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Biomedical subjects

Andrew J Hall

Publications and source records attributed to Andrew J Hall.

At least 19 recordsLinked to original sources

Direct extraction of penicillin G and derivatives from aqueous samples using a stoichiometrically imprinted polymer.

A molecularly imprinted polymer (MIP) prepared using penicillin G procaine salt as the template (PENGp) and a stoichiometric quantity of urea-based functional monomer to target the single oxyanionic species in the template molecule has been applied to the development of a molecularly imprinted solid-phase extraction (MISPE) procedure for the selective preconcentration of beta-lactam antibiotics (BLAs) from environmental water samples. Various parameters affecting the extraction efficiency of the polymer have been evaluated to achieve the selective preconcentration of the antibiotics from aqueous samples and to reduce nonspecific interactions. This resulted in an MISPE-HPLC method allowing the direct extraction of the analytes from the sample matrix with a selective wash using just 10% (v/v) organic solvent. On the basis of UV detection only, the method showed good recoveries and precision, ranging between 93% and 100% (RSD 3.8-8.9%, n = 3) for tap water and between 90% and 100% (RSD 4.2-9.1%, n = 3) for river water fortified with 30 or 60 microg L-1 (50 mL samples) penicillin G, penicillin V, nafcillin, oxacillin, cloxacillin, and dicloxacillin, suggesting that this MIP can be successfully applied to the direct preconcentration of BLAs in environmental water samples.

Chromatography, High Pressure Liquid↗

Polymeric receptors for the recognition of folic acid and related compounds via substructure imprinting.

A range of 2-acrylamidopyridines, showing subtle differences in solution binding toward carboxylic acids, has been investigated as functional monomers in molecular imprinting. Imprinting of N-Z-L-glutamic acid with one such monomer is shown to be effective in the creation of a molecularly imprinted polymer (MIP) with recognition properties for its template and also for larger molecules containing glutamic acid residues. In comparison to a MIP prepared via a more "traditional" approach, the new polymeric receptors exhibit reduced nonspecific binding. The new receptors are compared with previously reported urea-based receptors targeting the glutamic acid residue and receptors targeting the pteridine substructure of folic acid.

Acrylamides↗

Risk of deep vein thrombosis and pulmonary embolism after acute infection in a community setting.

BACKGROUND: Acute infection increases the risk of arterial cardiovascular events, but effects on venous thromboembolic disease are less well established. Our aim was to investigate whether acute infections transiently increase the risk of venous thromboembolism. METHODS: We used the self-controlled case-series method to study the risk of first deep vein thrombosis (DVT) (n=7278) and first pulmonary embolism (PE) (n=3755) after acute respiratory and urinary tract infections. Data were obtained from records from general practices who had registered patients with the UK's Health Improvement Network database between 1987 and 2004. FINDINGS: The risks of DVT and PE were significantly raised, and were highest in the first two weeks, after urinary tract infection. The incidence ratio for DVT was 2.10 (95% CI 1.56-2.82), and that for PE 2.11 (1.38-3.23). The risk gradually fell over the subsequent months, returning to the baseline value after 1 year. The risk of DVT was also higher after respiratory tract infection, but possible diagnostic misclassification precluded a reliable estimate of the risk of PE after respiratory infection. INTERPRETATION: Acute infections are associated with a transient increased risk of venous thromboembolic events in a community setting. Our results confirm that infection should be added to the list of precipitants for venous thromboembolism, and suggest a causal relation.

Acute Disease↗

Autoimmune diseases co-occurring within individuals and within families: a systematic review.

BACKGROUND: Autoimmune diseases have been observed to coexist both within individuals and within families. It is unclear whether clinical reports of comorbid autoimmune diseases represent chance findings or true associations. This systematic review evaluates the current level of evidence on the coexistence of selected autoimmune diseases within individuals and families. We reviewed the associations among 4 TH1-associated autoimmune diseases: insulin-dependent diabetes mellitus, autoimmune (Hashimoto) thyroiditis, rheumatoid arthritis, and multiple sclerosis. METHODS: Studies quantifying the coexistence between the selected diseases, published through March 2004, were identified from Medline and Embase searches. Study eligibility was determined on the basis of preestablished criteria, and relevant data were extracted according to a fixed protocol. We determined the prevalence of comorbid autoimmune disease according to index disease and then compiled summary statistics. Heterogeneity among studies was assessed by exact likelihood ratio tests and Monte Carlo inference. RESULTS: We found 54 studies that met the eligibility criteria. Of these, 52 studies examined the coexistence of disease within individuals and 9 studies examined within-family associations. The majority of studies were uncontrolled and did not account for confounding factors. There was substantial evidence for heterogeneity among studies. Although inconclusive, the data appear to support an increased prevalence of autoimmune thyroiditis among patients with rheumatoid arthritis and those with insulin-dependent diabetes mellitus, and an inverse association between rheumatoid arthritis and multiple sclerosis. CONCLUSION: Although the available evidence does not permit firm conclusions regarding comorbidities among the selected autoimmune diseases, results are sufficiently suggestive to warrant further study.

