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Biomedical subjects

A J Hall

Publications and source records attributed to A J Hall.

At least 109 records · Page 6Linked to original sources

The use of biological markers as predictive early-outcome measures in epidemiological research.

One of the possible uses of biomarkers in epidemiological research is as early-outcome measures to predict the occurrence of clinical disease and to elucidate the biological mechanism of pathogenesis. This use is conceptually less straightforward than the well established use of biomarkers to improve or extend exposure assessment or to study interindividual variations in disease susceptibility. In principle, this form of use could accelerate or otherwise facilitate etiological research. However, in practice, the recent review literature suggests that this mode of biomarker use, especially in cancer epidemiology, is the least clear-cut and the least well developed. The recurrent problem is identifying biomarkers that: (1) are on the causal pathway, (2) have a high probability of progression to clinical disease, and (3) account for all or most of the cases of the specified clinical outcome. Such biomarkers would be most useful if they conferred a long lead-time relative to clinical disease occurrence.

Biomarkers, Tumor↗

Cell mediated immunity after measles in Guinea-Bissau: historical cohort study.

OBJECTIVE: To investigate whether children who have had measles have reduced general cell mediated immunity three years later compared with vaccinated children who have not had measles. DESIGN: Historical cohort study. SETTING: Bissau, Guinea-Bissau. SUBJECTS: 391 children aged 3-13 years who were living in Bissau during a measles epidemic in 1991 and still lived there. These included 131 primary cases and 139 secondary cases from the epidemic and 121 vaccinated controls with no history of measles. MAIN OUTCOME MEASURES: General cell mediated immunity assessed by measurement of delayed type hypersensitivity skin responses to seven recall antigens. Anergy was defined as a lack of response to all antigens. RESULTS: 82 out of 268 cases of measles (31%) were anergic compared with 20 of the 121 vaccinated controls (17%) (odds ratio adjusted for potential confounding variables 2.2 (95% confidence interval 1.2 to 4.0); P 0.009). The prevalence of anergy was higher in secondary cases (33% (46/138)) than in primary cases (28% (36/130)), although this difference was not significant. Anergy was more common in the rainy season (unadjusted prevalence 31% (91/291) than in the dry season (11% (11/98)) (adjusted odds ratio 4.8 (2.2 to 10.3)). This seasonal increase occurred predominantly in the case of measles. CONCLUSION: Reduced general cell mediated immunity may contribute to the higher long term mortality in children who have had measles compared with recipients of standard measles vaccine and to the higher child mortality in the rainy season in west Africa.

Adolescent↗

The impact of the 1993 Braer oil spill on grey seals in Shetland.

Signs of acute respiratory distress were reported in moulting grey seals (Halichoerus grypus) hauled out on Lady's Holm, Shetland, following the Braer oil spill in January, 1993. Behavioural observations carried out between 16 January and 13 February 1993 showed that the proportion of animals exhibiting a discharge of nasal mucus was significantly higher than the proportion at a control site in the north (Papa Stour). The proportion of animals affected on Lady's Holm increased for up to one month following the spill. However, the time lag between exposure and peak response was approximately 30 days, longer than may be expected for an acute effect. The proportion of non-specific signs of respiratory distress in unexposed Shetland seals was assessed from observations made between 16 January and 25 January 1994. Symptoms similar to those seen in 1993 were also reported during this period, but the proportion of affected animals was higher in 1993. Symptoms were not observed at a grey seal moult site on the east coast of England in March 1993 and 1994. Grey seals moulting in Shetland during the time of the oil spill may have been acutely affected by exposure to hydrocarbons, but without sufficient baseline data on the occurrence of respiratory distress in grey seals it is difficult to determine the proportion attributable to other causes.

Animals↗

Measles and atopy in Guinea-Bissau.

BACKGROUND: Epidemiological studies have led to speculation that infections in early childhood may prevent allergic sensitisation but evidence to support this hypothesis is lacking. We investigated whether measles infection protects against the development of atopy in children of Guinea-Bissau, West Africa. METHODS: We conducted a historical cohort study in Bandim, a semi-rural district of Bissau, the capital of Guinea-Bissau. 395 young adults, first surveyed in 1978-80 aged 0-6 years, were followed up in 1994. Our analyses were restricted to 262 individuals still living in Bandim for whom a measles history, documented in childhood, was judged to be reliable. We defined atopy as skin-prick test positivity (> or = 3 mm weal) to one or more of seven allergens. FINDINGS: 17 (12.8 percent) of 133 participants who had had measles infection were atopic compared with 33 (25.6 percent) of 129 of those who had been vaccinated and not had measles (odds ratio, adjusted for potential confounding variables 0.36 [95 percent CI 0.17-0.78], p=O.O1). Participants who had been breastfed for more than a year were less likely to have a positive skin test to housedust mite. After adjustment for breastfeeding and other variables, measles infection was associated with a large reduction in the risk of skin-prick test positivity to housedust mite (odds ratio for Dermatophagoides pteronyssinus 0.20 [0.05-0.81], p=0.02; D farinae 0.20 [0.06-0.71], p=0.01). INTERPRETATION: Measles infection may prevent the development of atopy in African children.

