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Biomedical subjects

S Bennett

Publications and source records attributed to S Bennett.

At least 55 records · Page 3Linked to original sources

Lack of association between maternal antibody and protection of African infants from malaria infection.

Maternally derived antibodies are believed to protect infants against infection, but there is little direct evidence for a protective role of passively acquired antibodies against malaria. A longitudinal study of malaria infection in 143 infants was conducted in a region of southern Ghana where Plasmodium falciparum is endemic. Infants born in the high-transmission season were less likely to become infected in the first 20 weeks of life than children born in the low-transmission season. Plasma, obtained at birth, was tested for immunoglobulin G (IgG) and IgG subclasses to P. falciparum schizonts and recombinant circumsporozoite antigen, MSP-1(19), MSP-2, AMA-1, and Pf155 (also called ring-infected erythrocyte surface antigen). Antibody levels at birth were not associated with resistance to malaria infection. On the contrary, antibodies at birth were positively associated with infection, indicating that high levels of maternally derived antibodies represent a marker for intensity of exposure to malaria infection in infants. However, all five children who experienced high-density infections (>100 parasites/microl of blood) were seronegative for MSP-1(19) at the time of infection.

Adolescent↗

Design and analysis issues in cluster-randomized trials of interventions against infectious diseases.

This paper discusses the application of the cluster-randomized trial (CRT) design to evaluate the effectiveness of interventions against infectious diseases. In addition to the usual rationale for this design, there are a number of other advantages that are peculiar to the study of infectious diseases. In particular, CRTs are able to measure the overall effect of an intervention at the population level, capturing both the direct effect of an intervention on an individual's susceptibility to infection, and also the indirect effects due to changes in risks of transmission to other individuals, or to the mass effect or 'herd immunity' resulting from intervening in a large proportion of the population. We briefly review published CRTs of interventions against infectious diseases, most of which have been conducted in the developing countries where such diseases predominate. The focus is on trials in which communities or other large groupings are randomized, and in which impacts on infectious disease incidence or mortality are assessed. We then discuss three issues that are of special relevance to CRTs of infectious diseases. First, issues relating to the definition and size of clusters; secondly, the role of matching or stratification, and the choice of matching factors; and thirdly, the definition of direct and indirect effects of intervention, and methods of assessing these components in a CRT. We conclude by outlining some areas for future research.

Biometry↗

Serological prevalence of herpes simplex virus type 2 amongst GUM clinic attenders in a district general hospital setting.

Our objective was to determine the seroprevalence of herpes simplex virus (HSV) type 2 infection amongst genitourinary medicine (GUM) clinic attenders at a district general hospital using a commercially available enzyme immunoassay (EIA). In a prospective study, heterosexual patients attending the Department of GUM at Trafford General Hospital attending with a new clinical problem and having a blood sample taken for routine syphilis serology had the same sample tested for HSV type 2 antibodies. The prevalence of HSV type 2 seropositivity amongst participants was 9.9% (24/242) for men and 18.7% (46/246) for women. With respect to undiagnosed, asymptomatic infection the seroprevalence was 8.6% and 17% respectively. For those attenders locally resident the seroprevalence was 10.1% and 17.5% respectively, and undiagnosed, asymptomatic infection 8.5% and 17.1% respectively. Although seroprevalence figures in this study are lower than the only previous report in the UK, these results, nevertheless, show that seropositivity is not confined to large urban centres. Patients attending GUM clinics are likely to have high rates of undiagnosed HSV type 2 infection.

Antibodies, Viral↗

Health risk in agricultural villages practicing wastewater irrigation in central Mexico: perspectives for protection.

9,435 individuals participated in a cross-sectional survey in the irrigation districts of the Mezquital Valley (central Mexico). Exposure groups were: 848 households irrigating with untreated wastewater, 544 households irrigating with the effluent from a series of interconnected reservoirs, and 928 households farming with natural rainfall. The unit of analysis was the individual, and the health outcomes included diarrhoeal diseases and Ascaris lumbricoides infection. Water quality was assessed using faecal coliforms (FC) and nematode eggs, as suggested by (WHO, 1989) for the safe use of wastewater in agriculture. Children from households irrigating with untreated wastewater (10(8) FC/100 mL and 135 nematode eggs/L) had a 33% higher risk of diarrhoeal diseases and a fivefold increase in risk of A. lumbricoides infection (OR = 5.71) compared to children from the control group, farming with rainfall. The risk of A. lumbricoides infection in older individuals was even higher (OR = 13.18). The final analysis showed that drinking unboiled water and cultivating vegetables crops were both associated with a higher risk of diarrheal diseases (OR = 1.45 and 2.00); individuals infected with A. lumbricoides infection came mostly from landless households with poorer dwellings and low standards of sanitation (OR = 2.20, 2.23, 1.72 and 1.43, respectively). These results are discussed in the context of health protection measures and policy recommendations.

