Search PubMed⌕ Search

Biomedical subjects

R Harrison

Publications and source records attributed to R Harrison.

At least 37 records · Page 2Linked to original sources
PubMed2001

General practitioner participants in a telemedicine trial: comparisons with their peers.

A study was conducted to determine whether general practitioners (GPs) participating in a telemedicine trial were self-selected enthusiasts for information technology compared with GPs in general. We compared two experimental groups of GPs in London and Wales (n = 126) who had volunteered to participate in a telemedicine trial and two randomly selected groups of GPs from the same areas (total n = 300) who acted as controls. A postal questionnaire was used and achieved a 79% response rate. There were no significant differences in the demographic characteristics of the experimental and control groups in London and Wales, except that the London telemedicine GPs (mean age 41.9 years) were significantly younger than the London controls (mean age 46.6 years). The control GPs were similar to the telemedicine GPs in terms of frequency of computer use and their responses to statements about their attitudes to computers. In the combined telemedicine and control groups, 85% and 77% respectively said that they enjoyed using computers. Telemedicine GPs used computers more frequently for administrative purposes but they shared the same attitudes towards information technology as GPs in general. In all situations where GPs could exercise personal choice, the control and experimental groups were similar.

Adult↗
PubMed2001

Extubation failure in a large pediatric ICU population.

OBJECTIVE: To review a large population of children receiving mechanical ventilation to establish a baseline rate of extubation success and failure and to identify those characteristics that place a patient at greater risk of failing planned extubation. DESIGN: Retrospective chart review. SETTING: University-affiliated children's hospital with a 20-bed pediatric ICU. PATIENTS: All 632 patients receiving mechanical ventilation during the 2-year period from July 1, 1996, to June 30, 1998. METHOD: Patients receiving mechanical ventilation were identified via a computerized database. Charts were reviewed of all patients who were reintubated within 72 h of extubation. MEASUREMENTS AND RESULTS: There were 548 planned extubation events, of which 521 were successful. Twenty-seven patients failed planned extubation at least once; only the first attempt at extubation was included in the analysis. The failure rate of planned extubations was 4.9%. Including only patients who had received mechanical ventilation for > 24 h before extubation, the failure rate was 6.0%. For patients intubated > 48 h, the failure rate was 7.9%. The patients who failed extubation were found to be significantly younger and to have received mechanical ventilation longer than those who succeeded, in both the analysis of all patients receiving mechanical ventilation and the subgroup of those receiving mechanical ventilation > 24 h. When only patients who had received mechanical ventilation for > 48 h were analyzed, the difference in age was no longer significant, but the duration of ventilation before extubation was still significantly longer for those who failed. CONCLUSION: We determined the overall failure rate of planned extubations in a large population of pediatric patients to be 4.9%. Those patients who were younger and had received mechanical ventilation longer were more at risk for extubation failure.

Case-Control Studies↗
PubMed2001

A five year review of scar dehiscence in the Rotunda Hospital, Dublin.

The aims of this study were to identify risk factors for scar dehiscence in labour, to illustrate the clinical presentations of patients with scar dehiscence and to quantify the risk posed by the use of oxytocin in labour. This was a case controlled, 5 year retrospective study. Patients with scar dehiscence were identified from labour ward records with matched controls and chart review of case and control patients were performed. Our results showed that the vaginal delivery rate for trial of scar was 76.9%. The incidence of scar dehiscence was 0.043%. Oxytocic labour augmentation was a risk factor (OR 4.5, 95% CI 0.9313-42.8, p=0.065) but induction of labour using oxytocin was not (p=0.222). The commonest symptom of scar dehiscence was fetal distress (OR 12.3, 95% CI 1.9-81). There was no maternal or fetal mortality. We concluded that trial of labour after one caesarean section is acceptable practice with a good success rate and a low incidence of serious morbidity. The use of oxytocin to augment labour is associated with scar dehiscence.

Adult↗
PubMed2001

Glycine toxicity and unexpected intra-operative death.

