Biomedical subjects

M J Bell

Publications and source records attributed to M J Bell.

At least 19 recordsLinked to original sources

PubMed1999

Quinolinic acid in the cerebrospinal fluid of children after traumatic brain injury.

OBJECTIVE: To measure quinolinic acid, a macrophage-derived neurotoxin, in the cerebrospinal fluid (CSF) of children after traumatic brain injury (TBI) and to correlate CSF quinolinic acid concentrations to clinically important variables. DESIGN: A prospective, observational study. SETTING: The pediatric intensive care unit in Children's Hospital of Pittsburgh, a tertiary care, university-based children's hospital. PATIENTS: Seventeen critically ill children following severe TBI (Glasgow Coma Scale score <8) whose care required the placement of an intraventricular catheter for continuous drainage of CSF. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients ranged in age from 2 mos to 16 yrs (mean 6.0 yrs). CSF was collected immediately on placement of the ventricular catheter and daily thereafter. Quinolinic acid concentration was measured by gas chromatography/mass spectroscopy in 69 samples (4.0 +/- 0.4 [SEM] samples per patient). CSF quinolinic acid concentration progressively increased after injury (p = .034, multivariate analysis) and was increased in nonsurvivors vs. survivors (p = .002, multivariate analysis). CSF quinolinic acid concentration was not associated with age. Although overall CSF quinolinic acid concentration was not associated with shaken injury (p = .16, multivariate analysis), infants suffering with shaken infant syndrome had increased admission CSF quinolinic acid concentrations compared with children with accidental mechanisms of injury (p = .027, Mann-Whitney Rank Sum test). CONCLUSIONS: A large and progressive increase in the macrophage-derived neurotoxin quinolinic acid is seen following severe TBI in children. The increase is strongly associated with increased mortality. Increased CSF quinolinic acid concentration on admission in children with shaken infant syndrome could reflect a delay in presentation to medical attention or age-related differences in quinolinic acid production. These findings raise the possibility that quinolinic acid may play a role in secondary injury after TBI in children and suggest an interaction between inflammatory and excitotoxic mechanisms of injury following TBI.

Accidents, Traffic↗

PubMed1998

Management of common musculoskeletal problems: a survey of Ontario primary care physicians.

BACKGROUND: In Canada, primary care physicians manage most musculoskeletal problems. However, their training in this area is limited, and some aspects of management may be suboptimal. This study was conducted to examine primary care physicians' management of 3 common musculoskeletal problems, ascertain the determinants of management and compare management with that recommended by a current practice panel. METHODS: A stratified computer-generated random sample of 798 Ontario members of the College of Family Physicians of Canada received a self-administered questionnaire by mail. Respondents selected various items in the management of 3 hypothetical patients: a 77-year-old woman with a shoulder problem, a 64-year-old man with osteoarthritis of the knee and a 30-year-old man with an acutely hot, swollen knee. Scores reflecting the proportion of recommended investigations, interventions and referrals selected for each scenario were calculated and examined for their association with physician and practice characteristics and physician attitudes. RESULTS: The response rate was 68.3% (529/775 eligible physicians). For the shoulder problem, all of the recommended items were chosen by the majority of respondents. However, of the items not recommended, ordering blood tests was selected by almost half (242 [45.7%]) as was prescribing an NSAID (236 [44.7%]). For the knee osteoarthritis the majority of respondents chose the recommended items except exercise (selected by only 175 [33.1%]). Of the items not recommended, tests were chosen by about half of the respondents and inappropriate referrals (chiefly for orthopedic surgery) were chosen by a quarter. For the acutely hot knee, the majority of physicians chose all of the recommended items except use of ice or heat (selected by only 188 [35.6%]). Although most (415 [78.5%]) of the respondents selected the recommended joint aspiration for this scenario, 84 (15.9%) omitted this investigation or referral to a specialist. The selection of recommended items was strongly associated with training in musculoskeletal specialties during medical school and residency. INTERPRETATION: Primary care physicians' management of 3 common musculoskeletal problems was for the most part in accord with panel recommendations. However, the unnecessary use of diagnostic tests, inappropriate prescribing of NSAIDs, low use of patient-centred options such as exercise, and lack of diagnostic suspicion of infectious arthritis are cause for concern. The results point to the need for increased exposure to musculoskeletal problems during undergraduate and residency training and in continuing medical education.

