Biomedical subjects
Publications and source records attributed to J Todd.
This case report is only the third report of thyroid dysfunction following the administration of anti-lymphocyte globulin for severe aplastic anaemia. It is the first report of the development of Grave's disease. We discuss a possible mechanism by which this may occur and highlight instances of other immune-mediated diseases occurring in ALG treated patients.
An Arabidopsis fatty acid elongase gene, KCS1, with a high degree of sequence identity to FAE1, encodes a 3-ketoacyl-CoA synthase which is involved in very long chain fatty acid synthesis in vegetative tissues, and which also plays a role in wax biosynthesis. Sequence analysis of KCS1 predicted that this synthase was anchored to a membrane by two adjacent N-terminal, membrane-spanning domains. Analysis of a T-DNA tagged kcs1-1 mutant demonstrated the involvement of the KCS1 in wax biosynthesis. Phenotypic changes in the kcs1-1 mutant included thinner stems and less resistance to low humidity stress at a young age. Complete loss of KCS1 expression resulted in decreases of up to 80% in the levels of C26 to C30 wax alcohols and aldehydes, but much smaller effects were observed on the major wax components, i.e. the C29 alkanes and C29 ketones on leaves, stems and siliques. In no case did the loss of KCS1 expression result in complete loss of any individual wax component or significantly decrease the total wax load. This indicated that there was redundancy in the elongase KCS activities involved in wax synthesis. Furthermore, since alcohol, aldehyde, alkane and ketone levels were affected to varying degrees, involvement of the KCS1 synthase in both the decarbonylation and acyl-reduction wax synthesis pathways was demonstrated.
A serosurvey was conducted in a random sample of 259 women and 231 men in 12 rural communities in Mwanza Region, Tanzania, using a type-specific ELISA for Herpes simplex virus type 2 (HSV-2) infection. Seroprevalence rose steeply with age to approximately 75% in women >=25 years old and 60% in men >=30. After adjusting for age and residence, HSV-2 prevalence was higher in women who were married, in a polygamous marriage, Treponema pallidum hemagglutination assay (TPHA)-positive, had more lifetime sex partners, or who had not traveled. Prevalence was higher in men who were married, had lived elsewhere, had more lifetime partners, had used condoms, or were TPHA-positive. HSV-2 infection was significantly associated with recent history of genital ulcer. The association between HSV-2 infection and lifetime sex partners was strongest in those <25 years old in both sexes. This association supports the use of HSV-2 serology as a marker of risk behavior in this population, particularly among young people.
Infection with the human immunodeficiency virus (HIV) leads to a progressive immunodeficiency characterized by decreasing levels of CD4+ T lymphocytes. VaxSyn, a vaccine based on the recombinant envelope glycoprotein subunit (rgp160) of HIV-1IIIB, was used to immunize HIV-infected patients to determine whether its administration was beneficial with respect to slowing disease progression. A 3-year multicenter, randomized, placebo-controlled, double-blinded, efficacy and safety trial of repeated immunization with VaxSyn was used to evaluate the long-term impact on the progression of immunodeficiency. VaxSyn in alum, or alum alone, was given to 278 HIV-infected asymptomatic individuals with initial CD4 counts of > or =500 cells/mm3. Clinical findings, the CD4 count, and both virological and immunological parameters were followed. No significant differences were observed between the treatment and placebo control groups in rate of CD4 T cell decline, time to initiation of antiretroviral therapy, incidence of opportunistic infections, HIV RNA plasma viremia, HIV viral infectivity as measured by quantitative HIV coculture assay, and death. This study revealed no effect on either clinical or laboratory virological parameters from the administration of VaxSyn.
