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Biomedical subjects

J M Thompson

Publications and source records attributed to J M Thompson.

At least 19 recordsLinked to original sources

Marked increase in veno-occlusive disease of the liver associated with methotrexate use for graft-versus-host disease prophylaxis in patients receiving busulfan/cyclophosphamide.

The use of cyclosporine-A/methotrexate (CyA/MTX) for graft-versus-host disease (GVHD) prophylaxis is safe and effective for patients undergoing allogeneic bone marrow transplantation after preparation with cyclophosphamide and total body irradiation. We report 87 patients prepared for allogeneic transplant with busulfan 4 mg/kg/d orally for 4 days, followed by cyclophosphamide 60 mg/kg/d intravenously for 2 days (Bu4Cy2). A marked increase in hepatotoxicity was observed in 20 patients administered CyA/MTX, compared with 67 historical control patients who received CyA/methylprednisolone (CyA/MP) for GVHD prophylaxis with all other treatment and support variables remaining constant. The incidence of hyperbilirubinemia (bilirubin greater than or equal to 2 mg/dL) increased from 48% to 80% (P = .02), and the mean maximal bilirubin increased from 4.67 +/- 7.27 to 8.72 +/- 8.73 mg/dL (P = .04), when CyA/MTX was used in place of CyA/MP for GVHD prophylaxis. In addition, the incidence of veno-occlusive disease (VOD) increased from 18% to 70% (P = .0001), and death caused by VOD increased from 4.5% to 25% (P = .02). Survival was not significantly different for the two groups because of a higher non-VOD death rate in patients receiving CyA/MP for GVHD prophylaxis (P = .77). We suggest caution when using Bu4Cy2 in combination with CyA/MTX for GVHD prophylaxis.

Actuarial Analysis

Markers of inflammatory activation: upregulation of complement receptors CR1 and CR3 on synovial fluid neutrophils from patients with inflammatory joint disease.

Expression of the C3 receptors CR1 and CR3 was investigated on neutrophils from paired peripheral blood and synovial fluid samples from 34 patients with inflammatory joint disease (21 patients with rheumatoid arthritis (RA) and 13 patients with other articular diseases (OAD)). Using monoclonal antibodies (anti-CD35, anti-CD11b) and immunofluorescence flow cytometric analyses the percentages of positively labeled cells and the relative fluorescence intensities (as a measure of receptor number) were determined. CR1 and CR3 were found to be present on the majority (> 85%) of circulating neutrophils from normal subjects, RA and OAD patients, and on synovial fluid neutrophils from both patient groups. A strong correlation between neutrophil CR1 and CR3 expression was observed in peripheral blood samples from normal subjects (r = 0.81; P = 0.001), RA (r = 0.79; P = 0.001), and OAD patients (r = 0.83; P = 0.001); in each case the levels of CR3 expression were approximately twice those recorded for CR1. Both CR1 and CR3 expression was upregulated on synovial fluid neutrophils compared with that observed on the corresponding peripheral blood cells. Mean percentage increases observed were: RA patients: CR1, 16.5% (P < 0.001) and CR3, 28.7% (P < 0.001); and OAD patients: CR1, 4.1% and CR3, 26.9% (P = 0.001). Correlation of serum and synovial fluid IL-6, IL-8, and immune complex levels with neutrophil CR1 and CR3 expression failed to demonstrate any significant relationship between the concentrations of these soluble factors and receptor expression. Upregulation of CR1 and CR3 receptors, reflecting neutrophil activation within the inflamed joint, is a consistent finding in patients with inflammatory arthropathies.

Adult

First phase insulin release in the non-obese diabetic mouse: correlation with insulitis, beta cell number and autoantibodies.

