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Biomedical subjects

S Cliffe

Publications and source records attributed to S Cliffe.

17 recordsLinked to original sources
PubMed2006

Symptomatic toxoplasma infection due to congenital and postnatally acquired infection.

AIMS: To determine the incidence and severity of symptomatic toxoplasma infection presenting during childhood due to congenital or postnatally acquired infection. METHODS: Between 2002 and 2004, newly diagnosed children (<16 years) with signs or symptoms of congenital or ocular toxoplasmosis were reported by clinicians to the British Paediatric and Ophthalmic Surveillance Units or by toxoplasma referral laboratories. Confirmed cases were estimated to have a greater than 50% probability of congenital and/or ocular toxoplasmosis, based on clinical and serological findings. RESULTS: Thirty eight children had confirmed toxoplasma infection. Twenty two (58%) were classified with congenital infection (cumulative incidence for England and Wales 1.62[corrected]/100,000 live births; 95% CI 0.85[corrected] to 2.83[corrected]), of whom 2 (9%) were stillborn, 7 (32%) live births had intracranial abnormalities and/or developmental delay (5 of whom had retinochoroiditis), and 10 (45%) had retinochoroiditis with no other abnormalities reported. A further 16 (42%) children were classified as infected after birth; all had retinochoroiditis. CONCLUSIONS: The low burden of symptomatic congenital toxoplasmosis combined with the lack of evidence of an effective treatment support current policy not to offer prenatal or neonatal screening for toxoplasma infection. Primary prevention strategies need to address acquisition of infection in childhood which accounts for half the ocular disease due to toxoplasma infection in children in the UK and Ireland.

Abortion, Spontaneous↗
PubMed2006

Estimating adult HIV prevalence in the UK in 2003: the direct method of estimation.

BACKGROUND: Estimates of the total number of prevalent HIV infections attributable to the major routes of infection make an important contribution to public health policy, as they are used for planning services. METHODS: In the UK, estimates were derived through the "direct method" which estimated the total number of diagnosed and undiagnosed HIV infections in the population. The direct method has been improved over a number of years since first used in 1994, as further data became available such as the inclusion of newly available behavioural survey data both from the National Survey of Sexual Attitudes and Lifestyles (Natsal 2000) and community surveys of men who have sex with men (MSM). These data were used to re-estimate numbers of people unaware of their infection and provided ethnic breakdowns within behavioural categories. The total population was divided into 10 mutually exclusive behavioural categories relevant to HIV risk in the UK-for example, MSM and injecting drug users. Estimates of the population size within each group were derived from Natsal 2000 and National Statistics mid-year population estimates. The total number of undiagnosed HIV infections was calculated by multiplying the undiagnosed HIV prevalence for each group, derived from the Unlinked Anonymous HIV Prevalence Monitoring Programme surveys (UAPMP), by the population size. These estimates were then added to the prevalent diagnosed HIV infections within each group derived from the national census of diagnosed HIV infections, the Survey of Prevalent HIV Infections Diagnosed (SOPHID). The estimates were then adjusted to include all adults in the UK. Because undiagnosed HIV prevalence estimates were not available for each of the behavioural categories, the UAPMP prevalence estimates were adjusted using available data to provide the best estimates for each group. RESULTS: It is estimated that 53,000 individuals are infected with HIV in the UK in 2003, of whom 27% were unaware of their infection. Of the total of 53,000, an estimated 26,000 were among heterosexually infected and 24,500 among MSM. CONCLUSION: The direct method uses an explicit framework and data from different components of the HIV surveillance system to estimate HIV prevalence in the UK, allowing for a comprehensive picture of the epidemic.

Adolescent↗
PubMed2004

Interpreting neonatal HIV seroprevalence data in Great Britain: the importance of differential fertility.

In order to derive more accurate estimates of HIV infection among the general population in Great Britain from unlinked anonymous neonatal seroprevalence data, the differential HIV and fertility patterns amongst groups of women were explored. The HIV risk in women was estimated using neonatal seroprevalence data and reports of diagnoses of HIV infection in pregnant women. Live birth rates were estimated using population data and these were supplemented using data from a prospective European cohort of HIV-infected pregnant women. HIV prevalence was higher in women born in sub-Saharan Africa (SSA) and injecting drug users (IDUs) (2.50% and 0.29% respectively in London) compared to other women (0.068%). Fertility was also higher in women born in SSA (OR 1.33 using population data), whilst IDUs were more likely to have had a previous termination (OR 1.48 using the European cohort of HIV-infected pregnant women data). We conclude that when unlinked anonymous neonatal seroprevalence data is used to estimate general population prevalence, adjustments need to be made for fertility differentials in population subgroups at varying risk of HIV.