Adolescent↗

Osteoporosis therapies--future leads and current clinical trials. 13-14 December 1999, London, UK.

This IBC conference focused on research areas most likely to generate novel leads for future osteoporosis therapies. There was particular emphasis placed on inhibitors of bone resorption, including progress in the development of existing compounds, such as raloxifene (Evista; Eli Lilly & Co) and the nitrogen-containing bisphosphonates, as well as insights into novel agents, such as the integrin receptors. It was also generally accepted that the next generation of osteoporosis therapies would target osteoblasts with a view to stimulating bone formation. Potential for developing such novel therapies using genomic approaches was also presented.

Journal Article↗

Newborns develop a Th1-type immune response to Mycobacterium bovis bacillus Calmette-Guérin vaccination.

Data obtained in animals indicate that neonatal immune responses are biased toward Th2. This could reduce the efficacy of vaccines against viral and mycobacterial diseases. The ability of human newborns to develop a Th1 immune response upon immunization has not been studied. Since the vaccine Mycobacterium bovis bacillus Calmette-Guérin (BCG) triggers a Th1-type response in adults, we investigated whether it induces a similar response in newborns and whether age at vaccination influences immunogenicity. We found that BCG vaccination at birth induces a memory Th1-type response of similar magnitude to that when given later in life. This study demonstrates that human newborns can be immunized against pathogens controlled by a Th1 immune response.

Antigens, Bacterial↗

Elevated expression of FGF-2 does not cause prostate cancer progression in LNCaP cells.

BACKGROUND: Androgen-independent (AI) prostate cancer (CaP) resulting from progression of disease is untreatable. Such progression may relate to upregulation and autocrinicity of growth factor expression. We studied one candidate growth factor, basic fibroblast growth factor (FGF-2). METHODS: LNCaP cells made autocrine for FGF-2 by stable transfection with FGF-2 were examined for cancer progression, measured by 1) altered response to androgen, 2) ability to grow more quickly when cocultured with bone cells in vitro or to form tumors when coinoculated with bone cells in vivo, or 3) increase in metastatic ability. RESULTS: Stably transfected lines differed in FGF-2 protein expression. LNCaP-HF (high production of FGF-2) expressed more FGF-2 than LNCaP-LF (low production of FGF-2); controls were negative. In vitro, compared with LNCaPs, LNCaP-HF cells showed a slightly increased growth rate, reduced proliferation in response to androgen but not to estrogen or progesterone, and a decreased proliferative response to epidermal growth factor (EGF) and FGF-2. Although giving a slightly faster take rate, LNCaP-HF cells without Matrigel only formed small, fast-regressing tumors in male nude mice, and with Matrigel, did not differ from LNCaPs in growth rate or tumor size. No metastases occurred. No tumors grew in females. Mixed growth of FGF-2 transfectants with human fetal osteoblasts failed to cross-stimulate in vitro, or to allow tumor formation in vivo. CONCLUSIONS: Although FGF-2 is overexpressed in AI CaPs, our experiments show that upregulation of FGF-2 expression is not sufficient to cause androgen independence, tumorigenicity, or metastases production (i.e., prostate cancer progression) in LNCaP cells.

Animals↗

Thymic microenvironment and NZB mice: the abnormal thymic microenvironment of New Zealand mice correlates with immunopathology.

There are distinct microenvironmental abnormalities of thymic architecture in several murine models of SLE defined using immunohistochemistry and a panel of mAb dissected at thymic epithelial markers. To address the issue of the relationship between the thymic microenvironment and autoimmunity, we studied backcross (NZB x NZW) F1 x NZW mice in which 50% of offspring develop nephritis associated with proteinuria and anti-DNA antibodies. We reasoned that if thymic abnormalities are associated with development of disease, the correlation of abnormalities with lupus-like disease in individual backcross mice will form the foundation for identification of the mechanisms involved. In parallel, we directed a genetic linkage analysis, using markers previously shown to be linked to nephritis and IgG autoantibody production, to determine if such loci were similarly associated with microenvironmental changes. Our data demonstrate that all (NZB x NZW) F1 x NZW backcross mice with disease have microenvironmental defects. Although the microenvironmental defects are not sufficient for development of autoimmune disease, the severity of thymic abnormalities correlates with titers of IgG autoantibodies to DNA and with proteinuria. Consistent with past studies of (NZB x NZW) F1 x NZW mice, genetic markers on proximal chromosome 17 (near MHC) and distal chromosome 4 showed trends for linkage with nephritis. Although the markers chosen only covered about 10-15% of the genome, the results demonstrated trends for linkage with thymic medullary abnormalities for loci on distal chromosome 4 and distal chromosome 1. We believe it will be important to define the biochemical nature of the molecules recognized by these mAbs to understand the relationships between thymic architecture and immunopathology.