The ontogenic variation of beta cell function and its relationship with the degree of islet damage and levels of autoantibodies have been studied in the non-obese diabetic (NOD) mouse model. We conducted in vivo first phase insulin release (FPIR) in response to intravenous glucose and studied its correlation with the degree of insulitis, islet cell antibody (ICA) and insulin autoantibody (IAA) levels in female NOD mice cross-sectionally at days 40 (n = 19), 90 (n = 21), 150-160 (n = 21) and day 250 (n = 20). The mean +/- SEM FPIR values showed an age-related decline from day 40 (46.2 +/- 5.3 microU/ml) to day 150-160 (17.8 +/- 2.5 microU/ml) and then doubled at day 250 (34.5 +/- 5 microU/ml), while the mean +/- SEM insulitis scores increased progressively until day 150-160 (61.7 +/- 6.1%) and then declined slightly at day 250 to 50.2 +/- 6.2%. In female NOD mice with spontaneous diabetes (n = 4) and streptozotocin-induced diabetic Swiss mice (n = 5) FPIR was either absent or greatly attenuated. A statistically significant inverse correlation between FPIR and insulitis was found among NOD mice at days 90 (P = 0.02; r = -0.52) and 150-160 (P = 0.03; r = -0.48). However, no statistically significant correlation was observed at days 40 and 250. Morphometric techniques applied to day 150-160 pancreatic sections showed a statistically significant negative correlation between insulitis and beta cell number per unit area of islet tissue (P = 0.0001; r = - 0.75). At this age some islet beta cells showed different intensities of staining by immunofluorescence.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging

Mayo Medical Center Brain Injury Outpatient Program: treatment procedures and early outcome data.

The rehabilitation of persons with brain injuries has proved challenging; community reintegration is often unsuccessful. Herein we describe our intensive group-oriented outpatient treatment program for persons with brain injury and report outcome data for the graduates of the program thus far. This interdisciplinary program emphasizes the development of cognitive skills, compensation techniques, social skills, emotional adjustment, leisure skills, physical fitness, and health maintenance. Although goals are individually determined, independent living and employment are goals for most participants in the program. Before initial participation, all candidates undergo an extensive 2-day assessment. Typically, a patient remains in the program for approximately 6 months. The specific group treatment approaches used in the program are discussed. Outcome data are assessed with use of the Portland Adaptability Inventory and goal attainment scaling, as well as comparisons of preprogram and postprogram employment status and level of independent living. Our initial results support the conclusion that this comprehensive and integrated treatment program is efficacious in rehabilitating persons with mild to moderate sequelae of brain injury.

Adolescent

Postnatal depression and SIDS: a prospective study.

This study was carried out in response to reports from nurses to a post-neonatal mortality review committee that a number of mothers of infants dying from sudden infant death syndrome (SIDS) appeared to be depressed before the child's death. The New Zealand Cot Death Study was a 3 year multicentre case-control study for SIDS. There were 485 SIDS cases in the post-neonatal age group in the study regions, and these were compared with 1800 control infants. Infants of mothers with either a self-reported use of medication for psychiatric disorders, a history of hospitalization for psychiatric illness or a family history of postnatal depression had a significantly increased risk of SIDS compared with infants of mothers who were either not using medication (odds ratio (OR) = 1.45; 95% confidence interval (CI) = 1.03, 2.04) or were without a history of hospitalization for psychiatric illness (OR = 1.80; 95% CI = 1.03, 3.11) or a family history of postnatal depression (OR = 1.61; 95% CI = 1.06, 2.43). All mothers of infants born in the study areas over a 1 year period were eligible to complete a questionnaire measuring maternal depression when the infant was 4 weeks of age. Thirty-three infants subsequently died from SIDS, and they were compared with 174 controls. Fifteen (45.5%) of the mothers of cases were depressed, compared with 28 (16.1%) of the mothers of controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Case-Control Studies

Four modifiable and other major risk factors for cot death: the New Zealand study.

New Zealand's high mortality rate from sudden infant death syndrome (SIDS) prompted the development of the New Zealand Cot Death Study. A report of the analysis of the data from the first year has been published. This report now gives the major identified risk factors from the full 3 year data set. In this case-control study there were 485 infants who died from SIDS in the post-neonatal age group, and 1800 control infants, who were a representative sample of all hospital births in the study region. Obstetric records were examined and parental interviews were completed in 97.5% and 86.9% of subjects, respectively. As expected many risk factors for SIDS were confirmed including: lower socio-economic status, unmarried mother, young mother, younger school-leaving age of mother, younger age of mother at first pregnancy, late attendance at antenatal clinic, non-attendance at antenatal classes, Maori, greater number of previous pregnancies, the further south the domicile, winter, low birthweight, short gestation, male infant and admission to a special care baby unit. In addition, however, we identified four risk factors that are potentially amenable to modification.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors

Generalized seizures secondary to high-dose busulfan therapy.