Africa South of the Sahara↗
PubMed2001

National surveillance of HIV-1 subtypes for England and Wales: design, methods, and initial findings.

The HIV-1 infections detected in an ongoing national unlinked anonymous HIV surveillance program were subtyped and analyzed according to demographic and risk characteristics. Of the 893 anti--HIV-1--positive specimens allocated to an exposure group, 70% could be subtyped. Almost 25% of infections subtyped were non-B, mostly subtypes A, C, and D. Non-B infections were rare in homosexual and bisexual men and in drug injectors. Forty percent of infections in heterosexual men attending genitourinary medicine clinics were non-B subtypes; of these, 25% were subtype A infections and 59% were subtype C infections. For female clinic attendees, 61% were non-B subtype infections, of which 48% were subtype A infections and 42% were subtype C infections. Of the clinic attendees born in the United Kingdom and Europe, 14% of the men and 35% of the women were infected with non-B subtypes. In contrast, 78% of infections in antenatal patients were non-B subtypes, of which 61% were subtype A and 29% were subtype C. Extrapolation to the estimated 29,700 prevalent adult infections in the United Kingdom indicates that approximately 8,100 (27%) such infections are non-B subtypes and that these are found almost entirely in heterosexuals. The findings suggest spread of infection of non-B subtypes to heterosexuals born in the United Kingdom from individuals infected in regions of high prevalence.

Acute Disease↗
PubMed2000

The prevalence and genetic diversity of hepatitis C infection in antenatal clinic attenders in two regions of England.

The prevalence and genetic diversity of hepatitis C infection in women attending antenatal clinics in two regions of England was investigated to inform future surveillance and control measures. Women booking into antenatal care are routinely offered a test for immunity to rubella. Serum residues from these tests were unlinked, anonymized and archived as part of the Unlinked Anonymous Prevalence Monitoring Programme (UAPMP). The serum specimens were tested for anti-HCV using a cost-effective pooling strategy. After taking into account differential sampling from the UAPMP serum archive, the adjusted overall prevalence of anti-HCV was 0.43% (95% CI: 0.32-0.53) in London and 0.21% (95% CI: 0.14-0.28) in the Northern and Yorkshire region. Restriction fragment length polymorphism of amplified HCV RNA identified type 3a as the most common HCV genotype in these antenatal women. The prevalence of anti-HCV in antenatal women in the UK is low and consistent with that expected from injecting drug use.

Adolescent↗
PubMed1998

The relationship of HIV prevalence in pregnant women to that in women of reproductive age: a validated method for adjustment.

OBJECTIVE: To devise and validate a method for adjusting HIV seroprevalences in pregnant women to estimate population prevalences among all women in their child-bearing years. DESIGN: Birth and termination rates from women with known HIV infection in the United Kingdom were calculated according to the likely route of HIV infection and whether HIV infection was diagnosed. METHODS: Birth and termination rates were weighted and combined to produce summary statistics. Comparisons were then made with population birth and termination rates to derive summary relative inclusion ratios (RIRs), the relative probabilities of including HIV-infected and uninfected women in seroprevalence surveys of pregnant women. RESULTS: The derived RIRs for women having live births were close to unity: 1.03 [95% confidence intervals (CI) 0.90-1.17] for London and 0.80 (Cl, 0.71-0.89) for elsewhere in England and Wales. This indicates that currently observed overall seroprevalences among pregnant women having live births in London would be similar to those among all women of the same age, while elsewhere it would be slightly underestimated. Sensitivity analysis indicated that RIRs could, however, vary three-fold (0.47-1.56) according to the proportion of diagnosed maternal infections and the mix of maternal HIV-exposure categories. The method was validated by using it to predict the ratio of unlinked seroprevalences between women having terminations and live births in London. It predicted a ratio of 1.74: 1, which is close to the observed ratio of 2.07 : 1. CONCLUSIONS: Application of HIV seroprevalences from pregnant women to whole populations may need adjustment for fertility rates among HIV-infected women. A general method for this has been derived and validated. Gathering fertility data for HIV-infected women is a useful adjunct to serosurveillance.

Birth Rate↗
PubMed1998

Epidemiology and detection of HIV-1 among pregnant women in the United Kingdom: results from national surveillance 1988-96.

