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Biomedical subjects

S Walker

Publications and source records attributed to S Walker.

At least 37 records · Page 2Linked to original sources
PubMed2003

Male circumcision for prevention of heterosexual acquisition of HIV in men.

BACKGROUND: The findings from observational studies, reviews and meta-analyses, supported by biological theories, that circumcised men appear less likely to acquire human immunodeficiency virus (HIV) has contributed to the recent ground swell of support for considering male circumcision as a strategy for preventing sexually acquired infection. We sought to elucidate and appraise the global evidence from published and unpublished studies that circumcision can be used as an intervention to prevent HIV infection. OBJECTIVES: 1) To assess the evidence of an interventional effect of male circumcision for preventing acquisition of HIV-1 and HIV-2 by men through heterosexual intercourse 2) To examine the feasibility and value of performing individual person data (IPD) meta-analysis SEARCH STRATEGY: We searched online for published and unpublished studies in The Cochrane Library (issue 2, 2002), MEDLINE (April 2002), EMBASE (February 2002) and AIDSLINE (August 2001). We also searched databases listing conference abstracts, scanned reference lists of articles and contacted authors of included studies. SELECTION CRITERIA: We searched for randomized and quasi-randomized controlled trials of male circumcision or, in their absence, observational studies that compare acquisition rates of HIV-1 and HIV-2 infection in circumcised and uncircumcised heterosexual men. DATA COLLECTION AND ANALYSIS: Independent reviewers selected studies, assessed study quality and extracted data. We stratified studies based on study design and on whether they included participants from the general population or high-risk groups (such as patients treated for sexually transmitted infections). We expressed findings as crude and adjusted odds ratios (OR) together with their 95% confidence intervals (CI) and conducted a sensitivity analysis to explore the effect of adjustment on study results. We investigated whether the method of circumcision ascertainment influenced study outcomes. MAIN RESULTS: We identified no completed randomized controlled trials. Three randomized controlled trials are currently underway or commencing shortly. We found 34 observational studies: 16 conducted in the general population and 18 in high-risk populations. It seems unlikely that potential confounding factors were completely accounted for in any of the included studies. In particular, important risk factors, such as religion and sexual practices, were not adequately accounted for in many of the included studies. General population study results:The single cohort study (N = 5516) showed a significant difference in HIV transmission rates between circumcised and uncircumcised men [OR = 0.58; 95% CI: 0.36 to 0.96]. Results for the 14 cross-sectional studies were inconsistent, with point estimates for unadjusted odds ratios varying between 0.28 and 1.73. Six studies had statistically significant results, four in the direction of benefit and two in the direction of harm. The test for heterogeneity between the cross-sectional studies was highly significant (chi-square = 77.59; df = 13; P-value < 0.00001). Nine studies reported adjusted odds ratios with eight in the direction of benefit, ranging from 0.26 to 0.80. Use of adjusted results tended to show stronger evidence of an association although they remained heterogenous (chi-square = 75.2; df = 13; P-value < 0.00001). Only one case-control study was found (N = 51) which had a non-significant result [OR = 1.90; 95% CI: 0.50 to 7.20]. High-risk group study results:The four cohort studies identified found a protective effect from circumcision with point estimates for unadjusted odds ratios varying from 0.10 to 0.39. Two of these studies had statistically significant results. Two studies reported adjusted odds ratios, both protective with one being significant. The chi-square test for between-study heterogeneity was not significant (chi-square = 5.21; df = 3; P-value = 0.16). All eleven cross-sectional studies reporting unadjusted results found benefit from circumcision, eight of which had statistically significant results. Estimates of effnal studies reporting unadjusted results found benefit from circumcision, eight of which had statistically significant results. Estimates of effect varied from an unadjusted odds ratio of 0.10 to 0.66. Between-study heterogeneity was significant with the chi-square = 29.77; df = 10; P-value = 0.0009. Four of these studies reported adjusted odds ratios ranging from 0.20 to 0.59 and all were significant. One additional cross-sectional study only reported an adjusted odds ratio in the direction of benefit which was statistically significant. All three case-control studies found a protective effect of circumcision on HIV status, two being statistically significant. Point estimates varied from unadjusted odds ratios of 0.37 to 0.88. One reported an adjusted odds ratio showing a significant protective effect. Adverse effects:No studies reported on the adverse effects of circumcision. In most studies, circumcision had taken place during childhood or adolescence before the studies commenced. REVIEWER'S CONCLUSIONS: We found insufficient evidence to support an interventional effect of male circumcision on HIV acquisition in heterosexual men. The results from existing observational studies show a strong epidemiological association between male circumcision and prevention of HIV, especially among high-risk groups. However, observational studies are inherently limited by confounding which is unlikely to be fully adjusted for. In the light of forthcoming results from RCTs, the value of IPD analysis of the included studies is doubtful. The results of these trials will need to be carefully considered before circumcision is implemented as a public health intervention for prevention of sexually transmitted HIV.