Two patients without prior histories of neurologic disorders experienced generalized seizures while receiving high-dose busulfan (total dose 16 mg/kg) as part of a preparative regimen for allogeneic bone marrow transplantation. A review of the literature revealed 14 similar occurrences. Maintenance of therapeutic blood concentrations of phenytoin in subsequent patients at our institution has resulted in no further patients experiencing generalized seizures. Prophylactic anticonvulsant therapy should be considered in patients receiving high doses of busulfan.

Adolescent

Additive and nonadditive differences in postweaning growth and carcass characteristics of Devon, Hereford, and reciprocal-cross steers.

Postweaning growth and carcass characters of 110 steers from a complete two-breed diallel of the Devon and Hereford breeds were examined under two environments. Additive and nonadditive effects were estimated using linear contrasts for several growth and carcass traits. Steers from each of the four breed groups were grown postweaning to slaughter in high- and low-nutrition environments. Weights were recorded every 2 mo. At slaughter, hot carcass weight, longissimus muscle area, kidney and channel fat, and subcutaneous fat at nine sites were measured. Heterosis for postweaning growth rate was 3.9% (P less than .01) and for slaughter weight 5.0% (P less than .01). Within the low-nutrition environment during periods of slow and fast growth, the Devons and Herefords performed differently. The growth rate of the steers differed in the two environments; however, heterosis for slaughter weight was of the same magnitude in both environments. No differences existed between the straightbreds or between the reciprocal crosses for slaughter weight. Crossbred carcasses were 7.4% heavier (P less than .01) than the straightbred carcasses; however, this effect was removed after adjustment for differences in slaughter weight. Heterosis for longissimus muscle area and carcass fatness were not significant after adjusting for carcass weight. Additive differences occurred for carcass traits. Devon carcasses had more kidney and channel fat (P less than .05) at a constant hot carcass weight and differences occurred in the partitioning of fat within the subcutaneous depot. No significant maternal effects were observed for the carcass traits measured. Crossbreeding increased carcass weight without altering composition, and relative performance was not affected by the diverse environments.

Adipose Tissue

Pilot trial of prophylactic ursodiol to decrease the incidence of veno-occlusive disease of the liver in allogeneic bone marrow transplant patients.

Ursodiol is a hydrophilic, non-hepatotoxic bile salt indicated for the medical treatment of cholesterol gallstones. This pilot study explored the use of prophylactic ursodiol in an attempt to decrease the incidence and severity of veno-occlusive disease (VOD) of the liver following allogeneic bone marrow transplantation (BMT). Between February 1991 and January 1992, 22 consecutive patients undergoing BMT for hematologic malignancies received the BU(4)/CY(2) preparative regimen and CSA/MTX for GVHD prophylaxis. Ursodiol, 600-900 mg daily by mouth was begun at least 1 day prior to beginning the preparative regimen. Results for this pilot group were compared to a control group of 28 consecutive patients transplanted between June 1989 and January 1991 with the same regimen without ursodiol. There were no significant differences in disease or clinical status between the groups pretransplant. However, mean baseline AST levels were significantly higher in the ursodiol group, 28.0 U/l vs 18.1 U/l in the control group (p = 0.001). The median maximum bilirubin observed post-transplant was 2.35 mg/dl (range 0.9-45) in the ursodiol group, and 5.05 mg/dl (range 0.7-29.4) in controls. The incidence of VOD was 2/22 (9.1%) in the ursodiol group and 18/28 (64.3%) in controls (p = 0.0001). Death due to VOD occurred in 1/22 patients (4.5%) in the ursodiol group and in 6/28 (21.4%) controls (p = 0.12). Our data suggest that ursodiol may decrease the incidence of VOD in allogeneic BMT patients.

Adolescent

Morphological comparison by scanning electron microscopy of transient retina-muscle synapses and long-lived spinal cord-muscle synapses.

