Biomedical subjects
Publications and source records attributed to C White.
In emergencies, family court judges must often make rapid decisions, without benefit of thorough information, that have significant impact on people's lives. Action-oriented research was used to develop a model that would bring psychosocial factors to the legal system for the purpose of enhancing the judicial decision-making process in emergency and temporary child placement cases.
BACKGROUND: Although atopic eczema (AE) is a common disease, little is known about its causes. OBJECTIVES: To investigate the role of dietary and environmental factors associated with the development of AE by the age of 2 years. METHODS: A cohort of children was recruited before birth from a consecutive series of newly pregnant mothers presenting for antenatal care at three general practices in Ashford, Kent, U.K. Data up to the age of 2 years were available for 624 (97%) of the original cohort. AE was defined using components of the U.K. diagnostic criteria for AE, maternal report of doctor-diagnosed eczema and maternally reported eczema. Exposures of interest were family history of allergic disease, dietary and breastfeeding patterns, family size and exposure to indoor domestic allergens. RESULTS: The cumulative prevalence of AE using the U.K. diagnostic criteria was 14% (95% confidence interval, CI 11-17%). The prevalence of maternally reported doctor-diagnosed eczema was much higher (31%, 95% CI 27-35%) and almost half (45%) the mothers reported that their child had ever had eczema (95% CI 41-49%). The relationship between parental atopy, parental history of allergic disease and the child's eczema was consistently stronger for the mothers than the fathers. There was a marked increase in the prevalence of eczema with increasing maternal education and in less crowded homes, associations that remained significant after controlling for other factors. CONCLUSIONS: The associations with environmental factors are consistent with the hypothesis that more crowded houses, increased family size and birth order, which may possibly increase early exposure to infections, may offer protection from subsequent development of eczema.
An exploratory study of the experiences of parents caring for young children with seizure disorders and their perceived needs for information and support was conducted. A questionnaire and interview protocol was designed to elicit information about the child's seizure history, child and parent health history, medical and support services, child and family demographic information, parent experiences in caring for a young child with seizures, and perceptions about needs for information and support. Interviews were conducted with 31 parents who were recruited from a pediatric neurology clinic at a university hospital. Interviews were audiotaped, transcribed, and analyzed for major themes. The study revealed a broad range of experiences in caring for young children with seizures, and the early onset and severity of seizures often influenced these experiences. Obtaining information that was easily accessible and helped them to better understand their child's diagnosis and treatment was a challenge reported by many parents. In addition, interviews revealed that parents felt a need for support and information from individuals who were knowledgeable about the medical, developmental, emotional, and family issues related to coping with seizures in infants and young children. Recommendations for a comprehensive approach to the management of seizures for infants and young children are proposed, with particular focus on the role of nurses and early intervention professionals in providing information and support to families.
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Removal of adrenal steroids by adrenalectomy (ADX) slows or reverses the development of many forms of obesity in rodents, including those that are leptin or leptin receptor deficient. Obesity is associated with hyperleptinemia and leptin resistance. We hypothesized that glucocorticoids impair leptin receptor signaling and that removal thereof would activate the Janus kinase (JAK)-signal transducers and activators of transcription (STAT) signaling pathway. The inhibitory effect of leptin (2.5 microg icv) on food intake was enhanced in ADX rats. A combination of ribonuclease protection assays, RT-PCR, Western blots, and mobility shift assays was used to evaluate the leptin signaling pathway in whole hypothalami from sham-operated, ADX and corticosterone-replaced ADX (ADX-R) Sprague-Dawley rats that were treated acutely with either saline vehicle or leptin intracerebroventricularly. ADX increased the expression of leptin receptor mRNA, increased STAT-3 mRNA and protein levels, induced constitutive STAT-3 phosphorylation and DNA binding activity, and also reduced suppressor of cytokine signaling-3 (SOCS-3) mRNA and protein levels. ADX and leptin treatment increased STAT-3 phosphorylation, but with no concomitant increase in DNA binding activity. Leptin and ADX decreased NPY mRNA expression, but their combination did not further decrease NPY mRNA. Corticosterone supplementation of ADX rats partially reversed many of these effects. In conclusion, ADX through activation of STAT-3 and inhibition of SOCS-3 activates the JAK-STAT signaling pathway. These effects most probably explain the ability to prevent the development of obesity by removal of adrenal steroids.
