Alpha-amino acid phenolic ester derivatives: novel water-soluble general anesthetic agents which allosterically modulate GABA(A) receptors.

In the search for a novel water-soluble general anesthetic agent the activity of an alpha-amino acid phenolic ester lead, identified from patent literature, was markedly improved. In addition to improving in vivo activity in mice, good in vitro activity at GABA(A) receptors was also conferred. Within the series of compounds good enantioselectivity for both in vitro and in vivo activity was found, supporting a protein-mediated mechanism of action for anesthesia involving allosteric modulation of GABA(A) receptors. alpha-Amino acid phenolic ester 19, as the hydrobromide salt Org 25435, was selected for clinical evaluation since it retained the best overall anesthetic profile coupled with improved stability and water solubility. In the clinic it proved to be an effective intravenous anesthetic in man with rapid onset of and recovery from anesthesia at doses of 3 and 4 mg/kg.

Influenza surveillance in England and Wales: October 1995 to June 1996.

This report summarises information collected for the surveillance of influenza virus infection in England and Wales from October 1995 to June 1996 (weeks 40/95 to 25/96). Total respiratory disease' activity, as reported by the Birmingham Research Unit of the Royal College of General Practitioners, rose to peaks in weeks 48/95, 51/95, and 01/96. The first peak coincided with a peak in "influenza and flu-like illness'. The subsequent peaks were accounted for by an increase in reports of acute bronchitis, including bronchiolitis, and may have been associated with the annual rise in infections with respiratory syncytial virus. Influenza A virus was responsible for most infections, with moderate activity occurring in the early part of the winter, peaking in December (week 48/95). Influenza A subtype H3N2 predominated until week 07/96, after which subtype H1N1 accounted for most infections. Influenza activity was first seen in central and northern England, followed by the south of England, Wales, and Scotland. Circulating influenza viruses were antigenically similar to the components of the 1995/96 vaccine. International surveillance during 1995/96 has led to a different H3N2 component being included in the influenza vaccine recommended for 1996/97.

Legionnaires' disease surveillance: England and Wales, 1995.

One hundred and sixty cases of legionnaires' disease were reported to the PHLS Communicable Disease Surveillance Centre in 1995. Twenty cases (13%) were known to have died. Ninety cases (56%) were associated with travel (in the United Kingdom or abroad), four were associated with a stay in hospital, and the remaining 66 were presumed to have acquired infection in the community. One hundred and twenty-three cases (77%) occurred sporadically. Three community outbreaks and one outbreak at an industrial site were detected in England and Wales. One outbreak and five clusters were detected among visitors to Turkey, Spain, and Italy. Seven cases and one outbreak of nonpneumonic legionellosis were also reported. Cases of travel associated legionnaires' disease continue to account for the largest proportion of the total reported in 1995 and the number of hospital acquired cases continues to decline. A cause for concern in 1995 was a fall in the proportion of cases diagnosed by culture of the organism (from 16% in 1994 to only 9% in 1995). This corresponded with a small increase in the proportion of cases diagnosed solely by detection of antigen to L. pneumophila serogroup 1 in urine.

Impact of incomplete coverage of neonatal dried blood spot screening on estimating HIV-1 seroprevalence.

The aim of this study was to determine the extent to which selective under-coverage of births to mothers more likely to be at risk of HIV-1 infection will result in a significant under-estimation of the true neonatal seroprevalence. Census data, local birth statistics, maternity data and data from the prevalence monitoring programme were used to produce a model to predict the effects of under-coverage in the uptake of neonatal metabolic screening which has been observed in babies with a mother of ethnic group black African. The adjustment factor which allows for under-coverage is the relative inclusion ratio (RIR); the probability that samples from a group at different risk of HIV infection were included in the survey divided by the probability of inclusion for samples from all other babies. The RIR was found to be close to unity (0.97), indicating a minimal bias. Under usual conditions only if the relative inclusion ratio (RIR) declined to values of 0.87 or below would there be a substantial bias. Despite some selective under representation, the results obtained from the Unlinked Anonymous HIV Monitoring Programme Dried Blood Spot Survey would seem to identify levels of prevalence in the population of child-bearing women with a good degree of accuracy and remains a useful tool for resource allocation, planning of services, provision of care and counselling.

