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Biomedical subjects

R Brown

Publications and source records attributed to R Brown.

At least 217 records · Page 12Linked to original sources

The structure and correlates of kanashibari.

The present research is an examination of the parameters and correlates of kanashibari, operationally defined as being unable to move upon awakening or before falling asleep. Nonclinical Japanese individuals (N = 720), 34% of whom reported an experience of kanashibari at least once, were administered D. I. Templer's (1970) Death Anxiety Scale, R. Brown's (1990) Locus of Control Scale, and a questionnaire devised by the authors to collect information about kanashibari. The results showed that the kanashibari experience was positively correlated with death anxiety, with being a woman, and with external-other locus of control; this last measure assessed the extent to which these individuals felt that their lives were determined by fate, good luck, or chance.

Adolescent↗

Primary sensory neuron survival following targeted administration of nerve growth factor to an injured nerve.

Nerve injuries induce neurochemical changes within primary sensory neurons, including expression of neuropeptides, and a loss of a substantial proportion of the neurons may possibly be caused by a lack of neurotrophic support. In the present study the role of nerve growth factor (NGF) in preventing these changes was investigated in monkeys by giving NGF peripherally through a fibronectin (Fn) conduit. A sensory nerve (superficial radial) was transected and a gap of 5 mm was bridged with either autologous sural nerve graft (SNG), Fn, or Fn impregnated with NGF (Fn-NGF). After four months the dorsal root ganglia, that received the cutaneous afferents of the nerve, were removed and analysed by quantitative immunohistochemistry using antibodies to calcitonin gene related polypeptide (CGRP) and substance P. The percentage of immunostained cells was taken as an indication of neuronal survival. The results showed that SNG and Fn-NGF reduced the loss of CGRP positive sensory neurons compared with Fn alone. For substance P-positive neurons the differences were small with only a tendency towards reduction of neuronal death after NGF had been given, suggesting that NGF might act preferentially on a subpopulation of CGRP immunoreactive sensory neurons that do not coexist with substance P.

Animals↗

Breathlessness in spinal cord injury depends on injury level.

Little is known about the prevalence and predictors of breathlessness in individuals with neurologically complete chronic spinal cord injury (SCI). Between December 1992 and September 1993, we mailed a respiratory questionnaire to 1,147 community-based individuals with chronic SCI. The questionnaire included four questions about the presence of breathlessness during activities related to moving about. Of the 485 who replied (42 percent response rate), analysis was limited to adult males with neurologically complete motor injuries who reported using a hand-propelled wheelchair more than 50 percent of the time to get around. Of 130 subjects (33 tetraplegics, 53 high thoracic SCI, 44 lower injury levels), the patients with tetraplegia reported breathlessness more frequently (range for the four questions, 21-33%) than those with high thoracic (range, 9-15%) or lower injury levels (range, 2-11%). For each of the four questions there was a significant trend (p < 0.05) for subjects with higher levels of injury to report the greatest prevalence of breathlessness (tetraplegia > high thoracic > lower). The frequency of breathlessness was greatest in those with neurologically complete cervical injuries, an effect that was independent of obesity, smoking, age, and years since SCI. The mechanisms of breathlessness in SCI are unclear but elucidation might lead to strategies for providing relief.

Adult↗

Breathlessness and exercise in spinal cord injury.

After spinal cord injury (SCI), breathlessness during daily activities is common. In 308 individuals with SCI, the authors measured pulmonary function and administered a survey regarding health status, participation in wheelchair athletics, and breathlessness during different activities. The following questions were included: A. Are you troubled by shortness of breath when hurrying on the level or going up a slight hill?; B. Do you have to go slower than people of your own age on the level because of breathlessness?; C. Do you ever have to stop for breath when going at your own pace on the level?; and D. Do you ever have to stop for breath after going about 100 yards on the level? The analysis was restricted to 183 subjects with neurologically motor complete or incomplete SCI who, to get around, used hand-propelled wheelchairs more than 50% of the time. Of these, 56 (31%) reported breathlessness during some types of activities. Subjects with neurologically motor complete cervical or high thoracic SCI (T-6 and above) were more likely to report breathlessness than others (39% compared with 25%, p = .039). Among wheelchair athletes, the prevalence of breathlessness was 8/49 (16%) versus 48/134 (36%) for non-athletes (p = .011). Adjusting for smoking, neurological level, and history of obstructive lung disease, non-athletes were 2.3 times more likely to report breathlessness than athletes were (p = .049 to .075, depending on regression model). This relationship persisted when adjusted for percent predicted forced expiratory volume (FEV1) and maximal expiratory and inspiratory pressures. Therefore in SCI, wheelchair athletes are less likely to report breathlessness than non-athletes, but the mechanism does not appear to be improvement in respiratory muscle performance or pulmonary function.