A rare complication of the use of glycine irrigation fluid during prostatic surgery in a 69-year-old man is described. Following cystolithopexy and transurethral resection of the prostate for benign prostatomegaly, abdominal distension developed with increasing ventilatory pressures. Despite retroperitoneal fluid evacuation at subsequent urgent laparotomy, cardiac arrest occurred that was not amenable to resuscitation. At autopsy a traumatic defect in the posterior bladder wall filled with calculus debris was confirmed that did not communicate with the peritoneal cavity. Hyponatremia with markedly elevated levels of blood, urine, and body fluid glycine were demonstrated. Death was, therefore, attributed to glycine toxicity following tracking of glycine through a surgical defect in the posterior bladder wall. Careful dissection of surgical sites is required in such cases to demonstrate any additional trauma that may be associated with the fatal episode. Analysis of body fluids for glycine and electrolytes is also necessary to assist in the determination of possible mechanisms of death.

Aged↗
PubMed2000

The third human FER-1-like protein is highly similar to dysferlin.

Dysferlin, the protein product of the gene mutated in patients with an autosomal recessive limb-girdle muscular dystrophy type 2B (LGMD2B) and a distal muscular dystrophy, Miyoshi myopathy, is homologous to a Caenorhabditis elegans spermatogenesis factor, FER-1. Analysis of fer-1 mutants and of sequence predictions of the FER-1 and dysferlin ORFs has predicted a role in membrane fusion. Otoferlin, another human FER-1-like protein (ferlin), has recently been shown to be responsible for autosomal recessive nonsyndromic deafness (DFNB9). In this report we describe the third human ferlin gene, FER1L3, which maps to chromosome 10q23.3. Expression analysis of the orthologous mouse gene shows ubiquitous expression but predominant expression in the eye, esophagus, and salivary gland. All the ferlins are characterized by sequences corresponding to multiple C2 domains that share the highest level of homology with the C2A domain of rat synaptotagmin III. They are predicted to be Type II transmembrane proteins, with the majority of the protein facing the cytoplasm anchored by the C-terminal transmembrane domain. Sequence and predicted structural comparisons have highlighted the high degree of similarity of dysferlin and FER1L3, which have sequences corresponding to six C2 domains and which share more than 60% amino acid sequence identity.

Amino Acid Sequence↗
PubMed2000

The inhibition of flavoproteins by phenoxaiodonium, a new iodonium analogue.

Iodonium compounds, especially diphenylene iodonium and iodonium diphenyl are used extensively as inhibitors of NADH-ubiquinone reductase and NADPH oxidase activity. Here, the use of a new iodonium compound, phenoxaiodonium is reported. The IC(50) of neutrophil superoxide production, measured using the superoxide dismutase inhibitable rate of cytochrome c reduction, was approximately 0.75 microM, while 50% inhibition of mitochondrial respiration, measured by the rate of oxygen uptake using a Clark type oxygen electrode, was at approximately 20 microM. The inhibition of oxidation of xanthine to urate by xanthine oxidase was also studied, giving a K(i) of 0.2 microM. Inhibition of nitric oxidase synthase (NOS: from rat brain) by 0.2 microM phenoxaiodonium was equivalent to 1 mM N(G)-nitro-L-arginine methyl ester HCl (L-NAME), that is total abolition of activity. We conclude that phenoxaiodonium is an extremely good inhibitor of flavo-enzymes, but like diphenylene iodonium and iodonium diphenyl, will be of limited use as a pharmacological tool for the elucidation of the involvement of such enzymes in specific cellular functions.

Animals↗
PubMed2000

A new route to peroxynitrite: a role for xanthine oxidoreductase.

Peroxynitrite, a potent oxidising, nitrating and hydroxylating agent, results from the reaction of nitric oxide with superoxide. We show that peroxynitrite can be produced by the action of a single enzyme, xanthine oxidoreductase (XOR), in the presence of inorganic nitrite, molecular oxygen and a reducing agent, such as pterin. The effects of oxygen concentration on peroxynitrite production have been examined. The physiologically predominant dehydrogenase form of the enzyme is more effective than the oxidase form under aerobic conditions. It is proposed that XOR-derived peroxynitrite fulfils a bactericidal role in milk and in the digestive tract.

