In a controlled study involving thirty-four patients levamisole was shown to be as effective as D-penicillamine and more effective than placebo in the treatment of rheumatoid arthritis. Its action was slow and was accompanied by a reduction in erythrocyte sedimentation-rate, rheumatoid factor, and technetium index. These properties indicate that it has a specific action like that of D-penicillamine. Stimulation of cell-mediated immunity was evident in patients treated with levamisole, and there was a correlation between such changes and pain relief. Animal models confirmed the absence of anti-inflammatory effect and provided some evidence of enhancement of cell-mediated immunity and macrophage stimulation.

The effect of three intrauterine contraceptive devices (I.U.D.)-Lippes D, Dalkon Shield, and Copper 7-on menstrual blood-loss has been studied serially by objective methods in 279 women. All the women had a minimum of two cycles following delivery, abortion, cessation of lactation, or previous pill or I.U.D. use. All pads and tampons used for two further menstrual cycles before and for 12 cycles after I.U.D. insertion were collected, and the blood-loss was measured by extracting the haemoglobin by conversion to alkaline haematin. Mean menstrual blood-loss increased with all three devices. The amount of loss, the percentage of women losing more than 80 ml, the decline in haemoglobin concentration, and the incidence of anaemia during the 12 cycles following insertion were all greater among users of the Lippes Loop than of the Copper 7 with generally intermediate values for Dalkon Shield users. The mean increases in blood-loss were: for parous women fitted with the Lippes Loop, 48 ml, with the Dalkon Shield, 34 ml, and with the Copper 7, 18 ml; for nulliparae fitted with the small size of Dalkon Shield, 27 ml, and, with the Copper 7, 19 ml.

70 children with chronically relapsing mild-to-severe upper-respiratory-tract infections during autumn and winter participated in a six month double-blind placebo-controlled trial: 38 of them received about 1-25 mg/kg of levamisole twice daily for two consecutive days every week, the others were given placebo. During each of the three trial periods, levamisole proved superior to placebo in that it significantly reduced the number, the duration, and the severity of the infections. Moreover, in the group treated with the higher dose (i.e. greater than 2-5 mg/kg/day), the superiority of levamisole to placebo was much more clear-cut. No drug-related side-effects were reported.

Forty-eight patients with advanced squamous-cell lung cancer were treated with radical radiotherapy. Thereafter twenty-five received B.C.G. regularly and twenty-three did not. Differences in survival during the first year of observation and absence of peripheral metastases were significantly in favour of the patients treated with B.C.G. There was no response to B.C.G. in patients receiving palliative radiotherapy or cyclophosphamide nor in those with undifferentiated carcinoma.

60 patients have been entered into a randomised prospective study to answer the question-does a single postoperative injection of B.C.G. into the pleural space improve survival after surgery for lung cancer? 40 patients have been followed up for more than a year. B.C.G. improved survival in patients with a limited tumour burden: there were no recurrences and no deaths in 17 stage-I patients treated with intrapleural B.C.G. whereas 9 of 22 comparable control patients developed recurrent cancer and 5 died in the same interval (p=0.003). Intrapleural B.C.G. treatment did not seem to be beneficial in patients with more advanced disease. The hazards associated with injecting these living organisms into the pleural space have been reduced by preclinical laboratory testing in animals, use of a single limited dose of microorganisms, administration of isoniazid, and careful patient monitoring.

In an inquiry into the matching quality of preparations employed in double-blind controlled clinical trials, a panel of 4 observers studied 22 pairs of agents used in a sample of such trials, examining features which might make one preparation distinguishable from the other. 5 pairs of substances were an excellent match, being virtually indistinguishable, but in 7 pairs ther were obvious differences, detected by all 4 observers. The preparations used in cross-over studies were not specially well matched. Colour differences were most readily detected, followed by taste. The observers differed in their ability to detect differences between pairs of preparations, and 1 panel member was approximately 3 times more successful in doing so than another.

A cross-over controlled trial has been conducted among 32 adult patients with mite-sensitive asthma. The bedclothes and pillows of each subject were laundered and vacuum-cleaned and a plastic cover applied to the mattress for six weeks in an attempt to reduce exposure to mites. No improvement in daily peak-flow reading or drug usage was found in comparison with a control period.

59 outpatients with irritable bowel syndrome participated in a randomised double-blind trial. The patients in the treatment group received three biscuits daily each containing 10 g of ordinary miller's bran, whereas the patients in the control group received wheat biscuits of a similar appearance. The treatment period was 6 weeks. 52% of the patients in the treatment group noted subjective improvement compared with 65% in the control group. The results of this trial do not support the routine use of miller's bran in irritable bowel syndrome.

