Frequency of HIV testing among gay and bisexual men in the UK: implications for HIV prevention.

OBJECTIVES: The aim of the study was to explore HIV testing frequency among UK men who have sex with men (MSM) in order to direct intervention development. METHODS: Cross-sectional surveys were completed by 2409 MSM in Edinburgh, Glasgow and London in 2011 and a Scotland-wide online survey was carried out in 2012/13. The frequency of HIV testing in the last 2 years was measured. RESULTS: Overall, 21.2% of respondents reported at least four HIV tests and 33.7% reported two or three tests in the last 2 years, so we estimate that 54.9% test annually. Men reporting at least four HIV tests were younger and less likely to be surveyed in London. They were more likely to report higher numbers of sexual and anal intercourse partners, but not "higher risk" unprotected anal intercourse (UAI) with at least two partners, casual partners and/or unknown/discordant status partners in the previous 12 months. Only 26.7% (238 of 893) of men reporting higher risk UAI reported at least four tests. Among all testers (n = 2009), 56.7% tested as part of a regular sexual health check and 35.5% tested following a risk event. Differences were observed between surveys, and those testing in response to a risk event were more likely to report higher risk UAI. CONCLUSIONS: Guidelines recommend that all MSM test annually and those at "higher risk" test more frequently, but our findings suggest neither recommendation is being met. Additional efforts are required to increase testing frequency and harness the opportunities provided by biomedical HIV prevention. Regional, demographic and behavioural differences and variations in the risk profiles of testers suggest that it is unlikely that a "one size fits all" approach to increasing the frequency of testing will be successful.

"It has to speak to people's everyday life...": qualitative study of men and women's willingness to participate in a non-medical approach to Chlamydia trachomatis screening.

OBJECTIVE: To explore the factors associated with men and women's willingness to provide a urine sample for Chlamydia trachomatis screening in various non-medical settings. METHODS: Men and women aged 16-24 years attending non-medical settings were invited to participate in urine-based screening and later to participate in a follow-up in-depth interview. Participant observation techniques were also used to collect data on young people's response to the offer of screening. RESULTS: The views of 24 men and women revealed three themes in relation to willingness to participate, particularly among men: their raised awareness of chlamydia, particularly its asymptomatic nature; the convenience of the offer; and the "non-medical" nature of the screening. In contrast, women more often felt the public nature of the settings inhibited them from agreeing to take the test and, thus, acted as a barrier to their willingness to participate in screening. CONCLUSIONS: The gender difference in willingness to participate in non-medical screening suggests that extending the reach of screening could certainly assist in bringing more young men into screening but may not necessarily destigmatise screening for women. As such, the potential benefits to men must be considered in the context of the potential psychosocial harms to women.

HIV testing trends among gay men in Scotland, UK (1996-2005): implications for HIV testing policies and prevention.

OBJECTIVE: To examine trends in the HIV testing behaviour of gay men in Scotland over a 10-year period. METHODS: Seven cross-sectional surveys in commercial gay venues in Glasgow and Edinburgh (1996-2005). 9613 men completed anonymous, self-completed questionnaires (70% average response rate). RESULTS: Among 8305 respondents included in these analyses, HIV testing increased between 1996 and 2005, from 49.7% to 57.8% (p<0.001). The proportion of men who had tested recently (in the calendar year of, or immediately before, the survey) increased from 28.4% in 1996 to 33.2% in 2005, when compared with those who have tested but not recently, and those who have never tested (adjusted odds ratio 1.31, 95% CI 1.13 to 1.52). However, among ever testers, there was no increase in rates of recent testing. Recent testing decreased with age: 31.3% of the under 25, 30.3% of the 25-34, 23.2% of the 35-44 and 21.2% of the over 44 years age groups had tested recently. Among men reporting two or more unprotected anal intercourse partners in the previous year, only 41.4% had tested recently. CONCLUSIONS: HIV testing among gay men in Scotland increased between 1996 and 2005, and corresponds with the Scottish Government policy change to routine, opt-out testing in genitourinary medicine clinics. Testing rates remain low and compare unfavourably with near-universal testing levels elsewhere. The limited change and decline across age groups in recent HIV testing rates suggest few men test repeatedly or regularly. Additional, innovative efforts are required to increase the uptake of regular HIV testing among gay men.