Animals↗
PubMed2000

Reduction of organic nitrites to nitric oxide catalyzed by xanthine oxidase: possible role in metabolism of nitrovasodilators.

Xanthine oxidase (XO) was shown to catalyze the reduction of isoamyl and isobutyl nitrites to nitric oxide (NO) in the presence of xanthine under anaerobic conditions. NO was produced at a stoichiometric ratio of 2:1 versus urate generation, steady-state analysis of which showed Michaelis-Menten kinetics with xanthine as varied substrate and substrate inhibition with varied organic nitrite. Under the conditions of NO generation from isoamyl nitrite, XO was progressively inactivated by a mechanism involving conversion of Mo=S to Mo=O, yielding "desulfo" enzyme. It is proposed that XO is involved in the metabolism of organic nitrites to NO in vivo and that the observed inactivation serves to explain the phenomenon of tolerance.

Animals↗
PubMed2000

Reduction of nitrite to nitric oxide catalyzed by xanthine oxidoreductase.

Xanthine oxidase (XO) was shown to catalyze the reduction of nitrite to nitric oxide (NO), under anaerobic conditions, in the presence of either NADH or xanthine as reducing substrate. NO production was directly demonstrated by ozone chemiluminescence and showed stoichiometry of approximately 2:1 versus NADH depletion. With xanthine as reducing substrate, the kinetics of NO production were complicated by enzyme inactivation, resulting from NO-induced conversion of XO to its relatively inactive desulfo-form. Steady-state kinetic parameters were determined spectrophotometrically for urate production and NADH oxidation catalyzed by XO and xanthine dehydrogenase in the presence of nitrite under anaerobic conditions. pH optima for anaerobic NO production catalyzed by XO in the presence of nitrite were 7.0 for NADH and </=6.0 for xanthine. Involvement of the molybdenum site of XO in nitrite reduction was shown by the fact that alloxanthine inhibits xanthine oxidation competitively with nitrite. Strong preference for Mo=S over Mo=O was shown by the relatively very low NADH-nitrite reductase activity shown by desulfo-enzyme. The FAD site of XO was shown not to influence nitrite reduction in the presence of xanthine, although it was clearly involved when NADH was the reducing substrate. Apparent production of NO decreased with increasing oxygen tensions, consistent with reaction of NO with XO-generated superoxide. It is proposed that XO-derived NO fulfills a bactericidal role in the digestive tract.

Anaerobiosis↗
PubMed2000

Enhanced expression and activity of xanthine oxidoreductase in the failing heart.

The molecular basis for heart failure is unknown, but oxidative stress is associated with the pathogenesis of the disease. We tested the hypothesis that the activity of xanthine oxidoreductase (XOR), a free-radical generating enzyme, increases in hypertrophied and failing heart. We studied XOR in two rat models: (1) The monocrotaline-induced right ventricular hypertrophy and failure model; (2) coronary artery ligation induced heart failure, with left ventricular failure and compensatory right ventricular hypertrophy at different stages at 3 and 8 weeks post-infarction, respectively. XOR activity was measured at 30 degrees C and the reaction products were analysed by HPLC. In both models XOR activity in hypertrophic and control ventricles was similar. In the monocrotaline model, the hearts showed enhanced XOR activity in the failing right ventricle (65+/-5 mU/g w/w), as compared to that in the unaffected left ventricle (47+/-3 mU/g P<0.05, n=6-7). In the coronary ligation model, XOR activities did not differ at 3 and 8 weeks. In the infarcted left ventricle, XOR activity increased from 29.4+/-1.4 mU/g (n=6) in sham-operated rats, to 48+/-3 and 80+/-6 mU/g (n=8 P<0.05 v sham) in the viable and infarcted parts of failing rat hearts, respectively. With affinity-purified polyclonal antibody, XOR was localized in CD68+ inflammatory cells of which the number increased more in the failing than in sham-operated hearts. Our results show that the expression of functional XOR is elevated in failing but not in hypertrophic ventricles, suggesting its potential role in the transition from cardiac hypertrophy into failure.