Activities of Daily Living↗

Ex vivo expansion of CD34+ umbilical cord blood cells in a defined serum-free medium (QBSF-60) with early effect cytokines.

To investigate the clinically applicable conditions that support substantial expansion of both primitive and more mature hematopoietic cells of umbilical cord blood (UCB) for transplantation in adults, enriched CD34+ cells from 8 fresh UCB samples and 4 expanded UCB products were cultured in defined serum-free medium (QBSF-60) in the presence of a cytokine combination of SCF, Flt-3-ligand (FL), thrombopoietin (TPO), IL-3 for up to 2 weeks. Fresh medium with cytokines was supplemented or exchanged at day 4, day 7, and day 10. The proliferative response was assessed at day 7, day 10, and day 14 by evaluating the following parameters: nucleated cell (NC), clonogenic progenitors (colony-forming unit-granulocyte-macrophage [CFU-GM], burst-forming unit-erythrocyte [BFU-E], CFU-GEMM, and high-proliferative potential colony-forming cell [HPP-CFC]), immunophenotypes (CD34+ cells and CD34+ subpopulations), and LTCIC. Simultaneously numerical expansion of various stem/progenitor cells, including primitive CD34+CD38-HLA-DR- subpopulation and LTCIC, CD34+ cells, and clonogenic progenitors to mature nucleated cells, were continuously observed during the culture. An average 103.32 +/- 71.37 x 10(6) CD34+ cells (range 10.12 x 10(6)-317.9 x 10(6)) could be obtained from initial 1.72 +/- 1.13 x 10(6) UCB CD34+ cells after 10-14 days cultured under the described conditions. Sufficient CD34+ cells (>50.0 x 10(6)) for transplantation in adults would be available in all but one UCB collections after 10-14 days expansion. The expanded CD34+ cells sustained most of the in vitro characteristics of initial unmanipulated CD34+ cells, including clonogenic efficiency (of both primitive and committed progenitors), the proportion of CD34+CD38-HLA-DR- subpopulation, and the expansion potential. Initial addition of IL-3 to the cocktail of SCF + FL + TPO had positive effects on the expansion of both primitive and, especially, the more mature hematopoietic cells. It accelerated the expansion speed and shortened the optimal culture time from 14 days to 10 days. These results indicated that our proposed short-term culture system, consisting of QBSF-60 serum-free medium with a simple early acting cytokine combination of SCF + FL + TPO, could substantially support simultaneous expansion of various stem/progenitor cell populations involved in the different phases of engraftment. It would be a clinically applicable protocol for ex vivo expansion of CD34+ UCB cells.

Antigens, CD34↗

Sequential bilateral transplantation in Parkinson's disease: effects of the second graft.

Five parkinsonian patients who had received implants of human embryonic mesencephalic tissue unilaterally in the striatum 10-56 months earlier were grafted with tissue from four to eight donors into the putamen (four patients) or the putamen plus the caudate nucleus (one patient) on the other side, and were followed for 18-24 months. After 12-18 months, PET showed a mean 85% increase in 6-L-[18F]fluorodopa uptake in the putamen with the second graft, whereas there was no significant further change in the previously transplanted putamen. Two patients exhibited marked additional improvements after their second graft: 'on-off' fluctuations virtually disappeared, movement speed increased, and L-dopa could be withdrawn in one patient and reduced by 70% in the other. The improvement in one patient was moderate. Two patients with atypical features, who responded poorly to the first graft, worsened following the second transplantation. These findings indicate that sequential transplantation in patients does not compromise the survival and function of either the first or the second graft. Moreover, putamen grafts that restore fluorodopa uptake to normal levels can give improvements of major therapeutic value.

Adult↗

A pharmacodynamic explanation for the rapid onset/offset of rapacuronium bromide.