OBJECTIVE: To describe the epidemiology of HIV-1 infection in pregnant women in the United Kingdom. DESIGN: Serial unlinked serosurveillance for HIV-1 in neonatal specimens and surveillance through registers of diagnosed maternal and paediatric infections from reporting by obstetricians, paediatricians, and microbiologists. SETTING: United Kingdom, 1988-96. SUBJECTS: Pregnant women proceeding to live births and their children. MAIN OUTCOME MEASURES: Time trends in prevalence of HIV-1 seropositivity in newborn infants (as a proxy for infection in mothers); the proportions of mothers with diagnosed HIV-1 infections, and their characteristics. RESULTS: HIV-1 prevalence among mothers in London rose sixfold between 1988 and 1996 (0.19% of women tested; 1 in 520 in 1996). Apart from in Edinburgh and Dundee, levels remained low in Scotland (0.025%; 1 in 3970) and elsewhere in the United Kingdom (0.016%; 1 in 1930). Over a third of births to infected mothers in 1996 occurred outside London. In London the reported infections were predominantly among black African women, whereas in Scotland most were associated with drug injecting. The contribution of reported infection among African women increased over time as that of drug injecting declined. In Scotland 51% of mothers' infections were diagnosed before the birth. In England, despite a national policy initiative in 1992 to increase the antenatal detection rate of HIV, no improvement in detection was observed, and in 1996 only 15% of previously unrecognised HIV infections were diagnosed during pregnancy. CONCLUSIONS: HIV-1 infection affects mothers throughout the United Kingdom but is most common in London. Levels of diagnosis in pregnant women have not improved. Surveillance data can monitor effectively the impact of initiatives to reduce preventable HIV-1 infections in children.

Female↗
PubMed1994

Exploiting tumor hypoxia through bioreductive release of diffusible cytotoxins: the cobalt(III)-nitrogen mustard complex SN 24771.

PURPOSE: To assess the oxygen dependence of a novel cobalt-nitrogen mustard complex, SN 24771, designed to release a diffusible cytotoxic metabolite in hypoxic tumor microenvironments. METHODS AND MATERIALS: Oxygen dependence of cell killing was assessing in well-stirred single cell suspensions obtained by enzymatic dissociation of EMT6 spheroids, using a sensitive oxygen electrode to measure oxygen concentrations in solution. Cell killing in intact EMT6 spheroids was also compared with that in single cell suspensions. RESULTS: Cytotoxicity of SN 24771 in single cell suspensions was inhibited by very low concentrations of oxygen. The C50 value (O2 required for 50% inhibition of log cell kill) was ca. 0.02% O2 at 1 h, and the K value (O2 required to give a cytotoxic potency equal to the average of that at zero and infinite O2) was of a similar order. However, intact spheroids were much more sensitive to SN 24771 than could be accounted for by the K curve for single cell suspensions, this estimate being based on published data for the oxygen concentration profile in these spheroids. CONCLUSION: The cytotoxicity of SN 24771 is inhibited appreciably at oxygen concentrations which are too low to provide radiosensitization. In this respect, SN 24771 resembles organic bioreductive drugs such as quinones and nitroaromatic compounds. However, the extensive killing observed in multicellular spheroids is consistent with release of a diffusible nitrogen mustard on reduction. Bioreductive drugs with a low K value for activation, but which release a diffusible cytotoxin, may have desirable properties as tumor radiosensitizers.

Antineoplastic Agents↗
PubMed1994

Combining bioreductive drugs (SR 4233 or SN 23862) with the vasoactive agents flavone acetic acid or 5,6-dimethylxanthenone acetic acid.

PURPOSE: To determine whether 5,6-dimethylxanthenone acetic acid (DMXAA), a potent analogue of flavone acetic acid (FAA) inhibits blood flow in mouse mammary tumors, and to assess whether DMXAA enhances the antitumor effects of Tirapazamine (SR 4233) and the novel bioreductive drug SN 23862 (a dinitrobenbenzene mustard). METHODS AND MATERIALS: MDAH-MCa-4 mouse mammary tumors were grown i.m. in the leg of C3H/HeN mice. Tumor blood flow was assessed by the pertechnetate clearance method and subsequent growth delay was determined in the same tumors. RESULTS: Administration of DMXAA (65-70 mumol/kg) resulted in inhibition of tumor blood flow to approximately 25% of control values, with no recovery observed up to 36 h post-treatment. Combination of DMXAA with SR 4233 provided a significant increase in tumor growth inhibition relative to either drug alone. In this effect, DMXAA was qualitatively similar to FAA, but was approximately 10 x more potent. The interaction between DMXAA (65 mumol/kg) and SR 4233 (200 mumol/kg) was maximal with SR 4233 given between 15 min before and 60 min after DMXAA. For SN 23862, a similar enhanced growth delay was observed in combination with DMXAA, with no obvious time dependence between 15 min before and 4 h after DMXAA. When mean values for groups treated with SR 4233 (200 mumole/kg) alone and in combination with DMXAA (65-90 mumole/kg) were compared, a correlation was observed between tumor blood flow inhibition and subsequent growth delay. CONCLUSION: DMXAA is a potent inhibitor of blood flow in MDAH-MCa-4 tumors. Combination of this vasoactive drug with bioreductive agents leads to an enhanced antitumor effect. For SR 4233 and DMXAA, this enhanced effect may be predictable by measurement of tumor blood flow inhibition shortly after drug administration.