Animals↗
PubMed2000

Long-term results of a multi-institutional randomized trial comparing prognostic factors and surgical results for intermediate thickness melanomas (1.0 to 4.0 mm). Intergroup Melanoma Surgical Trial.

BACKGROUND: Ten- to 15-year survival results were analyzed from a prospective multi-institutional randomized surgical trial that involved 740 stages I and II melanoma patients with intermediate thickness melanomas (1.0 to 4.0 mm) and compared elective (immediate) lymph node dissection (ELND) with clinical observation of the lymph nodes as well as prognostic factors that independently predict outcomes. METHODS: Eligible patients were stratified according to tumor thickness, anatomical site, and ulceration, and then prerandomized to either ELND or nodal observation. By using Cox stepwise multivariate regression analysis, the independent predictors of outcome were tumor thickness (P < .001), the presence of tumor ulceration (P < .001), trunk site (P = .003), and patient age more than 60 years (P = .01). RESULTS: Overall 10-year survival was not significantly different for patients who received ELND or nodal observation (77% vs. 73%; P = .12). Among the prospectively stratified subgroups of patients, 10-year survival rates favored those patients with ELND, with a 30% reduction in mortality rate for the 543 patients with nonulcerated melanomas (84% vs. 77%; P = .03), a 30% reduction in mortality rate for the 446 patients with tumor thickness of 1.0 to 2.0 mm (86% vs. 80%; P = .03), and a 27% reduction in mortality rate for 385 patients with limb melanomas (84% vs. 78%; P = .05). Of these subgroups, the presence or absence of ulceration should be the key factor for making treatment recommendations with regard to ELND for patients with intermediate thickness melanomas. CONCLUSIONS: These long-term survival rates from patients treated at 77 institutions demonstrate that ulceration and tumor thickness are dominant predictive factors that should be used in the staging of stages I and II melanomas, and confer a survival advantage for these subgroups of prospectively defined melanoma patients.

Extremities↗
PubMed2000

Spatial models for hybrid zones.

We introduce a spatially explicit model of natural hybrid zones that allows us to consider how patterns of allele frequencies and linkage disequilibria change over time. We examine the influence of hybrid zone origins on patterns of variation at two loci, a locus under selection in a two-patch environment, and a linked neutral locus. We consider several possible starting conditions that represent explicit realizations of two alternative scenarios for hybrid zone origins: primary intergradation and secondary contact. Our results indicate that in some circumstances, differences in hybrid zone origins will result in substantially different patterns of variation that may persist for thousands of generations. Our conclusions are generally similar to those previously derived from partial differential equations, but there are also some important differences.

Alleles↗
PubMed2000

Consistency of multicenter measurements of heart rate variability in survivors of acute myocardial infarction.

Heart rate variability (HRV) analysis from 24-hour ambulatory ECG has been widely used in risk stratification of patients after myocardial infarction (MI). The accuracy of HRV assessment is known to potentially vary when different commercial systems are used. However, the consistency of HRV measurements has never been fully investigated. Twenty-six post-MI patients (mean age 59 +/- 8 years, 22 men) were studied, of whom 13 succumbed to sudden cardiac death (SCD) within 1 year and 13 remained alive for at least 3 years (MI survivors). Each patient had a 24-hour Holter ECG recorded before hospital discharge. HRV analysis was performed four times from the same recordings using three different Holter tape analysis systems (Marquette, Reynolds, and CardioData) by four independent operators (CardioData system was used twice, once in the United Kingdom and once in the United States). Mean normal-to-normal RR intervals (mNN) and 3 HRV parameters (SDNN, RMSSD, and HRV triangular index [HRVi]) were derived from each recording. The consistency of mNN and HRV measurements was evaluated by coefficient of variance (CV) and by the Bland-Altman method. The results demonstrated that (1) all indices measured by different systems were statistically similar (P = NS) except the measurement of RMSSD (P = 0.01), (2) the measurements of mNN were highly reproducible with a maximum mean difference of 1.8 +/- 13.8 ms and maximum limits of agreement from -14.6 to +15.6 ms. The maximum mean differences were--1.8 +/- 1.4 unit and 4.4 +/- 9.6 ms for HRVi and SDNN, respectively, and RMSSD was less reproducible with a maximum mean difference of--11.1 +/- 11.5 ms, and limits of agreement from -16.2 to +9.6 ms; and (3) the consistency of mNN (CV 0.9% +/- 0.9%) was significantly higher than that of HRVi, SDNN, and RMSSD (P < 0.0001). The consistency of HRVi was similar to that of SDNN (4.8% +/- 2.1% vs 5.7% +/- 4.8%, P = 0.4), and the consistency of RMSSD (26.6% +/- 13.3%) was significantly lower than that of the other measurements (P < 0.00001). In conclusion, the measurements of mNN by different analytical systems are the most consistent among the parameters studied. The global 24-hour measurements of HRV (SDNN and HRVi) are highly reproducible, whereas the measurement of short-term HRV components (RMSSD) is significantly less reproducible.