The management outcome of gonorrhoea in the northern region of England was assessed and compared with the recently published national guidelines. An audit questionnaire was completed by all genitourinary medicine (GUM) clinics in the region. Information with regard to demographic data, microscopy, culture results, test of cure, antibiotic use and sensitivity and contact tracing were recorded. A total of 420 cases of gonorrhoea were diagnosed in 1998. The ratio of males to females with gonorrhoea was 2.1:1. Half were heterosexual males and one-third females. Direct microscopy was positive in 85% of heterosexual males but in less than one-third of females. Ciprofloxacin was the most commonly used antibiotic. One-third of the isolates were resistant or partially resistant to penicillin. Health advisors saw 85% of patients and 41-68% of 'potential' contacts were seen. The management of gonorrhoea in the northern region of England complies with the national guideline recommendations.
This study was designed to compare outcome in terms of disease-free survival (DFS) in women with histologically negative axillary lymph nodes and documented low proliferative rate cancer to other well-defined prognostic factors including type of adjuvant treatment. Between 1988 and 1998, we studied 669 patients with invasive node-negative breast cancer up to 5 cm in size and low proliferative rate measured by flow cytometry to determine S-phase fraction (SPF) or by histochemistry (Ki67/MIB1). At a median follow-up of 53 months, 5-year DFS for the entire group was 94% and did not differ significantly by type of systemic adjuvant treatment: none (133 patients, 95% DFS), tamoxifen (441 patients, 94% DFS), or chemotherapy with doxorubicin and cyclophosphamide (95 patients, 92% DFS). In a multivariate prognostic factor analysis, only tumor size was significant; 5-year DFS was 96% for T1N0 cancer versus 89% for T2N0 cancer (P = 0.01). We have prospectively confirmed that a low rate of proliferation as measured by SPF or MIB1 determination confers an excellent prognosis in invasive node-negative breast cancer up to 5 cm in size, regardless of adjuvant treatment.
Using bioinformatics approaches, 34 potential multidrug resistance (MDR) transporter sequences representing 4 different transporter families were identified in the unannotated Enterococcus faecalis database (TIGR). A functional genomics campaign generating single-gene insertional disruptions revealed several genes whose absence confers significant hypersensitivities to known antimicrobials. We constructed specific strains, disrupted in a variety of previously unpublished, putative MDR transporter genes, as tools to improve the success of whole-cell antimicrobial screening and discovery. Each of the potential transporters was inactivated at the gene level and then phenotypically characterized, both with single disruption mutants and with 2-gene mutants built upon a delta norA deleted strain background.
OBJECTIVE: To investigate the knowledge, beliefs, and ethical concerns of nurses caring for patients dying in intensive care units. METHODS: A survey was mailed to 3000 members of the American Association of Critical-Care Nurses. The survey contained various scenarios depicting end-of-life actions for patients: pain management, withholding or withdrawing life support, assisted suicide, and voluntary and nonvoluntary euthanasia. RESULTS: Most of the respondents (N = 906) correctly identified the distinctions among the end-of-life actions depicted in the scenarios. Almost all (99%-100%) agreed with the actions of pain management and withholding or withdrawing life support. A total of 83% disagreed with assisted suicide, 95% disagreed with voluntary euthanasia, and 89% to 98% disagreed with nonvoluntary euthanasia. Most (78%) thought that dying patients frequently (31%) or sometimes (47%) received inadequate pain medicine, and almost all agreed with the double-effect principle. Communication between nurses and physicians was generally effective, but unit-level conferences that focused on grief counseling and debriefing staff rarely (38%) or never (49%) occurred. Among the respondents, 37% had been asked to assist in hastening a patient's death. Although 59% reported that they seldom acted against their consciences in caring for dying patients, 34% indicated that they sometimes had acted against their conscience, and 6% had done so to a great extent. CONCLUSIONS: Intensive care unit nurses strongly support good pain management for dying patients and withholding or withdrawing life-sustaining therapies to allow unavoidable death. The vast majority oppose assisted suicide and euthanasia. Wider professional and public dialogue on end-of-life care in intensive care units is warranted.
BACKGROUND: Little is known about the painfulness of procedures commonly performed in acute and critical care settings. OBJECTIVE: To describe pain associated with turning, wound drain removal, tracheal suctioning, femoral catheter removal, placement of a central venous catheter, and nonburn wound dressing change and frequency of use of analgesics during procedures. METHODS: A comparative, descriptive design was used. Numeric rating scales were used to measure pain intensity and procedural distress; word lists, to measure pain quality. RESULTS: Data were obtained from 6201 patients: 176 younger than 18 years and 5957 adults. Mean pain intensity scores for turning and tracheal suctioning were 2.80 and 3.00, respectively (scale, 0-5), for 4- to 7-year-olds and 52.0 and 28.1 (scale, 0-100) for 8- to 12-year-olds. For adolescents, mean pain intensity scores for wound dressing change, turning, tracheal suctioning, and wound drain removal were 5 to 7 (scale, 0-10); mean procedural distress scores were 4.83 to 6.00 (scale, 0-10). In adults, mean pain intensity scores for all procedures were 2.65 to 4.93 (scale, 0-10); mean procedural distress scores were 1.89 to 3.47 (scale, 0-10). The most painful and distressing procedures were turning for adults and wound care for adolescents. Procedural pain was often described as sharp, stinging, stabbing, shooting, and awful. Less than 20% of patients received opiates before procedures. CONCLUSIONS: Procedural pain varies considerably and is procedure specific. Because procedures are performed so often, more individualized attention to preparation for and control of procedural pain is warranted.