Feasibility and acceptability of offering rapid HIV tests to patients registering with primary care in London (UK): a pilot study.

OBJECTIVE: To assess the acceptability and feasibility of offering rapid HIV tests to patients registering with primary care in London, UK. METHODS: All Anglophone and Francophone patients aged between 18 and 55 years attending a large inner city general practice in London for a new patient health check were recruited. All eligible patients were offered a rapid HIV test on oral fluid and asked to participate in a qualitative interview. The uptake of rapid HIV testing among participants was measured and semistructured interviews were carried out focusing on the advantages and disadvantages of testing for HIV in primary care. RESULTS: 111 people attended the health check, of whom 85 were eligible, 47 took part in the study and 20 completed qualitative interviews. Nearly half of eligible participants (38/85, 45%) accepted a rapid HIV test. The main reason for accepting a test was because it was offered as "part of a check up". As a combined group, black African and black Caribbean patients were more likely to test in the study compared with patients from other ethnic backgrounds (p = 0.014). Participants in the qualitative interviews felt that having rapid HIV tests available in general practice was acceptable but expressed concerns about support for the newly diagnosed. CONCLUSIONS: Offering patients a rapid HIV test in primary care is feasible and could be an effective means to increase testing rates in this setting. A larger descriptive study or pragmatic trial is needed to determine whether this strategy could increase timely diagnosis and reduce the proportion of undiagnosed HIV infections in the UK.

Increased attendances of people of eastern European origin at sexual health services in London.

OBJECTIVE: To describe the service use of migrants from eight central and eastern European (CEE) countries at two central London genitourinary medicine (GUM) clinics before and after accession to the European Union on 1 May 2004. METHODS: KC60 data collected between 1 June 2001 and 30 April 2007. Data refer to new attendances and exclude those attending for follow-up appointments. RESULTS: 102,604 people attended the clinics at least once over the study period. Between May 2006 and 30 April 2007 individuals born in the eight CEE countries accounted for 7.9% of attendances among women and 2.5% of attendances made by men; the proportion increasing significantly over the 6-year study period (p<0.001). Syphilis was more likely in CEE men (age-adjusted odds ratio (OR) 2.98, 95% CI 1.07 to 8.29) and family planning services were more likely to be required for CEE women (23.9% vs 12.4%, age-adjusted OR 2.33, 95% CI 2.02 to 2.68, p<0.001), than for those born elsewhere. A larger proportion of men from CEE countries were recorded as homosexual or bisexual than men from other countries (38.3% vs 31.9%, p = 0.003). CONCLUSIONS: CEE migrants already have a substantial impact on GUM services in London. If attendance rates continue at the current level CEE women will soon account for over 10% of new attendances. Although the majority of CEE migrants are men, proportionately fewer CEE men accessed GUM services than women. Sexual and reproductive health services need to adapt quickly to meet the needs of this growing population.

Behaviourally bisexual men as a bridge population for HIV and sexually transmitted infections? Evidence from a national probability survey.

We consider the potential of behaviourally bisexual men (BBM) as a bridge population in sexually transmitted infection (STI)/HIV transmission by comparing sexual risk behaviours, attitudes and sexual health outcomes of BBM (defined as men who reported sex with men and women), with men who reported (i) exclusively male partners (MEMP) and (ii) exclusively female partners (MEFP), using a probability survey of the British general population aged 16-44 years, conducted between 1999 and 2001 (n = 5168 men). About 1.3% of men who reported sex in the past five years were BBM (44.1% of all men reporting male partners); 29.0% of BBM were married/cohabiting with women. Median partner numbers in this timeframe were seven among BBM, two among MEFP and 10 among MEMP. Similar proportions of BBM and MEMP reported STI diagnosis/es in the past five years, yet BBM were less likely than MEMP to report HIV-testing (odds ratio adjusted for sociodemographics: 0.31). BBM are thus mid-way between MEFP and MEMP in their sexual risk behaviour, but are similar to MEMP in reporting STI diagnosis/es. These data have implications for health promotion and partner notification, as BBM are unlikely to be appropriately targeted by safe-sex messages aimed at men identifying as gay.