BACKGROUND: Nondepolarizing muscle relaxants differ in their time course at the laryngeal adductors and the adductor pollicis, a result of differences in equilibration delays between plasma and effect sites, the sensitivity of each muscle to the relaxant, and the steepness of the concentration-effect relation at each muscle (the Hill factor). To determine whether similar differences exist for rapacuronium, a muscle relaxant with rapid onset and offset, the authors determined its pharmacodynamic characteristics. METHODS: The twitch tensions of the adductor pollicis and the laryngeal adductors (via a tracheal tube cuff positioned at the vocal cords) were measured in 10 volunteers who were anesthetized with propofoL Rapacuronium, 1.5 mg/kg, was given and blood samples were collected. A semiparametric effect compartment pharmacodynamic model was fit to values for rapacuronium plasma concentrations and twitch tension of the adductor pollicis and laryngeal adductors. RESULTS: Equilibration between the rapacuronium plasma concentration and both effect sites was rapid (typical values for the rate constant for equilibration between plasma and the effect site are 0.405 per min for the adductor pollicis and 0.630 per min for the laryngeal adductors) and was more rapid at the laryngeal adductors than at the adductor pollicis (ratio, 1.59+/-0.16; mean +/- SD). The steady state rapacuronium plasma concentration that depressed twitch tension by 50% and the Hill factor were similar for the two muscles. CONCLUSIONS: The rapid onset and offset of rapacuronium can be explained by the rapid equilibration between concentrations in plasma and at the effect site. Unlike the finding for other nondepolarizing muscle relaxants, the laryngeal muscles are not resistant to rapacuronium.

Adult↗

Influence of renal failure on the pharmacokinetics and neuromuscular effects of a single dose of rapacuronium bromide.

BACKGROUND: Because renal function affects the elimination of muscle relaxants, each new muscle relaxant must be evaluated in patients with renal failure. Accordingly, the neuromuscular effects and pharmacokinetics of rapacuronium were identified in patients with renal failure. METHODS: Rapacuronium (1.5 mg/kg) was administered to 10 healthy volunteers and 10 patients with renal failure who were undergoing non-transplant surgery, were 18-45 yr old, and were anesthetized with propofol. The adductor pollicis muscle twitch tension was monitored. Plasma samples were obtained frequently for a period of 8 h to measure the concentrations of ORG9487 and its metabolite, ORG9488. Pharmacokinetic parameters were determined using mixed-effects modeling. RESULTS: One patient was excluded from analysis because he was taking phenytoin chronically. Twitch depression at 1 min was less in patients than in healthy volunteers (median values: 92% in patients, 99% in volunteers). The times to 90% and peak twitch depression; to 10%, 25%, and 75% twitch recovery; and to 70% and 80% train-of-four ratios were similar in volunteers and patients. Rapacuronium's clearance was 32% less in patients with renal failure; in both groups, clearance decreased 0.909% per year of age compared with the value in a 30 yr old. The steady state distribution volume was 14% less in women than in men and 16% less in patients than in volunteers. For ORG9488, clearance was 85% less in patients than in volunteers. CONCLUSIONS: The neuromuscular effects of a single dose of rapacuronium are affected minimally by renal failure. However, the decreased clearance of rapacuronium and its potent metabolite in renal failure suggests that repeated dosing of rapacuronium may lead to prolonged effects in patients with renal failure.

Adolescent↗

Intramuscular rapacuronium in infants and children: dose-ranging and tracheal intubating conditions.

