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Summary A clinicalstudy of the use of intrathecal morphine in two groups

Summary and conclusionsA survey of all anaesthetists in the West Midlands region -that is, 10% of all the anaesthetists in England and Wales-showed that one in 10 of their children had been referred to a consultant because of a congenital or nonacquired anomaly. Abortions among anaesthetists' families were also common but more so when the mother was an anaesthetist. The anomalies were concentrated particularly in the central nervous system and musculoskeletal system, and girls were worst affected. The mean birth weights were below normal, more so when the mothers were anaesthetists. Girls with anomalies were particularly underweight. Other effects observed were unexpected infertility, cancer both in the adults and in the children, and, possibly, impaired intellectual development in the children. Many anaesthetising areas were inadequately ventilated, and scavenging devices despite their inefficiency are recommended as a stopgap measure. The results of the study closely resemble those of other studies with similar high response rates to requests for information.

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High-throughput screening of chemical libraries and the subsequent rapid progress of hit compounds through an iterative developmental test cascade are essential parts of modern molecular mechanism-based drug discovery. These processes depend on the use of efficient assay technologies and equipment. Enzyme-linked immunosorbent assays have historically been carried out in 96-well microtitre plates. Improvements in reagents and assay technologies mean that solid-phase immunoassays can be adapted for higher throughput to play an important role in modern drug discovery. The molecular chaperone heat-shock protein (Hsp) 90 is an important anticancer drug target because it maintains the conformation, stability, and function of many important oncogenic client proteins, including those involved with signal transduction, cell proliferation, survival, differentiation, motility angiogenesis, and metastasis. Using the standard inhibitors of the adenosine triphosphatase (ATPase) activity of Hsp90, geldanamycin (GA) and 17-allylamino-17- demethoxygeldanamycin (17AAG), novel solid-phase immunoassays have been validated using a time-resolved fluorescence (TRF) end point. Their utility for confirming the mechanism of action of Hsp90 inhibition in secondary cell-based assays has been shown and applied to the novel Hsp90 inhibitor CCT018159. Adaptation of these assays for later studies using human tumour xenografts and samples obtained from a Phase 1 trial of 17AAG is also described. Finally, comparison is made between the use and applicability of this type of immunoassay and other techniques such as western blotting, immunohistochemistry, and flow cytometry analysis.

An investigation, in volunteers, into the sensory effects of nitrous oxide and methoxyflurane showed that the subjective changes of reduction in visual awareness and heightened auditory awareness were not supported by objective measurement. Vision remained normal until the subjects became unresponsive, whilst hearing was in fact diminished. The analgesia produced by nitrous oxide was late in appearance relative to the other sensory changes and it disappeared very rapidly upon recovery. In contrast, analgesia appeared early with methoxyflurane and persisted well into the recovery period. The principal changes found were alterations in orientation in space, of intellectual attitudes, of mood and of emotional attitudes. The emotional attitudes were easily disturbed by extraneous noise or conversation and the need for a quiet approach not only to the induction of anaesthesia but also to the recovery from anaesthesia is stressed.

An investigation, in volunteers, into the sensory effects of nitrous oxide and methoxyflurane showed that the subjective changes of reduction in visual awareness and heightened auditory awareness were not supported by objective measurement. Vision remained normal until the subjects became unresponsive, whilst hearing was in fact diminished. The analgesia produced by nitrous oxide was late in appearance relative to the other sensory changes and it disappeared very rapidly upon recovery. In contrast, analgesia appeared early with methoxyflurane and persisted well into the recovery period. The principal changes found were alterations in orientation in space, of intellectual attitudes, of mood and of emotional attitudes. The emotional attitudes were easily disturbed by extraneous noise or conversation and the need for a quiet approach not only to the induction of anaesthesia but also to the recovery from anaesthesia is stressed.

We have been fortunate in our group that the executive committee has elected the medical superintendent as chairman of the executive committee. He has in the past spent a large amount of time on administration, so this position did not require him to radically alter his timetable. Nevertheless, in groups where the chairman does not already spend a large part of his time on administrative duties he must get considerable support from his colleagues within his specialty. But any clinician must be able to act as chairman either of his division or of the medical executive committee. The fact that one of our four consultant general surgeons is at the present time mayor of the city illustrates that many consultants can find time for this amount of administration if the will is there.Any group contemplating setting up this type of administration must insist on adequate clerical help to assist both the executive committee and the divisions with clerical work and also to produce and collate the necessary statistics.We agree with the Cogwheel report that it is difficult for hospitals with fewer than 20 to 30 consultants to have a divisional system of administration but consider that all but the smallest groups could elect a small executive committee from their medical advisory committee, who could then meet more regularly than the main committee and come to decisions more quickly and effectively than previously. ConclusionsWe agree with the Cogwheel report that each individual group must tailor the suggestions to their own requirements. If the hospital medical staff do not streamline their own administration before the reunification of the health service and the setting up of area health boards we will probably be administered increasingly by non-medicai administrators and have little say in the running of our hospitals.