Evaluating projects funded by the Western Australian Health Promotion Foundation: first results

The paper describes output measures of performance of the WesternAustralian Health Promotion Foundation (Healthway), using asystem known as graduated project evaluation (GPE). Resultsare reported at the basic and process levels of evaluation on588 health and sponsorship projects, and at the impact levelbased on surveys of 5710 spectators and participants at 53 sport,arts and racing events sponsored by Healthway funds. At thebasic and process levels the average Healthway project reached7449 people directly and generated media coverage of healthmessages on 27.3 occasions. It secured, on average, 0.99 healthystructural reforms in recreational or cultural venues, involvedthe participation of local community members in project administrationin 38% of instances, and provided 1596 person-hours of healtheducation. Non-smoking, safe drinking, nutrition, exercise,sun protection, safe sex and injury prevention health messageswere promoted using 24 different types of sponsor benefits.Of the 5710 respondents surveyed post-event, 67% were awareof the promoted health message and 82% of these understood whatthe message meant. Four per cent of all respondents intendedto take action ranging from seeking information to adoptingthe health behaviour. A comparison of the cost-effectivenessof small and large sponsorship projects is given to illustratethe use of GPE to inform funding decisions. Smaller projectsoutperformed larger projects on all available indicators. Wediscuss the peculiar features of the health promotion foundationconcept, methods to improve its performance and implicationsfor future research.     

Inhibition of experimental autoimmune encephalomyelitis in Lewis rats by nasal administration of encephalitogenic MBP peptides: synergistic effects of MBP 68-86 and 87-99

Induction of mucosal tolerance by inhalation of soluble peptides with defined T cell epitopes is receiving much attention as a means of specifically down-regulating pathogenic T cell reactivities in autoimmune and allergic disorders. Experimental autoimmune encephalomyelitis (EAE) induced in the Lewis rat by immunization with myelin basic protein (MBP) and Freund's adjuvant (CFA) is mediated by CD4+ T cells specific for the MBP amino acid sequences 68-86 and 87-99. To further define the principles of nasal tolerance induction, we generated three different MBP peptides (MBP 68-86, 87-99 and the non- encephalitogenic peptide 110-128), and evaluated whether their nasal administration on day -11, -10, -9, -8 and -7 prior to immunization with guinea pig MBP (gp-MBP) + CFA confers protection to Lewis rat EAE. Protection was achieved with the encephalitogenic peptides MBP 68-86 and 87-99, MBP 68-86 being more potent, but not with MBP 110-128. Neither MBP 68-86 nor 87-99 at doses used conferred complete protection to gp-MBP-induced EAE. In contrast, nasal administration of a mixture of MBP 68-86 and 87-99 completely blocked gp-MBP-induced EAE even at lower dosage compared to that being used for individual peptides. Rats tolerized with MBP 68-86 + 87-99 nasally showed decreased T cell responses to MBP reflected by lymphocyte proliferation and IFN-gamma ELISPOT assays. Rats tolerized with MBP 68-86 + 87-99 also had abrogated MBP-reactive IFN-gamma and tumor necrosis factor-alpha mRNA expression in lymph node cells compared to rats receiving MBP 110-128 nasally, while similar low levels of MBP-reactive transforming growth factor-beta and IL-4 mRNA expressing cells were observed in the two groups. Nasal administration of MBP 68-86 + 87-99 only slightly inhibited guinea pig spinal cord homogenate-induced EAE, and passive transfer of spleen mononuclear cells from MBP 68-86 + 87-99-tolerized rats did not protect naive rats from EAE. Finally, we show that nasal administration of MBP 68-86 + 87-99 can reverse ongoing EAE induced with gp-MBP, although higher doses are required compared to the dosage needed for prevention. In conclusion, nasal administration of encephalitogenic MBP peptides can induce antigen-specific T cell tolerance and confer incomplete protection to gp-MBP-induced EAE, and MBP 68-86 and 87-99 have synergistic effects. Non-regulatory mechanisms are proposed to be responsible for tolerance development after nasal peptide administration.      

Mutational analysis of the SOX9 gene in campomelic dysplasia and autosomal sex reversal: lack of genotype/phenotype correlations

It has previously been shown that, in the heterozygous state, mutations in the SOX9 gene cause campomelic dysplasia (CD) and the often associated autosomal XY sex reversal. In 12 CD patients, 10 novel mutations and one recurrent mutation were characterized in one SOX9 allele each, and in one case, no mutation was found. Four missense mutations are all located within the high mobility group (HMG) domain. They either reduce or abolish the DNA-binding ability of the mutant SOX9 proteins. Among the five nonsense and three frameshift mutations identified, two leave the C-terminal transactivation (TA) domain encompassing residues 402-509 of SOX9 partly or almost completely intact. When tested in cell transfection experiments, the recurrent nonsense mutation Y440X, found in two patients who survived for four and more than 9 years, respectively, exhibits some residual transactivation ability. In contrast, a frameshift mutation extending the protein by 70 residues at codon 507, found in a patient who died shortly after birth, showed no transactivation. This is apparently due to instability of the mutant SOX9 protein as demonstrated by Western blotting. Amino acid substitutions and nonsense mutations are found in patients with and without XY sex reversal, indicating that sex reversal in CD is subject to variable penetrance. Finally, none of 18 female patients with XY gonadal dysgenesis (Swyer syndrome) showed an altered SOX9 banding pattern in SSCP assays, providing evidence that SOX9 mutations do not usually result in XY sex reversal without skeletal malformations.      

