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Biomedical subjects

R Harris

Publications and source records attributed to R Harris.

At least 73 records · Page 4Linked to original sources
PubMed1999

The 'easy street' myth: self harm among aboriginal and non-aboriginal female sole parents in urban state housing.

OBJECTIVE: To test the hypothesis that, controlling for socio-demographic factors, destructive behaviour among Aboriginal and non-Aboriginal female sole parents will not be significantly different. METHOD: This study took place among an urban population of sole parents in Adelaide, South Australia, living in government housing. Two sample subsets were made up of 52 Aboriginal and 45 non-Aboriginal mothers from similar postcodes. Trained interviewers administered a questionnaire which, in addition to basic demographic data, elicited information concerning finance, housing, upbringing, experience of abuse and police interaction. The major issue of concern in the study was suicide attempt. RESULTS: 1-in-3 of the whole sample, 2-in-5 of the non-Aboriginal and 1-in-4 of the Aboriginal subset had attempted suicide at least once and half more than once. Statistical differences among 'attempters' vs. 'non-attempters', irrespective of ethnicity, included increased familial alcohol abuse, physical and sexual abuse, economic difficulty, poor self esteem and perceived discriminatory treatment by welfare agencies and, in the case of Aboriginals, by police. CONCLUSION: The social environment is critical to understanding destructive behaviour, including self-harm, regardless of culture or ethnicity. The data show that suicide attempts among female sole parents in State-housing is one of the few health indices for which Aboriginal statistics are less than for non-Aboriginals. IMPLICATIONS: It is evident that class, rather than ethnicity, better explains self-harm in this urban population. It is suggested that reluctance to access services, especially in times of crisis, relates in part to perceptions of care services and that, for Aboriginals, the value of culturally appropriate community-run services have specific public health and policy implications.

Adult↗
PubMed1999

National Confidential Enquiry into counselling for genetic disorders by non-geneticists: general recommendations and specific standards for improving care.

OBJECTIVES: To assess genetic counselling by non-geneticists and to improve clinical practice. DESIGN: National retrospective review of casenotes. SETTING: Antenatal, paediatric, medical, and surgical units. SAMPLE: 1293 genetic events were identified, involving potentially avoidable cases of Down's syndrome, neural tube defect, cystic fibrosis, beta thalassaemia major and late onset medullary carcinoma of the thyroid (multiple endocrine neoplasia). Notes were available for review in 888 (69%) of these cases. OUTCOMES: Documented counselling, offers of relevant genetic screening and prenatal diagnosis. RESULTS: Clinical audit was frustrated by poor quality hospital records lacking evidence of counselling. Non-geneticist clinicians concentrate on the management of disease, and may overlook the need for counselling and recording data which patients will later need for decisions about reproduction or disease prevention. Counselling, screening and prenatal diagnosis were sometimes impossible because of late booking in pregnancy, or because of delayed diagnosis of an earlier affected child with cystic fibrosis. There are marked regional inequalities of access to genetic services, particularly for minority ethnic groups with increased risks of thalassaemia. Although patients were selected for this enquiry because they had known high risks of genetic disorders, on average less than half were referred to medical geneticists. General recommendations relevant for improvement of care for patients and families with medical genetic needs and those specific for each disorder are given. CONCLUSIONS: Assessment of the quality of genetic care becomes increasingly important as genetic counselling spreads beyond the narrow confines of specialist genetic services. Even though the events studied in this enquiry largely occurred between 1991 and 1995, there is little reason to believe that clinicians in general have become markedly better trained in medical genetics. The General Medical Council and Medical Royal Colleges should urgently consider the need for a national policy for improving undergraduate and postgraduate medical, nursing and midwifery education in genetics. Commissioners of clinical services should require that genetic management be at least as well-documented as surgical operations, drug records and informed consent, perhaps by using a nationally agreed pro-forma for prenatal diagnosis. Regular audit of counselling provided by non-geneticists is necessary to confirm that clinical improvements are occurring and standards are being met. The Confidential Enquiry provides data for a systematic approach to clinical governance of genetics in all specialities. This sets the scene for multi-speciality NHS genetic services capable of giving patients greater consistency both in access and in quality.

