Nerve fibres are required to evoke a contact sensitivity response in mice

Previous work has indicated that the dermis and epidermis of skin contains abundant nerve fibres closely associated with Langerhans' cells. We have investigated whether these nerve endings are necessary for inducing and evoking a contact sensitivity (CS) response. Topical application of a general or a peptide (calcitonin gene-related peptide and substance P)-specific neurotoxin was employed to destroy the nerve fibres at skin sites subsequently used to induce or evoke the CS response. Elimination of nerve fibres abolished both induction and effector stages of the specific CS response. Denervation did not destroy the local Langerhans' cells, which were observed in increased numbers, or prevent them from migrating to lymph nodes. The local CS response was also abolished by systemic deletion of capsaicin-sensitive nerve fibres, suggesting that the loss of response was not non-specific but associated with the loss of specific nerve fibres. The results indicate that peptidergic nerve fibres are required to elicit a CS response and may be vital to the normal function of the immune system.     

Infection of patients by bloodborne viruses

BACKGROUND: Despite taking precautions, healthcare workers performing invasive procedures run a small risk of infection by bloodborne viruses. When injury occurs, the viral status of the patient is often unknown and testing requires informed consent, which may be refused. On the other hand, although the chance of transmission of infection from a healthcare worker to a patient is extremely small, such personnel have an obligation of disclosure and, if seropositive, are barred from performing invasive procedures. METHODS: The medical literature on bloodborne virus transmission between carers and patients was reviewed, and the UK Department of Health, General Medical Council and Royal College of Surgeons of England guidelines on the risk management of these infections were read, along with secondary references from all sources. RESULTS AND CONCLUSION: Patients have complete protection of confidentiality and the right to refuse testing, but these rights do not apply to the healthcare worker. When injured in circumstances in which the patient cannot or will not permit testing, carers can only submit to the risks of prophylactic treatment or go into denial. Infection may have devastating professional, personal and financial implications to carers and their dependants. Ways to re-establish a just balance between the legitimate rights of patients and healthcare workers are discussed.     

Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial

Context  Despite decades of use and considerable research, the role of estrogen alone in preventing chronic diseases in postmenopausal women remains uncertain. Objective  To assess the effects on major disease incidence rates of the most commonly used postmenopausal hormone therapy in the United States. Design, Setting, and Participants  A randomized, double-blind, placebo-controlled disease prevention trial (the estrogen-alone component of the Women's Health Initiative [WHI]) conducted in 40 US clinical centers beginning in 1993. Enrolled were 10 739 postmenopausal women, aged 50-79 years, with prior hysterectomy, including 23% of minority race/ethnicity. Intervention  Women were randomly assigned to receive either 0.625 mg/d of conjugated equine estrogen (CEE) or placebo. Main Outcome Measures  The primary outcome was coronary heart disease (CHD) incidence (nonfatal myocardial infarction or CHD death). Invasive breast cancer incidence was the primary safety outcome. A global index of risks and benefits, including these primary outcomes plus stroke, pulmonary embolism (PE), colorectal cancer, hip fracture, and deaths from other causes, was used for summarizing overall effects. Results  In February 2004, after reviewing data through November 30, 2003, the National Institutes of Health (NIH) decided to end the intervention phase of the trial early. Estimated hazard ratios (HRs) (95% confidence intervals [CIs]) for CEE vs placebo for the major clinical outcomes available through February 29, 2004 (average follow-up 6.8 years), were: CHD, 0.91 (0.75-1.12) with 376 cases; breast cancer, 0.77 (0.59-1.01) with 218 cases; stroke, 1.39 (1.10-1.77) with 276 cases; PE, 1.34 (0.87-2.06) with 85 cases; colorectal cancer, 1.08 (0.75-1.55) with 119 cases; and hip fracture, 0.61 (0.41-0.91) with 102 cases. Corresponding results for composite outcomes were: total cardiovascular disease, 1.12 (1.01-1.24); total cancer, 0.93 (0.81-1.07); total fractures, 0.70 (0.63-0.79); total mortality, 1.04 (0.88-1.22), and the global index, 1.01 (0.91-1.12). For the outcomes significantly affected by CEE, there was an absolute excess risk of 12 additional strokes per 10 000 person-years and an absolute risk reduction of 6 fewer hip fractures per 10 000 person-years. The estimated excess risk for all monitored events in the global index was a nonsignificant 2 events per 10 000 person-years. Conclusions  The use of CEE increases the risk of stroke, decreases the risk of hip fracture, and does not affect CHD incidence in postmenopausal women with prior hysterectomy over an average of 6.8 years. A possible reduction in breast cancer risk requires further investigation. The burden of incident disease events was equivalent in the CEE and placebo groups, indicating no overall benefit. Thus, CEE should not be recommended for chronic disease prevention in postmenopausal women.      