PIP: Census data, local fertility statistics, maternity data, and data from the HIV-1 prevalence monitoring program were used to develop a model to predict the effects of under-coverage of neonatal dried spot screening, which has been observed in infants with mothers of the Black African ethnic group. The data and statistics were limited to South London, England, which included the boroughs of Lambeth, West Lambeth, Southwark, and Camberwell. The model assumed HIV-1 prevalence values for African mothers to be 0-20% and 0-0.5% for all other mothers. It assumed a general fertility rate of 160/1000 for African mothers and 64/1000 for all other mothers. Coverage for neonatal dried spot screening was assumed to be 95.6% for African mothers and 98.15% for all other mothers. The relative inclusion ratio (RIR) (the probability that samples from a group at different risk of HIV infection were included in the survey divided by the probability of inclusion for samples from all other infants) was used as the adjustment factor allowing for under-coverage. The RIR was close to unity (0.975) (i.e., 95.6% actual coverage for African mothers in South London divided by 98.15% for all other mothers in South London), suggesting minimal bias. Under usual conditions, substantial bias would not occur unless RIR fell to values of 0.87 (i.e., coverage of 86% divided by 98.15%) or below. When HIV-1 prevalence was assumed to be 0.3% in all others, there was no difference between true and observed HIV-1 prevalence until it reached 3% in African mothers. At 3% HIV-1 prevalence for African mothers and 0.3% for all others, the difference was only 0.01% (i.e., observed prevalence of 0.34% compared to a true prevalence of 0.35%). These findings suggest that the Unlinked Anonymous HIV Monitoring Programme Dried Blood Spot Survey appears to identify accurately levels of HIV prevalence in the population of reproductive age women. It is still a useful tool for resource allocation, planning of services, provision of care, and counseling.

EWGLI: a European surveillance scheme for travel associated legionnaire s disease.

The European Working Group for Legionella Infections (EWGLI) was set up in 1986 and introduced the European Surveillance Scheme for Travel Associated Legionnaires Disease in 1987. The microbiologists working in reference laborat-ories and the epidemiolog

Influenza surveillance in England and Wales: October 1994 to June 1995.

This report summarises the information obtained by surveillance of influenza in England and Wales from October 1994 to June 1995 (weeks 40/94 to 25/95). Influenza B viruses were responsible for most infections, with moderate activity occurring throughout the winter, peaking in February. Influenza A became more active towards the end of the winter, and laboratory reports reached a peak in May (week 21/95). Influenza activity was seen first in Wales, then England, followed by Scotland. An increase in 'total respiratory disease' was reported in December 1994 by the Birmingham Research Unit of the Royal College of General Practitioners (RCGP) in England and Wales. This was probably due largely to an increase in reports of acute bronchitis, and was concurrent with the annual increase in respiratory syncytial virus infection which is often associated with bronchiolitis. Circulating influenza viruses were antigenically similar to components of the vaccine chosen for 1994/95. This report summarises the recommendations for the 1995/96 influenza vaccine.

Legionnaires' disease surveillance: England and Wales 1994.

One hundred and sixty cases of legionnaires' disease in England and Wales were reported to the PHLS Communicable Disease Surveillance Centre in 1994, a rate of 3.1 cases per million population. Twenty-seven cases died. Eighty-nine cases (56%) were associated with travel, either in the United Kingdom (UK) or abroad, and six with a stay in hospital; the remaining cases were presumed to have acquired infection in the community. Seven outbreaks were detected in England and Wales: one was associated with a holiday centre, one with a hotel in London, two with industrial sites, and three occurred in the community. A further four clusters were associated with travel abroad: Spain, Ibiza, the Channel Islands, and a Mediterranean cruise. One hundred and twenty-eight of the 160 cases (79%) were sporadic--that is, not known to be associated with outbreaks--43 of which (34%) were not associated with travel nor acquired in hospital.