BACKGROUND: Intravenous rapacuronium's rapid onset and short duration suggest that intramuscular rapacuronium might facilitate tracheal intubation without prolonged paralysis. Accordingly, the authors injected rapacuronium into the deltoid muscle to determine the optimal dose and time for intubation in pediatric patients. METHODS: Unpremedicated patients (aged, 2 months to 3 yr) were studied. Part I: Spontaneous minute ventilation (V(E)) and twitch tension were measured during N2O/halothane anesthesia. Rapacuronium (2.2-5.5 mg/kg, given intramuscularly, n = 23), succinylcholine (4 mg/kg, given intramuscularly, n = 12), or vecuronium (0.1 mg/kg, given intravenously, n = 15) was given. Time to 50% depression of V(E) and 10% recovery of twitch were measured. Dose for each patient was changed 10-20% according to the previous patient's response. Part II: In 22 patients anesthetized with 0.82-1.0% halothane, the optimal rapacuronium dose determined in part I (infants, 2.8 mg/kg; children, 4.8 mg/kg) was given intramuscularly. Laryngoscopy was scored. Time to laryngoscopy was increased or decreased 0.5 min according to the previous patient's response. RESULTS: Part I: Rapacuronium typically depressed ventilation in < or = 2 min with 10% twitch recovery in 20-60 min. With succinylcholine, median time to ventilatory depression was 1.3 and 1.1 min for infants and children, respectively; for vecuronium, 0.7 and 0.6 min. Part I: Intubating conditions were good-excellent at 3.0 and 2.5 min in infants and children, respectively; time to 10% twitch recovery (mean +/- SD) was 31 +/- 14 and 36 +/- 14 min in the two groups. CONCLUSIONS: This pilot study indicates that deltoid injection of rapacuronium, 2.8 mg/kg in infants and 4.8 mg/kg in children, permits tracheal intubation within 2.5-3.0 min, despite a light plane of anesthesia. Duration of action is intermediate.

Child, Preschool↗

Distance education and caregiver support groups: comparison of traditional and telephone groups.

OBJECTIVE: To implement and evaluate the impact of telephone caregiver groups, compared with traditional face-to-face, on-site caregiver groups. DESIGN: Quasi-experimental design comparing the two group types across time. SETTING: An urban tertiary rehabilitation hospital with a brain injury program servicing a vast geographical area. PARTICIPANTS: Caregivers of an adult person with a brain injury participated in either one of the 10 telephone groups (TGs) (N = 52 caregivers who completed a full set of research forms) or one of the 10 on-site groups (OGs) (N = 39 caregivers who completed a full set of research forms). The combined total from both groups was 91. INTERVENTION: Caregivers who lived within 40 km of the facility were placed in one of the OGs, and all others were placed in one of the TGs. Both types of groups met weekly for 9 to 10 weeks and were led by either social work or psychology professionals. The TGs met using teleconference technology. MAIN OUTCOME MEASURES: Profile of Moods States (POMS), Caregiver Burden Inventory (CBI), and the McMaster Model Family Assessment Devise (FAD), were administered 2 months before the first day of group, on the first day of group, on the last day of group, and 6 months after group. On the last day of group, a participant satisfaction survey was administered. RESULTS: There were similar amounts of improvements for the outcomes from OGs and TGs. Rural caregivers had fewer difficulties on all measures at all measurement intervals. In both types of group, participants showed a statistically significant improvement in POMS scores and a trend toward improvement in FAD and CBI results. Participants of both group types rated their experience highly, although rural caregivers were somewhat more satisfied. CONCLUSIONS: Telephone groups offer a method of providing support and education to rural caregivers that is as effective as traditional in-person OGs.

Adult↗

Trauma care regionalization: a process-outcome evaluation.