Circumcision, Male↗
PubMed2003

Anti-IgE for chronic asthma.

BACKGROUND: Omalizumab is a recombinant humanised monoclonal antibody directed against immunoglobulin E (IgE) to inhibit the immune system's response to allergen exposure. Omalizumab is directed against the binding site of IgE for its high affinity Fc receptor. It prevents free serum IgE from attaching to mast cells and other effector cells and prevents IgE mediated inflammatory changes. The complexes of Omalizumab and IgE formed as a result of treatment are small and not thought to be able to trigger complement activation or give rise to immune complex mediated pathology. OBJECTIVES: To determine the efficacy of anti-IgE in patients with allergic asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group Asthma trials register (February 2003) for potentially relevant studies. SELECTION CRITERIA: Randomised control trials examining anti-IgE administered in any manner for any duration. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed study quality and extracted and entered data. Three modes of administration were identified from the published literature (inhaled, intravenous and subcutaneous injection). Subgroup analysis was performed by asthma severity. Data were extracted from published and unpublished sources. MAIN RESULTS: Eight trials were included in the review, contributing a total of 2037 mild to severe allergic asthmatic participants with high levels of IgE. Treatment with intravenous and subcutaneous Omalizumab resulted in a 98 to 99% reduction in free IgE, reductions which were not observed following placebo treatment. Significant increases in the number of participants who were able to reduce (> 50% reduction in daily corticosteroid usage (four trials): odds ratio (OR) 2.50, 95% confidence interval (CI) 2.02 to 3.10; or completely withdraw their daily steroid intake (four trials): OR 2.50, 95%CI 2.00 to 3.13, were observed. Participants treated with Omalizumab were less likely to suffer an asthma exacerbation (stable steroid phase (three trials): OR 0.46, 95%CI 0.35 to 0.61; steroid reduction phase (three trials) OR 0.46, 95% CI 0.36 to 0.59). REVIEWER'S CONCLUSIONS: Omalizumab was significantly more effective than placebo at increasing the numbers of patients who were able to reduce or withdraw their inhaled steroids and was effective in reducing asthma exacerbations. Omalizumab was well tolerated, although the safety profile requires longer term assessment. Patient and physician assessment of the drug was positive. Further assessment in paediatric and severe adult populations is necessary, as is comparison with inhaled corticosteroids.

Anti-Asthmatic Agents↗
PubMed2003

Social and dietary determinants of body mass index of adult Jamaicans of African origin.

OBJECTIVES: To determine the relationships between body mass index (BMI) and diet, social and behavioural factors among adult Jamaicans of African origin. DESIGN: Cross-sectional. SETTING: Urban communities in Jamaica, West Indies. SUBJECTS: Three-hundred and sixty-three males and 561 females of African origin, aged 25-74 y. RESULTS: Women had higher mean BMIs (27.5+/-6.4 kg/m(2)) than men (23.4+/-4.3 kg/m(2)); 30.7% of women compared with 6.7% of men were obese. There was a tendency for obese men to have higher percentage of intakes from fat and less from carbohydrate, and women reported diets in which the percentage contribution of protein increased significantly with increasing BMI. In multivariate analyses, BMI was not explained by energy but was associated with protein intakes in females only. Predictors of relative weight were inversely related. Social (marital status) and behavioural (cigarette smoking) factors predicted BMI in both genders; older age in men and increased fibre intakes in women were associated with lower BMI. CONCLUSIONS: Social and behavioural factors are important determinants of body weight. Further investigations are needed which consider factors such as physical activity, genetic and other environmental variables as predictors of relative weight.

Adult↗
PubMed2003

Mothers of undernourished Jamaican children have poorer psychosocial functioning and this is associated with stimulation provided in the home.

