Detection rates for abnormal cervical smears: what are we screening for?

We analysed rates of detection for smear abnormalities in 255,000 women served by the Bristol screening programme. The programme began in 1966 with the aim of eradicating the 30-40 deaths each year in Bristol from cervical cancer. Organisation has been good and population uptake has been high for the past 15 years. Records were computerised in 1977. During the 1988 to 1993 screening round, 225,974 women were tested. New smear abnormalities were found in 15,551, of whom nearly 6000 were referred for colposcopy. These numbers are excessively high in comparison with the incidence of the malignancy we are trying to prevent. The effect of screening on death rates in Bristol is too small to detect. Our conclusion is that despite good organisation of the service, much of our effort in Bristol is devoted to limiting the harm done to healthy women and to protecting our staff from litigation as cases of serious disease continue to occur. The real lesson from 30 years' cervical screening is that no matter how obvious the predicted benefit may seem for any screening test, introduction should never take place without adequate prior evaluation of both positive and negative effects in controlled trials.     

Clinical predictors of HIV-1 infection among preschool children in Dar es Salaam, Tanzania

Seroprevalence of HIV-1 infection was determined in children aged between eighteen months and five years, attending maternal and child health (MCH) clinics in Dar es Salaam, Tanzania. A total of 889 children were eligible for the study, however seven children could not be enrolled because their mothers/guardians absconded and blood could not be drawn from 21 children due to refusal of mothers/guardians and from another 12 children due to technical reasons. Therefore, the participation rate was 95.5%. Of the 849 children screened, 14 (1.65%) were found to have IgG anti HIV-1 antibodies in their sera. The main clinical features found in children with symptomatic HIV-1 disease were weight loss, generalized lymphadenopathy, recurrent fevers, and prolonged diarrhoea. The utility of clinical features suggestive of HIV-1 infection (according to CDC classification) in identifying HIV-1 infection in children was evaluated and found to have high sensitivity (100%), specificity (96.9%) and negative predictive value (100%), but a low positive predictive value (35%). Marked variations in progression to symptomatic phase were noted, whereby some relatively young children had progressed to symptomatic phase (CDC class P-2A), while some older children were still in the asymptomatic stage (CDC class P-1 C). None of the symptomatic HIV-1 infected children presented with neurological disease, severe opportunistic infections, or malignancies. Although reduced mid-upper arm circumference and weight-for-age were associated with HIV seropositivity, these clinical parameters had low positive predictive values compared to the CDC classification.     

Genetic risk of neuropsychological impairment in schizophrenia: a study of monozygotic twins discordant and concordant for the disorder

We investigated the effect of the adenosine receptor agonist 5'-(N-ethylcarboxamido)adenosine (NECA) in catecholamine secretion from adrenal chromaffin cells that exhibit only the A2b subtype adenosine receptor. NECA reduced catecholamine release evoked by the nicotinic agonist 1,1-dimethyl-4-phenylpiperazinium (DMPP) in a time-dependent manner. Inhibition reached 25% after 30-40-min exposure to NECA. This effect on DMPP-evoked catecholamine secretion was mirrored by a similar (27.7 +/- 3.3%), slowly developing inhibition of [Ca2+]i transients induced by DMPP that peaked at 30-min preincubation with NECA. The capacity of the chromaffin cells to buffer Ca2+ load was not affected by the treatment with NECA. Short-term treatment with NECA failed both to modify [Ca2+]i levels and to increase endogenous diacylglycerol production, showing that NECA does not activate the intracellular Ca2+/protein kinase C signaling pathway. The inhibitory effects of NECA were accompanied by a 30% increase of protein phosphatase activity in chromaffin cell cytosol. We suggest that dephosphorylation of a protein involved in DMPP-evoked Ca2+ influx pathway (e.g., L-type Ca2+ channels) could be the mechanism of the inhibitory action of adenosine receptor stimulation on catecholamine secretion from adrenal chromaffin cells.     

Necrotizing enterocolitis

Advances in neonatal care have resulted in an enlarging population of vulnerable premature newborns at risk for necrotizing enterocolitis (NEC). This article presents data supporting a unifying hypothesis for the initiation of NEC based on bacteria as the inciting agent(s), and the preterm baby as the vulnerable host. Facts and controversies concerning the pathology, microbiology, clinical presentation, management and outcome of infants afflicted with NEC are presented.     

Anandamide- and delta9-tetrahydrocannabinol-evoked arachidonic acid mobilization and blockade by SR141716A [N-(Piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4 -methyl-1H-pyrazole-3-carboximide hydrochloride]

The purpose of this study was to investigate whether anandamide induces cannabimimetic responses, mainly mobilization of arachidonic acid, in primary cultures of rat brain cortical astrocytes. Confluent monolayer cultures of astrocytes, prelabeled with [3H]arachidonic acid, were incubated with anandamide or delta9-tetrahydrocannabinol (delta9-THC) in the presence or absence of thimerosal, a fatty acid acyl CoA transferase inhibitor and phenylmethylsulfonyl fluoride, an amidohydrolase inhibitor. Anandamide and delta9-THC induced a time- and concentration-dependent release of arachidonic acid in the presence, but not in the absence, of thimerosal. Anandamide- and delta9-THC-stimulated arachidonic acid release was pertussis toxin-sensitive, indicating a receptor/G-protein involvement. A novel and selective cannabinoid receptor antagonist, SR141716A [N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4- methyl-1H-pyrazole-3-carboximide hydrochloride], blocked the arachidonic acid release, suggesting a cannabinoid receptor-mediated pathway. In astrocytes, the magnitude of anandamide-induced arachidonic acid release was equal to that released by equimolar concentrations of delta9-THC. Furthermore, direct assay of amidohydrolase activity indicated that degradation of anandamide into arachidonic acid and ethanolamine was negligible in cortical astrocytes. Our results suggest that anandamide stimulates receptor-mediated release of arachidonic acid, and the receptor may be the cannabinoid receptor. Astrocytes, containing a cannabinoid receptor and lower or negligible amidohydrolase activity, may be an important brain cell model in which to study the cannabimimetic effects of anandamide at a cellular and molecular level.     

Carbohydrate chromatography: towards yoctomole sensitivity

Ward atmosphere was assessed with the help of the Ward Atmosphere Scale (WAS) by patients, nurses and physicians on 8 admission units before and after the introduction of the partial open door system. On average, on 45% of the days on which the units could have been potentially open, they were indeed at least temporarily open. Several significant changes in the WAS scores, mostly in desirable direction, were registered. However, close relationship with the partial opening of the units could be substantiated only with regard to the scale "praxis orientation"; still a positive result. No unequivocal relationships could be demonstrated between the introduction of the partial open door system and the changes in the frequency of "special events".