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Biomedical subjects

R Harris

Publications and source records attributed to R Harris.

At least 91 records · Page 5Linked to original sources
PubMed1999

Knowledge about medical genetics in health care.

Effective genetic services depend upon co-operation between medical geneticists and many different non-geneticist professionals to ensure that the most appropriate patients are referred to geneticists and that those that require long-term care receive it. Important determinants of the quality of genetic services are the knowledge that professionals have about clinical genetics and the equitable distribution of adequately resourced genetic centres. Consequently, we have investigated in a European context how much clinically relevant genetics non-geneticists know, how competent non-geneticists are in counselling their own patients, how well equipped specialist genetic centres are, who refers to genetic centres and what they refer and who offers continuing care to patients and families whose problems are not resolvable at a limited genetic clinic visit.

Journal Article↗
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↗
PubMed1999

A comparison of phonemic, semantic, and alternating word fluency in Parkinson's disease.

Word fluency in 45 medicated non-demented Parkinson's disease (PD) patients and 45 normal control subjects was studied with a Phonemic Word Fluency (PWF) task using the letters F, A, and S, a Semantic Word Fluency (SWF) task using the categories animals, boys' names, and states, and an Alternating Word Fluency (AWF) task requiring the person to alternate between colors and occupations, animals and states, and words beginning with C and P. The number of words generated did not differ for trials with F, A, S, or states, but PD patients generated significantly fewer animal names and boys' names. PD patients also generated significantly fewer words on each of the three AWF trials. The PD patients scored 21% lower than the normal control group on the total AWF score, but only 10% lower for the PWF and SWF scores. The greater impairment on the AWF task which requires the use of internal attentional control to rapidly shift mental set can be considered a type of executive functioning deficit. This is consistent with the growing literature suggesting frontal systems dysfunction in PD and with the view that dopaminergic treatment only incompletely restores functioning in the frontostriatal system.

Journal Article↗
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↗
PubMed1997

Central venous catheters coated with minocycline and rifampin for the prevention of catheter-related colonization and bloodstream infections. A randomized, double-blind trial. The Texas Medical Center Catheter Study Group.

BACKGROUND: Central venous catheters are a principal source of nosocomial bloodstream infections, which are difficult to control. OBJECTIVE: To determine the efficacy of catheters coated with minocycline and rifampin in preventing catheter-related colonization and bloodstream infections. DESIGN: Multicenter, randomized clinical trial. SETTING: Five university-based medical centers. PATIENTS: 281 hospitalized patients who required 298 triple-lumen, polyurethane venous catheters. INTERVENTION: 147 catheters were pretreated with tridodecylmethyl-ammonium chloride and coated with minocycline and rifampin. Untreated, uncoated catheters (n = 151) were used as controls. MEASUREMENTS: Quantitative catheter cultures, blood cultures, and molecular typing of organisms to determine catheter-related colonization and bloodstream infections. RESULTS: The group with coated catheters and the group with uncoated catheters were similar with respect to age, sex, underlying diseases, degree of immunosuppression, therapeutic interventions, and risk factors for catheter infections. Colonization occurred in 36 (26%) uncoated catheters and 11 (8%) coated catheters (P < 0.001). Catheter-related bloodstream infection developed in 7 patients (5%) with uncoated catheters and no patients with coated catheters (P < 0.01). Multivariate logistic regression analysis showed that coating catheters with minocycline and rifampin was an independent protective factor against catheter-related colonization (P < 0.05). No adverse effects related to the coated catheters or antimicrobial resistance were seen. An estimate showed that the use of coated catheters could save costs. CONCLUSIONS: Central venous catheters coated with minocycline and rifampin can significantly reduce the risk for catheter-related colonization and bloodstream infections. The use of these catheters may save costs.

Adolescent↗