Anti-neutrophil cytoplasmic antibodies (ANCA) directed against bactericidal/permeability increasing protein (BPI): a new seromarker for inflammatory bowel disease and associated disorders

It was our purpose to determine the immunodiagnostic value of ANCA directed against BPI in diseases known to be associated with ANCA, such as ANCA-associated vasculitides, inflammatory bowel disease (IBD) and the associated condition primary sclerosing cholangitis. The immunoreactivity of recombinant BPI (rBPI) was established in order to develop an ELISA specific for rBPI. By means of this assay, BPI-ANCA were assessed in sera of 178 patients with IBD or the associated disorder primary sclerosing cholangitis, 112 patients with ANCA-associated vasculitides, and in sera of 182 disease and 140 healthy controls. BPI-ANCA were found to be closely associated with IBD and primary sclerosing cholangitis (34% and 44% of ANCA-positive sera, respectively). By contrast, BPI-ANCA positivity was low (<10%) in the double-negative sera of patients with ANCA-associated vasculitides and in disease and healthy controls. BPI-ANCA appear to constitute an important marker for IBD and primary sclerosing cholangitis, but not for the ANCA-associated vasculitides.     

ORAL BROMFENAC 10 AND 25 MG COMPARED WITH SUBLINGUAL BUPRENORPHINE 0.2 AND 0.4 MG FOR POSTOPERATIVE PAIN RELIEF

The aim of this single-dose, randomized, positive control, double-dummy,double-blind, parallel group study was to compare oral bromfenac10 and 25 mg with sublingual buprenorphine 0.2 and 0.4 mg fortreatment of postoperative pain. We studied 91 patients withmoderate or severe pain after general surgical or orthopaedicoperations, using pain intensity, pain relief, adverse effect,mood and sedation outcomes. There was a sig nificant analgesicdose—response for buprenor phine, showing study sensitivity,but not for bromfenac. The two bromfenac treatments were significantlysuperior to the two buprenorphine treatments. Significantlymore patients reported nausea with buprenorphine. There wasevidence of a ceiling effect for analgesia with bromfenac. (Br.J. Anaesth. 1993; 71: 814–817) Address for correspondence: Oxford Regional Pain Relief Unit,Churchill Hospital, Oxford OX3 7LJ.     

Residents' perspectives of their first 2 weeks in a long-term care facility

• ? This study investigated residents' perspectives of their first 2 weeks in a long-term care facility (LTCF). Twelve residents were interviewed to determine their experiences during the first 2 weeks, their needs, priorities and expectations, and their views about how relocation from home could be facilitated. The constant comparative method of qualitative analysis (Glaser & Strauss, 1967) was used.
• ? Qualitative analysis of the audiotaped interviews revealed four main categories: emotional reactions, transition activities, reflecting on their situation, and connecting with a personal philosophy.
• ? Residents' responses indicated that if they had actively participated in the decision to be admitted, the adjustment to the LTCF was easier. Connecting with a personal philosophy was also a significant factor.
• ? Nursing implications include recognition of the importance of preparing residents for admission, involving them in the decision, and listening to their perspectives throughout the relocation experience.

     

Nosocomial respiratory syncytial virus infection in Canadian pediatric hospitals: a Pediatric Investigators Collaborative Network on Infections in Canada Study

OBJECTIVE: To determine nosocomial transmission of respiratory syncytial virus (RSV) in Canadian pediatric hospitals, outcomes associated with nosocomial disease, and infection control practices. DESIGN: A prospective cohort study in the 1992 to 1994 winter respiratory seasons. SETTING: Nine Canadian pediatric university-affiliated hospitals. PARTICIPANTS: Hospitalized children with symptoms of lower respiratory tract infection (at least one of cough, wheezing, dyspnea, tachypnea, and apnea) and RSV antigen identified in a nasopharyngeal aspirate. RESULTS: Of 1516 children, 91 (6%) had nosocomial RSV (NRSV), defined as symptoms of lower respiratory tract infection and RSV antigen beginning >72 hours after admission. The nosocomial ratio (NRSV/[com-munity-acquired RSV {CARSV})] + NRSV) varied by site from 2.8% to 13%. The median length of stay attributable to RSV for community-acquired illness was 5 days, but 10 days for nosocomial illness. Four children with NRSV (4. 4%) died within 2 weeks of infection, compared with 6 (0.42%) with CARSV (relative risk = 10.4, 95% confidence interval: 3.0, 36.4). All sites isolated RSV-positive patients in single rooms or cohorted them. In a multivariate model, no particular isolation policy was associated with decreased nosocomial ratio, but gowning to enter the room was associated with increased risk of RSV transmission (incidence rate ratio 2.81; confidence interval: 1.65, 4.77). CONCLUSIONS: RSV transmission risk in Canadian pediatric hospitals is generally low. Although use of barrier methods varies, all sites cohort or isolate RSV-positive patients in single rooms. Children with risk factors for severe disease who acquire infection nosocomially have prolonged stays and excess mortality.