Male circumcision could help protect against HIV infection.
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Circumcision, Male↗
Biomedical subjects
S Clark
Publications and source records attributed to S Clark.
Localization of a recessive gene for North American Indian childhood cirrhosis to chromosome region 16q22-and identification of a shared haplotype.
North American Indian childhood cirrhosis (NAIC, or CIRH1A) is an isolated nonsyndromic form of familial cholestasis reported in Ojibway-Cree children and young adults in northwestern Quebec. The pattern of transmission is consistent with an autosomal recessive mode of inheritance. To map the NAIC locus, we performed a genomewide scan on three DNA pools of samples from 13 patients, 16 unaffected siblings, and 22 parents from five families. Analysis of 333 highly polymorphic markers revealed 3 markers with apparent excess allele sharing among affected individuals. Additional mapping identified a chromosome 16q segment shared by all affected individuals. When the program FASTLINK/LINKAGE was used and a completely penetrant autosomal recessive mode of inheritance was assumed, a maximum LOD score of 4.44 was observed for a recombination fraction of 0, with marker D16S3067. A five-marker haplotype (D16S3067, D16S752, D16S2624, D16S3025, and D16S3106) spanning 4.9 cM was shared by all patients. These results provide significant evidence of linkage for a candidate gene on chromosome 16q22.
Adult↗
UK surgeons' guide to management of spinal deformity.
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Child↗
Large-scale test of hypothesised associations between the angiotensin-converting-enzyme insertion/deletion polymorphism and myocardial infarction in about 5000 cases and 6000 controls. International Studies of Infarct Survival (ISIS) Collaborators.
BACKGROUND: The original report of a possible association between myocardial infarction and the insertion/deletion (I/D) polymorphism of the gene for the angiotensin-1-converting enzyme (ACE) indicated a risk ratio for myocardial infarction with the DD genotype of 1.34 (95% CI 1.05-1.70), and the association was claimed to be particularly strong in a retrospectively defined low-risk subgroup (3.2 [95% CI 1.7-5.9). Subsequent investigations reached varying conclusions, but all were small, and much larger studies were needed. METHODS: 4629 myocardial infarction cases and 5934 controls were compared. Cases were UK men aged 30-54 years and women aged 30-64 years recruited on presentation to hospital with confirmed myocardial infarction. Controls were aged 30-64 years with no history of cardiovascular disease, but were siblings or children of myocardial infarction survivors, or spouses of such relatives. All risk-ratio calculations allow for this relatedness of some of the controls. An updated meta-analysis of previous studies was also conducted. FINDINGS: The ACE DD genotype was found in 1359 (29.4%) of the myocardial infarction cases and in 1637 (27.6%) of the controls (risk ratio 1.10 [95% CI 1.00-1.21]). The association between myocardial infarction and the DD genotype did not seem to be stronger in the subgroup defined as low risk by previously used criteria (234 [28%] of 836 cases and 911 [28%] of 3253 controls: risk ratio 1.04 [95% CI 0.87-1.24]), or in any other subgroup. Nor was the ACE I/D genotype predictive of subsequent survival. INTERPRETATION: This study involved many more cases than any previously reported study of this question, but did not confirm the existence of any substantial association. In an updated meta-analysis of these results with those of previously published studies, the risk ratio for myocardial infarction with the DD genotype seems to lie in the range 1.0 to about 1.1. Although an increase in risk of up to about 10-15% cannot be ruled out, substantially more extreme risks can be. Moreover, there are not especially strong associations in the subgroups previously selected for emphasis. These findings illustrate the need for some studies of candidate genes to involve much larger populations than is customary, without undue emphasis on retrospectively defined subgroups.
Adult↗
Factors affecting blood pressure responses to diet: the Vanguard study.