Transfer factor (T.F.) prepared from 5 x 10(8) lymphoid cells from 500 ml of a parent's blood was given to 40 Australian aboriginal children aged 2-46 months who had been in hospital with acute infection. Many had protein-calorie malnutrition. These and a control group of 35 similar children were assessed blind for at least 12 months. In T.F.-treated children there were significantly fewer episodes of diarrhoeal disease for periods in excess of 26 weeks. Recurrent moderate diarrhoeal disease was particularly reduced, and the onset of severe gastroenteritis may have been delayed. There was no protection against chest, middle-ear, or skin infection.

In fifteen patients with hyperkalaemic familial periodic paralysis, inhalation of salbutamol alleviated hyperkaleamia and paralysis precipitated by exercise or oral administration of potassium chloride. In-vitro studies with rat soleus muscles indicated that the hypokalaemic effect of salbutamol is related to stimulation of the active coupled transport of sodium and potassium in muscle cells. Follow-up studies proved that the inhalation of salbutamol is a simple and adequate method for the treatment of the paralytic episodes in these patients.

A clinical trial of levamisole, an orally effective modifier of the immune response, is reported in women with primary inoperable breast cancer (stage III). After being rendered clinically disease-free by radiotherapy to the breast, supraclavicular area, and axilla, patients were allocated alternately to a control group (no further treatment) and a levamisole-treated group (150 mg orally three times a week on alternate weeks) and were followed-up by physical examination and laboratory tests. In 43 patients (23 control and 20 levamisole), there was significant prolongation of the median disease-free interval (25 v. 9 months) and survival (90% v. 35% alive at 30 months) in the levamisole-treated group compared with the controls. Levamisole treatment was also associated with an increase in the percentage and intensity of delayed hypersensitivity skin reactions and in the absolute lymphocyte-counts. No significant toxicity of levamisole was observed.

Solid tumours contain poorly oxygenated cells, and these are disproportionately resistant to therapeutic radiation. Several methods of overcoming this problem have been used clinically, including the administration of hyperbaric oxygen during irradiation, radiotherapy with heavy nuclear particles such as neutrons from cyclotrons, optimum size and spacing of multiple doses of conventional radiation, and, most recently, chemical radiosensitisers. These radiosensitisers mimic the sensitising effect of oxygen and are active only against hypoxic cells. They do not, therefore, increase radiation response in well-oxygenated normal tissues. They are not rapidly metabollised and so can penetrate further than oxygen from the vascular capillaries and effectively reach the hypoxic cells in the tumour. Some of these drugs are of considerable clinical promise. The results of in vitro and in vivo studies with radiosensitisers are summarised and preliminary clinical work is described.

An elemental diet was used for long-term (up to 360 days) nutritional support in eight patients with Crohn's diesease. They had lost 30% (range 18-37%) of their weight in health. A whole-body monitor was used to measure total body potassium as an index of the lean tissue mass. Three preoperative patients who has been unable to maintain their weight on a normal diet were able to restore 10% per month of their lost lean tissue once they were established on an elemental diet. In five patients who had had a successful resection of their bowel lesion the postoperative rate of restoration of the lean tissue mass while taking an elemental diet was 18.5% per month, while in two control postoperative patients on a normal diet it was 19% per month.

A randomised controlled trial of the use of intravenous cysteamine in the treatment of severe paracetamol poisoning has been performed. Thirty-eight patients presenting 3-17 h after ingestion were admitted to the trial; of these eighteen received cysteamine. Two patients died from hepatic failure, one in each treatment group. Analysis of the series as a whole showed no advantage of cysteamine in preventing biochemical abnormalities of liver function except for aspartate aminotranferase and serum ferritin levels, which were significantly less after cysteamine therapy. Separate analysis of the patients treated within 9 h of paractamol ingestion and of those treated 9-17 h after paracetamol ingesion similarly showed no definite advantage of cysteamine. Histological evidence of liver damage showed a possible beneficial effect of cysteamine. Cysteamine therapy did not prevent renal or pancreatic damage.

Boys in a boarding-school given inactivated influenza-A or influenza-B vaccine have been observed during a simultaneous outbreak of influenza due to A/Port Chalmers, B/Hong Kong, and B/Intermediate strains. Influenza-B vaccine conferred substantial protection, the attack-rates in boys given B vaccine being 24% compared with 45% in a control group. A/Hong Kong vaccine, by preventing infection during the previous influenza A/England outbreak, left the boys vulnerable to influenza A/Port Chalmers. Influenza-A haemagglutination-inhibiting (H.I.) antibody acquired by natural infection was associated with more protection than H.I. antibody induced by vaccination. This difference was not seen with influenza-B H.I. antibody.