Animals↗

Timing a one-handed catch. I. Effects of telestereoscopic viewing.

The aim of this study was to examine the role of binocular and monocular information sources in specifying time-to-contact. More specifically, it was investigated whether the timing of the one-handed catch is consistent with a binocular tau-function strategy. Subjects (n=8) were required to time their grasp to catch a ball approaching with a constant spatial trajectory. The ball approached at three different constant velocities (1.5, 2.0 and 2.5 m/s). Vergence and disparity were manipulated through subjects wearing a telestereoscope to increase the effective interocular separation, under both binocular and monocular viewing. Subjects performed 24 trials in each of the four conditions. Subjects' started the opening of the hand earlier in the binocular telestereoscope condition when a ball approached with velocity of 1. 5 m/s. They then closed the hand earlier in the binocular telestereoscope condition at all ball approach velocities. There were no effects of telestereoscope on the timing of hand opening and closing under monocular viewing. This finding suggests the use of the binocular information in timing the grasp. However, there were effects of approach velocity under all conditions of monocular and binocular viewing. Subjects' closed the hand earlier as a function of increasing approach velocity. Together, the effects of the telestereoscope and approach velocity indicate that timing of the one-handed catch is not consistent with the use of a binocular "tau-function" variable. Rather, it is concluded that multiple sources of monocular and binocular information contribute to the regulation of timing.

Female↗

Profit, payment and pharmaceutical practices: perspectives from hospitals in Bangkok.

Means by which to improve the quality of care offered in the private sector have received increasing interest. This paper considers the influences upon hospital physician prescribing practices. It presents data on drug management practices and prescribing patterns in a sample of private for-profit, private non-profit and public hospitals in Bangkok. Clear differences emerge in prescription patterns between the different groups of hospitals: public hospitals exhibit greater use of essential drugs and generic prescribing than either group of private hospital, and prescriptions at private for-profit hospitals tended to have more essential drugs and drugs prescribed by generic name than non-profit hospitals. Prescribing patterns in public hospitals are probably largely explained by national government policy on pharmaceutical procurement. In contrast, prescribing patterns in private for-profit hospitals appear heavily influenced by pressure upon management to contain costs, in circumstances where high drug costs cannot be passed on to purchasers. Hence hospital management have developed policies encouraging the use of generic drugs and essential drugs. These same financial pressures also explain some less desirable forms of behaviour in private for-profit hospitals such as prescribing courses of antibiotic treatment of extremely short duration. Possible measures which government may take to encourage appropriate prescribing within private hospitals are discussed.

Data Collection↗

Manipulating visual informational constraints during practice enhances the acquisition of catching skill in children.

Previous motor learning studies examining the effects of practicing to catch one-handed under varying informational constraints on subsequent skill acquisition are equivocal, perhaps due to the use of relatively inexperienced adult participants. Ecological theory predicts that directing the learner's search for information in the perceptual-motor workspace can enhance skill acquisition. This study manipulated visual informational constraints on novice children (ages 9-10 years) learning to catch one-handed. A crossover transfer design was implemented in which one group acted as controls while two other groups practiced either without visual restrictions before transferring to full vision, or vice versa. The data indicated that learners forced to seek additional information sources under restricted viewing conditions demonstrated a greater positive, accumulative residual effect on acquiring a catching skill. The findings contradict current work on the specificity of practice hypothesis and suggest that varying visual informational constraints to encourage exploratory practice may represent a significant pedagogical approach to motor learning in sport.

Child↗

Simple sample size calculation for cluster-randomized trials.

BACKGROUND: Cluster-randomized trials, in which health interventions are allocated randomly to intact clusters or communities rather than to individual subjects, are increasingly being used to evaluate disease control strategies both in industrialized and in developing countries. Sample size computations for such trials need to take into account between-cluster variation, but field epidemiologists find it difficult to obtain simple guidance on such procedures. METHODS: In this paper, we provide simple formulae for sample size determination for both unmatched and pair-matched trials. Outcomes considered include rates per person-year, proportions and means. For simplicity, formulae are expressed in terms of the coefficient of variation (SD/mean) of cluster rates, proportions or means. Guidance is also given on the estimation of this value, with or without the use of prior data on between-cluster variation. CASE STUDIES: The methods are illustrated using two case studies: an unmatched trial of the impact of impregnated bednets on child mortality in Kenya, and a pair-matched trial of improved sexually-transmitted disease (STD) treatment services for HIV prevention in Tanzania.

