Biomedical subjects
Publications and source records attributed to R Williams.
In a prospective study, 60% of admissions to an academic hospital were infected with HIV. HIV infected children were younger, less likely to have been referred, more likely to have pneumonia and candidiasis, and had more health service attendances. This impact may be alleviated by appropriate primary and secondary level health care.
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OBJECTIVE: The objective of this study was to evaluate alternative procedures for improving the understanding of research consent disclosures by persons who have mental illness. METHODS: Three groups participated in the study: persons with schizophrenia (N=79), persons with depression (N=82), and a healthy control group (N=80). The participants were guided through an informed consent process in which two factors were manipulated. One was the structure of the disclosure form; either a typical disclosure form involving standard dense text was used, or a graphically enhanced form was used. The other was the interpersonal process: the presence or absence of a third-party facilitator, with iterative feedback given to participants for whom a facilitator was not present. Participants' understanding of the disclosure was assessed with the use of recall tests that involved paraphrasing and recognition tests that involved multiple choice. RESULTS: The mean understanding scores did not differ significantly between the depression and control groups, and the mean scores of the schizophrenia group were significantly lower than those of the other two groups. Neither the graphically enhanced consent disclosure form nor the presence of a third-party facilitator was associated with improved understanding. The use of iterative feedback was associated with improvement in comprehension scores in all groups. CONCLUSIONS: The use of a feedback procedure in the consent disclosure process during the recruitment of persons who are mentally ill may be a valuable safeguard for ensuring adequate understanding and appropriate participation in research.
Erythrocyte lysate (hemolysate) released from blood clot after subarachnoid hemorrhage is the causative agent for chronic cerebral vasospasm, a prolonged contraction of cerebral arteries. Fibroblasts, the outer layer cells of vessel wall that in contact with blood clot directly, may contribute to cerebral vasospasm. However, the effect of hemolysate on intracellular Ca2+ ([Ca2+]i) mobilization in fibroblasts has not been studied. We investigated hemolysate-induced [Ca2+]i mobilization in cultured neonatal human dermal and canine middle cerebral arterial fibroblasts by using fura-2 microfluorimetry. Hemolysate increased [Ca2+]i by releasing internal Ca2+ stores and promoting Ca2+ entry. Tyrosine kinase inhibitors partially but significantly reduced the effect of hemolysate. The major components of hemolysate, oxyhemoglobin (OxyHb) and adenosine triphosphate (ATP) failed to mimic the effect of hemolysate. In cultured canine middle cerebral arterial fibroblasts, hemolysate produced similar Ca2+ mobilization to that of dermal cells. OxyHb and ATP failed again to reproduce the effect of hemolysate. We conclude that hemolysate increases [Ca2+]i in fibroblasts and this effect of hemolysate is not mediated by OxyHb or ATP but by some unknown factors.
Examined the effects of cumulative prenatal substance exposure and cumulative environmental risk on the developmental trajectories of 278 infants, toddlers, and preschool children. Results indicated that both cumulative risk indexes were significantly correlated. Results also indicated that both indexes were related to decrements in developmental trajectories (intercept and slope) from 3 to 57 months of age. Both prenatal exposure and environmental risk added unique variance to the prediction of developmental level and rate of growth when entered after covariates (i.e., birth weight and sex). However, across a number of models with and without covariates, environmental risk accounted for more variance in developmental trajectories than did prenatal exposure. Implications are discussed.