Arthritis, Rheumatoid↗

Micronutrient intake and the risk of herpes zoster: a case-control study.

BACKGROUND: Herpes zoster can seriously impair quality of life and may also be a marker for age-related immune decline (immunosenescence). Diets low in micronutrients may increase the risk of zoster by temporarily compromising cell-mediated immune function or by hastening immunosenescence. METHODS: Primary objectives were to examine the association between risk of zoster and (i) dietary intake of vitamins A, B(6), C, E, folic acid, zinc, and iron, and (ii) fruit and vegetable consumption. We conducted a community-based case-control study. Cases were adults with incident zoster presenting to 22 general practices in London. Controls were individuals with no zoster history, matched to cases by age, sex, and general practice. Diet was ascertained for 243 cases and 483 controls using an interviewer-administered food-frequency questionnaire. We used conditional logistic regression to estimate odds ratios. RESULTS: There was a strong graded association between lower fruit intake and increasing zoster risk; in adjusted analysis, individuals who ate less than one piece of fruit per week had more than three times the risk of zoster compared with individuals who ate more than three portions per day. None of the dietary intakes of the seven micronutrients examined had a statistically significant association with zoster risk when considered singly. However, amongst individuals aged >60 years, a measure of combined micronutrient intake and vegetable intake showed similar dose-related associations with zoster risk. CONCLUSION: A cocktail of nutrients such as those found in fruit and vegetables may act together, particularly in older individuals, to maintain immune health and prevent zoster.

Adolescent↗

Improved imide receptors by imprinting using pyrimidine-based fluorescent reporter monomers.

[reaction: see text] Optically responsive receptors toward imides based on 6-substituted 2,4-bis(acrylamido)pyrimidines are presented. The monomers were readily prepared in good yield. Solution binding to 1-benzyluracil (BU) monitored by 1H NMR appeared lower than a previously reported pyridine-based monomer. However, as indicated by 1H NMR and IR spectral investigations, the association strength was demonstrated to be "masked" by dimerization of the pyrimidine-based monomer units. Thus, from dilution experiments, a dimerization constant of 731 M(-1) was estimated for the pyrimidine-based monomer 2,4-bis(acrylamido)-6-piperidinopyrimidine whereas for the pyridine-based monomer 2,6-bis(acrylamido)pyridine, no self-association was observed. This precluded an accurate determination of the binding constant for BU to the former monomer whereas for the latter a binding constant of 757 M(-1) was measured. Despite the strong self-association, the novel monomer was shown to lead to enhanced imprinting effects when compared to imprinted polymers prepared analogously, but using the pyridine-based monomer as the recognition element. This was attributed to a higher intrinsic binding affinity exhibited by the pyrimidine based host monomer vis a vis the guest and the existence in the former of more than one interaction site for the guest. The monomers exhibited fluorescence emission informative of the mode of monomer incorporation in the polymer and the presence of guest species. Thus, the fluorescence was rapidly and selectively quenched upon template addition, with the degree of quenching correlating with binding affinity and the amount of template bound to the polymer.

Journal Article↗

An economic analysis of a pneumococcal vaccine programme in people aged over 64 years in a developed country setting.

BACKGROUND: Polysaccharide pneumococcal vaccination for older adults is being introduced in developed country settings. Evidence of protection by this vaccine against pneumococcal pneumonia, or confirmation that illness and death from bacteraemia are prevented, is currently limited. Decisions are often made based on partial information. We examined the policy implications by exploring the potential economic benefit to society and the health sector of pneumococcal vaccination in older adults. METHODS: A model to estimate the potential cost savings and cost-effectiveness of a polysaccharide pneumococcal vaccine programme was based on costs collected from patients, the literature, and routine health-services data. The effect of a pneumococcal vaccine (compared with no vaccination) was examined in a hypothetical cohort aged over 64 years. The duration of protection was assumed to be 10 years, with or without a booster at 5 years. RESULTS: If it were effective against morbidity from pneumococcal pneumonia, the main burden from pneumococcal disease, the vaccine could be cost-neutral to society or the health sector at low efficacy (28 and 37.5%, respectively, without boosting and with 70% coverage). If it were effective against morbidity from bacteraemia only, the vaccine's efficacy would need to be 75 and 89%, respectively. If protection against both morbidity and mortality from pneumococcal bacteraemia was 50%, the net cost to society would be 2500 pounds per year of life saved ( 3365 pounds from the health-sector perspective). Results were sensitive to incidence, case-fatality rates, and costs of illness. CONCLUSIONS: A vaccine with moderate efficacy against bacteraemic illness and death would be cost-effective. If it also protected against pneumonia, it would be cost-effective even if its efficacy were low.