Clinical Competence↗
PubMed1999

Resting sestamibi imaging for the prognosis of low-risk chest pain.

OBJECTIVE: To assess the prognostic value of resting Tc-99m sestamibi scanning for adverse cardiac events (ACEs) in ED chest pain patients with a low probability of acute cardiac ischemia (ACI). METHODS: Sixty-nine consenting, hemodynamically stable patients with chest pain and a nondiagnostic electrocardiogram received an injection of 25 mCi of sestamibi during or within two hours of active pain. Scans were interpreted locally by a nuclear cardiologist or radiologist. Interrater reliability was assessed. ACEs of myocardial infarction (MI), death, or revascularization were assessed during the index hospitalization and over a one-year follow-up period. RESULTS: For ACEs, rest scanning with sestamibi had a sensitivity of 71% (95% CI = 0.33 to 0.97), a specificity of 92% (95% CI = 0.82 to 0.97), and an accuracy of 90% (95% CI = 0.87 to 0.99). The positive predictive value was 50% (95% CI = 0.19 to 0.82) and the negative predictive value was 97% (95% CI = 0.87 to 0.98). Sestamibi scanning was highly discriminating, with 62% of patients with positive scans but only 3% with negative scans having ACEs (p<0.001, log rank test). CONCLUSION: In patients with low-risk chest pain, sestamibi scanning has good specificity and moderate sensitivity for ACEs over a 12-month period.

Chest Pain↗
PubMed1999

Failure of exogenously administered interferon-gamma or blockage of endogenous interleukin-4 with specific inhibitors to augment the incidence of autoimmune diabetes in male NOD mice.

Interferon (IFN)-gamma and interleukin (IL)-4 are prototypic type 1 and type 2 cytokines which are known to play pathogenetic and protective roles, respectively, in NOD mouse IDDM. The capacity of male NOD mice to produce more IL-4 and less IFN-gamma within the insulitic lesions than females has been suggested to contribute to their lower incidence of diabetes. In this study we have tested the effects of prolonged prophylactic treatment of male NOD mice with rat IFN-gamma, mouse IFN-gamma, anti-IL-4 monoclonal antibody (mAb) and recombinant murine soluble IL-4 receptor (smIL-4R) on the diabetogenic events leading to insulitis and diabetes. None of these treatments influenced spontaneous and/or cyclophosphamide-induced autoimmune diabetogenesis in male NOD mice. Control mice exhibited comparable histological signs of insulitis and incidence of diabetes to those treated with either mouse/rat IFN-gamma or specific IL-4 inhibitors. On the contrary, both clinical and histological signs of diabetes were suppressed by prophylactic treatment with anti-IFN-gamma mAb. These findings indicate that the autoimmune diathesis of male NOD mice towards IDDM cannot be augmented by manipulation of endogenous IFN-gamma or IL-4.

Animals↗
PubMed1999

A clinical study of type 1 neurofibromatosis in north west England.

A clinical study of patients on the North West Regional Genetic Register with neurofibromatosis type 1 (NF1) identified 523 affected cases from 304 families. In those for whom relevant information was available, 86.7% (383 of 442) had more than six café au lait patches, 83.8% (310 of 370) had axillary freckling, 42.3% (151 of 357) had inguinal freckling, and 63% (157 of 249) had Lisch nodules. Cutaneous neurofibromas were present in 59.4% (217 of 365) and 45.5% (150 of 330) were noted to have subcutaneous tumours. Plexiform neurofibromas were present in 15.3% (80 of 523). A positive family history of NF1 was found in 71.2% (327 of 459) and 28.8% (132 of 459) of affected patients were considered to be the result of a new mutation. Learning difficulties of varying severity occurred in 62% (186 of 300). CNS tumours associated with NF1 were reported in 9.4% (49) of patients, optic gliomas occurring in 25 of these, 4.8% of patients. Some degree of scoliosis was reported for 11.7% (61), 1.9% (10) had pseudoarthrosis, 4.3% (23) had epilepsy, and 2.1% (11) had spinal neurofibromas. Actuarial analyses were carried out for both optic glioma and malignant nerve sheath tumours and the data are presented.