BACKGROUND: Regionalization of trauma care services in our region was initiated in 1993 with the designation of four tertiary trauma centers. The process continued in 1995 with the implementation of patient triage and transfer protocols. Since 1995, the network of trauma care has been expanded with the designation of 33 secondary, 30 primary, and 32 stabilization trauma centers. In addition, during this period emergency medical personnel have been trained to assess and triage trauma victims within minimal prehospital time. The objective of the present study was to evaluate the impact of trauma care regionalization on the mortality of major trauma patients. METHODS: This was a prospective study in which patients were entered at the time of injury and were followed to discharge from the acute-care hospital. The patients were identified from the Quebec Trauma Registry, a review of the records of acute-care hospitals that treat trauma, and records of the emergency medical services in the region. The study sample consisted of all patients fulfilling the criteria of a major trauma, defined as death, or Injury Severity Score (ISS) > 12, or Pre-Hospital Index > 3, or two or more injuries with Abbreviated Injury Scale scores > 2, or hospital stay of more than 3 days. Data collection took place between April 1, 1993, and March 31, 1998. During this period, four distinct phases of trauma care regionalization were defined: pre-regionalization (phase 0), initiation (phase I), intermediate (phase II), and advanced (phase III). RESULTS: A total of 12,208 patients were entered into the study cohort, and they were approximately evenly distributed over the 6 years of the study. During the study period, there was a decline in the mean age of patients from 54 to 46 years, whereas the male/female ratio remained constant at 2:1. There was also an increase in the mean ISS, from 25.5 to 27.5. The proportion of patients injured in motor vehicle collisions increased from less than 45% to more than 50% (p < 0.001). The mortality rate during the phases of regionalization were: phase 0, 52%; phase I, 32%; phase II, 19%; and phase III, 18%. These differences were clinically important and statistically significant (p < 0.0001). Stratified analysis showed a significant decline in mortality among patients with ISS between 12 and 49. The change in mortality for patients with fatal injuries (ISS > or = 50) was not significant. During the study period, the mean prehospital time decreased significantly, from 62 to 44 minutes. The mean time to admission after arrival at the hospital decreased from 151 to 128 minutes (p < 0.001). The latter decrease was primarily attributable to changes at the tertiary centers. The proportion of patients with ISS between 12 and 24 and between 25 and 49 who were treated at tertiary centers increased from 56 to 82% and from 36 to 84%, respectively (p < 0.001). Compared with the secondary and primary centers, throughout the course of the study the mortality rate in the secondary and tertiary centers showed a consistent decline (p < 0.001). In addition, the mortality rate in the tertiary centers remained consistently lower (p < 0.001). The results of multivariate analyses showed that after adjusting for injury severity and patient age, the primary factors contributing to the reduced mortality were treatment at a tertiary center, reduced prehospital time, and direct transport from the scene to tertiary centers. CONCLUSION: This study produced empirical evidence that the integration of trauma care services into a regionalized system reduces mortality. The results showed that tertiary trauma centers and reduced prehospital times are the essential components of an efficient trauma care system.

Adult↗

Motivating the obese child to move: the role of structured exercise in pediatric weight management.

BACKGROUND: The prevalence of childhood obesity is rapidly increasing. Successful prevention and treatment of childhood obesity depends on increasing the physical activity patterns of obese youth. However, motivating the obese child to participate in physical activity is difficult. METHODS: We designed a four-phase physical activity intervention, consisting of a structured progressive exercise program of moderate intensity, along with motivational methods to increase physical activity and improve body movement awareness. RESULTS: Seventy-three overweight children participated in the weight management program. They had a significant weight loss and reduction in body fat, which was maintained at 1-year follow-up. Subjects also maintained lean body mass and showed improved physical activity patterns. CONCLUSIONS: Progressive exercise, used in conjunction with nutrition and behavior modification, provides successful motivational strategies. These strategies encourage increased physical activity patterns, the adoption of regular structured exercise training, and the loss of excess body fat.

Adolescent↗

Gordonia desulfuricans sp. nov., a benzothiophene-desulphurizing actinomycete.

The taxonomic position of two actinomycetes isolated from soil was established using a polyphasic approach. The organisms, designated 213ET and 213F, were found to have chemical and morphological properties consistent with their assignment to the genus Gordonia. Nearly complete sequences of the 16S rDNA genes of the two strains were determined following the isolation and direct sequencing of the amplified genes. The tested strains were found to have identical 16S rDNA sequences and formed a phylogenetic line within the evolutionary radiation occupied by the genus Gordonia that was most closely related to Gordonia rubropertincta DSM 43197T. However, DNA-DNA relatedness data showed that strain 213ET and Gordonia rubropertincta DSM 43197T belonged to distinct genomic species. Strains 213ET and 213F also shared an identical phenotypic profile which distinguished them from representatives of validly described Gordonia species. The combined genotypic and phenotypic data show that strains 213ET and 213F merit recognition as a new species of Gordonia. The name proposed for the new species is Gordonia desulfuricans, for which the type strain is 213ET (= NCIMB 40816T).

Actinomycetales↗

Helicobacter pylori in the Canadian arctic: seroprevalence and detection in community water samples.