Adult↗

PubMed1998

Interstitial adenosine, inosine, and hypoxanthine are increased after experimental traumatic brain injury in the rat.

Adenosine is a putative neuroprotectant in ischemia, but its role after traumatic brain injury (TBI) is not clear. Metabolites of adenosine, particularly inosine and hypoxanthine, are markers of ischemia and energy failure. Adenosine triphosphate (ATP) breakdown early after injury and metabolism of cyclic adenosine monophosphate (cAMP) are potential sources of adenosine. Further delineation of the magnitude, location, time course, and source of production of adenosine after TBI is needed. We measured adenosine, inosine, and hypoxanthine in brain interstitial fluid after controlled cortical impact (CCI) in the rat. Rats (n = 15) were prepared for TBI induced by CCI. A microdialysis probe was placed in the cortex, and samples were collected every 10 min. After 3 h of equilibration, the catheter was removed, CCI was performed (4 m/sec, depth 2.5 mm), and the catheter was replaced. In the shams, the catheter was removed and replaced without CCI. The injury group included rats (n = 10) subjected to CCI. Within the injury group, the microdialysis probe was placed in the center of the eventual contusion (center, n = 5) or in the penumbral region (penumbra, n = 5). Purine metabolites were measured using ultraviolet-based high-pressure liquid chromatography. Adenosine, inosine, and hypoxanthine were dramatically increased after injury (61-fold, 37-fold, and 16-fold, respectively sham, all p < 0.05, two-way analysis of variance for repeated measures). No changes in cAMP were observed (p = 0.62 vs. sham). Adenosine peaked in the first 20 min and returned to near baseline 40 min, whereas inosine and hypoxanthine peaked at 30 min and remained increased for 40 min after CCI. Interstitial brain adenosine, inosine, and hypoxanthine were increased early after CCI in rats in the contusion and penumbra. ATP breakdown is a potential source of adenosine in this early period while metabolism of cAMP does not appear to play a role. Confirmation of these data in humans may suggest new strategies targeting this important metabolic pathway.

Adenosine↗

PubMed1998

Soluble adhesion molecules in CSF are increased in children with severe head injury.

Leukocyte-endothelial adhesion molecules, critical to the development of acute inflammation, are expressed in brain as part of the acute inflammatory response to traumatic brain injury (TBI). We measured the concentrations of the adhesion molecules P-selectin, ICAM-1, E-selectin, L-selectin, and VCAM-1 in ventricular cerebrospinal fluid (CSF) from children with severe TBI (Glasgow coma score < 8) and compared these findings with those from children with bacterial meningitis. P-selectin, an adhesion molecule associated with ischemia/reperfusion, was increased in children with TBI versus meningitis and control. Univariate and multivariate regression analyses demonstrated associations between CSF P-selectin and child abuse and age of < 4 years, and a significant, independent association between CSF intercellular adhesion molecule-1 (ICAM-1) and child abuse. These results are consistent with a specific acute inflammatory component to TBI in children. Future studies of secondary injury mechanisms and therapy after TBI should assess on the roles of P-selectin and ICAM-1 in injury and repair processes in brain after TBI.

Adolescent↗

PubMed1998

Quinolinic acid is increased in CSF and associated with mortality after traumatic brain injury in humans.