The Thunder Project II study described procedural pain in a variety of acute and critical care settings. The procedures studied were turning, tracheal suctioning, wound drain removal, nonburn wound dressing change, femoral sheath removal, and central venous catheter insertion. Turning had the highest mean pain intensity, whereas femoral sheath removal and central venous catheter insertion had the least pain intensity in adults. Nonwound dressing change had the highest pain intensity for teenagers. Pain occurred in procedures that are often repeated several times a day as well as in those that may be single events. There is a wide range of pain responses to any of these procedures; as a result, standardized and thoughtful pain, and distress assessments are warranted. Planning of care, including the use of preemptive analgesic interventions, needs to be individualized. Future studies are needed to describe patient responses to other commonly performed nursing procedures and to identify effective interventions for reducing procedural pain and distress.
Congenital malformations represent the major risk of pregnancy in diabetic women. Prevention needs strict glycemic control before and during pregnancy. The risk of maternal and foetal complications is particularly high among patients with diabetic nephropathy, and a multidisciplinary approach is necessary. Before pregnancy, nephropathy is evaluated on serum creatinine and 24 hour urinary albumin and protein excretions. We discuss the interactions between diabetic nephropathy and pregnancy: the care of the other diabetic complications, the course of renal function during and after pregnancy, the influence of nephropathy on maternal and foetal complications and prevention of the latter by strict control of blood pressure and glycaemia before and during pregnancy. All these elements should be taken into account when discussing pregnancy with diabetic women with nephropathy wishing to become pregnant. The need to take preventive measures should be emphasised but the practice of systematically discouraging pregnancy without careful evaluation should be avoided.
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The intracellular calcium concentration ([Ca2+]i) was monitored in fura-2-loaded myocytes isolated from the rat gastric antrum and voltage clamped at -60 1r1rqmV1qusing the perforated patch clamp technique. The rate of quench of fura-2 fluorescence by Mn2+ was used as a measure of capacitative Ca2+ entry. Cyclopiazonic acid (5 microM) did not affect the holding current but produced a sustained elevation in steady-state [Ca2+]i that was dependent on the presence of external calcium. Cyclopiazonic acid increased Mn2+ influx with physiological external [Ca2+], but not in Ca2+-free conditions. Cyclopiazonic acid increased the rate of [Ca2+]i rise following a rapid switch from Ca2+-free to physiological [Ca2+] solution. Sustained application of carbachol (10 microM) produced an elevation in steady-state [Ca2+]i that was associated with an increased rate of Mn2+ influx. Application of cyclopiazonic acid in the presence of carbachol further elevated steady-state [Ca2+]i without changing Mn2+ influx. Ryanodine (10 microM) elevated steady-state [Ca2+]i either on its own or following a brief application of caffeine (10 9i1s1sqmMc1q). Cyclopiazonic acid had no further effect when added to cells pre-treated with ryanodine. Neither caffeine nor ryanodine increased the rate of Mn2+ influx. When brief applications of ionomycin (25 microM) in Ca2+-free solution were used to release stored Ca2+, ryanodine reduced the amplitude of the resulting [Ca2+]i transients by approximately 30 %, indicating that intracellular stores were partially depleted. These findings suggest that continual uptake of Ca2+ by the sarcoplasmic reticulum Ca2+-ATPase into a ryanodine-sensitive store limits the bulk cytoplasmic [Ca2+]i under resting conditions. This pathway can be short circuited by 10 microM ryanodine, presumably by opening Ca2+ channels in the sarcoplasmic reticulum. Depletion of stores with cyclopiazonic acid or carbachol also activates capacitative Ca2+ entry.
