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Biomedical subjects

A J Hall

Publications and source records attributed to A J Hall.

At least 19 recordsLinked to original sources

Preparation for a pneumococcal vaccine trial in The Gambia: individual or community randomisation?

In preparation for a large phase-3 trial of pneumococcal polysaccharide/conjugate vaccine among infants in The Gambia, the relative merits of community and individual randomisation were considered. The impact of vaccination might be enhanced in a community randomised trial if there was a substantial 'herd' effect. This might occur if those vaccinated comprise a substantial proportion of potential transmitters of infection. However, there are few data on the sources of pneumococcal infections in The Gambia and with the high degree of mobility of people in The Gambia, it seems unlikely that any herd effect would be strong. In the absence of a herd effect, a community-randomised trial would have lower power for the mortality end-points compared to an individually randomised trial of the same size. In addition, a community-randomised trial might not provide sufficient control against potential confounders and blinding might be difficult to sustain if the vaccine has a strong effect. An individually randomised trial seems a better strategy under the conditions prevailing in The Gambia.

Bacterial Vaccines

Hepatitis B vaccination in infancy in The Gambia: protection against carriage at 9 years of age.

To estimate the efficacy in The Gambia (West Africa) of infant hepatitis B vaccination against infection and carriage with the virus at the age of 9 years. The HBV status of 9-year old children vaccinated in infancy was compared to that of unvaccinated children of the same age. Eight percent of the vaccinated children had been infected by HBV compared to 50% of the unvaccinated control group; HBV carrier status was 0.6 and 10% respectively, resulting in a vaccine efficacy of 83% against infection and of 95% against chronic carriage. The results show that infant vaccination provides a high level of protection at the age of nine years against both HBV infection and chronic carrier status and no booster dose of vaccine is required in the first decade. These findings support the WHO recommendation for the introduction of HBV vaccination into the Expanded Programme on Immunization in Africa.

Carrier State

Lipopolysaccharide induction of tissue factor in THP-1 cells involves Jun protein phosphorylation and nuclear factor kappaB nuclear translocation.

Tissue Factor (TF) gene expression is transiently induced in human monocytic THP-1 cells by lipopolysaccharide (LPS). We characterized the transcription factor complexes binding to the TF gene promoter LPS response element (LRE) (-220 to -172), which contains binding sites for nuclear factor kappaB (NFkappaB) and activator protein 1 (AP1) transcription factors, and examined the nature of the activation of these factors during a 24-h time course of LPS stimulation. We found proteolysis of the cytoplasmic inhibitory protein IkappaBalpha and nuclear translocation of the NFkappaB/Rel family proteins p65 and c-Rel, corresponding to the transient binding of a p65/c-Rel heterodimer to the kappaB-like site of the LRE. AP1 binding to the LRE was found to be constitutive, with the majority of the AP1 complexes being JunD/Fra-2 heterodimers. A change in the activation state of the AP1 complexes was, however, found to be transient, as determined by JunD phosphorylation of AP1 bound to the proximal binding site. This directly correlates to the transient activation of Jun N-terminal kinase (SAPK/JNK). These data indicate that LPS induction of TF gene expression in monocytic THP-1 cells is regulated by both the transient phosphorylation of Jun-family proteins and the nuclear translocation and transient binding of NFkappaB/Rel proteins.

Base Sequence

Prevalence of antibodies against hepatitis A and E viruses among rural populations of the Chaco region, south-eastern Bolivia.

We conducted a cross-sectional study to determine the seroprevalence of antibodies against hepatitis A and hepatitis E viruses (HAV and HEV) in the population of two rural areas, Camiri and Villa Montes, of the Chaco region, south-eastern Bolivia. HAV antibodies were detected in 461 (94.1%) of 490 serum samples tested, not differing significantly between sexes and study areas. The HAV seropositivity rate (64.7%) was high even in the youngest age group (1-5 years). The prevalence of HEV was 7.3%, with no significant differences between sexes. The prevalence of HEV antibodies in the population of the Camiri area (10.4%) was significantly higher than in the Villa Montes area (4.4%), possibly due to the better quality of drinking water in the Villa Montes area. In the population </= 30 years of age, the HEV seropositivity rate (4.4%) was significantly lower than in the >/= 31 year-old group. This is consistent with findings in other countries. This is the first report of the prevalence of HEV infection in Bolivia.