OBJECTIVES: To compare mothers of undernourished children with mothers of adequately nourished children on maternal depression, parenting self-esteem, social support and exposure to stressors and to determine if these variables are independently related to undernutrition and stimulation provided in the home after controlling for socio-economic status. DESIGN: A case control study. SETTING: Children and their mothers were recruited from 18 government health centres in the Kingston, St Andrew and St Catherine parishes of Jamaica. SUBJECTS: One hundred and thirty-nine mothers of undernourished children (WAZ< or =-1.5z scores) aged 9 - 30 months and 71 mothers of adequately nourished children (WAZ > -1z scores) matched for sex and age group were enrolled into the study. RESULTS: Mothers of undernourished children came from poorer homes but had similar social support to mothers of adequately nourished children. They were more depressed, had lower levels of parenting self-esteem (both P<0.01), reported higher levels of economic stress (P<0.001) and provided a less stimulating home environment (P<0.05). However, after controlling for social background variables there was no independent relationship between either psychosocial function or home stimulation and nutritional status. Undernutrition was found to be mainly explained by economic factors. The mothers' self-esteem was independently associated with the level of stimulation provided to the child. CONCLUSIONS: When caring for undernourished children attention should be paid to the psychosocial status of the mother as well as the physical condition of the child. SPONSORSHIP: Thrasher Research Fund; Campus Research and Publication Fund, UWI, Jamaica.

Case-Control Studies↗
PubMed2003

Trends in mortality rates for infectious and parasitic diseases in Australia: 1907-1997.

AIMS: To characterize long-term mortality trends for infectious and parasitic diseases in Australia during the twentieth century, explore influencing factors and provide suggestions to health policy-makers. METHODS: A descriptive study was conducted. Deaths due to communicable diseases from 1907 to 1997 were tallied, according to the International Classification of Diseases version 9 (ICD-9). Trends in infectious disease mortality in overall population and in the 0-4 years age group were examined and standardized by sex. Death rates were also studied for: (i) diarrhoea/enteritis, (ii) pneumonia and all respiratory diseases and (iii) tuberculosis. RESULTS: There has been a substantial decline in -mortality from communicable diseases over the study period. The death rate dropped from 258.9 per 100,000 population in 1907 to 7.2 per 100,000 population in 1997. Six phases of the decline were observed. CONCLUSIONS: A combination of improved living conditions and access to readily available treatments over the twentieth century played an important role in the reduction of infectious disease mortality in Australia.

Age Distribution↗
PubMed2003

[4199 biopsies from the endoscopic normal lower duodenum].

Lower duodenal biopsies (LDB) are not taken at every oesophago-gastro-duodenoscopy (EGD). In the present study, biopsies from the endoscopic normal lower duodenum were checked as a measure of quality assurance. From 1996 to 2000, 9,955 EGD were performed and 4,199 LDB were taken (42.2 %). Of these, 667 showed pathological histology (15.9 %). A non-specific inflammation was seen in 537 cases and lymphangiectasia in 30 cases. Signs of indigenous sprue were described histologically in 6 LDB. In 4 of the 6 first diagnoses, the LDB was taken owing to clinical suspicion of malabsorption syndrome. Giardia lamblia could be detected in 22 patients. Only 6 of the 22 patients had diarrhoea. A total of 18 clinically relevant first diagnoses were made by LDB in asymptomatic patients with normal endoscopic findings in the duodenum. In order to make a relevant first diagnosis, 233 LDB had to be taken. LDB can be dispensed within EGD when there is neither diarrhoea nor loss of weight, and no anemia, iron deficiency, vitamin deficiency, macrocytosis, hypoproteinaemia, meteorism, joint symptoms or fever.

Adult↗
PubMed2003

[Vasoconstrictive Therapies for Bleeding Esophageal Varices and their Mechanisms of Action].

Variceal bleeding is one of the most dramatic complications in gastroenterology and has a high mortality rate. Early treatment with vasoactive drugs can save lives when skilled endoscopists are not immediately available. Vasoactive drugs like terlipressin, somatostatin or octreotide are not only indicated as first-choice emergency treatment, but they also increase the success rate of endoscopic treatments. Whereas the efficacy and mechanisms of action of terlipressin to arrest haemorrhage and to improve the disturbed cardiovascular situation of cirrhotic patients, including those with hepatorenal syndrome, are well documented, the efficacy and mechanisms of action of somatostatin and octreotide remain unclear and uncertain. On account of its vasoconstrictive effects on the dilated splanchnic blood vessels, terlipressin reduces blood flow into the portal vein and, thus, reduces portal venous pressure and blood flow through porto-systemic shunts. As a consequence, variceal bleeding is arrested, central and arterial hypovolaemia is corrected, and activation of the renin-angiotensin-aldosterone system as well as the sympathetic nervous system is reduced, leading to lower intrahepatic and intrarenal resistance. The result is an improvement of organ perfusion - including perfusion of the kidneys and the liver - as well as an improvement of the hyperdynamic cardiovascular situation and a better survival rate. Whereas terlipressin has been shown to stimulate kidney function and to prolong survival time in patients with bleeding esophageal varices as well as those with hepatorenal syndrome, no such promising effects were observed with somatostatin or octreotide.