Allergens↗

Managing HIV. Part 5: Treating secondary outcomes. 5.11 HIV and eye disease.

Blindness is a threatening complication of HIV infection, but one that can be prevented by correct diagnosis and management of ocular disease. The general practitioner can play a vital role in diagnosis by being familiar with the types of ocular disease seen at different stages of HIV infection.

AIDS-Related Opportunistic Infections↗

Aflatoxin exposure and cytogenetic alterations in individuals from the Gambia, West Africa.

Aflatoxin-albumin adducts in peripheral blood provide a measure of exposure to aflatoxin over the previous 2-3 months. In the present study, the levels of these adducts were determined in a group of individuals from The Gambia, West Africa and were compared in a cross-sectional study to the levels of various cytogenetic alterations (chromosomal aberrations, micronuclei, sister chromatid exchanges) in the same individuals to test whether an increase in genetic damage is associated with an increased exposure in this population. Of 35 subjects tested for aflatoxin-albumin adducts, all but 3 were positive. There were no correlations between the adduct level and the number of cytogenetic abnormalities at the individual level. A comparison of the cytogenetic alterations was made between Gambian individuals and a group of 22 healthy people from Italy where aflatoxin exposure is expected to be low. The levels of structural chromosomal aberrations, sister chromatid exchanges and micronuclei were all higher in the former group. Overall, these data are indicative of a higher exposure to genotoxins in Gambian subjects, one of which are aflatoxins, but suggest that more specific genetic markers of aflatoxin exposure are required to further examine the link between aflatoxin exposure and genetic alterations.

Adolescent↗

Epidemiological patterns of hepatitis B virus (HBV) in highly endemic areas.

This paper uses meta-analysis of published data and a deterministic mathematical model of hepatitis B virus (HBV) transmission to describe the patterns of HBV infection in high endemicity areas. We describe the association between the prevalence of carriers and a simple measure of the rate of infection, the age at which half the population have been infected (A50), and assess the contribution of horizontal and perinatal transmission to this association. We found that the two main hyper-endemic areas of sub-Saharan Africa and east Asia have similar prevalences of carriers and values of A50, and that there is a negative nonlinear relationship between A50 and the prevalence of carriers in high endemicity areas (Spearman's Rank, P = 0.0086). We quantified the risk of perinatal transmission and the age-dependent of infection to allow a comparison between the main hyper-endemic areas. East Asia was found to have higher prevalences of HBeAg positive mothers and a greater risk of perinatal transmission from HBeAg positive mothers than sub-Saharan Africa, though the differences were not statistically significant. However, the two areas have similar magnitudes and age-dependent rates of horizontal transmission. Results of a simple compartmental model suggest that similar rates of horizontal transmission are sufficient to generate the similar patterns between A50 and the prevalences of carriers. Interrupting horizontal transmission by mass immunization is expected to have a significant, nonlinear impact on the rate of acquisition of new carriers.

Adult↗

Serogroup-specific epidemiology of Streptococcus pneumoniae: associations with age, sex, and geography in 7,000 episodes of invasive disease.

A study sample of 7,010 episodes of invasive Streptococcus pneumoniae disease was obtained by combining 13 existing datasets. Disease episodes due to each of 12 pneumococcal serogroups (1, 3-9, 14, 18, 19, and 23) were then compared with episodes in a constant internal control group to describe serogroup-specific variations in disease frequency by age, sex, and geographic origin. The results are presented as odds ratios (with 95% confidence intervals) derived by logistic regression, with adjustment for the major confounders, including dataset of origin. Variation in the male:female ratios between serogroups is small, suggesting that capsular characteristics are an unlikely explanation for the male preference of S. pneumoniae. Serogroups associated with higher nasopharyngeal prevalence (e.g., 19 and 24) are relatively more common in Europe and North American, while the invasive serotypes 1 and 5 are much more common in South America. The custom of reporting serogroup frequencies in two age groups, children and adults, conceals much of the variation in the age distributions across the whole span of life. The reduction of risk associated with serogroups 6, 14, 18, 19, and 23 beyond childhood follows different gradients, being most abrupt in serogroups 14 and most gradual in serogroup 18. The relative risk of disease with serotype 1 declines steadily throughout life, while with serotypes 3 and 8 it increases over middle age. Serogroups 7 and 23 are found unusually frequently in the third decade of life. Because of the wide differences in the epidemiology of individual serogroups of S. pneumoniae, it is questionable whether pneumococcal infection should continue to be classified as a single disease entity.