Adolescent

What level of hepatitis B antibody is protective?

This study assessed the level of vaccine-induced hepatitis B surface antibody that is protective against hepatitis B infection and carriage in The Gambia. Sera from 700 of a cohort of 1041 children vaccinated against hepatitis B in infancy were serially tested for markers of hepatitis B until age 7 years. No absolute level of protection against infection was found, but all children who attained a peak antibody response to vaccination of >=10 IU/L were protected against carriage of hepatitis B surface antigen. Two-thirds of 45 infected children experienced brief infection (determined by loss of core antibody). This transient infection was likely related to surface antibody level. The data support the use of the peak antibody response as the best indicator of protection against carriage and suggest that most infections after vaccination are short-lived.

Antibody Affinity

Mansonella ozzardi infection in Bolivia: prevalence and clinical associations in the Chaco region.

A cross-sectional survey carried out in the Chaco region of Bolivia showed that 26% (77 of 296) and 0.7% (2 of 298) of the rural population of the Camiri and Villa Montes areas, respectively, harbored Mansonella ozzardi microfilariae (mf). No significant differences were observed between sexes. The lowest prevalence (9%) was in the 0-14-year-old age group, with no children <11 months of age infected. The prevalence increased sharply in the 25-34-year-old age group (32%), and continued increasing in the older age classes. Microfilaremia, ranging from 1 to 305 mf/20 microl of blood, was lowest in 0-14-year-old children (geometric mean concentration = 1.1 mf/20 microl), and increased with age (>100 mf/20 microl in people >44 years old). An expected increasing sensitivity with the blood volume examined was observed. No significant association between clinical symptoms (fever, skin rash, pruritus, headache, lymphedema, elephantiasis, and articular pain) and microfilaremia was observed.

Adolescent

Hepatitis B virus DNA in relation to duration of hepatitis B surface antigen carriage.

This study determined the prevalence and concentration of hepatitis B virus (HBV) DNA in chronic carriers of hepatitis B surface antigen (HBsAg) in The Gambia, West Africa. Ninety-nine young child carriers aged three to four years, 115 older child carriers aged five to 14 years, 71 adult carriers and 105 infected children who were not carriers were included. Detection of HBV DNA was performed by dot blot hybridisation using a radioactive phosphorus (32P) method and by non-radioactive enhanced chemiluminescence (ECL). Chromoscan-3 equipment was used to quantify DNA, and ECL and the 32P method were compared. Sensitivity and specificity of ECL were 95.8% and 100% respectively, with a detection limit of 0.3 pg/microL (0.3 x 10(5) genomic copies) compared to 0.15 pg/microL (0.15 x 10(5) genomic copies) for the 32P-labelled probe. The prevalence of HBV DNA was 74% (74/99) in young carriers, 30% (35/115) in older child carriers and 12.6% (9/71) in adult carriers. The geometric mean (GM) values for HBV DNA were significantly different between age groups (P = 0.031) and HBV DNA, which declined significantly with age (r = 0.16, P < 0.001 for log32P values), ranged from 1.48 pg/microL in young carriers to 0.29 pg/microL in adults over 24 years. The GM value of HBV DNA was related to duration of carriage. Higher values were found in young carriers known to be HBsAg-positive for less than three years compared with adult carriers of at least 20 years' duration. The GM (95% confidence limit [CL]) values were 1.48 pg/microL (1.42, 1.53) and 0.29 pg/microL (0.25, 0.33) respectively. The level of HBV DNA in hepatitis B envelope antigen (HBeAg)-positive carriers was higher than in HBeAg-negative carriers, the GM (95% CL) being 1.23 pg/microL (1.19, 1.27) and 0.34 pg/microL (0.25, 0.42) respectively.

Adolescent

Domestic pets as risk factors for alveolar hydatid disease in Austria.