A cross-sectional questionnaire survey was conducted among 892 randomly selected pupils, aged 12 and above, attending 18 primary schools (PS) and five secondary schools (SS) in four communities of Mwanza Region in Tanzania. The goals were to assess the level of knowledge adolescents have about sexual and reproductive health (SRH), to assess the magnitude of SRH problems and to help design appropriate interventions. Median age of respondents was 15 years (range 12-20 years) and 14 years (range 12-19 years) for PS boys and girls, respectively, and 19 years (range 16-24 years) and 17 years (range 14-19 years) for SS boys and girls. Eighty per cent of PS boys and 68% of PS girls were already sexually active; the corresponding figures were 89% for SS boys and 48% for SS girls. Vaginal sex was the most common first sexual act reported by SS pupils, but 40% of PS pupils reported orogenital sex and 9% of PS pupils reported anal sex as their first sexual act. Almost half of PS girls have had sex with adults, including teachers and relatives. 'Forced sex' was reported by nearly half of PS and SS girls. Fourteen per cent of PS girls had already been pregnant, and over half of these pregnancies ended in illegally induced abortions. Despite a rather high (30%) lifetime rate of condom use, 33% and 25% of PS boys and girls, respectively, reported past experience of sexually transmitted diseases (STDs). STD rates were lower among SS pupils who had a better knowledge of STDs/HIV and fertility issues and reported higher condom use. The survey demonstrated the great vulnerability of school-going adolescents of Mwanza Region to consequences of sexual intercourse. The response should urgently come in the from of comprehensive adolescent SRH programmes.
Use of a common set of human immunodeficiency virus type 1 (HIV-1) RNA standards eliminated differences among absolute HIV-1 RNA copy number estimates made with three commercially available assays. The relative changes in the viral RNA levels determined by the commercial assays were similar and were unaffected by the use of a common set of standards.
OBJECTIVES: (i) To determine the microbial aetiologies of vaginal discharge in STD clinic and antenatal clinic (ANC) attenders; (ii) to evaluate the performance and costs of a new WHO algorithm for the detection of gonococcal and chlamydial infections in women complaining of vaginal discharge and/or genital itching, using a risk assessment. METHODS: Two groups were enrolled: (i) 395 consecutive female patients attending a hospital outpatient clinic complaining of genital discharge or itching; and (ii) 628 consecutive pregnant women reporting at an urban ANC these symptoms. Patients were interviewed by a nurse, who applied the WHO risk score. They were then referred to the study room for interview concerning the same and other risk factors, examined, and sampled for Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), Trichomonas vaginalis (TV), and Candida albicans (CA). Sensitivity, specificity, positive predictive value, overtreatment and correct treatment rates, and cost of drugs per true case treated were estimated. RESULTS: The prevalence of NG and/or CT infections was 11.4% and 8% at the STD clinic and the ANC respectively. The most prevalent pathogens were CA (38% at both clinics) and TV (25% at the STD clinic and 34% at the ANC). The sensitivity of the WHO algorithm for NG and/or CT was 62% at the STD clinic and 46% at the ANC, and the specificities were 64% and 84% respectively. The operational feasibility of the method was good. The cost of drugs per true case treated in applying the risk assessment approach was $3.5 among nonpregnant women and $5.0 among pregnant women. This compared favourably with respective costs of $8.8 and $25.0 in applying the syndromic management alone. CONCLUSIONS: The WHO risk assessment algorithm for the diagnosis of NG and/or CT infections among women complaining of genital discharge can considerably reduce overtreatment of NG and/or CT in both pregnant and non-pregnant women, but in this study it failed to identify 38% of non-pregnant and 54% of pregnant women with these infections. The elements of the risk score may need adjustment in different settings.