Adolescent↗

Type 1 angiotensin II receptors in human endometrium.

From evidence based on the use of specific receptor subtype antagonists, it has generally been assumed that human uterine tissue contains only type 2 (AT2) angiotensin II (AII) receptor subtype. Using a monoclonal antibody, 6313/G2, directed against a specific sequence in the extracellular domain of the type 1 AII receptor (AT1), in immunocytochemical studies, we show here that AT1 receptor is expressed in human endometrium. In particular, positive staining was seen in the endometrial glandular epithelium, and in the vascular endothelium, while the myometrium and endometrial stroma were negative. The most intense staining was observed during the late proliferative phase and less in the luteal phase. The ligand binding assay, using [125I]-angiotensin II, revealed high concentrations of AII receptors both in the endometrium and in the myometrium. Competition studies using losartan (AT1 specific) and CGP42112B (AT2 specific) showed that both AT1 and AT2 receptor subtypes were present in the endometrium, though only the AT2 receptor subtype was detected in the myometrium. Immunoblotting confirmed that the antibody 6313/G2 detected a single protein with a molecular weight of approximately 60 kDa. These data clearly demonstrate the presence of endometrial AT1 receptors whose expression appears to be under hormonal control.

Adult↗

AIDS and the eye. A 10-year experience.

BACKGROUND: The AIDS database at Fairfield Hospital, Melbourne, maintains information on eye pathology as identified by the three visiting ophthalmologists. Patients underwent an eye consultation: if they had ocular symptoms; if signs were seen on direct ophthalmoscopy by physicians; or when their CD4+ve cell count fell below 50/microL. The first AIDS-associated eye signs were identified in mid-1984. In the subsequent decade, 3257 patients in Victoria tested positive for HIV, and 845 of the 1123 who developed AIDS were treated at Fairfield Hospital. METHODS: We undertook a retrospective review of the Fairfield Hospital database to identify the AIDS-associated ocular problems seen. RESULTS: Some 723 patients had an eye consultation. In the earliest stage of HIV infection, minor non-specific ophthalmic involvement may occur. As the disease progresses, microvasculopathy (cottonwool spots and haemorrhages) appears. External disease also occurs such as molluscum contagiosum and Kaposi's sarcoma of the conjunctiva. With more suppression of the immune system, opportunistic infections become common, and have a considerable visual morbidity. Cerebral toxoplasmosis (117 patients) is only rarely associated with ocular involvement (three patients), but cytomegalovirus (CMV) commonly causes retinitis [204 patients (24%)]. It has been the AIDS-defining illness in 26 patients. A majority had the disease confined to one eye. Mean CD4 cell count at onset is 15 +/- 5 microL and it has been associated with a viraemia in all but two patients. Late complications of CMV retinitis include relapse in 41 (20%), spread to the other eye in 24 (12%), and retinal detachment in 30 (15%). Visual impairment follows from retinal destruction, optic nerve involvement, and retinal detachment. CONCLUSION: The ophthalmic workload from late ocular complications of AIDS is increasing. Newer and more effective methods of treatment are being developed. Ophthalmologists are becoming more aware of the need for universal precautions to avoid risks from this and other blood-borne infections.

AIDS-Related Opportunistic Infections↗

Vogt-Koyanagi-Harada syndrome in patients of Vietnamese ancestry.

BACKGROUND: Vogt-Koyanagi-Harada syndrome (VKH), is an idiopathic, multisystem inflammatory disorder primarily involving the eye. HLA typing has shown a strong association between the HLA-DR4 antigen and people of Japanese, Han Chinese and Hispanic ancestry with VKH. This study reviewed the clinical features and HLA typing of Vietnamese patients with VKH. PATIENTS AND METHODS: A retrospective review of four unrelated Vietnamese patients with VKH seen in private practice and hospital clinic. The American Uveitis Society (1978) criteria for VKH diagnosis were satisfied. Standard microcytotoxic assays for Class I antigens and HLA-DNA typing of Class II DR antigens (DRB1 genotyping) by the PCR-SSO method were performed. RESULTS: The clinical features of VKH in Vietnamese were comparable to those seen in other Asian races. HLA-DR4 was present in three of the four VKH patients. Two of these patients also expressed the allele DRB1*0405. DISCUSSION: The strong association between HLA-DR4 and the DRB1*0405 allele and VKH seen in Japanese people, may well also exist in Vietnamese people. The HLA association suggests an immunogenetic predisposition to VKH.