OBJECTIVE: Many North American arctic communities are characterized by risk markers associated with Helicobacter pylori (H. pylori) infection, including overcrowded housing and inadequate water supply and sanitation systems. Our aim was to determine the seroprevalence of H. pylori infection in two traditional Inuit communities in the central Canadian arctic and to test for the presence of H. pylori, by polymerase chain reaction (PCR), in local water supplies. METHODS: Samples of venous whole blood from adults and capillary blood from children were collected and analyzed by enzyme immunoassay and Helisal Rapid Test, respectively, for IgG antibody to H. pylori. Antibodies to CagA were detected by enzyme immunoassay, and ABO and Lewis antigens were also determined. Demographic and clinical information were collected by questionnaire. Water samples from each community were tested for H. pylori by PCR. RESULTS: One hundred-thirty (50.8%) of 256 subjects from the two communities were positive for H. pylori IgG antibodies. Seropositive subjects were more likely to be male, compared with seronegative individuals (p = 0.01). Antibody status did not differ with respect to age, community, alcohol or cigarette use, number of persons per household, gastrointestinal complaints or previous investigations, medications, or presence of blood group O, Lewis a-b+. CagA antibodies were detected in 78 (61.9%) of 126 H. pylori-seropositive subjects tested; however, 41 (35.3%) of 116 H. pylori-seronegative subjects were also CagA positive. Water samples taken from the water delivery truck in Chesterfield Inlet and two lakes near Repulse Bay were positive for H. pylori. CONCLUSION: The seroprevalence of H. pylori in the study group was higher than rates in southern Canadian populations, but lower than the seroprevalence previously documented in a Canadian subarctic Indian (First Nations) community. The detection of H. pylori in local water supplies may indicate a natural reservoir for the organism or possible contamination from human sewage.

ABO Blood-Group System↗

Prevention of human diaphragm atrophy with short periods of electrical stimulation.

We determined whether prolonged complete inactivation of the human diaphragm results in atrophy and whether this could be prevented by brief periods of electrical phrenic nerve stimulation. We studied a subject with high spinal cord injury who required removal of his left phrenic nerve pacemaker (PNP) and the reinstitution of positive-pressure ventilation for 8 mo. During this time, the right phrenic nerve was stimulated 30 min per day. Thickness of each diaphragm (tdi) was determined by ultrasonography. Maximal tidal volume (VT) was measured during stimulation of each diaphragm separately. After left PNP reimplantation, VT and tdi were measured just before the resumption of electrical stimulation and serially for 33 wk. On the previously nonfunctioning side, there were substantial changes in VT (from 220 to 600 ml) and tdi (from 0.18 to 0.34 cm). On the side that had been stimulated, neither VT nor tdi changed appreciably (VT from 770 to 900 ml; tdi from 0.25 to 0.28 cm). We conclude that prolonged inactivation of the diaphragm causes atrophy which may be prevented by brief periods of daily phrenic nerve stimulation.

Atrophy↗

The bronchoprotective effect of inhaled salmeterol in preschool children: a dose-ranging study.

The optimal dose of salmeterol in infants and preschool children is not known. The aim of this study was to assess the bronchoprotective effect of different doses of salmeterol using methacholine-induced wheeze in children aged <4 yrs. Children <4 yrs old with a history of recurrent wheeze underwent two methacholine challenges within 7 days. One hour before each challenge they were pretreated in double-blind fashion using a metered-dose inhaler and Babyhaler spacer. Placebo was given before one challenge, and either 25, 50 or 100 microg of salmeterol before the other. Both the dose and treatment order were random. The provocative concentration of methacholine causing wheeze (PCwheeze) was measured on each occasion. Studies were terminated when wheeze occurred or arterial oxygen saturation (Sa,o2) fell below 91%. Of the 42 children enrolled, 33 completed the study. Two subjects refused the challenge test, two failed to return and five developed upper respiratory tract infections or wheeze between the two tests. The mean (range) age of the population was 27 (8-46) months. Ratios of PCwheeze between treatment and placebo challenges were calculated for each dosage group. The treatment/placebo ratios (95% confidence intervals) were 1.2 (0.6-2.4) for 25 microg, 2.5 (1.4-4.6) for 50 microg (p<0.01), and 4.0 (2.1-7.4) (p<0.001) for 100 microg doses. In recurrently wheezy children aged <4 yrs a single dose of salmeterol between 25 and 100 microg has a dose-dependent effect on methacholine-induced wheeze, and this is significantly different from placebo at 50 and 100 microg. This study suggests that the Babyhaler effectively delivers salmeterol to children <4 yrs of age and that doses between 50-100 microg are efficacious.

Administration, Inhalation↗