin D3 in initial daily doses of 1microgram and 4000 I.U., respectively, combined with 0.5 g calcium. 1,25(OH)2D3 quickly corrected hypocalcaemia, reduced serum-alkaline-phosphatases and serum-immunoreactive-parathyroid-hormone, and more than doubled the urinary excretion rate of calcium. D3 had similar, but less pronounced effects. 7 out of 8 patients on 1,25(OH)2D3, developed hypercalcaemia which necessitated a reduction in dosage. None of the patients on D3 treatment developed hypercalcaemia. The percentage fall in creatinine clearance was greater during treatment than before treatment in all patients on 1, 25 (OH)2D3 (P less than 0.01) and in 7 of 9 patients on vitamin D3 treatment (though the group change here was not significant). Deterioration of renal function is a major limitation of the clinical use of 1, 25(OH)2D3 and D3 in non-dialysed patients with C.R.F. In fact, the decrased formation of 1, 25(OH)2D3 seen in C.R.F. might protect renal function at the expense of abnormalities in mineral metabolism.

In a randomised double-blind controlled trial 53 patients received 5 daily subcutaneous injections of ancrod ('Arvin') after operation for fractured neck of femur, and 52 patients received saline fractured neck of femur, and 52 patients received saline injections. Deep-vein thrombosis (D.V.T.) was detected by bilateral ascending venography or necropsy 6--16 days after surgery. The frequency of D.V.T. and bilateral D.V.T. was significantly lower in the ancrod group (P less than 0.01). The frequency of major D.V.T. (thrombi in veins proximal to the calf, or calf-vein thrombi more than 3 cm long) was also significantly lower in the ancrod group (P less than 0.001). No complications of ancrod prophylaxis occurred. Ancrod reduced plasma-fibrinogen, and hence plasma and blood viscosity, during the first week after surgery; preoperative levels of fibrinogen and viscosity were not associated with post-operative D.V.T. Subcutaneous ancrod is a simple and effective alternative to oral anticoagulants for the reduction of the frequency of D.V.T. after operation for hip fracture, and merits assessment in other high-risk groups of patients.

The effect of naloxone on dental postoperative pain was studied to examine the hypothesis that endorphins mediate placebo analgesia. All patients had extraction of impacted mandibular third molars with diazepam, N2O, and local block with mepivacaine. 3 h and 4 h after surgery naloxone or a placebo was given under randomised, double-blind conditions. Pain was evaluated on a visual analogue scale. Patients given naloxone reported significantly greater pain than those given placebo. Patients given placebo as their first drug was either placebo responders, whose pain was reduced or unchanged, or nonresponders whose pain increased. Naloxone given as a second drug produced no additional increase in pain levels in nonresponders but did increase pain levels of placebo responders. Nonresponders had a final mean pain rating identical to that of responders who received naloxone as their second drug. Thus the enhancement of reported pain produced by naloxone can be entirely accounted for by its effect on placebo responders. These data are consistent with the hypothesis that endorphin release mediates placebo analgesia for dental postoperative pain.

The response of plasma-25-hydroxyvitamin D (25[OH]D) to different exposures to ultraviolet irradiation has been studied in patients in long-stay geriatric wards. Increases sufficient to bring the plasma-25(OH)D into the normal range may be obtained with doses less than those required to produce erythema. The provision of such background irradiation may be a suitable method of preventing vitamin-D deficiency in elderly subjects who receive very little exposure to sunlight.

In a prospective, randomised, double-blind trial to determine if cephalothin plus an aminoglycoside is more nephrotoxic than methicillin plus an aminoglycoside, patients were assigned to one of four treatment groups: cephalothin and gentamicin (C.G.), cephalothin and tobramycin (C.T.), methicillin and gentamicin (M.G.), or methicillin and tobramycin (M.T.). The incidence of definite nephrotoxicity was: C.G., 7/23 (30.4%); C.T., 5/24 (20.8%); M.G., 2/20 (10%); and M.T., 1/23 (4.3%). There was no statistically significant difference in nephrotoxicity between the combined gentamicin groups (C.G. and M.G.) and the combined tobramycin groups (C.T. and M.T.). Definite nephrotoxicity developed in 12/47 (25.5%) of the combined cephalothin groups (C.G. and C.T.) and in only 3/43 (7%) of the combined methicilllin groups (M.G. and M.T.). The combination of cephalothin plus an aminoglycoside is therefore more nephrotoxic than the combination of methicillin plus an aminoglycoside.

In a double-blind, placebo-controlled, cross-over trial, clonidine eliminated objective signs and subjective symptoms of opiate withdrawal for 240--360 min in eleven addicts in a hospital setting. In an open pilot study of the effects of clonidine on longer-term opiate abstinence and symptoms, the same patients did well while taking clonidine for one week. There was only one documented instance of heroin use, in a patient who did not take clonidine after hospital discharge. 6 weeks or more after the study, four patients were back on reduced doses of methadone, one was on tricyclic antidepressants, and seven were off of all opiates. All eleven patients were doing well. These data suggest that opiate withdrawal is due to increased neuronal activity in areas such as the locus coeruleus which are regulated by both alpha-2 adrenergic and opiate receptors.

Tienilic acid, a diuretic with uricosuric properties, was compared with cyclopenthiazide, in an open, random-order, within-patient crossover study (3 months on each drug) in 36 hyperuricaemic hypertensive patients. All were on an established dose of cyclopenthiazide; most were also on a beta-blocker which they continued to take in their usual dose. A mean dose of 210 mg of tienilic acid gave the same antihypertensive and diuretic effect as a mean dose of 0.41 mg of cyclopenthiazide. Serum uric acid was very much lower when patients were on tienilic acid (0.29 mmol/l) than on cyclopenthiazide (0.50 mmol/l). Apart from slightly higher serum-chloride and serum-urea during the period on tienilic acid, no major differences in serum-electrolytes, renal-function tests, glucose tolerance, and fasting lipids were observed. Audiometric tests showed that tienilic acid was not ototoxic. S.G.O.T. and S.G.P.T. rose to pathological values in 3 women when they were on tienilic acid, to a lesser extent, in 2 men when they were on cyclopenthiazide. There is no definite evidence that the changes in the transaminases were related to tienilic acid. Some postural hypotension or slight fluid retention occurred during the initial, dose-finding period, and 3 patients had mild indigestion but no patient had to discontinue the trial because of side-effects.