Aniline Mustard↗
PubMed1992

Hypoxia-selective antitumor agents. 5. Synthesis of water-soluble nitroaniline mustards with selective cytotoxicity for hypoxic mammalian cells.

Nitroaniline mustards have potential as hypoxia-selective cytotoxic agents, with reductive metabolism activating the nitrogen mustard by converting the electron-withdrawing nitro group to an electron-donating hydroxylamine or amine. However, the parent compounds have poor aqueous solubility, and their potencies are limited by low reduction potentials (E1/2 ca. -600 mV versus the normal hydrogen electrode) and corresponding slow rates of nitro reduction. To address these limitations, a series of 4-nitroaniline mustards bearing hydrophilic side chains attached via an electron-withdrawing carboxamide group was prepared and evaluated for hypoxia-selective cytotoxicity against Chinese hamster cell lines. The N-[(N,N-dimethylamino)ethyl]carboxamide derivatives proved to have excellent aqueous solubility and improved cytotoxic potency, but their reduction potentials, while higher than the non-carboxamide compounds, were still low and little selectivity for hypoxic cells were observed. A series of carboxamides of 2,4-dinitroaniline mustard was also prepared. These compounds had reduction potentials in the desired range (E1/2 ca. -450 mV by cyclic voltammetry) and were more toxic to hypoxic than aerobic UV4 cells. The most selective compounds were 5-[N,N-bis(2-chloroethyl)amino]-2,4-dinitrobenzamide (20, SN 23862) and its water-soluble N-[(N,N-dimethylamino)ethyl]carboxamide analogue. These showed selectivities of 60- to 70-fold for hypoxic UV4 cells. The selectivity of 20 was much superior to that of its aziridine analogue (23, CB 1954), which was only 3.6-fold more toxic to hypoxic than oxic cells in the same system. Compound 20 is a much less efficient substrate than CB 1954 for the major aerobic nitroreductase from rat Walker tumor cells, NAD(P)H:quinone oxidoreductase (DT diaphorase). Lack of aerobic bioactivation of 20 by DT diaphorases may be responsible for its higher hypoxic selectivity than that of 23.

Aniline Compounds↗
PubMed1991

The characterisation of immobilised lignin peroxidase by flow injection analysis.

Immobilised lignin peroxidase has been investigated using a flow system in the steady state and by flow injection analysis (FIA). In the steady state, the extreme sensitivity of the enzyme towards inactivation by H2O2 resulted in a stable response only in the presence of saturating levels of organic substrate and at very low (10 microM) peroxide concentrations. By contrast, the low contact time during FIA led to a stable response to injections of 100 microM H2O2. At higher peroxide concentrations a reproducible inactivation was observed, allowing a study of factors affecting both activity and stability. Lignin peroxidase substrates that undergo at least semi-reversible oxidation/reduction, including high-molecular-weight lignin fractions, could be detected by electrochemical reduction of the oxidation products. With this detection system it was possible to demonstrate the role of veratryl alcohol as mediator. This mediated oxidation of lignin functioned only when all components were present simultaneously, and was not observed when lignin was separated from the site of veratryl alcohol oxidation.

Acetonitriles↗
PubMedDate not supplied

Surveillance for the impact in the UK of HIV epidemics in South Asia.