OBJECTIVES: The study was done to assess patients in the Post-Coronary Artery Bypass Graft (Post-CABG) trial to determine prognostic factors for atherosclerosis progression. BACKGROUND: Saphenous vein grafts (SVGs) are effective in relieving angina and, in certain patient subsets, in prolonging life. However, the progression of atherosclerosis in many of these grafts limits their usefulness. METHODS: The Post-CABG trial studied moderate versus aggressive lipid-lowering and low-dose warfarin versus placebo in patients with a history of coronary artery bypass surgery and found that more aggressive lipid lowering was effective in preventing progression of atherosclerosis in SVGs, but warfarin had no effect. Using variables measured at baseline, we sought the independent prognostic factors for atherosclerosis progression in SVGs, employing the statistical method of generalized estimating equations with a logit-link function. RESULTS: Twelve independent prognostic factors for atherosclerosis progression were found. In the order of their importance they were: maximum stenosis of the graft at baseline angiography, years post-SVG placement; the moderate low-density lipoprotein-cholesterol (LDL-C) lowering strategy; prior myocardial infarction; high triglyceride level; small minimum graft diameter; low high-density lipoprotein-cholesterol (HDL-C); high LDL-C; high mean arterial pressure; low ejection fraction; male gender; and current smoking. CONCLUSIONS: This study identified Post-CABG patient and SVG characteristics associated with saphenous vein graft atherosclerosis progression. These data provide a basis for rational risk factor management to prevent progression of SVG atherosclerosis.
OBJECTIVES: To evaluate the long-term effects of finasteride on symptoms, acute urinary retention (AUR), and the need for benign prostatic hyperplasia (BPH)-related surgery in relationship to baseline symptom severity. METHODS: A total of 3040 men with BPH were treated for 4 years with finasteride or placebo. The changes from baseline in symptoms and the incidence of BPH-related surgery and AUR were determined in men with mild (less than 8), low-moderate (8 to 12), high-moderate (13 to 19), and severe (greater than 19) baseline quasi-American Urological Association symptoms for all patients and for the subgroup with a baseline prostate-specific antigen (PSA) level of 1.4 ng/mL or greater. RESULTS: In patients who completed the 4-year study, the change in symptom score, stratified by baseline symptom severity, was +1.4 +/- 0.5 (mild), -0.8 +/- 0.3 (low-moderate), -3.6 +/- 0.3 (high-moderate), and -7.7 +/- 0.5 (severe) in finasteride-treated patients and, respectively, +3.4 +/- 0.5, +0.7 +/- 0.3, -1.4 +/- 0.3, and -5.3 +/- 0.6 in placebo-treated patients (between-group P <0.01). The between-group differences were greater in the subgroup of patients with a baseline PSA of 1.4 ng/mL or greater. The risk of BPH-related surgery increased among placebo patients with increasing baseline symptom severity to a greater extent than the risk of AUR. Finasteride reduced the risk of AUR or the need for BPH-related surgery in all subgroups (P <0.001), especially in men with a baseline PSA of 1.4 ng/mL or greater. CONCLUSIONS: Compared with placebo, finasteride had a beneficial effect on symptoms, AUR, and BPH-related surgery in all symptom categories. BPH-related surgery, but not AUR, occurred more commonly in placebo-treated men with more severe baseline symptoms. The greatest absolute benefit of finasteride on symptoms and the reduction in risk of AUR and surgery was in men with higher baseline symptom scores and a baseline PSA level of 1.4 ng/mL or greater.
BACKGROUND: The Post Coronary Artery Bypass Graft Trial, designed to compare the effects of 2 lipid-lowering regimens and low-dose anticoagulation versus placebo on progression of atherosclerosis in saphenous vein grafts of patients who had had CABG surgery, demonstrated that aggressive lowering of LDL cholesterol (LDL-C) levels to <100 mg/dL compared with a moderate reduction to 132 to 136 mg/dL decreased the progression of atherosclerosis in grafts. Low-dose anticoagulation did not significantly affect progression. METHODS AND RESULTS: Approximately 3 years after the last trial visit, Clinical Center Coordinators contacted each patient by telephone to ascertain the occurrence of cardiovascular events and procedures. The National Death Index was used to ascertain vital status for patients who could not be contacted. Vital status was established for all but 3 of 1351 patients. Information on nonfatal events was available for 95% of surviving patients. A 30% reduction in revascularization procedures and 24% reduction in a composite clinical end point were observed in patients assigned to aggressive strategy compared with patients assigned to moderate strategy during 7.5 years of follow-up, P=0. 0006 and 0.001, respectively. Reductions of 35% in deaths and 31% in deaths or myocardial infarctions with low-dose anticoagulation compared with placebo were also observed, P=0.008 and 0.003, respectively. CONCLUSIONS: -The long-term clinical benefit observed during extended follow-up in patients assigned to the aggressive strategy is consistent with the angiographic findings of delayed atherosclerosis progression in grafts observed during the trial. The apparent long-term benefit of low-dose warfarin remains unexplained.
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