Aged↗

Urea host monomers for stoichiometric molecular imprinting of oxyanions.

A series of urea-based vinyl monomers was synthesized and investigated for their ability to function as polymerizable hosts for the molecular imprinting of N-Z-D- or L-glutamic acid in polar media (DMSO or DMF). The monomers were synthesized in one step from a polymerizable isocyanate and a nonpolymerizable amine or vice versa, with yields typically over 70%. Prior to polymerization their solution binding properties vis-a-vis tetrabutylammonium benzoate in DMSO were investigated by 1H NMR, UV-vis and fluorescence monitored titrations. The affinities of the urea monomers for benzoate depended upon the substitution pattern of the urea, with all diaryl ureas exhibiting high affinity. EDMA-based imprinted polymers prepared in DMF or DMSO against Z-D-(or L)-glutamic acid using 2 equiv of the urea monomer and 2 equiv of base were able to recognize the imprinted dianion as well as larger molecules containing the glutamic acid substructure. The affinity, reflected in liquid chromatography retention data, correlated with the solution binding properties of the corresponding monomers.

Anions↗

Vaccine coverage with hepatitis B and other vaccines in the Colombian Amazon: do health worker knowledge and perception influence coverage?

OBJECTIVES: We conducted a vaccination coverage survey in the Colombian Amazon, an area highly endemic for hepatitis B (HB), where HB vaccine was introduced in 1992. The aim was to measure vaccine coverage and factors influencing it, especially those related to health services. METHODS: A total of 3573 children younger than 11 years were randomly selected from four populations. Vaccination status was ascertained through the vaccination card and a questionnaire on socio-demographic factors was applied to children's caretakers. Health workers (HW) in charge of vaccination in rural and urban areas were interviewed regarding knowledge and practices in vaccination. Individual and HW characteristics were related to individual vaccination using logistic regression. RESULTS: Overall cumulated vaccination coverage was high for polio (96%, 95% CI: 94-98), measles (94%, 95% CI: 92.8-95.2), BCG (91%, 95% CI: 90-93), DPT (90%, 95% CI: 88-92) and HB (88%, 95% CI: 86-90). However, <50% of children completed the primary course of vaccination in the first year of life. Individual factors improving the likelihood of being either fully or HB vaccinated were: age>1 year, living in Leticia, being affiliated to the social security, and living in a house with a roof made of tiles rather than palm tree leaf. Among the variables related to HWs, poor knowledge of vaccine contraindications predicted a lower chance of being fully or HB vaccinated in the population served by them, even after controlling for individual variables. CONCLUSIONS: The HB control program in Colombia has achieved good coverage in one of the most endemic areas of the country. However, barriers to vaccination arise from inequities in the distribution of health insurance and inadequate HW knowledge.

Attitude of Health Personnel↗

Chronic hepatitis B virus infection in the Asia-Pacific region and Africa: review of disease progression.

Countries in the the Asia-Pacific region and Africa tend to have the highest prevalence of hepatitis B infection worldwide. Hepatitis B infection progresses from an asymptomatic persistently infected status to chronic hepatitis B, cirrhosis, decompensated liver disease and/or hepatocellular carcinoma. The aim of this review was to summarize rates and risk factors for progression between disease states in the Asia-Pacific region and Africa. A literature search was conducted employing MEDLINE and EMBASE (1975-2003) using the following key words: hepatitis B, natural history, disease progression, cirrhosis, hepatocellular carcinoma, mortality, Africa and the Asia-Pacific region. Bibliographies of articles reviewed were also searched. Ranges for annual progression rates were: (i) asymptomatic persistent infection to chronic hepatitis B, 0.84-2.7%; (ii) chronic hepatitis B to cirrhosis, 1.0-2.4%; and (iii) cirrhosis to hepatocellular carcinoma, 3.0-6.6%. Patients with asymptomatic persistent infection and chronic hepatitis B had relatively low 5-year mortality rates (<4%); rates (>50%) were much higher in patients with decompensated liver disease and hepatocellular carcinoma. No data were found for progression rates in African populations. Hepatitis B e antigen was a risk factor for chronic hepatitis B, and bridging hepatic necrosis in chronic hepatitis B increased the risk of cirrhosis. Risk factors for hepatocellular carcinoma included cirrhosis, co-infection with hepatitis C virus, and genetic and environmental factors. In this review, wide ranges of disease progression estimates are documented, emphasizing the need for further studies, particularly in Africa, where progression rates are largely not available. Summarizing information on factors associated with disease progression should assist in focusing efforts to arrest the disease process in those at most risk.