Child, Preschool↗

Patient satisfaction in Bangkok: the impact of hospital ownership and patient payment status.

INTRODUCTION: Patient satisfaction with care received is an important dimension of evaluation that is examined only rarely in developing countries. Evidence about how satisfaction differs according to type of provider or patient payment status is extremely limited. OBJECTIVE: To (i) compare patient perceptions of quality of inpatient and outpatient care in hospitals of different ownership and (ii) explore how patient payment status affected patient perception of quality. METHODS: Inpatient and outpatient satisfaction surveys were implemented in nine purposively selected hospitals: three public, three private for-profit and three private non-profit. RESULTS: Clear and significant differences emerged in patient satisfaction between groups of hospitals with different ownership. Non-profit hospitals were most highly rated for both inpatient and outpatient care. For inpatient care public hospitals had higher levels of satisfaction amongst clientele than private for-profit hospitals. For example 76% of inpatients at public hospitals said they would recommend the facility to others compared with 59% of inpatients at private for-profit hospitals. This pattern was reversed for outpatient care, where public hospitals received lower ratings than private for-profit ones. Patients under the Social Security Scheme, who are paid for on a capitation basis, consistently gave lower ratings to certain aspects of outpatient care than other patients. For inpatient care, patterns by payment status were inconsistent and insignificant. CONCLUSIONS: The survey confirms, to some extent, the stereotypes about quality of care in hospitals of different ownership. The results on payment status are intriguing but warrant further research.

Adolescent↗

Expression of p190A during apoptosis in the regressing rat ventral prostate.

After hormonal ablation, 90% of the secretory epithelial cells of the prostate undergo apoptosis, and the remaining cells are reorganized as the tissue is remodeled. Using differential display RT-PCR of total RNA extracted from the rat ventral prostate before and 4 days after castration, we have cloned and sequenced a number of complementary DNAs whose cognate messenger RNAs (mRNAs) may be either up- or down-regulated during prostatic regression. One sequence of particular interest, 25.2, is up-regulated after castration and is homologous to p190, a protein associated with cytoskeletal reorganization. RT-PCR has confirmed that the steady state level of p190A mRNA is increased in the rat ventral prostate after castration, and Western blot analysis indicates that the protein levels for p190A also increase. The steady state level of p190B mRNA, the second isoform of p190, does not appear to change significantly after hormone ablation. Immunohistochemical analysis demonstrates that p190A is up-regulated primarily in the columnar epithelial cells that actively undergo cell death after hormone ablation. As Rho-GAP signaling had been shown to be influenced by p190 levels, leading to the disassembly of focal adhesion contacts and the loss of cytoskeletal architecture, we also measured the changes in Rho-GAP during prostate regression. Rho-GAP levels do not change significantly, suggesting that changes in stoichiometry of the interaction between p190A and Rho-GAP may be a prerequisite for the initiation of cytoplasmic condensation. These intracellular events coupled with the proteolytic degradation of the extracellular matrix appear to be integral to the apoptotic process in glandular epithelia.

Animals↗

A pilot study describing local residents' perceptions of asthma and knowledge of asthma care in selected Chicago communities.

STUDY OBJECTIVES: To understand inner-city Chicago residents' perception of the prevalence and severity of asthma as well as their knowledge of asthma control and management. DESIGN: Cross-sectional survey using a random digital telephone dialing method. SETTINGS: Five inner-city Chicago communities where a high prevalence and mortality of asthma have been recognized. PARTICIPANTS: All the residents in the selected communities with a residential telephone had an equal opportunity to be surveyed. MEASUREMENTS AND RESULTS: The unit of measurement was the household. Only one adult member (age 18 or older) in any randomly selected household was interviewed. The survey included questions modified from the Chicago Asthma Surveillance Initiative study. A total of 2,322 phone calls with 527 successful contacts were made over 1,938 distinct phone lines, resulting in a response rate of 175 of 527 calls (33.2%). Seventy-nine of the participants (45.1%) reported that at least one of their family members (including themselves) has asthma. Eight persons (4.6%) reported asthma as one of the top three health concerns in their community. Of the top three health reasons mentioned for children's being absent from school, only seven persons (4%) mentioned asthma. Participants were unlikely to perceive that the problems with access to asthma care and environmental triggers for asthma in their communities were any worse compared with other communities. Participants having family members with diagnosed asthma scored no better when asked general-knowledge questions about asthma or its signs and triggers than those without a family member having asthma. CONCLUSIONS: The participants' knowledge and beliefs about the seriousness of asthma revealed in this study appeared unlikely to enhance or support compliance with the challenging requirements of the National Asthma Education and Prevention Panel guidelines. The study was conducted with a small sample, and the results should be carefully interpreted.

Adult↗