10-year update on chemotherapy for non-small cell lung cancer.

BACKGROUND: A 1995 meta analysis of chemotherapy in patients with advanced non-small cell carcinoma indicated clinical benefit from cisplatin based chemotherapy. Subsequent studies have aimed to increase the efficacy or decrease the toxicity of chemotherapy. PATIENT AND METHODS: Illustrative studies and meta analyses of different aspects of chemotherapy which have taken place over the last decade, are reviewed. RESULTS: The use of novel (third generation) chemotherapy agents has resulted in a further increase in patient survival. Gemcitabine was shown to be associated with an increase in progression free survival when compared to other third generation agents as well as a strong tendency to increased overall survival. An increase in survival was also shown with doublet chemotherapy regimes as compared to the use of single agents only. The use of triplet agent chemotherapy results in no further increased survival, but increased toxicity. Cisplatin is associated with increased survival over carboplatin based chemotherapy regimens when third generation agents are used, but increased nausea and vomiting. Non-platin third generation combinations give equivalent survival to platin-based regimens. CONCLUSIONS: First line chemotherapy given to patients with advanced NSCLC should be two-drug combination regimen. Non-platin containing regimens may be used as an alternative to platinum based regimens in the first line.

Prevalence of HIV, hepatitis B and associated risk behaviours in clients of a needle-exchange in central London.

In order to determine the prevalence of risk behaviour for, and antibodies to HIV and hepatitis B in clients of a needle-exchange scheme in central London we employed an anonymous, self-administered questionnaire along with salivary antibody testing by immunoglobulin (Ig) G antibody capture immunoassay. Two hundred and thirty-two subjects (193 men, 39 women; median age 32) participated; a response rate of 89%. Clients were long-term, frequent injectors. Lending used equipment at any time was reported by 55%, and borrowing by 52%. Of those who had shared needles and syringes during the last year, the majority had lent to, or borrowed from, one person only (53 and 55%, respectively). Younger clients (less than 29 years of age) reported more recent sharing than older clients (greater than 30 years of age). Five out of 211 (2.4%) samples tested for anti-HIV were positive. One hundred and eleven out of 199 (56%) samples were positive for anti-hepatitis B core (HBc). In this population of needle-exchange attenders there is no evidence of further spread of HIV, and a low prevalence of HIV infection appears to have been sustained. However, the high prevalence of anti-HBc provides evidence of previous risk behaviour and so constant vigilance is necessary if further viral spread is to be avoided. This study has established an acceptable method for the anonymous surveillance of current risk behaviour and salivary antibodies to HIV and hepatitis B virus (HBV) in a drug-using population.

Evaluation of needle exchange in central London: behaviour change and anti-HIV status over one year.

From November 1987 to October 1988, numbers of clients, visits made and syringes dispensed and returned were monitored at the needle exchange of the Middlesex Hospital, London, UK. A sample of clients were interviewed 1 month after entry to the scheme and again 3 months later to evaluate changes in injecting and sexual risk behaviours for HIV infection. Clients were asked to donate saliva for anti-HIV immunoglobulin G (IgG) antibody capture radioimmunoassay (GACRIA). The rate of lending and borrowing used injecting equipment fell, both compared with rates prior to entry to the scheme and during the period of study. Frequency of injecting did not increase and there was reduced incidence of abscesses. There was a highly significant correlation between multiple sexual partners and condom use and a reduction in the proportion of clients with multiple partners. On entry to the study, seven out of 121 (6%) clients were anti-HIV positive; after 3 months, a further two clients tested were found to be anti-HIV positive. Anti-HIV positivity prevalence for the year of study was nine out of 121 (7%). The scheme attracts clients, reduces injecting-related risk for HIV infection and has high equipment return rates. Saliva testing is acceptable to clients. Continued monitoring of anti-HIV in saliva is indicated.