Africa↗

Epilepsy and neurocysticercosis in rural Bolivia: a population-based survey.

PURPOSE: To evaluate the frequency of neurocysticercosis (NCC) in a well-defined prevalent cohort of epilepsy patients in the rural area of the Cordillera province. METHODS: We carried out a two-phase door-to-door neuroepidemiologic survey in a sample of 10,124 subjects in a rural area of the Cordillera Province, Bolivia, to detect the prevalence of the most common neurologic disorders including epilepsy. A team of health workers administered a standard screening instrument for neurologic diseases; subjects found positive at the screening phase underwent a complete neurologic examination. Epilepsy patients were diagnosed according to the definition proposed by the International League Against Epilepsy (ILAE, 1993). Epilepsy patients identified this way underwent electroencephalographic recording, computed tomography (CT) scan, and serologic evaluation to detect antibodies against Taenia solium by enzyme-linked immunoelectrotransfer blot. RESULTS: At the end of the survey, we detected 124 defined prevalent epilepsy patients. On the basis of the classification proposed by the ILAE in 1981, partial seizures were the most common type diagnosed (66 patients, 53.3%). Of the 124 patients, 105 underwent CT scan, and a serum sample was taken to detect antibodies against T. solium in 112 patients; for 97 patients, both neuroradiologic and serologic data were available. Considering radiologic, serologic, and clinical features, of these 124 patients, 34 (27.4%) fulfilled the diagnostic criteria for definitive or probable NCC proposed in 2001. Of these 34 patients 24 (70.6%) had partial seizures. CONCLUSIONS: Our data confirm a high frequency of NCC among a well-defined prevalent cohort of epilepsy patients.

Bolivia↗

Hepatocellular carcinoma and polymorphisms in carcinogen-metabolizing and DNA repair enzymes in a population with aflatoxin exposure and hepatitis B virus endemicity.

High rates of hepatocellular carcinoma (HCC) in The Gambia, West Africa, are primarily due to a high prevalence of chronic hepatitis B virus infection and heavy aflatoxin exposure via groundnut consumption. We investigated genetic polymorphisms in carcinogen-metabolizing (GSTM1, GSTT1, HYL1*2) and DNA repair (XRCC1) enzymes in a hospital-based case-control study. Incident HCC cases (n = 216) were compared with frequency-matched controls (n = 408) with no clinically apparent liver disease. Although the prevalence of variant genotypes was generally low, in multivariable analysis (adjusting for demographic factors, hepatitis B virus, hepatitis C virus, and TP53 status), the GSTM1-null genotype [odds ratio (OR), 2.45; 95% confidence interval (95% CI), 1.21-4.95] and the heterozygote XRCC1-399 AG genotype (OR, 3.18; 95% CI, 1.35-7.51) were significantly associated with HCC. A weak association of the HYL1*2 polymorphism with HCC was observed but did not reach statistical significance. GSTT1 was not associated with HCC. The risk for HCC with null GSTM1 was most prominent among those with the highest groundnut consumption (OR, 4.67; 95% CI, 1.45-15.1) and was not evident among those with less than the mean groundnut intake (OR, 0.64; 95% CI, 0.20-2.02). Among participants who had all three suspected aflatoxin-related high-risk genotypes [GSTM1 null, HLY1*2 (HY/HH), and XRCC1 (AG/GG)], a significant 15-fold increased risk of HCC was observed albeit with imprecise estimates (OR, 14.7; 95% CI, 1.27-169). Our findings suggest that genetic modulation of carcinogen metabolism and DNA repair can alter susceptibility to HCC and that these effects may be modified by environmental factors.

Adult↗

Absence of TP53 codon 249 mutations in young Guinean children with high aflatoxin exposure.