Adolescent↗
PubMed1998

Assembly mechanism of the oligomeric streptolysin O pore: the early membrane lesion is lined by a free edge of the lipid membrane and is extended gradually during oligomerization.

Streptolysin O (SLO) is a bacterial exotoxin that binds to cell membranes containing cholesterol and then oligomerizes to form large pores. Along with rings, arc-shaped oligomers form on membranes. It has been suggested that each arc represents an incompletely assembled oligomer and constitutes a functional pore, faced on the opposite side by a free edge of the lipid membrane. We sought functional evidence in support of this idea by using an oligomerization-deficient, non-lytic mutant of SLO. This protein, which was created by chemical modification of a single mutant cysteine (T250C) with N-(iodoacetaminoethyl)-1-naphthylamine-5-sulfonic acid, formed hybrid oligomers with active SLO on membranes. However, incorporation of the modified T250C mutant inhibited subsequent oligomerization, so that the hybrid oligomers were reduced in size. These appeared as typical arc lesions in the electron microscope. They formed pores that permitted passage of NaCl and calcein but restricted permeation of large dextran molecules. The data indicate that the SLO pore is formed gradually during oligomerization, implying that pores lined by protein on one side and an edge of free lipid on the other may be created in the plasma membrane. Intentional manipulation of the pore size may extend the utility of SLO as a tool in cell biological experiments.

Animals↗
PubMed1998

Efficacy of a dry fibrin sealant dressing for hemorrhage control after ballistic injury.

OBJECTIVE: To determine if a dry fibrin sealant dressing (DFSD) will provide superior hemostasis when compared with regular gauze in a ballistic injury animal model. DESIGN: A nonsurvival randomized goat study. SETTING: A federal biomedical research institute. SUBJECTS: Eighteen anesthetized Angora goats. INTERVENTIONS: Uncontrolled hemorrhage was induced by a complex ballistic extremity injury. Control of hemorrhage was achieved by applying and holding pressure with the DFSD or regular gauze for 2 minutes. The dressings were left in place for 1 hour. MAIN OUTCOME MEASURES: Total blood loss, mean arterial pressure, ballistic injury, and mortality were recorded after 1 hour. RESULTS: The injuries were equivalent for the 2 groups. No animal mortality was seen. After 1 hour, the mean (+/-SEM) blood loss was 124+/-64 mL in the DFSD-treated group and 377+/-64 mL in the gauze dressings-treated group (P=.01). Twenty minutes after injury, the mean arterial pressure was 95.0 mm Hg (+/-SEM, +/-4.7 mm Hg) in the DFSD-treated group and 70.0+/-5.0 mm Hg in the gauze dressings-treated group. The difference persisted for the remainder of the study (P=.01). CONCLUSION: The DFSD was superior to gauze in decreasing blood loss and maintaining blood pressure while retaining the simplicity of standard dressing application.

Animals↗
PubMed1998

Patient assessment: validation of a nursing instrument.