PIP: From November 1987-October 1988, numbers of clients, visits made, and syringes dispensed and returned were monitored at the needle exchange of the Middlesex Hospital, London, United Kingdom. A sample of clients was interviewed 1 month after entry to the scheme and again 3 months later to evaluate changes in injecting practices and sexual behaviors for HIV infection. Clients were asked to donate saliva for anti-HIV immunoglobulin G (IgG) antibody capture radioimmunoassay. The rate of lending and borrowing used injecting equipment fell, both compared with rates prior to entry to the scheme and during the period of study. Frequency of injecting did not increase and there was reduced incidence of abscesses. There was a highly significant correlation between multiple sexual partner and condom use and a reduction in the proportion of clients with multiple partners. On entry to the study, 7 of 121 (6%) clients were anti-HIV positive; after 3 months, an additional 2 clients were anti-HIV positive. Anti-HIV positivity prevalence for the year of study was 9 of 121 (7%). The scheme attracts clients, reduces injecting rates. Saliva testing is acceptable to clients. Continued monitoring of anti-HIV in saliva is indicated.

Risk behaviour and HIV prevalence in international travellers.

OBJECTIVE: To assess risk factors for infection and to determine HIV prevalence in a sample of international travellers. DESIGN: A cross-sectional survey of new patients attending a hospital outpatient clinic, and self-completion of an anonymous questionnaire on sexual behaviour prior to and during travel. Urine samples were tested for the presence of antibodies to HIV. SETTING: The Hospital for Tropical Diseases, London, UK. SUBJECTS: All new patients over a 6-month period. RESULTS: Of 782 people approached, 757 (97%) agreed to participate: 141 (18.6%) had had new sexual partners during their most recent trip abroad. Almost two-thirds of those having sex abroad did not use condoms on every occasion with a new partner, and 5.7% contracted a sexually transmitted disease (STD) during their most recent trip; 26% of men from World Health Organization Pattern I countries who had new sexual partners abroad paid for sex. Sixteen out of 731 (2.2%) participants were HIV-antibody-positive. HIV positivity was associated with being born in east, central or southern Africa, having symptoms of an STD since arriving in the United Kingdom and being treated for an STD since arrival. CONCLUSION: The rates of unsafe sex and payment for sex abroad reported by these international travellers indicate the potential for contracting and transmitting STD, including HIV, in both their foreign and domestic sexual partnerships. With the increasing HIV incidence in Asia (the most common destination for UK travellers after sub-Saharan Africa), the number of cases of HIV contracted abroad may rise in the future.

Awareness of sexual partners' HIV status as an influence upon high-risk sexual behaviour among gay men.

OBJECTIVE: To evaluate the extent to which 'high-risk' sexual behaviour is influenced by awareness of partners' HIV status among gay men. DESIGN: Structured interviews and collection of saliva samples for anonymous linked testing for HIV-1 antibodies. SETTING: Genitourinary medicine clinics and the gay community. SUBJECTS: Men (n = 677) who reported sexual contact with another man in the last 5 years. RESULTS: The majority of respondents (63%) had had an HIV-antibody test. Analysis of data showed that in 15% of the respondents' 1380 partnerships, HIV status was known by both parties. However, the majority of partnerships involved only safe sex. Only 26% of the partnerships in which unprotected penetrative anal sex had occurred involved mutual knowledge of HIV status and was most likely to occur with regular rather than non-regular/causal partners. Logistic regression revealed that this latter association could not be explained in terms of mutual HIV status knowledge. CONCLUSIONS: Despite widespread HIV testing, the majority of gay men engaging in high-risk sex are unaware of their partner's HIV status.

PIP: The authors interviewed and collected saliva samples from 677 men who reported having sexual contact with other men in the preceding five years to assess the extent to which high-risk sexual behavior is influenced by awareness of partners' HIV status among gay men. Participants of mean age 32.6 years of a range of 16-71 years were recruited from genitourinary medicine clinics and the gay community over the period March 1991-April 1992. 52% were from London, 21% from Manchester, 18% from central England, 6% from Bristol, and 3% from elsewhere. 63% had previously had an HIV-antibody test. 94 (16%) of the 580 satisfactory saliva samples tested for HIV-1 antibodies were seropositive; 17 men were previously unaware of their HIV-positive serostatus. The 577 men who reported having a sex partner within the previous month provided information on 1380 partners during the period. 45% of the sexually active men reported engaging in some kind of penetrative anal sex in the previous month, while 23% reported having unprotected anal sex in the previous month. HIV status was known by both parties, however, in only 15% of the 1380 partnerships. 891 partnerships involved no penetrative anal sex and 1107 involved only nonpenetrative or penetrative sex always with a condom. Further, 26% of the partnerships in which unprotected penetrative anal sex took place involved mutual knowledge of HIV status and was most likely to occur with regular instead of nonregular/casual partners. It is of interest that 114 partners were known to be married and 311 were of unknown marital status. Higher social class was associated with a reduced likelihood of having risky sex and high-risk sex was more common in partnerships in which there was an age gap in excess of two years between partners.