Retinal neurons will form cholinergic synapses on muscle cells in tissue culture, however, these inappropriate synapses are transient. Although within 24 hrs. myotubes are readily innervated, by 7 days of coculture no physiological response can be detected. In contrast, spinal cord neurons form long-lived synapses on muscle cells which can be detected for several weeks. In this study, we examined retina-muscle and spinal cord-muscle cocultures to determine whether retinal neurons withdrew their processes from muscle cells, and preferentially maintained contacts on other retinal neurons. Using scanning electron microscopy, we observed that during the first 24 hrs. of coculture both types of neurons extend processes along myotubes. The neurite outgrowth occurs concomitantly with the observed increase in physiologically detected synaptic muscle responses. Over the next 6 days, retinal neurite contacts on the muscle cells are withdrawn, while spinal cord contacts remain. Retinal neurons remain in contact with other retinal neurons at day 7 of coculture. Thus, retinal neurons form and maintain synapses on their appropriate target (other retinal neurons); whereas, they withdraw contacts from inappropriate targets (muscle cells). By contrasting retinal and spinal cord synapses on muscle cells, we hope to elucidate the mechanisms of synaptic recognition and maintenance.

Animals

Treatment for acute myelocytic leukemia with allogeneic bone marrow transplantation following preparation with BuCy2.

One hundred twenty-seven patients with acute myelocytic leukemia (AML) were given busulfan 4 mg/kg on each of 4 days and cyclophosphamide 60 mg/kg on each of 2 days (BuCy2) followed by allogeneic bone marrow transplantation from an HLA-identical or one antigen disparate sibling. For 71 patients in first complete remission, 23 in second complete remission or initial relapse, and 33 patients with primary refractory disease, second or subsequent relapse, or a preceding hematologic disorder, the 3-year leukemia-free survival (LFS) is 63.1%, 32.6%, and 24.2% respectively. The actuarial probability of relapse for each group is 14.1%, 40.6%, and 61.0%. In multivariate analyses, relapse and decreased LFS were associated with advanced disease phase and with M4/M5 French-American-British classification. The LFS of first remission patients was adversely associated with a short time interval from diagnosis to transplantation. This study indicates that BuCy2 is an attractive preparative regimen for marrow transplantation in patients with AML and that prognostic factors for relapse and LFS are similar those described for regimens containing total body irradiation.

Adult

Immunoglobulin isotype composition of circulating and intra-articular immune complexes in patients with inflammatory joint disease.

The immunoglobulin (Ig) heavy chain isotype composition of intra-articular and circulating immune complexes (ICs) were determined by a Raji cell flow cytometric assay in paired serum and synovial fluid samples from 15 patients with rheumatoid arthritis (RA) and 15 patients with other articular diseases (osteoarthritis, ankylosing spondylitis, gout, psoriatic arthritis, Reiter's disease). ICs were most prevalent in synovial fluid samples of patients with RA but were infrequently detected in serum and synovial fluid samples from the non-RA patients. ICs in patients with RA were heterogeneous both in the prevalence of Ig subclasses identified and in the distribution of the respective Ig isotypes within the complexes. Furthermore, differences were observed in the Ig isotype composition of ICs in paired serum and synovial fluid samples indicating that circulating ICs may not always arise simply by spill-over from articular sites. The possible mechanisms for IC formation in RA are discussed with reference to four patients who displayed features of extra-articular disease.

Adult

Immunocytochemical localization of leucomyosuppressin-like peptides in the CNS of the cockroach, Leucophaea maderae.

Immunocytochemistry was used to determine sites of synthesis and pathways for the transport of the neuropeptide, Leucomyosuppressin (pQDVDHVFLRFamide) in the cockroach, Leucophaea maderae. This study led to identification of neurons in the brain and thoracic ganglia reactive to polyclonal antibodies raised against this peptide. No immunoreactive cells were found in the subesophageal or abdominal ganglia. Although the corpus cardiacum contained no intrinsic cells immunoreactive to LMS antibodies, the periphery of this organ and that of the nervi corporis allati contain an abundance of LMS-reactive terminals.

Amino Acid Sequence

EMG muscle scanning: comparison to attached surface electrodes.

Electromyographic (EMG) muscle scanning measures brief samples of integrated muscle action potentials from individual muscles using a hand-held scanner with post-style electrodes. This "scanning" technique is widely used by biofeedback practitioners to quickly assess muscle activity in the diagnosis of musculoskeletal disorders. In an effort to compare muscle scanning with the established technique using attached surface electrodes, ten healthy subjects (25-35 years old) were scanned using 2-second sampling at five bilateral muscle sites while simultaneously monitoring the same sites with surface electrodes. This was repeated using 10-second scanning samplings. Pearson's product-moment correlations between scanning for 2 seconds and prolonged surface recording at all sites were 0.54-0.89. Scanning for 10 seconds improved the correlations to 0.68-0.91. EMG scanning for 2 seconds compares favorably with attached surface electrode recording. Comparisons are further improved by 10-second scans.

