Epileptogenesis and enhanced prepulse inhibition in GABA(B1)-deficient mice.

The recent cloning of two GABA(B) receptor subunits, GABA(B1) and GABA(B2), has raised the possibility that differences in GABA(B) receptor subunit composition may give rise to pharmacologically or functionally distinct receptors. If present, such molecular diversity could permit the selective targeting of GABA(B) receptor subtypes specifically involved in pathologies such as drug addiction, spasticity, pain, and epilepsy. To address these issues we have developed a GABA(B1) subunit knockout mouse using gene targeting techniques. In the brains of GABA(B1) null mice, all pre- and postsynaptic GABA(B) receptor function was absent demonstrating that the GABA(B1) subunit is essential for all GABA(B) receptor-mediated mechanisms. Despite this, GABA(B1) null mice appeared normal at birth, although by postnatal week four their growth was retarded and they developed a generalized epilepsy that resulted in premature death. In addition, GABA(B1) heterozygote animals showed enhanced prepulse inhibition responses compared to littermate controls, suggesting that GABA(B1) deficient mice exhibit increased sensorimotor gating mechanisms. These data suggest that GABA(B) receptor antagonists may be of benefit in the treatment of psychiatric and neurological disorders in which attentional processing is impaired.

Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia.

The vanilloid receptor-1 (VR1) is a ligand-gated, non-selective cation channel expressed predominantly by sensory neurons. VR1 responds to noxious stimuli including capsaicin, the pungent component of chilli peppers, heat and extracellular acidification, and it is able to integrate simultaneous exposure to these stimuli. These findings and research linking capsaicin with nociceptive behaviours (that is, responses to painful stimuli in animals have led to VR1 being considered as important for pain sensation. Here we have disrupted the mouse VR1 gene using standard gene targeting techniques. Small diameter dorsal root ganglion neurons isolated from VR1-null mice lacked many of the capsaicin-, acid- and heat-gated responses that have been previously well characterized in small diameter dorsal root ganglion neurons from various species. Furthermore, although the VR1-null mice appeared normal in a wide range of behavioural tests, including responses to acute noxious thermal stimuli, their ability to develop carrageenan-induced thermal hyperalgesia was completely absent. We conclude that VR1 is required for inflammatory sensitization to noxious thermal stimuli but also that alternative mechanisms are sufficient for normal sensation of noxious heat.

The structure of regional conflict in northern ethiopia.

A conventional view of regional conflict in Ethiopia is that it is the result of the domination and exploitation of conquered peoples by the central Ethiopian state. The pattern of regional conflict does not, however, fit this explanation. The most important threat to the central government today comes not from the recently conquered pastoral and sedentary peoples of southern Ethiopia but from the northern highlands (Eritrea, Tigray, northern Wollo and Gonder) which have been associated with the Ethiopian state for many centuries. A more satisfactory explanation needs to take into account both the political and economic bases of revolt in northern Ethiopia following the 1974 revolution. Politically, the people were alienated from a national government of which they had previously often been a dominant part. Economically, the progressive marginalisation and agricultural degradation of the northern highlands was accelerated by the policies of the post-1974 government, policies which brought immediate and important benefits to the southern regions.

Economic consequences of two drug-use control systems in a teaching hospital.

Length of stay (LOS), total cost per admission (TCA), and pharmacy cost per admission (DCA) were determined for two drug-use control systems in a 1058-bed university hospital; a centralized unit dose drug distribution system served as a control. The two study systems were (1) pharmacist monitoring of drug therapy in the patient-care area and (2) centralized pharmacist monitoring of computerized patient profiles. LOS data were collected retrospectively for 659 patients admitted during a seven-month control interval. LOS, TCA, and DCA data were collected prospectively for 496 patients admitted during a five-month experimental interval. Each study system was assigned to one of three teams making rounds among intact patient groups. LOS differences were compared between intervals and by month. After corrections were made for differences in patient mix, the drug-use control system in which pharmacists were assigned to the patient-care area yielded a 1.5-day-shorter average LOS, $1293 lower average TCA (p less than 0.05), and $155 lower average DCA than under the unit dose system. The drug-use control system in which pharmacists were assigned to monitor patients' drug therapy from a central location was associated with a 0.13-day-shorter average LOS, $235 lower average TCA, and $55.13 lower average DCA than under the unit dose system. No systematic differences between teams, other than drug-use control system, appeared to explain the differences in LOS, TCA, and DCA. A drug-use control system based in a patient-care area, overseen by clinically experienced pharmacists, may result in shorter LOSs and lower total costs than centralized systems for general-medical inpatients of teaching hospitals.

A design for flexible intestinal cannulas.

A design for a cannula made by fixing silicone rubber tubing to rigid internal and external flanges is described. These cannulas have been used to fit simple duodenal, simple ileal and abomasal fistulas in adult lactating cattle for periods up to 1 year and have caused minimal tissue reaction at the site of fistulation.