BACKGROUND: Detection and management of gonococcal and/or chlamydial infections in women is a challenge, particularly in developing countries where laboratory tests are not always available. The World Health Organisation (WHO) has developed a risk assessment approach to identify cervical infections among women complaining of vaginal discharge. We have evaluated this approach as a screening strategy among women attending an urban antenatal clinic (ANC) in Tanzania. OBJECTIVES: (i) To measure the prevalence of pathogens associated with sexually transmitted diseases (STD) and reproductive tract infections (RTI) in an urban population of ANC attenders in Tanzania; (ii) to examine characteristics of pregnant women associated with cervical infections; and (iii) to evaluate the performance of a WHO risk assessment algorithm and alternative risk scores for the detection of cervical infections in pregnant women. METHODS: A systematic sample of 660 pregnant women reporting for routine antenatal care at an urban clinic was enrolled. Women were interviewed by a nurse, who applied the WHO risk score. They were referred to a study room for interview about sociodemographic and behavioural factors, examination, and sampling for Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, Candida albicans, and bacterial vaginosis. Sensitivity, specificity, positive predictive value (PPV), and theoretical cost per true case treated were estimated for the diagnosis of cervical infection with N gonorrhoeae and/or C trachomatis for the WHO and other risk scores. RESULTS: The prevalence of any vaginal or cervical infection was 68%. Prevalence rates of various pathogens were: C albicans 39%, T vaginalis 16%, bacterial vaginosis 24%, N gonorrhoeae 2.3%, C trachomatis 5.9%, any cervical infection (N gonorrhoeae and/or C trachomatis) 7.4%. The WHO score identified only five of 49 women with N gonorrhoeae and/or C trachomatis (sensitivity 10.2%). The specificity and the PPV were 92% and 9.8% respectively. The theoretical cost per true case treated on the basis of the WHO score was over $18. Several risk factors were associated with cervical infection on univariate analysis, but only six remained significant at the 10% level after multivariate analysis. These were: never use of contraceptives (OR 3.09), more than one partner in the past 3 months (OR 3.32), partner with symptoms of genital discharge syndrome (GDS) (OR 7.55), frothy vaginal discharge (OR 1.88), 5-19 polymorphonucleocytes per high power field on cervical smear (OR 3.28), or more than 20 polymorphonucleocytes per high power field (OR 16.08), and wet preparation showing evidence of T vaginalis infection (OR 1.96). Scores based on these variables failed to attain high sensitivities or PPVs (all below 40%) although the costs per true case treated were cheaper than for the WHO score. CONCLUSION: Risk assessment for the screening and management of N gonorrhoeae and/or C trachomatis among women presenting at routine antenatal services appears feasible and acceptable, but of limited value in this population because of its low sensitivity. The optimal risk score may vary considerably from one place to another. The quest for simple, cheap, and reliable tests to diagnose N gonorrhoeae and C trachomatis infections still remains a high priority on the international STD technology research agenda.
Peripherally inserted central catheters (PICCs) can meet the needs of patients requiring short- to intermediate-term intravenous therapy in a variety of settings. PICCs minimise insertion and catheter-related complications when compared to other central venous access devices (CVADs). PICCs have been introduced in the UK mainly through innovative advanced nursing practice.
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The HIV epidemic in sub-Saharan Africa has been characterised by the predominance of heterosexual transmission. Patterns of sexual behaviour have been implicated in the spread of the epidemic, but few quantitative data are available on sexual behaviour in rural populations in Africa. This paper reports data from a survey of 1117 adults aged 15-54 years selected randomly from twelve rural communities in Mwanza Region, Tanzania. Sexual debut occurred early, 50% of women and 46% of men reporting first sex before age 16. On average, women married 1.8 years and men 6.1 years after their sexual debut. In women, age at sexual debut appears to have increased over time, in parallel with an increase in age at first marriage. Men were generally married later, to women around five to ten years younger than themselves. Marital dissolution and remarriage were common in both sexes. Reported numbers of sexual partners were compared with those recorded in a population survey in Britain. More men reported 10 or more lifetime partners, or three or more partners in the past year, in rural Mwanza (48% and 29%) than in Britain (24% and 6%). Women reported fewer partners, and results were broadly similar to British data. Casual sex during the past year was reported by 53% of the men and 15% of the women, but only 2% of men reported sexual contact with bar girls or commercial sex workers. Only 20% of men and 3% of women had ever used a condom. Interventions are needed to reduce the high levels of sexual partner change and casual sex, and low levels of condom use, recorded in this rural population. Targeting of interventions to traditional "core groups" may be of limited value in rural areas, and additional strategies are needed, focusing particularly on teenagers who are at high risk of HIV and other sexually transmitted diseases.
The impact of long-term changes in plasma viremia, produced by effective combination antiretroviral therapy, on human immunodeficiency virus (HIV) burden within tissue reservoirs is unknown. Fifteen patients who had received at least 1 year of therapy with two or three drug combinations of zidovudine, didanosine, and nevirapine had suitable samples of lymph node tissue obtained by ultrasound-guided core needle biopsy. HIV RNA was extracted from homogenized tissue samples and quantitated using a modified branched DNA assay. Results were correlated with antiretroviral treatment effect on the basis of plasma virus load measurements over the preceding 12-18 months. A statistically significant negative correlation was observed between magnitude of treatment effect on plasma viremia and lymph node virus load. These data suggest that combinations of antiretroviral drugs that produce sustained suppression of plasma HIV RNA may also be able to reduce the virus burden in lymphoid tissues.