Clinical Trials as Topic↗
PubMed2003

Distribution of technetium-99m-labelled QVAR delivered using an Autohaler device in children.

QVAR, an extrafine hydrofluoroalkane/beclomethasone dipropionate formulation, has been shown to double lung deposition in adults. The aim of the present study was to assess the total body deposition and distribution of technetium-99m-labelled (99mTc) QVAR in children after inhalation via an Autohaler. Sixteen male asthmatic children (5-14 yrs) inhaled labelled drug (<4 MBq 99mTc; 100 microg beclomethasone dipropionate) via an Autohaler within 30 min after salbutamol (200 microg) administration. Simultaneous anterior and posterior planar scintigraphic scans (120 s acquisition time) were collected after inhalation of labelled drug. Mean+/-SD lung deposition of labelled drug (attenuation-corrected; percentage of ex-actuator dose) was 36.9+/-9.2, 46.5+/-11.6 and 54.1+/-10.7% in children aged 5-7, 8-10 and 11-14 yrs, respectively. Combined oropharyngeal and gastrointestinal deposition was 59.7+/-8.2, 48.9+/-12.3 and 40.3+/-11.8%. Lung deposition positively correlated with the forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). Gastrointestinal dose negatively correlated with the FEV1, FVC, height and age. In older children (11-14 yrs), lung deposition was almost identical to that reported in adults using QVAR. In children aged 5-10 yrs, lung deposition using QVAR was greater than the levels measured using other commercial aerosol delivery systems. Oropharygeal and gastrointestinal deposition was inversely related to age.

Administration, Inhalation↗
PubMed2003

Nutritional status of older adults in urban Jamaica.

The aim of the study was to determine the energy intake and nutritional status of a sample of Jamaican adults, and to compare them among different age groups. Measured height and weight data from a survey in Spanish Town, Jamaica, consisting of 2100 adults aged 25-74 years, with 22 per cent over age 60 years, were used to calculate body mass index (BMI). Using BMI cut-off points of 20 and 27, the prevalence of underweight and overweight, respectively, were determined for different age groups. Energy intake was calculated from a food frequency questionnaire from 967 of the respondents. Among males, mean daily energy intake declined from a high of 3681 kcal (15,401 kJ) for 25-29 year-olds, to a low of 2227 kcal (9318 kJ) for those aged 70-74 years. Corresponding numbers among females were 2935 kcal (12,280 kJ) and 1844 kcal (7715 kJ), respectively. Among those aged 65-74 years, 26.9 per cent of males and 50 per cent of females report daily energy intakes of less than 1600 kcal (6694 kJ) (below the lowest recommended dietary allowance (RDA)), compared to 4.5 and 13.7 per cent of males and females aged 25-34 years. While there are moderate declines in the prevalence of overweight, the prevalence of male underweight increased from 4 per cent among 50-54 year-olds to over 35 per cent among those 65 years and older; and among females the corresponding numbers are from 2 per cent to 10 per cent. All trends with age were significant (p < 0.005). There are significant declines in energy intake, and alarming increases in the prevalence of underweight with increasing age among males. These results are cause for concern and further research in this area is warranted.

Adult↗
PubMed2002

Grass pollen sublingual immunotherapy for seasonal rhinoconjunctivitis: a randomized controlled trial.

BACKGROUND: Previous studies suggest that sublingual immunotherapy (SLIT) represents a safer alternative to injection immunotherapy but equivalent efficacy is yet to be confirmed. OBJECTIVE: To evaluate the efficacy and safety of SLIT in grass pollen-induced seasonal rhinoconjunctivitis. METHODS: A randomized, placebo-controlled trial in 56 adults over 18 months. Outcome measures included diary scores of seasonal symptoms and medication use, overall assessments, conjunctival and intradermal provocation tests and serum antibody measurements. To investigate possible mechanisms, sublingual biopsies were taken for measurement of local T cells, antigen-presenting cells and IL-12 mRNA expression. RESULTS: There were no significant differences between the immunotherapy (IT) and placebo groups for diary symptom scores (P = 0.48) or rescue medication (P = 0.19). The patients' overall assessment of hayfever severity compared with previous years showed a highly significant improvement in favour of the IT group (P < 0.02). After treatment the late skin response was smaller (P = 0.003) and the ratio of serum allergen-specific IgG4/IgE was higher (P = 0.05) in the IT group. Both of these variables correlated with the clinical response to SLIT. There were no differences between groups in either the sublingual epithelium or lamina propria for numbers of CD3+ cells (epithelium: P = 0.9, lamina propria: P = 0.2), CD1a+ cells (P = 0.3, P = 0.25), CD68+ cells (P = 0.9, P = 1.0) or IL-12 mRNA+ cells (P = 0.6, P = 0.4). Local side-effects were minor and there were no serious treatment-related adverse events. CONCLUSION: Grass pollen sublingual immunotherapy was well tolerated. Although there was no significant change in diary scores, the improvement in overall assessments, which correlated with inhibition of the late skin response and increases in serum IgG4 : IgE ratio, indicates the need for larger, dose-ranging studies.