OBJECTIVES: To evaluate the work life and job satisfaction of pediatric generalists and subspecialists in comparison to each other and to a group of general internists and internal medicine subspecialists. METHODS: Data were collected by survey of a national sample of 5704 general pediatricians, subspecialty pediatricians, general internists, internal medicine subspecialists, and family physicians who were selected randomly from the American Medical Association Masterfile using stratified sampling with disproportionate weighting to ensure ethnic diversity and representation of high managed care areas. Surveys were mailed up to 4 times and contained 150 items that reflected 10 facets of physician job satisfaction as well as an assessment of individual and practice demographic information. This study reports data from all groups except for family medicine. RESULTS: The adjusted response rate was 58% for general pediatricians (n = 590), 67% for specialty pediatricians (n = 345), and 52% (n = 1823) for the entire pool. In comparison with general internists, general pediatricians were more likely to be female (44% vs 24%); to work part time (20% vs 12%); to have lower annual income ($125 679 vs $143 875); and to report significantly higher levels of job, career, and specialty satisfaction on a 5-point scale (3.81 vs 3.52, 3.80 vs 3.55, and 3.76 vs 3.17 respectively). In comparison with internal medicine subspecialists, pediatric subspecialists were more likely to be female (42% vs 22%); to work in academically affiliated settings (35% vs 17%); to have lower incomes ($156 284 vs $192 006); to receive significantly less time for a complete history and physical examination (39 minutes vs 51 minutes); and to report similar levels of job, career, and specialty satisfaction (3.69 vs 3.71, 3.74 vs 3.78, and 3.60 vs 3.47 respectively). Of all 4 physician groups, general pediatricians worked the fewest hours (50/week), spent the greatest percentage of time in the office and the lowest percentage in the hospital (58% and 16%, respectively), saw the lowest percentage of patients with complex medical and complex psychosocial problems (15% and 17%, respectively), and were the least likely to endorse symptoms of burnout or job stress (13% and 18%, respectively). In comparison, pediatric subspecialists worked longer hours (59/week), spent the lowest percentage of time in the office and the greatest percentage of time in the hospital (22% and 44%, respectively), saw a much higher percentage of patients with complex medical and complex psychosocial problems (46% and 25%, respectively), and reported significantly higher levels of burnout and job stress (23% and 26%, respectively). CONCLUSIONS: Despite lower incomes, general pediatricians reported the highest levels of satisfaction and the least job stress of all 4 physician groups, whereas pediatric subspecialists reported levels of stress and burnout that raise significant concerns for the workforce of pediatric subspecialists of the future. Initiatives that improve clinical workload, balance inpatient and outpatient hours, and increase personal time of pediatric subspecialists should be considered.
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BACKGROUND: Drug dosages utilized during controlled clinical trials are not always optimal for patients encountered in day-to-day practice. The original trials of risperidone, a novel antipsychotic, suggested that an initial target dose of 6 mg/day was appropriate, but these trials were necessarily conducted among patients who were chronically impaired, hospitalized, and often partly drug resistant. DATA SOURCES: Relevant data relating to the dosage of risperidone identified through an online (MEDLINE) search using the keywords risperidone, schizophrenia, schizoaffective disorder dementia, bipolar disorder, and dose were supplemented by a review of international and U.S. Congress abstracts in which the dose of risperidone was specifically described. CONCLUSION: On the basis of naturalistic studies, clinical audit, phase 4 trials, positron emission tomography data, and 5 years of clinical experience, the currently recommended target dose of risperidone is 4 mg/day for most patients, with less-rapid titration than previously recommended. Moreover, a lower dose than this and slower titration may be appropriate for elderly patients, young patients, and first-episode patients.
B lymphocyte stimulator (BLyS; also known as TNFSF20, BAFF, TALL-1, zTNF4, and THANK), a tumor necrosis factor ligand family member, has recently been identified as a factor that promotes expansion and differentiation of the B cell population, leading to increases in serum immunoglobulin levels. Here, pharmacokinetic parameters for BLyS administered i.v. and s.c. to mice are described, and the effects of different dosing regimens on serum and salivary immunoglobulin levels as well as splenic cell populations are reported. The pharmacokinetics of BLyS following i.v. injection are monophasic with a half-life of 160 min, a clearance of 0.22 ml/min-kg, and a volume of distribution of 53 ml/kg. Systemic administration of BLyS to mice resulted in increased serum IgG, IgA, IgM, and IgE and salivary IgA as well as splenic B cell population expansion and differentiation. The i.v. and s.c. routes of administration were pharmacologically equivalent, even though s.c. bioavailability of BLyS is only 25%. BLyS (s.c.) dramatically elevated serum IgG and IgA levels, and the duration of the responses after cessation of treatment (t(1/2) = 4.4 and 1.3 days, respectively) are similar to the half-lives of endogenous IgG and IgA in mice. The IgM response is more modest than that of IgG and IgA but lasts longer (t(1/2) = 7.0 days) than the half-life of endogenous IgM. A linear pharmacodynamic response was identified between days of dosing x log(dose), and increases in serum IgG, IgA, and IgM indicating that the response is more sensitive to the duration of dosing than to the cumulative dose. The implications of these findings for therapeutic administration of BLyS are discussed.
