Familial patterns of narcolepsy were investigated in a clinic population of 334 unrelated narcoleptic patients. 40% of probands had at least 1 family member with an isolated daytime sleepiness complaint and 6% had a positive family history of narcolepsy. Multicase families were rare; only two families were found with 3 or more affected relatives. Family members often shared the same HLA-DR2 haplotype as the proband but did not have narcolepsy. However, the risk of disease for first-degree relatives was six to eighteen times greater than that for unrelated individuals. Although most patients were HLA-DR2+, 2 new HLA-DR2- individuals were found. The data predict that as many as 9% of unrelated North-American white patients with narcolepsy will be DR2-. Analysis of these and other data indicates that although strongly associated with disease, the HLA-DR2 haplotype is neither sufficient nor necessary for the development of narcolepsy.

The immunosuppressive drug, FK 506, increased the regeneration response that follows 40% and 70% hepatectomy in rats. The effect was similar to that obtained with cyclosporin.

FK 506 was given for immunosuppression in 14 liver recipients. The drug was used in the first 10 cases because the recipients under conventional immunosuppression had rejection, nephrotoxicity, or both. This salvage therapy was successful in 7 of the 10 attempts. 2 of the 10 patients in the original salvage group as well as 4 new patients underwent fresh orthotopic liver transplantation under FK 506 plus low-dose steroids from the outset. None of these 6 patients had rejection although 1 with preexisting cor pulmonale and coronary atherosclerosis died of a myocardial infarction. In addition, 2 of the 14 liver recipients were given cadaveric kidneys, either from the same donor or from a different donor, and a third was given a pancreas as well as a kidney from the liver donor. There were no rejections of the kidney and pancreas grafts, and serious side-effects were not encountered.

The effect of psychosocial intervention on time of survival of 86 patients with metastatic breast cancer was studied prospectively. The 1 year intervention consisted of weekly supportive group therapy with self-hypnosis for pain. Both the treatment (n = 50) and control groups (n = 36) had routine oncological care. At 10 year follow-up, only 3 of the patients were alive, and death records were obtained for the other 83. Survival from time of randomisation and onset of intervention was a mean 36.6 (SD 37.6) months in the intervention group compared with 18.9 (10.8) months in the control group, a significant difference. Survival plots indicated that divergence in survival began at 20 months after entry, or 8 months after intervention ended.

When the atomic nucleus of 125I decays by orbital electron capture followed by internal conversion, numerous very-low-energy electrons (Auger electrons) are emitted, so that the energy density in the immediate vicinity of the decay site is extremely high. 125I incorporated into DNA was as effective as densely ionising 5.3 MeV alpha-particles from 210Po in reducing the sperm-head population in mice. Hence the biological risks of Auger-electron emitting radionuclides widely used in biology and medicine ought to be reassessed.

The effects of probenecid, a known inhibitor of glucuronidation, on the pharmacokinetics of zidovudine were assessed in eight subjects receiving zidovudine as treatment for human immunodeficiency virus infection. Zidovudine plasma concentrations were measured while subjects were receiving zidovudine alone, after 3 days of zidovudine plus 500 mg probenecid every 8 h, and after 3 days of zidovudine plus 500 mg probenecid plus 260 mg quinine sulphate every 8 h. A median increase of 80% in the area under the zidovudine plasma concentration/time curve occurred with the addition of probenecid. Quinine sulphate prevented the probenecid effect but had no effect on zidovudine kinetics when taken without probenecid by four other subjects. All of the effects were secondary to changes in zidovudine metabolism, since neither probenecid nor quinine changed the renal elimination of zidovudine. Probenecid could be used in combination with zidovudine to extend the interval between doses and reduce the daily requirement for zidovudine, thus enhancing convenience and reducing costs.

A sicca syndrome with parotid enlargement, pulmonary insufficiency, and lymphadenopathy was seen in 12 patients infected with human immunodeficiency virus (HIV), only 1 of whom has had an opportunistic infection during 304 patient months of study. There was a striking increase in numbers of circulating CD8 lymphocytes and the prevalence of HLA-DR5 was greatly increased. In patients with this diffuse infiltrative lymphocytosis syndrome (DILS) the CD8 lymphocytosis, which probably depends on histocompatibility antigen status, may influence disease progression in HIV infection.

Plasma endotoxin was measured in 64 patients undergoing primary liver replacement. Endotoxin concentrations increased during the anhepatic phase of the operations, and remained high for several days. Although the severity of endotoxaemia did not correlate with duration of the anhepatic phase, there was a correlation between endotoxaemia and the need for perioperative platelet transfusions, ventilator dependency postoperatively, and one-month case-fatality.