We tested the hypothesis that quinolinic acid, a tryptophan-derived N-methyl-D-aspartate agonist produced by macrophages and microglia, would be increased in CSF after severe traumatic brain injury (TBI) in humans, and that this increase would be associated with outcome. We also sought to determine whether therapeutic hypothermia reduced CSF quinolinic acid after injury. Samples of CSF (n = 230) were collected from ventricular catheters in 39 patients (16 to 73 years old) during the first week after TBI, (Glasgow Coma Scale [GCS] < 8). As part of an ongoing study, patients were randomized within 6 hours after injury to either hypothermia (32 degrees C) or normothermia (37 degrees C) treatments for 24 hours. Otherwise, patients received standard neurointensive care. Quinolinic acid was measured by mass spectrometry. Univariate and multivariate analyses were used to compare CSF quinolinic acid concentrations with age, gender, GCS, time after injury, mortality, and treatment (hypothermia versus normothermia). Quinolinic acid concentration in CSF increased maximally to 463 +/- 128 nmol/L (mean +/- SEM) at 72 to 83 hours after TBI. Normal values for quinolinic acid concentration in CSF are less than 50 nmol/L. Quinolinic acid concentration was increased 5- to 50-fold in many patients. There was a powerful association between time after TBI and increased quinolinic acid (P < 0.00001), and quinolinic acid was higher in patients who died than in survivors (P = 0.003). Age, gender, GCS, and treatment (32 degrees C versus 37 degrees C) did not correlate with CSF quinolinic acid. These data reveal a large increase in quinolinic acid concentration in CSF after TBI in humans and raise the possibility that this macrophage-derived excitotoxin may contribute to secondary damage.

Adolescent↗

PubMed1998

Perthes disease affecting three female first-degree relatives.

Perthes disease has an incidence of 1 in 4,750 live births (1 in 3,000 boys, but only 1 in 11,800 girls). Although there is evidence for a genetic predisposition to Perthes disease, more than two family members are rarely affected. We report the first recorded case of Perthes disease affecting three female first-degree relatives.

Child↗

PubMed1998

Surgical stabilisation of the lower limb in osteogenesis imperfecta using the Sheffield Telescopic Intramedullary Rod System.

The Sheffield Expanding Intramedullary Rod System was developed after experiencing problems with existing rod systems in the management of osteogenesis imperfecta. Between 1986 and 1996 we treated 74 bones in the lower limb in 28 children at a median follow-up of 5.25 years. We have reviewed 24 children with a total of 60 rods. Before surgery, all children had had multiple fractures of the lower limb. At review eight patients had experienced no further fractures, but three had suffered five or more subsequently. Before initial stabilisation, 15 children had never walked, and only three (13%) used walking as their main means of mobility. After surgery, half of those who showed motor arrest were able to walk (p = 0.016). The number of patients able to walk, with or without aids, increased to 17 (p = 0.0001). We have experienced no evidence of epiphyseal damage after the procedure, and complication rates requiring rod exchange have been low (7%).

Child↗

PubMed1998

A randomized controlled trial to evaluate the efficacy of community based physical therapy in the treatment of people with rheumatoid arthritis.