OBJECTIVE: The researchers hoped to confirm the sensitivity and specificity of a single screening question for problem drinking: "When was the last time you had more than X drinks in 1 day?", where X=4 for women and X=5 for men. STUDY DESIGN: Cross-sectional study. POPULATION: Adult patients presenting to 3 emergency departments in Boone County, Missouri, for care within 48 hours of an injury. OUTCOMES MEASURED: The answers to the question were coded as never, more than 12 months ago, 3 to 12 months ago, and within the past 3 months. Problematic drinking was defined as either hazardous drinking (identified by a 29-day retrospective interview) or a past-year alcohol use disorder (defined by questions from the Diagnostic Interview Schedule). RESULTS: There was a 70% participation rate. Of 2517 interviewed patients: 29% were hazardous drinkers; 20% had a past-year alcohol use disorder; and 35% had either or both. Considering "within the last 3 months" as positive, the sensitivity of the single question was 86%, and the specificity was 86%. In men (n=1432), sensitivity and specificity were 88% and 81%; in women, 83% and 91%. Using the 4 answer options for the question, the area under the receiver-operating characteristic curve was 0.90. Controlling for age, sex, tobacco use, injury severity, and breath alcohol level in logistic regression models changed the findings minimally. CONCLUSIONS: A single question about the last episode of heavy drinking has clinically useful sensitivity and specificity in detecting hazardous drinking and alcohol use disorders.
OBJECTIVE: To evaluate a new technique for processing endometrial cytology for the diagnosis and exclusion of endometrial cancer. STUDY DESIGN: All women at risk for endometrial cancer with clinical indications for endometrial biopsy were evaluated by endometrial brush biopsy (Tao Brush, Cook OB-GYN, Bloomington, Indiana) and Pipelle (Cooper Surgical, Shelton, Connecticut) endometrial biopsies during one office visit. Patients were followed longitudinally for the development of endometrial cancer or until undergoing dilatation and curettage or hysterectomy. All comparisons were analyzed using the chi 2 or t test. RESULTS: One hundred one women (mean age, 58; range, 35-86) had endometrial biopsies performed. Median follow-up was > 21 months (range, 3-29). Twenty-two had cancer or atypia, while the remaining had benign diagnoses. When correlated with the final diagnosis, the Tao Brush had 95.5% sensitivity and the Pipelle, 86% sensitivity. Both devices had 100% specificity, positive predictive value of 100% and negative predictive value of 98%. When the results of the two biopsy devices are considered together, the positive and negative predictive value for detecting or excluding endometrial cancer was 100%. Based on 1998 Medicare reimbursements, a simultaneous second office biopsy using the Tao brush could save approximately $67 per case as compared to a sonohistogram and much more when compared to dilatation and curettage. CONCLUSION: Endometrial cancer can be reliably detected and excluded using these two distinct office biopsy devices simultaneously during one office visit. In patients with an indication for endometrial biopsy, no further diagnostic test may be necessary to exclude or diagnose endometrial cancer or atypia.
BACKGROUND: Competitive athletes, including adolescents, seek ways to gain advantage over competitors. One ergogenic aid is creatine, a naturally occurring nitrogen compound found primarily in skeletal muscle. Increasing creatine levels may prolong skeletal muscle activity, enhancing work output. METHODS: A questionnaire assessing awareness and use of creatine supplementation was completed by 674 athletes from 11 high schools. Data were statistically analyzed to determine variation among groups. RESULTS: Of those surveyed, 75% had knowledge of creatine supplements, and 16% used creatine to enhance athletic performance. Percentage of use increased with age and grade level. Awareness and use were greater among boys than girls. Adverse effects were reported by 26%. Most athletes consumed creatine using a method inconsistent with scientific recommendations. CONCLUSIONS: Use of creatine by adolescent athletes is significant and inconsistent with optimal dosing. Physicians, athletic trainers, and coaches should disseminate proper information and advise these adolescent athletes.