To study physiologic factors affecting the blood pressure (BP) response to nonpharmacologic maneuvers, fasting blood glucose, insulin, lipid and mineral levels, urinary mineral excretion, and the calcium regulating hormones parathyroid hormone (PTH) and 1,25 dihydroxyvitamin D (1,25 (OH)2D) were measured in 71 unmedicated hypertensive (26 hypertensive only [HT], 45 hypertensive hyperlipidemic [HTHL]), and 87 normotensive hyperlipidemic (NTHL) control subjects before and during a 10-week multicenter, randomized controlled trial comparing a prepared meal plan (CCNW) with a self-selected diet (SSD) based on nutritionist counseling. Blood pressure fell to a greater extent in hypertensive versus normotensive subjects (-8+/-1/-5+/-1 v -2+/-1/-2+/-1 mm Hg, P < .0001/P < .0001), and on CCNW versus SSD diets (delta systolic BP [SBP]/delta diastolic BP [DBP], P = .033/P = .002). Diet-induced weight change was the strongest correlate of changes in BP (SBP: r = 0.360, P < .0001; DBP: r = 0.414, P < .0001), which, on multivariate analysis for deltaSBP, could partly be accounted for by diet-induced changes in fasting glucose (r = 0.215, P = .009) and cholesterol (r = 0.219, P = .006) levels. Independently of weight, diet-induced changes in SBP also were significantly related to concomitant changes in urinary excretion of potassium (r = -0.285, P = .001), magnesium (r = -0.254, P = .003), and calcium relative to sodium (r = -0.200, P = .021), but not to sodium per se; and to changes in serum potassium (r = -0.249, P = .002), phosphorus (r = -0.279, P = .001), PTH (r = 0.288, P = .0006), and 1,25 D (r = 0.202, P = .017). We conclude that the ability of diet to lower BP successfully may result from the additive contributions of multiple components. Independently of weight loss and the associated changes in circulating glucose and cholesterol, BP is influenced by the increasing provision of minerals such as potassium, magnesium, and calcium, perhaps by virtue of their suppressive effects on circulating vasoactive calcium regulating hormones.
Adult↗
Induction of immunological memory in UK infants by a meningococcal A/C conjugate vaccine.
The induction of immunological memory to serogroup A and C polysaccharides in UK infants immunized with three doses of a meningococcal A/C oligosaccharide CRM197 conjugate vaccine was investigated. Forty UK infants vaccinated previously with three doses of a meningococcal A/C oligosaccharide-CRM197 conjugate vaccine at 2, 3 and 4 months of age, were revaccinated at a mean age of 145.6 weeks with either a 10 or 50 microg dose of licensed meningococcal A/C polysaccharide vaccine. Serogroup-specific antibody and serum bactericidal antibody (SBA) responses were measured by enzyme-linked immunosorbent assay and serum bactericidal assays, respectively. Following challenge, anti-serogroup A and C polysaccharide antibody levels rose from pre-booster geometric mean concentrations (GMC) of 3.1 and 2.1 microg/ml respectively to 19.6 and 21.0 microg/ml 1 month post-booster. Serum bactericidal antibody geometric mean titres (GMTs) for serogroups A and C increased 156- and 113-fold from 2.1 and 7.1 pre-booster respectively to 327.4 and 800.7 post-booster. A serogroup A control group of 45 children received a 10 microg dose of licensed meningococcal A/C polysaccharide vaccine (with no prior history of serogroup A vaccination) had serogroup A SBA GMTs of 2.3 pre-vaccination rising to 8 post-vaccination with corresponding GMCs of 0.8 and 10.8 microg/ml. These rises in SBA following serogroup A/C conjugate vaccination are indicative of immunological priming.
Antibodies, Bacterial↗
Sudden-onset asthma exacerbations: clinical features, response to therapy, and 2-week follow-up. Multicenter Airway Research Collaboration (MARC) investigators.
Sudden-onset asthma exacerbations may have different triggers and responses to treatment than slower-onset exacerbations. The authors studied this hypothesis among patients with severe asthma exacerbations. The Multicenter Airway Research Collaboration prospectively enrolled patients presenting to 64 North American emergency departments with asthma exacerbations. Of 1,847 patients aged 18-54 yrs, 900 had severe exacerbations (peak expiratory flow rate (PEFR) <50% predicted or hospitalized without PEFR). These patients were divided into sudden-onset (< or =3 h of symptoms) and slower-onset (>3 h of symptoms) groups. Fourteen per cent (95% confidence interval, 11-16%) of patients with severe asthma exacerbations had sudden-onset exacerbations. Sudden-onset patients were similar to slower-onset patients, except triggers of their exacerbations were more often respiratory allergens, exercise or psychosocial stress and less often respiratory infections. Sudden-onset patients were more likely to have used oral beta-agonists and salmeterol in the preceding 4 weeks. Although initial PEFRs and management were similar, sudden-onset patients had a greater improvement in PEFR (35 versus 28% p<0.001). Sudden-onset patients were less often discharged on systemic corticosteroids, but had similar 2-week relapse rates compared with slower-onset patients. Among patients presenting with severe asthma exacerbations, sudden-onset exacerbations had a different pattern of triggers and greater improvement with treatment than slower-onset exacerbations.