The aim of this study is to evaluate the reliability and validity of the Byron Physical Assessment Framework (BPAF). The BPAF is a systems based checklist of physiological measurements, signs, and symptoms designed to structure and document the assessment of a patients physical condition by nursing staff. Initially the BPAF was refined using extensive literature review and expert opinion to improve the comprehensiveness and clarity for its intended purpose. As a result the content validity of the BPAF was supported. Inter-rater reliability between both expert-expert and novice-expert pairings was assessed. A total of 68 assessments were conducted by pairs of qualified nurses with patients on general medical and surgical wards and a nursing-led unit in one London Hospital. Reliability of the dichotomous data items of the BPAF was found to be generally good (kappa > 0.6) with only one item showing a poor reliability (kappa < 0.20). Reliability for continuous items such as pulse and respiratory rate was surprisingly low with evidence of large variation between raters in addition to systematic bias. With relatively little teaching, novice assessors were able to use the BPAF and achieve good inter-rater reliability with expert assessors although this was lower than the reliability of the expert diads. The utilisation of the BPAF to fulfil intended purpose was assessed by examining completed assessments and the outcome in terms of nurses' actions in light of new abnormal findings. Both were found to be fair, showing that the BPAF does affect the actions of nurses although it could be utilised more.

Confounding Factors, Epidemiologic↗
PubMed1998

Evaluating precursor-directed biosynthesis towards novel erythromycins through in vitro studies on a bimodular polyketide synthase.

BACKGROUND: Modular polyketide synthases (PKSs) catalyse the biosynthesis of complex polyketides using a different set of enzymes for each successive cycle of chain extension. Directed biosynthesis starting from synthetic diketides is a potentially valuable route to novel polyketides. We have used a purified bimodular derivative of the erythromycin-producing polyketide synthase (DEBS 1-TE) to study chain extension starting from a variety of diketide analogues and, in some cases, from the alternative acyl-CoA thioester substrates. RESULTS: Chain initiation in vitro by DEBS 1-TE module 2 using a synthetic diketide analogue as a substrate was tolerant of significant structural variation in the starter unit of the synthetic diketide, but other changes completely abolished activity. Interestingly, a racemic beta-keto diketide was found to be reduced in situ on the PKS and utilised in place of its more complex hydroxy analogue as a substrate for chain extension. The presence of a diketide analogue strongly inhibited chain initiation via the loading module. Significantly higher concentrations of diketide N-acetylcysteamine analogues than their corresponding acyl-CoA thioesters are required to achieve comparable yields of triketide lactones. CONCLUSIONS: Although a broad range of variation in the starter residue is acceptable, the substrate specificity of module 2 of a typical modular PKS in vitro is relatively intolerant of changes at C-2 and C-3. This will restrict the usefulness of approaches to synthesise novel erythromycins using synthetic diketides in vivo. The use of synthetic beta-keto diketides in vivo deserves to be explored.

Catalysis↗
PubMed1998

Induction of cytokines and anti-cytokine autoantibodies in cerebrospinal fluid (CSF) during experimental bacterial meningitis.

We have recently described the induction of anti-cytokine autoantibodies (Aabs) in the serum as a novel mechanism for cytokine regulation during bacterial infections. Here we use the infant rat-model of Haemophilus influenzae type b (Hib) meningitis to examine the induction of five potentially important cytokines and their autoantibody responses in the CSF. Protein levels of the cytokines interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), IL-4 and IL-10 were detected at day 3 post-inoculation (p.i.) with maximum induction at day 8. Thereafter, these levels of cytokines had become undetectable. Increased Aab titres to these cytokines, except IL-4, were registered with peak levels between days 7 and 9. Upon re-inoculation with Hib at day 30, regeneration of Aabs was recorded 7 days later (i.e. at day 37). To control the specificity of these Aabs, preincubation of the CSF with a cytokine inhibited the binding effects of that particular cytokine, but not those of any other cytokine. Aabs dose-dependently inhibited IFN-gamma-induced MHC expression by peritoneal macrophages and TNF-alpha-mediated L929 cytotoxicity. Our data demonstrate for the first time the existence of the anti-cytokine antibodies in the CSF of the meningitis Hib model. Furthermore, the data present a role for the Aabs in cytokine regulation, which is consistent with the previously demonstrated effects of the Aabs in the serum.

Animals↗
PubMed1998

Using an office system intervention to increase breast cancer screening.