OBJECTIVE: To evaluate the short term efficacy of a community based physical therapy (PT) program for people with rheumatoid arthritis (RA) through a single blind randomized controlled trial. METHODS: Adults with active RA were referred by their physician for community based PT. Participants were randomized to either an immediate intervention group [experimental group (EG)] or a wait list control group (CG). The intervention was a standardized program of education and exercise consisting of at least 4 visits or 3 h of PT over 6 weeks. Baseline, 6, and 12 week assessments were by a blinded independent assessor. The primary outcome instrument was the Stanford Arthritis Self-Efficacy Scale (SES) and secondary outcome measures included the ACREU Rheumatoid Arthritis Knowledge Questionnaire (KQ) and visual analog scale for pain (VAS). Duration of morning stiffness, grip strength, and tender joint count were also collected at each assessment. Outcome analysis was conducted using analysis of variance. RESULTS: Of 150 eligible and randomized participants, 127 completed the study according to protocol. Baseline analysis showed no differences between the EG and CG for demographics, disease status, or other characteristics. At the 6 week assessment, primary outcome analysis for those who completed the protocol identified a mean change (improvement) of 13.5% in the EG and 5.8% in the CG, representing a 7.7% difference in change scores between the 2 groups [F(1,121) = 6.03; p = 0.015]. A statistically significant difference in change scores was also identified for the KQ [F(1,120) = 6.67; p = 0.011], but not for the VAS. Disease status measures did not change, except for duration of morning stiffness, which improved by 68.8 min in the EG and 8.3 min in the CG (F(1,121) = 4.50; p = 0.036]. CONCLUSION: Four hours of a community based PT intervention delivered over 6 weeks significantly improved self-efficacy, disease management knowledge and morning stiffness in people with RA.

Adult↗

PubMed1998

Antithyroid arthritis syndrome.

We describe a recent clinical case experience of antithyroid arthritis syndrome and literature search from 1965 to 1996 on antithyroid medication and associated arthritis using MEDLINE and EMBASE. The antithyroid arthritis syndrome is a transient migratory polyarthritis that occurs within 2 months of starting thionamide treatment, and resolves within 4 weeks of stopping therapy. Discontinuation of medication is necessary. Alternative forms of treatment for hyperthyroidism should be sought. Nonsteroidal antiinflammatory drug or treatment of the rheumatic complaints is recommended or if unsuccessful, corticosteroid treatment.

Aged↗

PubMed1998

A case of Stevens-Johnson syndrome associated with oxaprozin therapy.

We describe a case of Stevens-Johnson syndrome (SJS) associated with oxaprozin ("Daypro"), a relatively new nonsteroidal antiinflammatory drug (NSAID) of the propionic acid group. Our literature review shows that among the NSAID associated with SJS, oxicams have the highest risk. The risk is low for the propionic acid group. Indeed, the prevalence of their use was too low to permit an analysis of individual drugs. This is the first reported case of SJS associated with oxaprozin. Although the patient we describe survived the reaction, we think it is important to report such a potentially fatal reaction to a relatively newly available medication.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1998

Postradiation morphea.

We describe a 54-year-old woman who developed right breast morphea after radiotherapy following a lumpectomy for infiltrating lobular carcinoma. Skin biopsy confirmed the histological features of morphea. Treatment was initiated with both topical and intralesional steroid, resulting in marked improvement. Morphea following radiotherapy is an infrequently recognized phenomenon. However, when diagnosed early it may be effectively managed with local steroid treatment.

Administration, Topical↗

PubMed1997

Comparison of the interleukin-6 and interleukin-10 response in children after severe traumatic brain injury or septic shock.

Inflammation may play an important role in the evolution of damage after traumatic brain injury (TBI). IL-6 and IL-10 are markers of inflammation that are pro- and anti-inflammatory in nature, respectively. They have been used as an index of the degree of inflammation in diseases including sepsis and meningitis. We hypothesized that both IL-6 and IL-10 would be increased in the cerebrospinal fluid (CSF) of children after TBI. We measured ventricular CSF concentrations of these metabolites (ELISA) each of the first 3 days after TBI in 15 children. CSF IL-6 was increased on day 1 (p < 0.05 vs days 2 or 3). CSF IL-10 was similarly increased on day 1 (p < 0.05). CSF IL-6 after TBI is similar to serum IL-6 levels previously reported in children with septic shock. In contrast, the CSF IL-10 response was markedly attenuated following TBI compared to sepsis. These data suggest a unique balance between pro- and anti-inflammatory cytokines in brain after TBI.

Brain Injuries↗

PubMed1997

The role of adenosine during the period of delayed cerebral swelling after severe traumatic brain injury in humans.