Adult↗
Control of an outbreak of respiratory syncytial virus infection in immunocompromised adults.
Respiratory syncytial virus (RSV) is increasingly recognized as an important pathogen in immunocompromised adults, particularly those receiving bone marrow transplants, and, given the ease with which it spreads, represents a significant nosocomial problem. We describe an outbreak of RSV infection involving eight patients on a haematology/oncology ward which was controlled by early screening of patients and staff. Positive patients were cohort nursed on a separate ward and basic infection control measures including use of gowns and gloves were enforced. Children under age 12 were denied ward access. All patients with lower respiratory tract infection, and bone marrow transplant recipients with upper respiratory symptoms, were treated with nebulized ribavirin. There were no deaths. We conclude that awareness of the risk of RSV infection in immunocompromised patients coupled with rapid diagnosis and treatment, screening of symptomatic patients and staff, cohort nursing of cases and basic infection control procedures can prevent spread of RSV infection and reduce morbidity.
Adult↗
Asthma education in the Emergency Department. On behalf of the MARC Investigators.
STUDY OBJECTIVE: We surveyed emergency department-based asthma researchers to study the presence of formal asthma education programs (AEPs), and examined data from prospective cohort studies to compare sites with and without AEPs. METHODS: We contacted site investigators in the Multicenter Airway Research Collaboration (MARC) in July 1998 by mail, fax, or telephone. Main outcomes were the percentage of sites using AEPs and the percentage of AEPs using each of 7 "key" teaching items in national guidelines. MARC data provided site and patient characteristics. RESULTS: All 77 site investigators (100%) responded to the survey. Using a scale from 1 to 5 (mean+/-SD), respondents identified instruction in proper inhaler technique (4.8+/-0.5), "spacer" use (4.3+/-0.7), recognition of asthma triggers (4.3+/-0.8), and rationale for medications (4. 6+/-0.6) as priorities for teaching. Twelve sites (16%; 95% confidence interval [CI] 8% to 26%) had AEPs; most (8) were at pediatric sites. Patients presenting to sites with AEPs were younger (22+/-16 years versus 25+/-15 years, P <.001), more likely to be uninsured (26% versus 23%, P <.001), and less likely to be taking inhaled corticosteroids (30% versus 37%, P <.001). AEP sites uniformly stressed "key" items, except for "written action plan" (50% of sites) and "peak flow diary" (33% of sites). CONCLUSION: Although asthma researchers agree that patient education is very important, few EDs involved in asthma research use AEPs. Sites with AEPs appear to serve patients at higher risk of poor asthma outcomes. Further study is needed to address the effectiveness of AEPs in the ED.
Administration, Inhalation↗
Meningococcal C polysaccharide vaccine induces immunologic hyporesponsiveness in adults that is overcome by meningococcal C conjugate vaccine.
Widespread use of meningococcal AC polysaccharide (MACP) vaccines has raised concerns about induction of hyporesponsiveness to C polysaccharide. Whether meningococcal C conjugate (MCC) vaccine overcomes any immunologic refractoriness following MACP vaccination in adults was investigated. University students vaccinated 6 months previously with MACP vaccine were randomized to receive MACP or MCC vaccine, and antibody responses were compared with those of previously unvaccinated students receiving MACP or MCC vaccine. In students primed with MACP vaccine, MCC vaccine induced significantly higher IgG and serum bactericidal antibody levels than did a second dose of MACP vaccine. Responses to a second dose of MACP vaccine were significantly lower than to the first dose. Previous receipt of MACP vaccine reduced serum bactericidal antibody but not IgG responses to MCC vaccine compared with those in previously unvaccinated students. This confirms that MACP vaccine induces immunologic hyporesponsiveness to C polysaccharide in adults, but this can be overcome with MCC vaccine. Repeated vaccination with MACP vaccine may be ineffective, and MCC vaccines should provide better long-term protection.
Adolescent↗
SRP Meeting: Land Remediation--Liabilities and Practicalities.
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Radiation Protection↗
Testing for hereditary breast and ovarian cancer in the southeastern United States.