Many indicators of socioeconomic status used for adults are inappropriate for use in research on adolescents. In a school-based survey of 4079 Scottish schoolchildren using a self-completion questionnaire, over 20% of 11-15 year olds were unable to provide a substantive response on father's occupation. In contrast, indicators derived to construct a family affluence scale, which included car ownership, telephone ownership and the child having their own unshared bedroom, resulted in a 98% response rate; and 92% of children responded to a question on their weekly spending money. The intercorrelations between the conventional indicator of father's occupation and each family affluence and spending money were examined, and their associations with a range of health indicators and health behaviour measures compared. Father's occupational status and family affluence were moderately correlated and showed broadly similar patterns of association with the selected health measures although there were also some distinct differences. Child's spending money was only weakly correlated with father's occupation and showed rather different patterns of association with health measures. A case is made for the use of multiple indicators of socioeconomic status in adolescent health surveys, and it is argued that that the family affluence scale provides a useful and easily applied additional indicator to father's occupation or an alternative measure of socioeconomic background where occupational data are unavailable.
Type 1 diabetes is a common polygenic disease. Fine mapping of polygenes by affected sibpair linkage analysis is not practical and allelic association or linkage disequilibrium mapping will have to be employed to attempt to detect founder chromosomes. Given prior evidence of linkage of the Jk-D18S64 region of chromosome 18q12-q21 to type 1 diabetes, we evaluated the 12 informative microsatellite markers in the region for linkage with disease by the transmission disequilibrium test (TDT) in a UK data set of type 1 diabetic families (n = 195). Increased transmission of allele 4 of marker D18S487 to affected children was detected (P = 0.02). Support for this was extended in a total of 1067 families from four different countries by isolating, and evaluating by the TDT, two novel microsatellites within 70 kb of D18S487. Evidence for linkage and association was P = 5 x 10(-5) and 3 x 10(-4), respectively. There was no evidence for increased transmission of associated alleles to nonaffected siblings. Analysis of an additional 390 families by the TDT did not extend the evidence further, and reduced support in the total 1457 families to P = 0.001 for linkage and P = 0.003 for association. However, evidence for linkage by affected sibpair allele sharing was strong (P = 3.2 x 10(-5)) in the second data set. Heterogeneity in TDT results between data sets was, in part, accounted for by the presence of more than one common disease-associated haplotype (allelic heterogeneity) which confounds the analysis of individual alleles by the TDT. Guidelines for strategies for the mapping of polygenes are suggested with the emphasis on collections of large numbers of families from multiple populations that should be as genetically homogeneous as possible.
A region of linkage to type 1 diabetes has been defined on human chromosome 10p11-q11 (IDDM10; P = 0.0007) using 236 UK and 76 US affected sibpairs and a 1 cM resolution microsatellite marker map. Analysis by the transmission disequilibrium test (TDT) in 1159 families with at least one diabetic child, from the UK, the US, Norway, Sardinia and Italy provided additional support for linkage at D10S193 (P = 0.006, Pc = 0.17). Notably, 5.1 cM distal to D10S193, marker D10S588 also provided positive TDT results (P = 0.009, Pc = 0.25) but the allele under analysis was also preferentially transmitted to nonaffected siblings (P = 0.0008, Pc = 0.02). This allele was positively associated in an independent UK case control study and, importantly, was neutrally transmitted in control CEPH families. These results suggest a type 1 diabetes susceptibility locus on chromosome 10p11-q11 (provisionally designated IDDM10) and demonstrate the necessity of analysis of non affected siblings in disease families, as well as analysis of control families.