Infection with hepatitis viruses and chronic exposure to high levels of dietary aflatoxins are the major etiologic agents for hepatocellular carcinoma in west Africa. A challenge for the prevention of hepatocellular carcinoma in this region is that both hepatitis B virus and aflatoxin exposures start early in life; indeed, aflatoxin exposures can start in utero and continue unabated throughout childhood. A mutation in the TP53 tumor suppressor gene at codon 249 (TP53 Ser249 mutation) has been reported previously for hepatocellular carcinoma tumors and matched plasma DNA samples in individuals from areas with high aflatoxin exposure. We examined whether the TP53 Ser249 mutation could be observed in DNA found in plasma of young children (ages 2-5 years) from Guinea, west Africa, a region of high aflatoxin exposure. Plasma aflatoxin-albumin adducts were present in 119 of 124 (96%) of the children, geometric mean of positives 9.9 pg/mg albumin (95% confidence interval, 8.8-11.0 pg/mg). This is the level and prevalence of exposure observed previously in adults. Following PCR amplification of plasma-derived DNA and detection using mass spectrometry, none of the samples were found to contain the TP53 Ser249 mutation. Because approximately 50% of the hepatocellular carcinomas in adults in west Africa have this specific TP53 Ser249 mutation, a lack of detection in samples from children ages <5 years may indicate that a window of opportunity for intervention exists that could be exploited to lower hepatocellular carcinoma risk.

Adenoma, Liver Cell↗

Case-control study of mosquito nets against malaria in the Amazon region of Colombia.

The degree of effectiveness of mosquito nets against malaria in the Americas has remained uncertain. We carried out a case-control study of net use and mild malaria in the Amazonas state of Colombia. Two hundred ninety cases were enrolled via the Health Department services, and 977 community-based controls matched for age, sex, and place of residence. We found that a large proportion of the population (96% of controls) slept under nets. Nevertheless, we found a benefit of impregnated nets compared with no net use: adjusted odds ratio (OR) for mild malaria 0.44, 95% confidence interval (CI) 0.20-0.98. Nonimpregnated nets had a benefit that was only slightly smaller but not statistically significant (OR for mild malaria 0.54, 95% CI 0.25-1.18). Travel in the previous month had an odds ratio of 6.2 (95% CI 3.1-8.8) and a population attributable fraction of 13% compared with 11% for failure to use an impregnated net. We conclude that, in the Amazon region, promotion of mosquito net use and impregnation is justified, and that there is a need for measures to protect travelers from malaria.

Adolescent↗

Risk of myocardial infarction and stroke after acute infection or vaccination.

BACKGROUND: There is evidence that chronic inflammation may promote atherosclerotic disease. We tested the hypothesis that acute infection and vaccination increase the short-term risk of vascular events. METHODS: We undertook within-person comparisons, using the case-series method, to study the risks of myocardial infarction and stroke after common vaccinations and naturally occurring infections. The study was based on the United Kingdom General Practice Research Database, which contains computerized medical records of more than 5 million patients. RESULTS: A total of 20,486 persons with a first myocardial infarction and 19,063 persons with a first stroke who received influenza vaccine were included in the analysis. There was no increase in the risk of myocardial infarction or stroke in the period after influenza, tetanus, or pneumococcal vaccination. However, the risks of both events were substantially higher after a diagnosis of systemic respiratory tract infection and were highest during the first three days (incidence ratio for myocardial infarction, 4.95; 95 percent confidence interval, 4.43 to 5.53; incidence ratio for stroke, 3.19; 95 percent confidence interval, 2.81 to 3.62). The risks then gradually fell during the following weeks. The risks were raised significantly but to a lesser degree after a diagnosis of urinary tract infection. The findings for recurrent myocardial infarctions and stroke were similar to those for first events. CONCLUSIONS: Our findings provide support for the concept that acute infections are associated with a transient increase in the risk of vascular events. By contrast, influenza, tetanus, and pneumococcal vaccinations do not produce a detectable increase in the risk of vascular events.

Acute Disease↗

Effectiveness of Haemophilus influenzae type b vaccination against bacterial pneumonia in Colombia.

AIMS: To assess the effectiveness of a Hib vaccination program against X-ray defined bacterial pneumonia in children <2 years in Colombia. METHODS: 389 cases of radiologically confirmed pneumonia were recruited from hospitals in Bogota and Medellin, Colombia. Two controls per case, matched on age, sex, and socio-economic level, were selected from children attending child health services at the hospitals where pneumonia cases were admitted. RESULTS: The risk of having X-ray confirmed pneumonia decreased with each Hib dose received; the vaccine effectiveness was 47% (2-72%) among those receiving one dose; 52% for two doses received, and 55% for three doses. These effectiveness levels remained after adjusting for other factors associated with risk of pneumonia. CONCLUSIONS: This study indicates that trials may have underestimated the proportion of radiological pneumonia in the under 2s that is due to Hib. This suggests that the impact of the vaccination will be greater than expected if it can be extended to reach the poorest children, who are at the greatest risk.

Case-Control Studies↗