OBJECTIVES: To detail characterization of mutations and uncharacterized variants in the breast cancer susceptibility genes BRCA1 and BRCA2, as observed in a population of breast cancer patients from the southeastern United States, and to examine baseline characteristics of women referred for counseling and testing and provide a preliminary look at how counseling and testing affected intentions toward prophylactic surgery. BACKGROUND: Mutations in the BRCA1 and BRCA2 genes give rise to a dramatically increased risk of developing breast or ovarian cancer or both. There are many reports about special populations in which deleterious mutations are present at a high frequency. It is useful to study these genes in more heterogeneous populations, reflecting different geographic regions. Interest in preventive surgery for gene carriers is high in women and their surgeons. METHODS: Women were recruited through a prospective clinical trial of counseling and free genetic testing. BRCA1 and BRCA2 were screened for mutations using standard techniques, and results were given to participants. Baseline questionnaires determined interest in preventive surgery at the beginning of the study. Follow-up questionnaires for those who completed testing surveyed interest in prophylactic surgery after counseling and receiving test results. RESULTS: Of 213 women who completed counseling and testing, 44 (20.6%) had 29 separate mutations; there were 11 Jewish women carrying three founder mutations. Twenty-eight women (13.1%) had uncharacterized variants in BRCA1 or BRCA2; nine were not previously reported. Women overestimated their chances of possessing a deleterious gene mutation compared to a statistical estimate of carrier risk. A number of women changed their intentions toward preventive surgery after genetic counseling and testing. CONCLUSIONS: Hereditary breast cancer due to mutations in BRCA1 and BRCA2 was a heterogeneous syndrome in the southeastern United States. Most mutations were seen just once, and uncharacterized variants were common and of uncertain clinical significance. In general, positive test results tended to reinforce intentions toward prophylactic surgery. In contrast, women not interested in surgery at the time of entry tended to remain reluctant after testing and counseling.
Attitude to Health↗
The bactericidal activity of gemifloxacin (SB-265805).
The bactericidal activity and mechanisms of action of the new fluoroquinolone gemifloxacin were investigated against the laboratory strains Escherichia coli KL16, Staphylococcus aureus E3T and Streptococcus pneumoniae C3LN4. Gemifloxacin was found to be highly bactericidal against these bacteria, producing a biphasic dose-response curve typical of the fluoroquinolones. This novel fluoroquinolone was more bactericidal than all other fluoroquinolones so far tested (ciprofloxacin, ofloxacin, enoxacin, lomefloxacin, levofloxacin, clinafloxacin, trovafloxacin, DV-7751 and sitafloxacin) against S. aureus and was more bactericidal than most other fluoroquinolones against E. coli or Str. pneumoniae. These data show gemifloxacin to be an improved member of the fluoroquinolone class of antibacterial agents.
Anti-Infective Agents↗
Prevalence of gestational diabetes mellitus in polycystic ovarian syndrome (PCOS) patients pregnant after ovulation induction with gonadotrophins.
Our aims were: 1. To investigate if women with PCOS who become pregnant using gonadotrophins have a higher incidence of gestational diabetes mellitus (GDM) compared to spontaneously pregnant matched control women, 2. To compare the prevalence of GDM in PCOS women with that in women with hypo/eugonadotrophic hypogonadism and in unexplained infertility and 3. To investigate differences in pregnancy outcomes between the groups. This was a retrospective case-control study. Women with PCOS were matched with a control by age, BMI, and ethnicity. There were 60 women with PCOS, 11 with hypogonadotrophic hypogonadism, 6 with eugonadotrophic hypogonadism, and 12 with unexplained infertility. Control women were those who attended a major public hospital for antenatal care and delivery We found no difference in the prevalence of GDM between the PCOS (22%) and the controls (17%) or between the PCOS and other groups. Women with GDM (diet or insulin controlled) had a significantly higher BMI than women without GDM (p = 0.019). There was no difference in pregnancy outcomes between the groups. There was a significant dependence of babies' birthweight on mother's BMI (p<0.001).
Adult↗
Can the control of bodily orientation be significantly improved in a group of older adults with a history of falls?
