Laboratory investigation of an E. coli O157:H7 outbreak associated with swimming in Battle Ground Lake,Vancouver, Washington

Escherichia coli O157:H7 has been associated with a number of waterborne outbreaks, but it has never been recovered from an implicated environment. This paper reports on an August 1999 outbreak of E. coli O157:H7 associated with swimming in Battle Ground Lake in Clark Country, Washington. E. coli O157:H7 was isolated from duck feces, as well as from two water samples. The authors used pulsed-field gel electrophoresis to compare these isolates with patient isolates for genetic homology. All the isolates yielded the same restriction fragment patterns. In addition, using polymerase chain reaction, the authors found patient isolates and environmental isolates to have the same virulence factors (Stx, eaeA, and hly).     

Effects of n-3 fatty acids on cartilage metabolism

Although the clinical benefits of dietary supplementation with n-3 polyunsaturated fatty acids (PUFA) has been recognised for a number of years, the molecular mechanisms by which particular PUFA affect metabolism of cells within the synovial joint tissues are not understood. This study set out to investigate how n-3 PUFA and other classes of fatty acids affect both degradative and inflammatory aspects of metabolism of articular cartilage chondrocytes using an in vitro model of cartilage degradation. Using well-established culture models, cartilage explants from normal bovine and human osteoarthritic cartilage were supplemented with either n-3 or n-6 PUFA, and cultures were subsequently treated with interleukin 1 to initiate catabolic processes that mimic cartilage degradation in arthritis. Results show that supplementation specifically with n-3 PUFA, but not n-6 PUFA, causes a decrease in both degradative and inflammatory aspects of chondrocyte metabolism, whilst having no effect on the normal tissue homeostasis. Collectively, our data provide evidence supporting dietary supplementation of n-3 PUFA, which in turn may have a beneficial effect of slowing and reducing inflammation in the pathogenesis of degenerative joint diseases in man.     

Neurophysiology and pharmacology of female genital sexual response

Vaginal sexual arousal is a vasocongestive and neuromuscular event controlled by facilitatory parasympathetic and inhibitory sympathetic inputs. Autonomic preganglionic parasympathetic and inhibitory sympathetic fibers to the vagina and clitoris originate in the spinal cord in the sacral parasympathetic nucleus at the sacral level and in the dorsal gray commissure and the intermediolateral cell column at the thoracolumbar level, respectively. Parasympathetic fibers are conveyed by the pelvic nerve, and sympathetic fibers are conveyed by the hypogastric nerve and the paravertebral sympathetic chain. The activity of these spinal nuclei is controlled by descending projections from the brain and sensory afferens (conveyed in the pudendal, hypogastric, pelvic, and vagus nerves) from the genitalia. A key but unresolved issue concerns the neurotransmitters involved in the control of genital sexual arousal. At the peripheral level, acetylcholine plays a minor role in the regulation of vaginal blood flow, however, recent data suggests that it may be involved in the control of vaginal smooth muscle contractions. Vasoactive intestinal peptide and nitric oxide may be responsible for the increase in vaginal blood flow during sexual arousal, whereas noradrenaline is likely inhibitory. Within the central nervous system, serotoninergic projections from the brain to the spinal cord likely inhibit the induction of genital arousal by peripheral informations (spinal reflex). Although some neurotransmitters regulating the display of sexual behavior have been identified (for example, dopamine), their involvement in the control of genital sexual arousal has not been invested. Anatomical and electrophysiological data point to a contribution of the paraventricular nucleus of he hypothalamus and the median preoptic area, respectively, as key elements in the control of genital arousal. The recent development of models allowing the assessment of vaginal sexual arousal in anesthetized female rats should assist in deciphering the neurochemical pathways controlling vaginal sexual arousal and the development of suitable pharmacological treatment for female sexual dysfunctions.     

Fiblast (trafermin) in acute stroke: results of the European-Australian phase II/III safety and efficacy trial

BACKGROUND: Trafermin (basic fibroblast growth factor) has been shown to reduce infarct volume in acute ischemic stroke models, and to promote functional recovery and new synapse formation when given to animals with completed cerebral infarction. A previous study in acute stroke patients suggested that trafermin was safe and well tolerated when given over a 3-hour period over a wide dose range. METHODS AND RESULTS: Double-blind, parallel group, placebo-controlled trial of a single 24-hour intravenous infusion of trafermin. Patients having onset of stroke symptoms within 6 h and a baseline score of >/=7 on the NIH Stroke Scale (>/=2 motor) were randomized to receive 5 or 10 mg of trafermin or placebo intravenously infused over 24 h. The primary efficacy outcome was a categorized combination of the Barthel and Rankin scales assessed at 90 days. A total of 286 patients had been enrolled at 55 sites in 11 countries when the sponsor directed that enrollment be stopped because an interim analysis of efficacy data predicted too small a chance of demonstrating a statistically significant benefit after recruitment of the planned 900 patients. The 5-mg group showed a slight but nonsignificant advantage over placebo (OR 1.2, 95% CI 0.72-2.00, p = 0.48); the 10-mg group showed a nonsignificant disadvantage (OR 0.74, 95% CI 0.44-1.22, p = 0.24). Mortality rates at 90 days were 17% in the 5-mg group, 24% in the 10-mg group and 18% in the placebo group. Treatment with trafermin was associated with an increased leukocytosis and a decrease in blood pressure: mean decrease in systolic blood pressure from baseline was 19 mm Hg in the 5-mg group, 22 mm Hg in the 10-mg group and 8 mm Hg in the placebo group. In a post hoc subgroup analysis, patients in the 5-mg group treated more than 5 h after the onset of symptoms showed an apparent advantage over placebo (OR 2.1, 95% CI 1.00-4.41, p = 0.044; after age adjustment: OR 1.9, 95% CI 0.91-4.13, p = 0.08). CONCLUSIONS: With the proper treatment regimen, trafermin can likely be given safely to stroke patients. The 5-mg dose showed a trend toward a treatment advantage. The ideal time window for this agent may exceed 5 h. This may open new avenues for acute stroke therapy, aiming at enhancing recovery mechanisms rather than immediate neuroprotection.     