Cerebrovascular failure with an increase in cerebral blood volume or hyperemia contributes delayed cerebral swelling after severe traumatic brain injury (TBI) in humans. One mediator that could be involved in this process is adenosine, which stimulates a concurrent reduction in cerebral metabolic rate and an increase in cerebral blood flow (CBF). We hypothesized that during the delayed phase after TBI in humans: 1) CSF adenosine concentration is associated with uncoupling of CBF and CMRO2, and 2) adenosine formation is driven by mediator-stimulated cAMP production in injured brain. We serially measured CBF and AVDO2, and CSF adenosine, lactate and cAMP after severe TBI in 13 humans. After 6-18 h, global CBF was increased and AVDO2 was reduced vs all other time periods, defining the uncoupling phase as the period between 18 h and 5 days. CSF adenosine concentration was negatively associated with AVDO2 and strongly associated with death (both p < 0.05), CSF lactate peaked during the initial 18 h, but remained increased for 5 days. CSF cAMP concentration was not increased (vs normal). The association between CSF adenosine concentration and death, and the correlation between uncoupling of CBF and oxidative metabolism and CSF adenosine concentration support our first hypothesis. In contrast, the low levels of cAMP in CSF observed in these patients, but persistently increased CSF lactate, refute our second hypothesis. We speculate that hyperglycolysis or occult ischemic foci are possible sources of ATP breakdown and adenosine formation, and that adenosine is playing a neuroprotective role.

Adenosine↗

PubMed1997

Interleukin-6 and interleukin-10 in cerebrospinal fluid after severe traumatic brain injury in children.

Cytokines may play an important role in the pathophysiology of traumatic brain injury (TBI) in children. Interleukin-6 (IL-6) is a proinflammatory cyotkine that plays a role in regenerative processes within the central nervous system (CNS), whereas interleukin-10 (IL-10) is an antiinflammatory cytokine. Both have been measured in serum and cerebrospinal fluid (CSF) as an index of the degree of inflammation in diseases, including sepsis and meningitis. We hypothesized that both IL-6 and IL-10 would be increased in the CSF of children after severe TBI. Fifteen children who sustained severe TBI (Glascow Coma Score [GCS] < or = 7) were studied. Standard neurointensive care was provided. Ventricular CSF collected the first 3 days after TBI was analyzed for IL-6 and IL-10 concentrations by ELISA. Controls were 20 children who were evaluated for meningitis with diagnostic lumbar puncture subsequently found to have no CSF pleocytosis and negative cultures. IL-6 was increased in children after TBI versus controls on all days studied (day 1, 3158.2 +/- 621.8 pg/ml; day 2, 1111.6 +/- 337.0 pg/ml; day 3, 826.7 +/- 193.5 pg/ml vs. 20.6 +/- 5.8 pg/ml, p < 0.0001, Mann-Whitney Rank Sum). IL-10 was increased in children after TBI vs controls on all days studied (day 1, 47.2 +/- 12.9 pg/ml; day 2, 21.0 +/- 6.7 pg/ml; day 3, 15.5 +/- 5.9 pg/ml vs. 8.9 +/- 7.5 pg/ml, p < 0.01). Increased IL-10 concentrations were independently associated with age < 4 years and mortality (p = 0.004 and 0.04, respectively, multivariate linear model). This study demonstrates that IL-6 is increased after TBI in children to levels similar to those reported in adults and is the first to show that IL-10 is increased in CSF of humans after TBI. These data suggest that there may be an age-dependent production of IL-10 after TBI in children.

Adolescent↗

PubMed1997

Salmon calcitonin nasal spray in the prevention of corticosteroid-induced osteoporosis.