OBJECTIVES: To determine whether, because of the extensive recent spread of HIV infection in South Asia, South Asians (those people who classify themselves as Indian, Pakistani, Bangladeshi or Sri Lankan in origin) resident in the UK were at increased risk of HIV infection and to review current surveillance systems for detecting any such increase. DESIGN: Analysis of: ethnic grouping and probable country of infection recorded on voluntary confidential reports of AIDS cases and newly diagnosed HIV infections; blood donation testing data; reports of imported gonorrhoea infections; country of birth data from the unlinked anonymous (UA) survey of Sexually Transmitted Disease (STD) clinic attenders; district of residence data from the UA survey of pregnant women; ethnic grouping of prevalent diagnosed HIV infections. RESULTS: Few reported AIDS cases or HIV infections were found in people of South Asian ethnic origin and few reported HIV or gonorrhoea infections were associated with exposure in South Asia. Data derived from the UA programme suggested as yet no increase in HIV prevalence in either STD clinic attenders born in South Asia or in pregnant women resident in districts containing substantial numbers of ethnic South Asians. CONCLUSIONS: There was no evidence that South Asians resident in the UK are currently at greater risk of HIV infection than people of white ethnicity or, therefore, that south Asian heterosexuals are a group deserving priority in HIV prevention. However, as rapid spread of HIV infection is being recorded in the Indian subcontinent, continuous monitoring is necessary. This will be facilitated by improved collection of ethnic group information in all surveillance activities.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Quantitative analysis of the lobular distribution of S-phase in rat liver following dietary administration of di(2-ethylhexyl)phthalate.

A simple image-analysis method is described, whereby the distribution of hepatocytes that have entered S-phase, as distinguished by the incorporation of bromodeoxyuridine, can be related to the position of the central and portal veins of the hepatic lobule. Hepatocyte S-phase was induced in the livers of male and female F344 rats by administration of di(2-ethylhexyl)phthalate (DEHP) in the diet for 7 days at 2 dose levels, and these livers were used to develop the procedure. The distributions of the S-phase between control and DEHP-treated livers were compared using statistical techniques. The results showed notable differences in the distribution of S-phase between male and female rats as well as limited dose-related effects.

Animals↗
PubMedDate not supplied

Markov chain Monte Carlo estimation of a multiparameter decision model: consistency of evidence and the accurate assessment of uncertainty.

Decision models are usually populated 1 parameter at a time, with 1 item of information informing each parameter. Often, however, data may not be available on the parameters themselves but on several functions of parameters, and there may be more items of information than there are parameters to be estimated. The authors show how in these circumstances all the model parameters can be estimated simultaneously using Bayesian Markov chain Monte Carlo methods. Consistency of the information and/or the adequacy of the model can also be assessed within this framework. Statistical evidence synthesis using all available data should result in more precise estimates of parameters and functions of parameters, and is compatible with the emphasis currently placed on systematic use of evidence. To illustrate this, WinBUGS software is used to estimate a simple 9-parameter model of the epidemiology of HIV in women attending prenatal clinics, using information on 12 functions of parameters, and to thereby compute the expected net benefit of 2 alternative prenatal testing strategies, universal testing and targeted testing of high-risk groups. The authors demonstrate improved precision of estimates, and lower estimates of the expected value of perfect information, resulting from the use of all available data.

AIDS Serodiagnosis↗
PubMedDate not supplied

Can this merger be saved?

In this fictional case study, a merger that looked like a marriage made in heaven to those at corporate headquarters is feeling like an infernal union to those on the ground. The merger is between Synergon Capital, a U.S. financial-services behemoth, and Beauchamp, Becker & Company, a venerable British financial-services company with strong profits and an extraordinarily loyal client base of wealthy individuals. Beauchamp also boasts a strong group of senior managers led by Julian Mansfield, a highly cultured and beloved patriarch who personifies all that's good about the company. Synergon isn't accustomed to acquiring such companies. It usually encircles a poorly managed turnaround candidate and then, once the deal is done, drops a neutron bomb on it, leaving file cabinets and contracts but no people. Before acquiring Beauchamp, Synergon's macho men offered loud assurances that they would leave the tradition-bound company alone-provided, of course, that Beauchamp met the ambitious target numbers and showed sufficient enthusiasm for cross-selling Synergon's products to its wealthy clients. In charge of making the acquisition work is Nick Cunningham, one of Synergon's more thoughtful executives. Nick, who was against the deal from the start, is the face and voice of Synergon for Julian Mansfield. And Mansfield, in his restrained way, is angry at the constant flow of bureaucratic forms, at the rude demands for instant information, at the peremptory changes. He's even dropping broad hints at retirement. Nick has already been warned: if Mansfield goes, you go. Six commentators advise Nick on how to save his job by bringing peace and prosperity to the feuding couple.

Administrative Personnel↗