In 473 consecutive febrile patients a sensitive and rapid chromogenic limulus assay was used to assess the value of endotoxaemia versus bacteraemia for predicting development of the syndrome of septicaemia. In each patient three blood specimens for culture and endotoxin testing were obtained at the onset of fever. Blood pressure, urinary output, and the occurrence of thrombocytopenia and metabolic acidosis were recorded prospectively during three days of follow-up. Septicaemia developed in 19 patients (4%). The sensitivity, specificity, and likelihood ratio for a positive result with the endotoxin assay were 79%, 96%, and 20, respectively. The corresponding indices for bacteraemia were 89%, 78%, and only 4. The results suggest that endotoxaemia is a clinically valid indicator for impending gram-negative septicaemia (positive predictive value 48%) and that the absence of endotoxaemia virtually rules out the risk that septicaemia will ensue (negative predictive value 99%).

Topoisomerases are DNA-modifying enzymes that are becoming increasingly important in clinical practice. These enzymes form a target for antibiotics, autoantibodies, and antitumour drugs, and may also be involved in the pathogenesis of certain genetic disorders. Strategies for clinical manipulation of these nuclear enzyme targets are discussed.

High affinity recognition sites for benzodiazepines are part of the gamma-aminobutyric acid (GABA) supramolecular complex on the plasma membrane of neurons in the mammalian brain. Synthetic agonist benzodiazepines promote GABA-ergic neurotransmission, and hence the hypnotic and anxiolytic effects of this class of drugs, by binding to these sites. A normal physiological role for these binding sites is unknown, and an endogenous ligand for benzodiazepine receptors has not been definitely identified in normal animals. In animals and human beings with hepatic encephalopathy, however, benzodiazepine receptor antagonists have induced amelioration of the encephalopathy, and an endogenous substance that competitively binds to benzodiazepine receptors has been found in cerebrospinal fluid. These findings suggest that an endogenous ligand for the benzodiazepine receptor with agonist properties contributes to hepatic encephalopathy by promoting GABA-ergic neurotransmission.

Immunosuppression in AIDS might be due to the immune response rather than to the pathogenicity of the virus. The basis of the immunosuppression could be molecular mimicries involving viral gp-110, CD4 molecules, antibodies, and CD4-acceptor sites. Whether an individual develops auto-immunosuppressive responses or mounts a harmless defence against (or coexists with) the virus follows the general rules of lymphocyte repertoire selection. MHC and V region genes and other polymorphic loci, together with the previous state of the immune system, particularly at early developmental periods, are factors that influence the response. Vaccination against gp 110-HIV might thus protect against infection but at the same time cause auto-immunosuppression and disease.

Genomic imprinting might play an important part in the development of several tumours. It is suggested that in Wilms' tumorigenesis, imprinting normally renders inactive a transforming gene on the maternally derived chromosome 11, leaving intact the paternally inherited chromosome 11 and the Wilms' transforming gene that it carries. A similar mechanism might account for the inheritance patterns of other tumours.