Integrating the triptans into clinical practice

The triptans (selective serotonin agonists) are becoming the first-line alternatives in the acute pharmacological treatment of migraine, at least for attacks of moderate-to-severe intensity. Although clinical trials demonstrate significant differences in efficacy between triptan tablets, they often appear similar in efficacy when used in clinical practice, particularly after dose adjustments. Most patients with migraine consider drugs that can be administered orally to be the most user-friendly. However, gastrointestinal absorption may be impaired during migraine attacks because gastric motility is inhibited, and there is a risk that nausea during the attack will culminate in vomiting. Furthermore, in addition to their antimigraine properties, triptans may prolong the gastric emptying time. For this reason the absorption of any triptan taken orally during the migraine attack will be erratic and treatment effects inconsistent. Despite these barriers to good efficacy and high reliability, the tablet is the most commonly used triptan formulation.     

Rural families caring for a relative with dementia: barriers to use of formal services

Planning for the care of increasing numbers of elderly persons with dementia has become an urgent health services concern in Canada and elsewhere, yet little is known about the challenges of providing appropriate dementia care in rural areas. A community-based approach was used to obtain input from decision-makers and others to develop the objectives and design for a study of rural dementia care in the province of Saskatchewan, Canada. The resulting study design, which used both qualitative and quantitative methods, was then pilot tested in one rural health district (16,000 km2, population 20,000). This paper describes the study development process and reports selected findings from focus groups conducted with home care staff and family members, focussing on the theme of low use of formal supportive services such as home care and support groups by family caregivers. Participants identified eight barriers to the use of formal services, described consequences of low service use, and suggested strategies for addressing this concern.     

Synthetic AIDS vaccine by targeting HIV receptor

A class of synthetic peptide immunogens for the cell surface HIV receptor complex has been developed to elicit antibodies that block viral entry by inhibiting gp120-CD4 interaction. These peptides extend our HIV receptor-directed approach from passive immunotherapy with mAb B4 (Proc. Natl. Acad. Sci. U.S.A. 96 (1999) 10367) to active immunization by a synthetic peptide-based vaccine. A peptide site from CD4 was identified as a B cell epitope capable of mimicking a susceptible site on the HIV receptor complex, and then rendered immunogenic. An effective target antigenic site (B cell epitope) for the cell surface HIV receptor complex was selected by epitope mapping from among diverse CD4 and chemokine receptor peptides. It is a cyclized sequence modified from the CDR2-like domain of CD4 (AA 39-66), that was predicted to produce steric hindrance of the discontinuous recognition site of mAb B4. The immunogenicity of the targeted epitope was augmented by tandem combination with promiscuous T helper cell epitopes (Th). The antibody response to this class of immunogens attained sufficient concentrations and affinities of the correct specificity to block the interactions of HIV env glycoprotein with the cellular receptor, and prevent infection. The polyclonal antibodies generated against these fusion constructs in multiple animal species neutralized a broad array of HIV-1 primary isolates from clades A to E. Despite eliciting antibodies to the key CD4 immunomodulatory molecule, the site-specific and chemically defined immunogens displayed no overt immunotoxicity in baboons and have potential for the immunotherapy and immunoprophylaxis of HIV infection.     

Ethnic differences in social correlates of diet

Little is known about whether culture influences social correlates of dietary behaviors. Questionnaires on parent- and child-reported family and peer influences on children's fruit, juice and vegetable consumption were analyzed for ethnic group differences in responses. Grade 4-6 students completed the questionnaires in the classroom and their parents completed telephone or in-home interviews. Analyses of variance across ethnic categories and chi2 analysis of differences in ethnic group composition between clusters of scales were conducted. Few ethnic group differences were detected, suggesting substantial commonality among respondents. Ethnic differences might be accommodated by interventions tailored to particular behaviors among ethnic groups.     

Building confidence for work as house officers: student experience in the final year of a new problem-based curriculum

INTRODUCTION: Newly qualified doctors require an appropriate level of confidence for their new roles. Development of this confidence was a key objective in the final year of a new integrated course with an emphasis on student self-direction. CONTEXT: There are 5 placements in the final year course. Students use a Learning Planner to help them choose suitable placements and objectives to serve their learning needs. Educational supervision focuses on helping students determine their objectives and assessing them against these. METHODS: Course evaluation was by means of a questionnaire during final assessments. Cohorts of 310 and 316 students in successive years completed the evaluation. The interrelationship between variables was explored using logistic regression. RESULTS: 220/310 students in the 2000 cohort and 214/316 in the 2001 cohort agreed they felt confident with their prospective role as a pre-registration house officer (PRHO). Confidence was significantly associated with confidence in their clinical skills, belief in their ability to cope with uncertainty and feeling able to work as a team member. The experience of the 2 hospital placements and (in 2000 only) the elective was associated with increased confidence. In all placements helpful educational supervision and the achievement of the self-directed learning plan was associated with increased confidence as a potential doctor. CONCLUSION: Students perceive a relationship between learning experiences in the final year of a self-directed course and development of confidence for their future role. Whilst further elucidation of the nature of this relationship is required, this provides encouragement to curriculum planners to promote self-direction.