OBJECTIVE: To determine the short-term effectiveness of a biofeedback-based, computerized intervention that applied the principles of the ecological theory of perception and control of bodily orientation to the rehabilitation of older adults with a history of falling. PARTICIPANTS: Forty-five older adults (X = 78.5 years) with a history of falls were assigned to either a control (n = 21) or intervention group (n = 24). DESIGN: A 2 x 2 (Group x Time) mixed factorial design with repeated measures on the second factor. SETTING: A motor control research laboratory in a university setting. MEASUREMENT: Impairments in multiple dimensions of balance (i.e., dynamic postural control and sensory organization) were measured before and after an 8-week balance intervention using the 100% Limits of Stability Test and Sensory Organization Test. More functional limitations in balance and/or mobility were measured using two clinical tests: Berg Balance Scale and Timed Up and Go test. MAIN RESULTS: Repeated measures multivariate analyses and follow-up testing indicated significant improvements in the dynamic balance and sensory integration capabilities in the case of the intervention group only (P < .03). Significant improvements were also observed in the two clinical measures of balance and mobility evaluated before and after the intervention for the intervention group only. CONCLUSIONS: Theory-driven rehabilitation programs that focus on manipulating individual, task, and environmental constraints concurrently can significantly improve the control of bodily orientation of older adults with a previous history of falls in both static and dynamic action environments. Moreover, the significant improvements in functional performance observed for the intervention group suggest that interventions emphasizing task-specific practice are not the only means by which an older adult's ability to perform daily activities requiring postural control can be improved.
Accidental Falls↗
Relation between phase of menstrual cycle and emergency department visits for acute asthma.
Hormonal fluctuations during the menstrual cycle are hypothesized to influence the course of asthma among women. A recent study found that almost 50% of emergency department (ED) visits occur during the perimenstrual phase. Our prospective cohort study in 64 EDs examined the relation between phase of menstrual cycle and visits for acute asthma. A total of 288 women with acute asthma were evaluated with a standardized patient interview and medical record review after excluding subjects who were pregnant, on hormonal therapy, postmenopausal, status post hysterectomy, had incomplete reproductive data, or whose ED visit fell more than 28 d after their last menstrual period. Only 13% reported reproductive factors as a personal asthma trigger. For all subjects, ED asthma visits were classified by menstrual phase: 33% were preovulatory (Days 5 to 11), 26% were periovulatory (Days 12 to 18), 20% were postovulatory (Days 19 to 25), and 21% were perimenstrual (Days 26 to 4), p = 0.008. There was no significant association between phase of menstrual cycle and asthma severity. Our data indicate that ED visits for acute asthma among women are more frequent during the preovulatory phase in contrast to other studies reporting more visits in the perimenstrual phase.
Acute Disease↗
A pilot study examining changes in dust lead loading on walls and ceilings after lead hazard control interventions.
The U.S. Department of Housing and Urban Development (HUD) guidelines on lead hazard control instruct contractors to clean floors, windows, walls, ceilings, and other horizontal surfaces to remove lead-contaminated dust and debris after lead interventions are conducted. This dust removal activity adds costs to each project. The need to clean floors and windows is well documented in the HUD guidelines. However, there is substantially less documentation to support the recommendation to clean walls and ceilings. We examined whether it is necessary to clean walls and ceilings after lead hazard control (LHC) interventions by comparing dust lead loadings measured on these surfaces before an LHC intervention to dust lead loadings after the intervention. Twenty-two dwelling units undergoing substantial LHC measures consistent with the HUD guidelines were enrolled in the study. There was a significant increase in dust lead loading on walls and ceilings between the pre- and postintervention. The change in wall dust lead loading was substantial and created potentially harmful lead exposures. Although statistically significant, the change in ceiling dust lead loading was minimal and the postintervention dust lead loadings were far below the existing federal floor dust lead clearance standard. These results strongly support the recommendations in the HUD guidelines to clean walls after LHC interventions and do not provide sufficient justification to alter the current recommendation to clean ceilings after lead work.
Child↗
A comparison of hydrofibre and alginate dressings on open acute surgical wounds.
This study aimed to compare the performance of a hydrofibre (Aquacel) and an alginate (Sorbsan) dressing on acute surgical wounds left to heal by secondary intention. A total of 100 patients were prospectively randomised pre-operatively to receive either the hydrofibre or the alginate dressing. Dressing performance was measured at operation, at 24 hours and seven days. Parameters measured included ease of: application and removal of the first dressing; re-application on the first postoperative day; and removal and re-application one week postoperatively. The hydrofibre dressing received higher scores for all of these categories. Patients in this group also experienced less pain (mild or none) on removal of the first dressing and at one week. However, these results did not achieve statistical significance, and should be seen as a trend. Nevertheless, the authors recommend the use of hydrofibre dressings on open acute surgical wounds.
Acute Disease↗