Adult↗

Morbilliviruses in marine mammals.

Two of the three recently discovered aquatic morbilliviruses have been responsible for mass mortalities among marine mammals; both affect more than one host species, but susceptibility to infection varies considerably between species. Apparent differences between the dynamics of aquatic morbilliviruses and their terrestrial counterparts may be a consequence of high levels of interspecific transmission.

Animals↗

Response to hepatitis B vaccine in a cohort of Gambian children.

In a cohort of 1000 Gambian children immunized with four doses of 10 micrograms of plasma-derived hepatitis B virus vaccine, 44 subjects (4.4%) showed no response (< 10 mIU/ml; 6 subjects) or low specific antibody response (10 to 99 mIU/ml; 38 subjects) to hepatitis B surface antigen. Serologic indices, potentially correlated with low immunologic response, were investigated in sera obtained from these children and in sex-, age- and village-matched controls who showed a normal response. The presence of circulating immune complexes in similar proportion of responding and poorly responding children together with a low prevalence of rheumatoid factors suggested that polyclonal B cell activation was not correlated with the subnormal humoral response. Concentrations of serum immunoglobulin (Ig) and IgG subclasses did not differ in the two groups. Some of the African prevalent Ig allotypes were determined, but no significant differences in the two groups were found. The humoral response to hepatitis B surface antigen did not correlate with the response to tetanus toxoid.

Antigen-Antibody Complex↗

Hepatitis B vaccination: the cost effectiveness of alternative strategies in England and Wales.

OBJECTIVE: To assess the cost effectiveness of adding universal hepatitis B vaccination in infancy or pre-adolescence to a policy of selective vaccination of at risk groups. DESIGN: Costs of a selective policy and additional costs of universal vaccination policies were estimated from costs of vaccine delivery and published data on target populations. Additional years of life gained were calculated for each policy by applying life tables to estimates of mortality attributable to hepatitis B. SETTING: England and Wales. RESULTS: Compared with no vaccination, vaccination in infancy was the most cost effective followed by vaccination in preadolescence. Selective vaccination was the least effective (cost per year of life gained 2568 pounds, 2824 pounds, and 8564 pounds respectively). Adding vaccination in infancy or at pre-adolescence to a selective policy cost 1537 pounds or 1658 pounds per year of life gained. Discounting years gained in the future at 6% per annum, however, made pre-adolescent vaccination more cost effective than infant or selective vaccination (51,817 pounds, 94,821 pounds, and 124,779 pounds per discounted year of life gained). Adding pre-adolescent vaccination to a selective policy cost 32,125 pounds per discounted year of life gained and infant vaccination, 77,085 pounds. CONCLUSIONS: Universal vaccination against hepatitis B was more cost effective than selective vaccination in a low prevalence country. Discounting future health gain, however, made universal infant vaccination lest cost effective than universal pre-adolescent vaccination. If future health gained is as important as present gain the addition of universal vaccination to a selective policy is equivalent to the cost per quality adjusted year of life from renal transplantation or breast cancer screening.

Child↗

Altered skeletal growth in Perthes' disease: an anthropometric study of children from rural India.

In contrast to the features of Perthes' disease (PD) in England, children with PD in South west India are older and from rural areas. To test whether rural Indian children with PD demonstrate abnormalities in skeletal growth similar to those noted in English children, we studied 52 affected children and 100 normal controls. Each child had a detailed anthropometric evaluation; various body segments were measured. The study demonstrated that rural Indian children with PD showed impaired skeletal growth, with the feet most severely affected. The pattern of growth alteration was almost identical to that of English children with PD. The results suggest that despite difference in age of onset and rural-urban differences in Indian and English children with PD, a common etiologic factor responsible for skeletal retardation is active in both groups.

Adolescent↗

Do bedbugs transmit hepatitis B?

An intervention study was done over two years in seven Gambian villages to determine the contribution of bedbugs to hepatitis B transmission. In addition, fortnightly questionnaires were completed for each child to assess other possible routes of transmission. The intervention, insecticide spraying of the child's dwelling, was highly effective in reducing exposure to bedbugs but there was no effect on hepatitis B infection. No other risk factor for transmission was identified despite a consistent village-to-village variation in the rate of childhood infection. The major mode of transmission of hepatitis B in childhood remains unknown.

Animals↗