Risk behaviour, anti-HIV and anti-hepatitis B core prevalence in clinic and non-clinic samples of gay men in England, 1991-1992.

OBJECTIVE: To describe the sexual risk behaviour of and HIV and hepatitis B antibody prevalence in gay men in England. DESIGN: Cross-sectional. RESPONDENTS: Gay men recruited from community settings (bars, clubs, gay organizations) and genito-urinary clinics in London, Manchester, the Midlands and Bristol; men who participated in an earlier study. METHODS: Interview including demographic information, sexual behaviour, partner type and health service use. Subjects donated saliva, which was screened for antibodies to HIV-1 by immunoglobulin G (IgG) antibody capture enzyme-linked immunosorbent assay (GACELISA) and to hepatitis B core (HBc) antigen by IgG antibody capture radioimmunoassay (GACRIA). RESULTS: Ninety-four out of 580 (16.2%) men were HIV-antibody-positive; 6.2% of men aged < or = 25 years were positive versus 19.5% of men aged > or = 26 years. HIV-antibody prevalence was highest in London (21.1%), and twice that previously reported outside London (10.5%). Ninety-four out of 568 (16.5%) men were HBc-antibody-positive; 6.9% of men aged < or = 25 years were positive versus 19.7% of men aged > or = 26 years. Anti-HBc prevalence was highest in London (19.8 versus 12.7% outside London). Manual workers were more likely to be anti-HBc-positive, as were men who reported recent high-risk intercourse. Sexually transmitted diseases associated with frequent partner change (gonorrhoea, non-specific urethritis) were reported. CONCLUSION: The HIV epidemic in gay men in England continues, particularly outside London, where prevalence was double that of previous studies. We found relatively high rates of infection in young men whose main sexual experience has been in a time of unprecedented awareness of AIDS. Our data on hepatitis B suggests that further pro-active immunization programmes are urgently required. These findings add to concerns about provision of interventions targeting gay men.

HIV infection in injecting drug users attending centres in England and Wales, 1990-1991.

OBJECTIVE: To monitor trends in HIV infection and associated risk behaviours in injecting drug users (IDU) in England and Wales. DESIGN: Ongoing voluntary unlinked anonymous cross-sectional survey. METHOD: IDU attending centres in 1990 and 1991 were invited to complete a brief questionnaire requesting demographic and behavioural information, and to provide a saliva sample to be tested for antibodies to HIV and to the core antigen of hepatitis B virus (HBV). RESULTS: In 1990, 1.2% (19 out of 1543) of samples from 33 centres, and in 1991 1.8% (25 out of 1417) of samples from 37 centres contained antibody to HIV. Antibody t9 HBV core-antigen was found in 33 and 31% of IDU in 1990 and 1991, respectively. The prevalence of HIV infection in IDU attending centres in London (4.2%) was higher than in those attending centres elsewhere (0.8%). The prevalence of HIV infection in 1991 varied between individual centres from 0 to 10.6%, and at many centres outside London no IDU were infected with HIV. In the same year the prevalence of past infection with HBV varied from 14 to 54%, and IDU who had evidence of HBV infection were found among attenders in nearly all centres. The prevalences of sharing injecting equipment and risky sexual behaviour were high at many centres. The prevalence of HIV infection was higher in IDU who had started to inject in 1985 or earlier, than in those who started injecting later. In each year, approximately half the IDU surveyed reported having had a voluntary confidential HIV-antibody test, and the prevalence of HIV infection was five times higher in those tested than in those who had not been tested. CONCLUSIONS: HIV prevalence in IDU attending centres in England and Wales was low in 1990-1991. There is some indication that IDU have modified their injecting or sexual behaviour, but even at existing reduced levels of risk behaviour, transmission can occur in HIV is introduced into previously unexposed groups.