Adult

Level of medical care required for mass gatherings: the XV Winter Olympic Games in Calgary, Canada.

STUDY OBJECTIVE: To determine the level of medical care required for mass gatherings and describe the types of medical problems encountered in a major winter event. DESIGN: Standard charts were available for 3,395 encounters. Interviews with medical staff showed that the few unrecorded encounters were for very minor medical problems. A four-tiered triage system (low, moderate, urgent, and emergent) developed before the Games was applied to each chart retrospectively by a single emergency physician. Chi-squared tests were used to test significant differences. SETTING: This winter sporting and entertainment event had 12 urban and rural venues. Medical staff (98 physicians, 161 nurses, and 337 first-aid attendants) were based in 28 advanced life support (ALS) clinics. The medical service operated for four weeks. TYPE OF PARTICIPANTS: There were 1.8 million spectator-days. Patients included spectators, athletes, and support staff. INTERVENTIONS: First-aid attendants referred patients to the clinics, where nurses conducted initial assessments and referred patients to physicians at the venue, or more rarely, to local hospital emergency departments. Paramedic ambulances were stationed at the venues. The triage system was not used for patient management. MEASUREMENTS AND MAIN RESULTS: Only 40 urgent and one emergent medical problems were encountered. The majority of patients could have been managed by trained nurses working alone under standing orders. Fifty patients were transported to the hospital by ground ambulance and three by helicopter. No significant differences were found in the low acuity levels experienced at indoor urban venues, outdoor urban venues, and the rural cross-country ski venue. The Alpine ski venue was characterized by significantly higher acuity and a long prehospital transfer phase. CONCLUSION: Owing to the low acuity encountered and the availability of Calgary's ALS ambulance service, we concluded that physician-based ALS teams were not required for patient management at the urban venues. Such teams were found to be required at the rural Alpine ski venue. Other reasons for using physicians are discussed, as is development of a standard triage system for mass gatherings.

Alberta

Comparison of invasive and non-invasive measurements of continuous arterial pressure using the Finapres.

A comparison was made of arterial pressures measured invasively from a radial arterial cannula and non-invasively from the middle finger using the 2300 Finapres (Ohmeda) during induction and maintenance of anaesthesia. Digital outputs of both pressures were captured directly onto computer hard disk; data recorded during flushing of the arterial line were excluded from analysis. We studied 53 patients undergoing cardiac, major vascular and neurosurgical procedures; 17705 comparisons of systolic, diastolic and mean pressure were analysed. Overall correlations between Finapres and invasive pressures were poor (r = 0.82, 0.68 and 0.78 for systolic, diastolic and mean pressures, respectively). The Finapres exhibited a high level of accuracy and precision in some recordings. However, patient data sets showed marked variability in average pressure differences (invasive minus Finapres) when examined individually or grouped by operation type. Unexplained variations in pressure difference with time and absolute pressure were observed also. Whilst providing useful beat-to-beat information on arterial pressure trends, the Finapres cannot be recommended as a universal substitute for invasive arterial pressure monitoring.

Adult

Localization of leucomyosuppressin-like peptides in the central nervous system of the stable fly with immunocytochemistry.

An antiserum raised against leucomyosuppressin (LMS), the first insect neuropeptide shown to inhibit contraction of both visceral and skeletal muscles of insects, revealed the presence of LMS-like material in neurons of the adult stable fly, Stomoxys calcitrans (L.). Cells and their processes immunoreactive to the LMS antiserum were found in the brain, subesophageal, and thoracico-abdominal ganglia, with the majority of these neurons in the thoracico-abdominal ganglion. Positive immunostaining after preabsorption of the antibodies with the molluscan tetrapeptide FMRFamide, which absorbs the antibodies directed against the C-terminal FLRFamide of LMS, indicates that structural similarities between LMS and the stable fly neuropeptide(s) extend beyond a similar C-terminal tetrapeptide sequence.

Animals