To identify the risk of pet ownership (i.e., cats and dogs) for alveolar echinococcosis caused by Echinococcus multilocularis, the habits and activities of 21 patients (histologic confirmation or positive serology with corresponding evidence on an ultrasonogram, radiograph, or computed tomography scan) in Austria during the period 1967-1997 were compared with the habits and activities of 84 controls matched by sex, age, and residence. Cat ownership (odds ratio (OR) = 6.47, 95% confidence interval (CI) 1.54-27.29) and hunting (OR = 7.83, 95% CI 1.16-52.77) were independent risk factors associated with alveolar hydatid disease. The study is not in agreement with the hypothesis that eating mushrooms or certain wild berries which grow near the ground are the main risk factors for acquiring this disease. No other behavior patterns or activities studied were identified as risk factors.

Adolescent

A continuum mechanics approach to determining the cellular velocity field with a wool follicle.

A model, based on the principles of continuum mechanics, is presented for the analysis of cell-velocity fields within wool follicles. The model requires specification of three follicle characteristics in the form of spatially varying fields: viscosity, cell density and cell production rate. The viscosity is introduced as an attempt to model both complex intercellular interactions and individual cell deformation as the cells move. It is demonstrated that the distribution of cell production is more important than axial variation in viscosity in determining the overall flow pattern.

Animals

Maternal measles antibody decay in rural Bangladeshi infants--implications for vaccination schedules.

Considerable numbers of measles cases occur below the target age for vaccination in the Indian sub-continent. The immunogenicity of measles vaccine in infancy is dependent on the rate of decay in maternal antibody since this antibody interferes with vaccine induced seroconversion. This study investigated maternal antibody decay in a rural population in Bangladesh and evaluated possible risk factors for early decay. Measles antibodies were assessed using both ELISA and Plaque Reduction Neutralization (PRN) test in 330 infant-mother pairs in a cross-sectional survey. PRN was more sensitive method than ELISA for determining antibody levels. Antibody levels decreased rapidly in infants with increasing age. By the age of 5 months, 67% (28/42) infants had practically no protective antibody left (30 mIU ml-1 or below). Only 12% infants at 5 months of age, and 5% at 8 months, had levels greater than 120 mIU ml-1--stated to 'protect' children. Multiple regression showed that maternal age was the only variable associated with the level of antibody (maternal weight, height and MUAC were not associated), decreasing by 1.06 mIU ml-1 for each year of age (P = 0.002). Infant's antibody concentration decreased with age by an average 2 mIU mL-1 for every month of life (P < 0.0001), and was determined by the maternal antibody concentration (P < 0.0001) (child's length, weight, MUAC, mother's gestational age and parity were not associated). The relatively rapid antibody decay suggests that the target age for measles vaccination might be reduced. Further, as the cohort of vaccinated mothers enters reproductive age in Bangladesh, a more rapid decay of antibody may be expected in future generations of Bangladeshi children. The information presented here suggests that a formal trial of standard measles vaccine at younger ages is justified in this population as it could confer considerable benefit in reducing infant measles.

Adult

Serotype distribution and prevalence of resistance to benzylpenicillin in three representative populations of Streptococcus pneumoniae isolates from the coast of Kenya.

As surveillance data from sub-Saharan Africa are few, three representative populations of Streptococcus pneumoniae isolates were examined in Kenya for serotype distribution and Etest minimum inhibitory concentrations (MICs) of benzylpenicillin: (1) 75 lung aspirate or blood culture isolates from 301 consecutive adult patients with pneumonia, (2) 112 invasive isolates from continuous pediatric inpatient surveillance over 4 years, and (3) 97 nasopharyngeal isolates from systematically selected sick children. The proportions with benzylpenicillin MICs of > or = 0.1 microgram/mL were 0.27, 0.29, and 0.47, respectively. Vaccine-related serotypes accounted for 96% of invasive isolates from children and 90% of those from human immunodeficiency virus (HIV)-seropositive adults. Serotype 1 accounted for 44% of pneumococci from HIV-seronegative patients but only 5% of those from HIV-seropositive patients (P = .0002). Of serotype 1 isolates, 98% were susceptible to benzylpenicillin, but serogroups 13, 14, 19, and 23 were strongly associated with an MIC of > or = 0.1 microgram/mL.