The effect of the UL42 protein on the DNA polymerase activity of the catalytic subunit of the DNA polymerase encoded by herpes simplex virus type 1.

The effect that the UL42 protein of herpes simplex virus type 1 has on the DNA polymerase activity of the DNA polymerase catalytic subunit (Pol) of the same virus has been investigated. The observed effects are critically dependent on the salt used and its concentration, such that the UL42 protein may inhibit, have little or no effect on, or activate the Pol activity, depending on the condition used. The observed effects are due to the values for Km(app) for activated DNA and Vmaxapp for Pol and the Pol-UL42 protein complex differently varying with salt concentration.

Design and synthesis of pyrrolidine-5,5-trans-lactams (5-oxo-hexahydro-pyrrolo[3,2-b]pyrroles) as novel mechanism-based inhibitors of human cytomegalovirus protease. 1. The alpha-methyl-trans-lactam template.

Mechanism-based inhibitors of human cytomegalovirus (HCMV) protease have been designed based on the pyrrolidine-5,5-trans-lactam ring system. New routes to the beta-methyl-, desmethyl-, and alpha-methyl-pyrrolidine-5,5-trans-lactam templates have been developed from 2,4-diaminobutyric acid. ESI/MS studies have shown that these inhibitors can bind covalently and reversibly to the viral enzyme in a time-dependent manner by a mechanism which is consistent with acylation of HCMV deltaAla protease at the active site nucleophile Ser 132. SAR in this series of pyrrolidine-5, 5-trans-lactams has defined the relative stereochemisty of the methyl substituent adjacent to the lactam carbonyl, the functionality on the lactam nitrogen, and the mechanism of action of this novel series of serine protease inhibitors against the HCMV deltaAla protease. Activity decreases on moving from the alpha-methyl to the desmethyl to the beta-methyl series. This selectivity is the opposite of that observed for these templates against the elastase and thrombin enzymes. The activity against HCMV deltaAla protease is the greatest with inhibitors based on the Cbz-protected alpha-methyl-5,5-trans-lactam template which have low micromolar activity against the viral enzyme.

Investigation of the covalent modification of the catalytic triad of human cytomegalovirus protease by pseudo-reversible beta-lactam inhibitors and a peptide chloromethylketone.

An investigation into the interaction between human cytomegalovirus (HCMV) protease and several beta-lactams, with characterization of the resulting acylenzymes using mass spectrometry, is reported. The time dependence of the inhibitors is highlighted by making comparisons of values obtained for inhibition and acylation. Analysis of inactivated HCMV protease revealed a beta-lactam: protease stoichiometry of 1. Subsequent enzymatic digestion with trypsin, peptide mapping using liquid chromatography coupled with electrospray ionization mass spectrometry and sequencing by nanoelectrospray tandem mass spectrometry (NanoES-MS/MS) allowed the identification of the site of covalent modification and confirmed Ser 132 as the active site hydroxyl nucleophile. Further, treatment of the protease with a peptide chloromethylketone and sequence analysis using NanoES-MS/MS of the alkylated enzyme confirmed His 63 as the active site imidazole nucleophile.

Changes in dentate granule cell field potentials during afterdischarge initiation triggered by 5 Hz perforant path stimulation.

A failure of early paired pulse depression often precedes the onset of intermittent spontaneous seizures in animal models of status epilepticus. In the present study, changes in the strength of early and late paired pulse depression of dentate granule cell field potentials were compared in the unanesthetized rat during the initiation of a single afterdischarge (AD) evoked by perforant path stimulation (0.1 ms pulse duration, 5 Hz, 12-18 s duration, 50-1000 microA). Late paired pulse depression was measured by sequential changes in the population spike (PS) amplitude during 5 Hz stimulation (200 ms interpulse interpulse interval, IPI). When 5 Hz stimulation triggered an AD, the population spike (PS) was initially depressed and then increased to above pre-train values, indicating a loss of late paired pulse depression by the middle of the train. Early paired pulse depression was measured by inserting paired pulses (20 ms IPI) at spaced intervals throughout the 5 Hz train. In contrast to late paired pulse depression, early paired pulse depression remained at maximum strength until an abrupt failure was detected coincident with AD initiation. Two experimental treatments shown to increase the strength of late paired pulse depression, administration of the N-methyl-D-aspartate antagonist, MK-801 (0.25 mg/kg, i.p.), and the development of kindled seizures, produced an increase in AD thresholds and in the initial depression in the PS amplitude during 5 Hz stimulation. Together, these results suggest that a failure of late paired pulse depression may be a precipitating event in AD initiation triggered by 5 Hz stimulation in the unanesthetized rat.