The objectives were to determine the efficacy and safety of nasal salmon calcitonin 200 IU daily in the prevention of corticosteroid-induced osteoporosis. A minimized, double-blind, placebo-controlled trial was carried out in corticosteroid-treated patients with polymyalgia rheumatica. The setting was a tertiary care university-affiliated hospital and a total of 31 patients were enrolled. The primary outcome measure was the percentage change in bone mineral density of the lumbar spine in the two treatment groups from baseline to 1 yr of follow-up. The mean +/- S.D. bone mineral density of the lumbar spine in the calcitonin-treated group decreased by 1.29 +/- 6.76% and in the placebo group by 4.95 +/- 3.50% after 12 months. The observed difference of 3.65 +/- 2.10% between groups is statistically significant (P < 0.05). Nasal salmon calcitonin prevented loss of bone in the lumbar spine as measured by dual-energy X-ray absorptiometry.

Absorptiometry, Photon↗

PubMed1997

Cerebrospinal fluid adenosine concentration and uncoupling of cerebral blood flow and oxidative metabolism after severe head injury in humans.

OBJECTIVE: Uncoupling of cerebral blood flow (CBF) and oxidative metabolism is observed after severe head injury in comatose patients; however, the mechanism(s) involved remain undefined. Adenosine can produce cerebral vasodilation and reduce neuronal activity and is a possible mediator of uncoupling. We hypothesized that cerebrospinal fluid (CSF) adenosine concentrations would be increased during uncoupling of CBF and oxidative metabolism, defined as a narrow arterio-jugular venous oxygen difference [D(a-v)O2 4 vol%] after head injury. METHODS: Adenosine concentrations were measured using fluorescent-based high-pressure liquid chromatography in 67 CSF samples obtained from 13 comatose (Glasgow Coma Scale score 7) adult patients who sustained a severe closed head injury. At the time each sample was obtained, CBF was measured by the xenon-133 method, and blood samples were obtained for determination of D(a-v)O2. RESULTS: CSF adenosine concentration was negatively associated with D(a-v)O2 (P < 0.05, generalized multivariate linear regression model). In addition, CSF adenosine concentration was increased when D(a-v)O2 was 4 versus > 4 vol% (38.5 [3.2-306.3] versus 14.0 [2.7-795.5] nmol/L, respectively, median [range]; P < 0.025) and in patients who died versus survivors (40.1 [6.9-306.3] versus 12.9 [2.7-795.5] nmol/L, respectively, median [range]; P < 0.001). CONCLUSION: The association between increased CSF adenosine concentration and a reduction in global cross-brain extraction of oxygen supports a regulatory role for adenosine in the complex balance between CBF and oxidative and nonoxidative metabolism severe head injury in humans.

Adenosine↗

PubMed1997

Modern trends for external fixation of fractures in children: a critical review.

There is considerable controversy about the use of external fixation to manage children's fractures. The indications for external fixation are examined in the light of the available evidence in the literature. A general overview of surgical considerations, including the type of fixator, pin placement, and duration of treatment, is given with an assessment of possible complications. External fixation offers a safe and effective management option and may perhaps be the subject of randomized controlled trials in the future.

Child↗

PubMed1997

Development of an instrument to measure knowledge in individuals with rheumatoid arthritis: the ACREU rheumatoid arthritis knowledge questionnaire.

OBJECTIVE: Education is an important component of community based rehabilitation programs for people with rheumatoid arthritis (RA). This study describes the development of a questionnaire to measure knowledge in this context. METHODS: Items were generated using focus group methodology and covered the domains of prognosis, pain management, medications, joint protection, energy conservation, exercise, and coping strategies. RESULTS: After extensive pretesting, the questionnaire was administered to 252 people with RA. The final 31 item questionnaire had acceptable internal consistency (Cronbach's alpha: 0.76, n = 185), test-retest reliability (r = 0.91, p < or = 0.001), content and construct validity. Sensitivity to change was confirmed in the context of a 6 week home based physiotherapy educational intervention. CONCLUSION: The RA knowledge questionnaire is a reliable, valid, and sensitive instrument for measuring the effect of a RA educational intervention.

Adult↗