OBJECTIVE: To evaluate an innovative approach to continuing medical education, an outreach intervention designed to improve performance rates of breast cancer screening through implementation of office systems in community primary care practices. DESIGN: Randomized, controlled trial with primary care practices assigned to either the intervention group or control group, with the practice as the unit of analysis. SETTING: Twenty mostly rural counties in North Carolina. PARTICIPANTS: Physicians and staff of 62 randomly selected family medicine and general internal medicine practices, primarily fee-for-service, half group practices and half solo practitioners. INTERVENTION: Physician investigators and facilitators met with practice physicians and staff over a period of 12 to 18 months to provide feedback on breast cancer screening performance, and to assist these primary care practices in developing office systems tailored to increase breast cancer screening. MEASUREMENTS AND MAIN RESULTS: Physician questionnaires were obtained at baseline and follow-up to assess the presence of five indicators of an office system. Three of the five indicators of office systems increased significantly more in intervention practices than in control practices, but the mean number of indicators in intervention practices at followup was only 2.8 out of 5. Cross-sectional reviews of randomly chosen medical records of eligible women patients aged 50 years and over were done at baseline (n = 2,887) and follow-up (n = 2,874) to determine whether clinical breast examinations and mammography, were performed. Results for mammography were recorded in two ways, mention of the test in the visit note and actual report of the test in the medical record. These reviews showed an increase from 39% to 51% in mention of mammography in intervention practices, compared with an increase from 41% to 44% in control practices (p = .01). There was no significant difference, however, between the two groups in change in mammograms reported (intervention group increased from 28% to 32.7%; control group increased from 30.6% to 34.0%, p = .56). There was a nonsignificant trend (p = .06) toward a greater increase in performance of clinical breast examination in intervention versus control practices. CONCLUSIONS: A moderately intensive outreach intervention to increase rates of breast cancer screening through the development of office systems was modestly successful in increasing indicators of office systems and in documenting mention of mammography, but had little impact on actual performance of breast cancer screening. At follow-up, few practices had a complete office system for breast cancer screening. Outreach approaches to assist primary care practices implement office systems are promising but need further development.

Aged↗
PubMed1998

New conformational constraints in isotopically (13C) enriched oligosaccharides.

Multidimensional heteronuclear NMR studies have been applied to the resonance assignment and conformational analysis of 13C-enriched Neu5Acalpha2-3Galbeta1-4Glc. It is demonstrated that three-dimensional ROESY-HSQC experiments provide through-space distance restraints which cannot be observed with conventional homonuclear 1H techniques due to resonance overlap. In particular, connectivities demonstrating the existence of the "anti" conformation about the Galbeta1-4Glc glycosidic linkage are unambiguously observed. It is shown that 13C isotopic enrichment of the trisaccharide at a level >95% enables straightforward measurement of trans-glycosidic 1H-13C and 13C-13C coupling constants and a Karplus-type relation is derived for the latter. In total 15 conformational restraints were obtained for the trisaccharide in aqueous solution, all of which were in excellent agreement with theoretical parameters computed from a 5 ns molecular dynamics simulation of the glycan.

CA-19-9 Antigen↗
PubMed1998

Large format ink-jet poster production: a case report.

To complement the services offered by the Medical Illustration Department of Frenchay Hospital, Bristol, we decided to look at the possibility of producing posters using the ink-jet process. Our designers wanted to use the full scope of their computers and software to expand their design talents. The method of cutting and pasting sheets of paper onto card seemed old fashioned and denied clients the benefit of the exciting techniques that have become available. After seeking sponsorship, a drug company gave 8000 Pounds towards setting up the department's poster printing service. A Kodak DS1000 printer was installed together with Posterjet and Posterworks software and we went into production, servicing not only our hospital but others in the area who gave their support for the service. High quality photographic reproduction was achieved and clients and consultants were very pleased with the results. The designers were happy that their skills were being used and interest in this and other services in the department have increased. The resulting increased income has helped finance other projects. The printer has enabled us also to see output proofs before sending work off to be offset printed--a very useful tool and a cost-saving process.

Image Processing, Computer-Assisted↗