Baseline data and design for a randomized intervention study of dietary change in religious organizations

BACKGROUND: Reducing dietary fat has been identified as a potential means of preventing chronic disease. Several studies have identified methods of changing dietary fat consumption in small, intensive intervention settings. Fewer studies have examined how to improve dietary habits of individuals in the general public. METHODS: The Eating for a Healthy Life (EHL) project was a randomized trial [n = 40 religious organizations (ROs) and 2175 individuals, 1099 in intervention]. The study tested an intervention package of self-help books, motivational messages, and social interactions designed to change dietary behaviors (lowering fat, increasing fruit and vegetable consumption) among members of religious organizations aged 18 and over. The primary outcomes are fat- and fruit- or vegetable-related behaviors measured using the Fat and Fiber Behavior (FFB) Questionnaire. RESULTS: Religious organizations and their members participated fully in the initial study activities. CONCLUSIONS: This study will support a rigorous test of the intervention package.     

Effects of estrogen plus progestin on gynecologic cancers and associated diagnostic procedures: the Women's Health Initiative randomized trial

Context  The effects of continuous combined hormone therapy on gynecologic cancers have not been investigated previously in a randomized trial setting. Objective  To determine the possible associations of estrogen plus progestin on gynecologic cancers and related diagnostic procedures. Design, Setting, and Participants  Randomized, double-blind, placebo-controlled trial of 16 608 postmenopausal women, who had not had a hysterectomy at baseline and who had been recruited from 40 US clinical centers between September 1993 and October 1998 (average follow-up, 5.6 years). Intervention  One tablet per day containing 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate (n = 8506) or placebo (n = 8102). Main Outcome Measure  Incident invasive cancer of the ovary and endometrium. Results  In 5.6 years of follow-up, there were 32 cases of invasive ovarian cancer, 58 cases of endometrial cancer, 1 case of nonendometrial uterine cancer, 13 cases of cervical cancer, and 7 cases of other gynecologic cancers. The hazard ratio (HR) for invasive ovarian cancer in women assigned to estrogen plus progestin compared with placebo was 1.58 (95% confidence interval [CI], 0.77-3.24). The HR for endometrial cancer was 0.81 (95% CI, 0.48-1.36). No appreciable differences were found in the distributions of tumor histology, stage, or grade for either cancer site. The incidence of other gynecologic cancers was low and did not differ by randomization assignment. More women taking estrogen plus progestin required endometrial biopsies (33% vs 6%; P<.001). Conclusions  This randomized trial suggests that continuous combined estrogen plus progestin therapy may increase the risk of ovarian cancer while producing endometrial cancer rates similar to placebo. The increased burden of endometrial biopsies required to assess vaginal bleeding further limits the acceptability of this regimen. These data provide additional support for caution in the use of continuous combined hormones.      

Assessing service quality in paediatric audiology and early deaf education

Quality monitoring and assurance is a key aspect of evidence-based service provision in health and education. Part I of the present paper summarizes the results from a survey in which performance of health-based paediatric audiology services in the UK was assessed against existing good practice guidelines (NDCS, 1994, 1996). The results of the survey indicated varied levels of provision, with guidelines commonly not followed. Part II of the paper reports the detailed development of two short questionnaires designed to provide scores (out of 100) reflecting aspects of service quality in paediatric audiology services and in early deaf education services. The results from the use of the two indices (the Paediatric Audiology Service Index (PASI) and the Deaf Education Early Service Index (DEESI)) are presented along with data from some component questions. Although some services are functioning close to guideline levels of service, the overall distribution of scores is such as to raise serious concerns about the variability of quality and the consequent inequity of provision for children with permanent hearing loss and their families in both health and education services.     

Outcome of congenital diaphragmatic hernia

The outcome of congenital diaphragmatic hernia (CDH) differs for different stages of the fetus or infant's life (i.e., antenatal, immediate postnatal, and postoperative). Assessing combined data from nonrandomized studies is technically difficult. Following recognized methods of reviewing such trials, we aimed to review the available literature on the outcome of CDH to provide a guide to clinicians when counselling parents who have a fetus/infant with this condition. Thirty-five studies reporting data for CDH from 1985 to March 1998 were identified using a high sensitive search strategy, hand-searching journals, and reviewing references of relevant studies. These were systematically reviewed. The median overall mortality was 58% (interquartile range (IQR), 43-65%) for babies diagnosed in utero, 48% (IQR, 35-55%) if born alive, and 33% (IQR, 18-54%) postoperatively. Diagnosis before 25 weeks of gestation is not a uniformly bad prognostic indicator (median mortality, 60%). Outcome was worse for those fetuses with other anomalies (median mortality, 93%). The median percentage mortality for all infants born alive and treated in extracorporeal membrane oxygenation (ECMO) centers was 34% (IQR, 26-47%). Median percentage mortality for all ECMO-treated infants was 44% (IQR, 35-50%). Different treatment strategies may have a variable impact on outcome. These figures, together with local data, may help in parental counselling on prognosis for fetuses/infants with CDH.