Adult

A review of hepatitis C virus (HCV) vertical transmission: risks of transmission to infants born to mothers with and without HCV viraemia or human immunodeficiency virus infection.

BACKGROUND: Hepatitis C virus (HCV) vertical transmission studies have reported conflicting findings, possibly due to differences in HCV transmission risk factors among maternal populations, or to methodological differences. METHODS: Systematic review of worldwide published and unpublished HCV vertical transmission studies. Standardized diagnostic criteria were applied to minimize methodological differences, and transmission rates recalculated according to maternal HCV viraemic and human immunodeficiency virus (HIV) infection status. RESULTS: In all, 976 eligible infants from 28 studies were followed up sufficiently for recalculation of transmission rates. Overall transmission rates were less than 10% in 8/12 studies of HIV negative mothers, compared with 2/7 studies comprising at least 50% HIV-coinfected mothers. Rates from 409 viraemic mothers in 15 studies ranged from 0% to 41%, being less than 10% from HIV negative mothers in 6/13 studies and from HIV positive mothers in 1/6 studies. Nine studies measured maternal viraemia levels, with only 2/30 transmitting mothers having < 10(6) copies/ml of HCV RNA. Eight transmissions were identified overall from non-viraemic mothers. Significant transmission rate variation remained after accounting for maternal viraemia and HIV coinfection, possibly due to differences in other vertical transmission risk factors, in frequencies of postnatal transmission, or residual differences in study methodologies. CONCLUSIONS: Overall, HCV transmission is largely restricted to infants born to HCV viraemic mothers, and low risks among most HIV negative mothers may be due to lower HCV viraemia levels. International agreement on standardized diagnostic criteria for HCV vertical transmission would facilitate pooling of individual findings, to allow more precise transmission estimates and further investigation of risk factors.

Adult

Visual outcome and progression of retinopathy after cataract surgery in diabetic patients.

PURPOSE: Diabetes mellitus is a major cause of visual impairment in developed countries through retinopathy and is frequently complicated by cataract formation. The present study examines the visual outcome of cataract surgery in diabetic pat ents. METHODS: A retrospective study was performed over a 26 month period in a general hospital eye clinic. Eighty-five consecutive diabetic patients who underwent cataract surgery were categorized according to their type of diabetes, duration and treatment, operative technique, pre-operative visual acuity (VA) and degree of retinopathy. Visual acuity and retinopathy status were recorded at a minimum of 4 months postoperatively. Factors affecting visual outcome and progression of retinopathy were then examined. RESULTS: Of the 107 eyes of the 85 consecutive cases, 55 were without retinopathy (NR), 21 had background retinopathy (BDR), six had background retinopathy with macular oedema (BDR/MO), four had proliferative retinopathy and 12 cases had inadequate fundal view. In the NR and BDR groups, 90 and 81% of patients, respectively, had improved VA compared with 33% of patients with BDR/MO. Retinopathy progressed in 50% of BDR/MO patients compared with progression in 9 and 19% of NR and BDR patients, respectively. CONCLUSION: The present study illustrates the poor visual outcome in patients with severe, untreated retinopathy, particularly maculopathy, following cataract surgery. Larger prospective studies are needed to better define risk groups and pre-operative treatment strategies.

Aged

Blood chemistry and hematology of gray seal (Halichoerus grypus) pups from birth to postweaning.

Serum and plasma samples were collected from 92 gray seal (Halichoerus grypus) pups, all less than 5 wk old, and from 21 yearlings during the breeding season at the Isle of May, Firth of Forth, Scotland, for hematologic and clinical chemistry analysis. In the pups, total WBC, total protein, and glucose values increased until weaning and declined during the postweaning fast. Liver enzymes, particularly alkaline phosphatase, were high at birth and decreased steadily with age, most rapidly during the postweaning fast. In the yearlings, total WBC, erythrocyte sedimentation rates, and rectal temperatures were significantly higher than in the pups and glucose levels were significantly lower. Therefore, consideration should be given to the growth phase of gray seal pups (lactation or postweaning fast) or stage of development when hematology and clinical chemistries are used for diagnostic purposes.

Animals