The Kidd blood group locus encodes a urea transporter which is expressed on human red cells and in the kidney. This gene is located on chromosome 18q12, and evidence for linkage and association with type 1 diabetes mellitus has been reported. To investigate this further, the genetic basis for the blood group Jk(a)/Jk(b) polymorphism was first determined by sequencing reverse-transcribed reticulocyte RNAs from Jk(a+b-) and Jk(a-b+) donors. The Jk(a)/Jk(b) polymorphism was caused by a transition (G838A), resulting in a Asp280Asn amino acid substitution and an MnlI restriction fragment length polymorphism (RFLP). Using the MnlI RFLP, we found that the Jk(a)/Jk(b) polymorphism was not in linkage disequilibrium with type 1 diabetes in 228 multiplex UK and US families tested.
BACKGROUND: Evidence from ecological studies and from studies of and sexually transmitted disease (STD) patients in sub-Saharan Africa suggests that there is a protective effect of male circumcision against HIV infection. There are, however, few population-based studies that have controlled adequately for potential confounding factors. METHODS: Data from five population-based studies in north-western Tanzania were used to investigate the association between male circumcision and the risk of HIV infection and STD. The effects of circumcision on HIV prevalence, syphilis (positive Treponema pallidum haemagglutination; TPHA) and self-reported STD were analysed, controlling for a range of demographic and sociocultural variables, and indicators of sexual behaviour. RESULTS: In north-western Tanzania, circumcision was previously restricted to Muslims and specific ethnic groups, but is now more widespread, particularly in urban areas and among more educated men. Assessment of the reliability and validity of self-reported circumcision status showed that these data could be considered fairly accurate, although there was some tendency for circumcision to be over-reported. On univariate analysis, circumcision status was unrelated to HIV prevalence in most studies. After controlling for confounding variables, however, there was a modest but significant reduction of the HIV prevalence among circumcised men [odds ratio (OR), 0.62; 95% confidence interval (CI), 0.48-0.81]. This effect appeared stronger in urban areas (OR, 0.46; 95% CI, 0.32-0.68) and roadside villages (OR, 0.65; 95% CI, 0.42-1.01) than in rural areas and islands (OR, 1.00 and 1.01 respectively). There was no association between circumcision status and syphilis serology (TPHA), but there was a positive association between circumcision and self-reported STD, although this was not significant after adjustment for confounding variables. CONCLUSION: Male circumcision has a protective effect against HIV infection in this population, which may be stronger in urban areas and roadside settlements than in the rural areas. Ethnic group and religious denomination are no longer the sole determinants of male circumcision.
OBJECTIVE: To examine the association between HIV infection and patterns of sexual behaviour and other risk factors in a rural Tanzanian population in a case-control study, nested within a randomized trial of improved sexually transmitted disease treatment. METHODS: All HIV-positive patients from the baseline survey of the randomized trial were eligible as cases. Cases (n = 338) and controls (a random sample of one in eight HIV-negative persons; n = 1078) were interviewed about risk factors for HIV infection using a structured questionnaire. RESULTS: A significantly higher HIV prevalence was found among men and women not currently employed in farming [men: odds ratio (OR), 2.08; women: OR, 3.65], women who had travelled (OR, 3.27), educated women (OR, 4.51), and widowed/ divorced people compared with those currently married (men: OR, 3.10; women: OR, 3.54). Two spouse-related factors were significantly associated with HIV, even after adjustment for the sexual behaviour of the index case: HIV was more prevalent in men with younger spouses (P = 0.020 for trend) and in women married to men currently employed in manual work, office work or business (OR, 2.20). In women only, blood transfusions were associated with a higher HIV prevalence (OR, 2.40), but only a small population attributable fraction (4%). There was an increased HIV prevalence associated with increasing numbers of injections. Reported number of lifetime sexual partners was significantly associated with HIV infection (women: OR, 7.33 if > or = 10 lifetime partners compared with < or = 1; men: OR, 4.35 for > or = 50 compared with < or = 1). After adjustment for confounders, male circumcision was associated with a lower HIV prevalence (OR, 0.65; P = 0.11). CONCLUSIONS: In these rural communities, many HIV infections occur through sexual transmission. Some people are at high risk of HIV infection through large numbers of sex partners, whereas some are at risk through their spouse or regular partner. The role of circumcision in HIV transmission is unclear. Commercial sex seems to play a negligible role in HIV transmission in these communities. Our results confirm marked heterogeneity in HIV risk, indicating the scope for risk reduction strategies.