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In June 2000, twenty-eight infertile couples were treated by in vitro fertilization and embryo transfer at our initial assisted reproduction programme carried out in conjunction with Midland Fertility Services, Aldridge, Birmingham, England. A pre-requisite for treatment was that on day 3 of the menstrual cycle the levels of follicle stimulating hormone (FSH) and oestradiol (E2) should be < 10 i mu/l and < 100 pg/ml respectively in the female partner. The ages of the women ranged from 26 to 42 years with a mean age of 35.5 years. Down regulation was carried out by using buserelin acetate 0.5 microgram subcutaneously from day 21 of the cycle for 21 days. This process was completed when the ovaries and pituitary gland were quiescent and the endometrial thickness < 4 mm in diameter. On completion of down regulation the gonadotrophin hormone, pergonal (dosage of 150-450 units) was used for ovarian hyperstimulation. A total of 294 oocytes (mean of 10.5, range 2-45) were retrieved of which 138 were fertilized (mean of 4.9, range of 0-28). Twenty-four patients each received a mean of two embryos. Five patients (20.8%) had positive pregnancy tests. Three patients (0.1%) developed ovarian hyperstimulation syndrome (OHSS), one had the severe, and two, the mild form of the syndrome. All three cases were treated successfully. The success at the initial IVF controlled ovarian hyperstimulation augers well for the future of infertile couples seeking treatment at the Fertility Management Unit, The University of the West Indies, Jamaica.
The rising incidence of TB in the UK in the last decade has been attributed mainly to the persistently high TB rates amongst ethnic minority groups. The epidemiology of TB in these groups is presently poorly understood. The aim of this ecological study was to investigate the relationship between TB and poverty in the South Asian ethnic groups. TB notification rates in South Asians residing in Kirklees (West Yorkshire) were correlated with eight indices of deprivation. Spearman's correlation coefficient analysis suggested a strong relationship between notification rates and material deprivation (r = 0.58 [p value = 0.009 for a two-tailed test]). A similar association was also observed for unemployment (r = 0.51 [p value = 0.02 for a two-tailed test]), but not for overcrowding. This study suggests a link between TB and deprivation in ethnic minority groups in the UK.
OBJECTIVE: Catholic adults in the West of Scotland, who are mainly of Irish origin, have been shown to suffer excess morbidity and mortality compared to the general population. A major contributing factor to this inequality is socio-economic disadvantage. This paper investigates the health and socio-economic position of Catholics in the youngest generation. DESIGN: Secondary analysis of baseline data from the West of Scotland 11-16 STUDY: Teenage Health, which is a longitudinal school-based survey. SETTING: One hundred and thirty five primary schools in Glasgow and surrounding districts. SUBJECTS: Two thousand five hundred and eighty six final-year pupils (average age eleven years and three months), born in 1983/1984. RESULTS: Comparing Catholics and non-Catholics on a range of indicators of general health, recent acute symptoms, chronic conditions, mental health and physical measures, we found no evidence of any systematic health inequality. A few indicators did show statistically significant differences at the five percent level, but these were not in any consistent direction. In terms of household socio-economic position, though, we found strong evidence of disadvantage for Catholics. Catholic children were more likely to have parents of manual social class, without any formal qualifications, who were less likely to own their home or a car, more likely to express difficulty 'making ends meet', and more likely to live in a deprived area. CONCLUSIONS: We discuss the prospects for diminishing socio-economic inequality over time between Catholics and non-Catholics in this cohort, which will depend on Catholic social mobility. We consider the likelihood of enduring health equality for Catholics, which will depend on the effects of different influences on health over the life course.
Genital herpes has been associated with increased efficiency of the sexual transmission and enhanced replication of human immunodeficiency virus type 1 (HIV-1). In this study we demonstrate that exposure to infectious or heat-inactivated herpes simplex virus (HSV) type 1 or 2 virions increases HIV-1 expression in macrophages at least in part by inducing NF-kappaB activity. Neutralizing antibodies to the HSV glycoprotein gB or gD markedly attenuated these virion-mediated effects on HIV-1 expression in macrophages. Thus HSV infection of macrophages that reside in genital mucosal tissue induces HIV-1 replication in these cells. Our study may have implications for the management of patients who are coinfected with the two viruses.