Adult↗
PubMed1999

Surveillance of work-related asthma in selected U.S. states using surveillance guidelines for state health departments--California, Massachusetts, Michigan, and New Jersey, 1993-1995.

PROBLEM/CONDITION: Cases of work-related asthma (WRA) are sentinel health events that indicate the need for preventive intervention. WRA includes new-onset asthma caused by workplace exposure to sensitizers or irritants and preexisting asthma exacerbated by workplace exposures. REPORTING PERIOD: This report reviews cases of WRA identified by state health departments from January 1, 1993, through December 31, 1995, as well as follow-up investigations of cases and associated workplaces conducted through June 30, 1998. DESCRIPTION OF THE SYSTEMS: State-based surveillance and intervention programs for WRA are conducted in California, Massachusetts, Michigan, and New Jersey as part of the Sentinel Event Notification Systems for Occupational Risks (SENSOR) cooperative agreement program, initiated by CDC's National Institute for Occupational Safety and Health (NIOSH). RESULTS: From 1993 through 1995, a total of 1,101 cases of WRA were identified by SENSOR surveillance staff members in California, Massachusetts, Michigan, and New Jersey. Of these 1,101 cases, 19.1% were classified as work-aggravated asthma, and 80.9% were classified as new-onset asthma. Objective evidence substantiating asthma work-relatedness was documented in the medical records of 3.4% of WRA cases identified in the two states (Michigan and New Jersey) where medical records are routinely reviewed for this information. Indoor air pollutants, dusts, cleaning materials, lubricants (e.g., metalworking fluids), and diisocyanates were among the most frequently reported causes of WRA. In addition, a well-recognized cause of occupational asthma - natural rubber latex - was identified in a new setting, the healthcare industry. The most common industries associated with WRA cases included transportation equipment manufacturing (19.3%), health services (14.2%), and educational services (8.7%). Air sampling for agents known to induce occupational asthma was performed in Michigan for comparison with established federal time-weighted average exposure limits. Sixteen (13.4%) of 119 workplaces tested had airborne concentrations exceeding NIOSH recommended exposure limits (RELs); 11 (9.1%) of 121 workplaces had concentrations exceeding permissible exposure limits (PELs) of the Michigan Occupational Safety and Health Act (MIOSHA) program. INTERPRETATION: The surveillance data findings confirm well-recognized causes of asthma and have identified new putative causes (e.g., cleaning materials and metalworking fluids). Because the surveillance program depends on physicians' recognizing asthma work-relatedness and reporting diagnosed cases, the data are considered an underestimate of the magnitude of the WRA problem. The data also indicate that physicians are not commonly performing objective physiologic tests to substantiate a WRA diagnosis. Workplace findings suggest a need to evaluate existing exposure standards for specific agents known to induce occupational asthma (e.g., diisocyanates). Case-based surveillance can help improve the recognition, control, and prevention of WRA. The SENSOR model also provides a mechanism for workers and physicians to request workplace investigations aimed at primary prevention for other workers. PUBLIC HEALTH ACTION: NIOSH and state health department representatives are working to establish a long-term agenda for state-based surveillance of work-related conditions and hazards. The results from the SENSOR WRA programs described in this report support inclusion of WRA as a priority condition warranting surveillance at the state level.

Asthma↗