NMDA receptor activation during epileptiform responses in the dentate gyrus of epileptic patients.

We previously showed that a low frequency (1 Hz) train of perforant path stimulation evokes burst discharges in the dentate gyrus of hippocampal slices obtained from patients surgically treated for intractable temporal lobe epilepsy. We report here that multiple population spikes that characterize the burst discharge are blocked reversibly by the specific NMDA receptor antagonist, D-(-)-2-amino-5-phosphonovaleric acid (D-APV). The epileptiform discharge evoked in human dentate gyrus by stimulation trains of 1 Hz could be reproduced in the rat dentate gyrus in vitro by the same stimulation protocol but required the presence of low concentrations (0.2-0.6 mM) of extracellular magnesium. We suggest that low frequency orthodromic stimulation of dentate granule cells through the perforant path progressively evokes an increase in the activation of NMDA receptors resulting in burst discharges in tissue from epileptic patients.

The Health of the Nation target on syringe sharing: a role for routine surveillance in assessing progress and targeting interventions.

The Health of the Nation initiative in the United Kingdom includes a target aimed at reducing the proportion of current injecting drug users who share syringes. The PHLS Collaborative Survey of Salivary Antibodies to HIV and Hepatitis B core in injecting drug users is a comprehensive and national surveillance mechanism which routinely collects data that can be used to monitor progress toward this target. Nineteen per cent of injecting drug users (353/1876) in 1992 and 18% (375/2138) in 1993 shared previously used injecting equipment (difference of -1.3%, 95% Cl -3.7%, 1.1%). Only with further years of data collection will it be possible to tell if this decline represents a real change in behaviour. There was a substantial reduction in the proportion of sharers who received previously used needles and syringes from more than one person, from 45% (138/305) in 1992 to 27% (81/298) in 1993 (fall of 18%, 95% Cl 11%, 26%). This decline could indicate a real reduction in risk behaviour that is not reflected in the target. Monitoring this aspect of sharing could be an important supplementary measure. Women were more likely to have share (adjusted OR = 1.87, 95% Cl 1.53, 2.28) and the likelihood of sharing declined with age (adjusted OR of each 5-year age band = 0.75, 95% Cl 0.72, 0.79). Particular attention should be given to interventions which aim to reduce sharing among women and young people. Clients of agencies at which the main service provided was syringe exchange were less likely to have shared than attenders of other types of agencies (adjusted OR = 0.69, 95% Cl 0.51, 0.93). This suggests that syringe exchange schemes play a role in reducing the transmission of HIV infection.

Female control of sexuality: illusion or reality? Use of vaginal products in south west Uganda.

This paper reports on a trial of vaginal products that were distributed and used by 131 women and 21 men in south west Uganda. It focuses specifically upon the issue of female control in heterosexual relationships and examines whether methods which are ostensibly under women's control, will in practice give women greater control of their sexual health. Participants were invited to select two from a range of vaginal products that included the female condom, contraceptive sponge, film, tablets, foam and gel, and use each for five weeks and their favourite product for a further three months. They were interviewed up to seven times over a five-month period. Although the women perceived that a major advantage of the products (with the exception of the female condom) was that they could be used secretly, less than 40% were using the products without their partner's knowledge after one week and this proportion declined over time with only 22% using the products secretly after ten weeks. In the main male partners were told as women felt it their duty to inform them. In general the women were very much more positive about the products than they were about the male condom, as were the men. A contributory factor to their popularity among women was the greater control they gave them. Even though, use of these products in practice often involved negotiation with male partners, the fact that use was contingent on women's action was empowering and increased somewhat their ability to control their sexual health.