Administration, Sublingual↗
PubMed2002

Comparative effects of permanent biventricular and right-univentricular pacing in heart failure patients with chronic atrial fibrillation.

BACKGROUND: One third of chronic heart failure patients have major intraventricular conduction and uncoordinated ventricular contraction. Non-controlled studies suggest that biventricular pacing may improve haemodynamics and well-being by reducing ventricular asynchrony. The aim of this trial was to assess the clinical efficacy and safety of this new therapy in patients with chronic atrial fibrillation. METHODS: Fifty nine NYHA class III patients with left ventricular systolic dysfunction, chronic atrial fibrillation, slow ventricular rate necessitating permanent ventricular pacing, and a wide QRS complex (paced width >or=200 ms), were implanted with transvenous biventricular-VVIR pacemakers. This single-blind, randomized, controlled, crossover study compared the patients' parameters, as monitored during two 3-month treatment periods of conventional right-univentricular vs biventricular pacing. The primary end-point was the 6-min walked distance, secondary end-points were peak oxygen uptake, quality-of-life, hospitalizations, patients' preferred study period and mortality. RESULTS: Because of a higher than expected drop-out rate (42%), only 37 patients completed both crossover phases. In the intention-to-treat analysis, we did not observe a significant difference. However, in the patients with effective therapy the mean walked distance increased by 9.3% with biventricular pacing (374+/-108 vs 342+/-103 m in univentricular;P =0.05). Peak oxygen uptake increased by 13% (P=0.04). Hospitalizations decreased by 70% and 85% of the patients preferred the biventricular pacing period (P<0.001). CONCLUSION: As compared with conventional VVIR pacing, effective biventricular pacing seems to improve exercise tolerance in NYHA class III heart failure patients with chronic atrial fibrillation and wide paced-QRS complexes. Further randomized controlled studies are required to definitively validate this therapy in such patients.

Aged↗
PubMed2001

[Enteropathy-associated T-cell lymphoma. Manifestation as diet-refractory coeliac disease and ulcerating jejunitis].

HISTORY AND CLINICAL FINDINGS: A 61-year-old woman in poor general health was admitted to hospital because of progressive diarrheo, flatulence, fatigue and weight loss. The patient had a history of coeliac disease with poor dietary compliance over many years. Hence, the present clinical deterioration was unresponsive to a gluten-free diet. INVESTIGATIONS: Laboratory results showed signs of inflammation and malabsorption. The endoscopy of the duodenum revealed a flattened mucosal architecture, as is typical for coeliac disease. Enteroscopy revealed many small jejunal lesions. Histological examination of mucosa showed typical signs of coeliac disease without definite signs of lymphoma. Immunhistochemical analysis showed atypical intraepithelial T-cells, while the molecular biological study revealed a monoclonal T-cell clone, both supporting the diagnosis of an enteropathy associated T-cell lymphoma (EATCL). DIAGNOSIS AND THERAPY: The patient was enrolled in a study on intestinal non-Hodgkin lymphomas and accordingly received 6 courses of CHOP-chemotherapy. Clinical and histological improvement has lasted for over a year. CONCLUSION: Patients with coeliac disease unresponsive to a gluten-free diet or with a deteriorating clinical condition may have an enteropathy-associated T-cell lymphoma. This can manifest itself in the form of an ulcerative jejunitis. In the early stages of disease, immunhistochemical and molecularbiological analyses may lead to the correct diagnosis.

Celiac Disease↗
PubMed2001

Management of hepatitis B virus infections in two gibbons and a western lowland gorilla in a zoological collection.

Since 1996, three primates newly arrived at London Zoo have been found to be infected with hepatitis B virus. The species involved were white-cheeked gibbons (Hylobates leucogenys leucogenys and Hylobates leucogenys siki) and a western lowland gorilla (Gorilla gorilla gorilla). The protocols for the practical management of these cases, including the immunisation of susceptible non-human primates and the staff with recombinant hepatitis B vaccine are described, and the origin and evolution of hepatitis B infection in primates are discussed.

Animals↗