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Biomedical subjects

R Carbotte

Publications and source records attributed to R Carbotte.

8 recordsLinked to original sources

Cognitive difficulty in physicians.

PURPOSE: Remediation of some incompetent physicians has proven difficult or impossible. The authors sought to determine whether physicians with impaired competency had neuropsychological impairment sufficient to explain their incompetence and their failure to improve with remedial continuing medical education (CME). METHOD: During a one-year period, 1996-97, all 27 participants in the Physician Review Program (PREP) conducted at McMaster University, a physician competency assessment program, undertook a detailed neuropsychological screening battery. RESULTS: Nearly all physicians assessed as competent also performed well on the neuropsychological testing. However, a significant number (about one third) of the physicians who performed poorly on the competency assessment had neuropsychological impairments sufficient to explain their poor performances. The difficulties were more marked in elderly physicians. CONCLUSION: A significant minority of incompetent physicians have cognitive impairments sufficient to explain both their incompetence and, probably, their failure to improve with remedial CME. Testing physicians for these impairments is important: to detect and treat reversible conditions, to manage irreversible conditions that preclude successful educational intervention, and to facilitate compensation in this instance. Serious consideration should be given to the incorporation of neuropsychological screening in all intensive physician review programs.

Adult↗

Does treatment with L-thyroxine influence health status in middle-aged and older adults with subclinical hypothyroidism?

OBJECTIVE: To determine if health-related quality of life (HRQL) in patients of middle age and older with elevated thyroid-stimulating hormone (TSH) and normal total thyroid hormone levels-subclinical hypothyroidism-improves with L-thyroxine replacement therapy. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Outpatient clinic. PATIENTS: Thirty-seven patients with subclinical hypothyroidism, most with symptoms consistent with hypothyroidism, over 55 years of age. INTERVENTIONS: Placebo or L-thyroxine replacement therapy to achieve normal TSH level. MEASUREMENTS AND MAIN RESULTS: Disease-specific and general HRQL, cognitive function, bone mineral density, lipid levels. The mean daily dose of L-thyroxine replacement in the active group was 68 +/- 21 micrograms. TSH decreased by 8.6 mIU/L (95% confidence interval [CI] 4.1 to 13.1) and T4 increased by 27.9 nmol/L (95% CI 14.8 to 41.2). There was a statistically significant improvement in a composite psychometric memory score in treated versus control patients; all other outcomes showed similar findings in the two groups. Although confidence intervals for most measures did not exclude an important improvement in HRQL with thyroid replacement, no measure of symptoms or HRQL either showed clinically important trends in favor of treatment, or approached conventional levels of statistical significance. CONCLUSIONS: In middle-aged and older patients with elevated TSH and normal T4, it may not be harmful to follow biochemical and clinical status even in the presence of nonspecific symptoms potentially associated with hypothyroidism.

Aged↗

Behavior and immune status of MRL mice in the postweaning period.

The notion that the MRL-lpr substrain is a useful model of behavioral and cognitive deficits found in systemic autoimmune diseases is supported by the recent findings of behavioral dysfunction in autoimmune MRL-lpr mice compared to their congenic control MRL +/+ mice. However, it has not been established whether the altered behavioral profile in MRL-lpr mice is the result of the autoimmune process itself or reflects a subtle difference in genetic background or both. To address the question whether MRL-lpr mice are born with behavioral dysfunction the present study compares the behavior of the two MRL substrains in the early postweaning period, when their immune status does not show detectable difference. Results show that the prediseased (4- to 6-week-old) MRL-lpr mice are not distinguishable from the congenic MRL +/+ controls on most behavioral measures except for speed of locomotion and novelty-induced hyperactivity in activity monitors. The immune status of the two substrains is also similar except for a lower hematocrit in the MRL-lpr group. Surprisingly, low amounts of antinuclear and brain-reactive antibodies (possibly transferred from diseased mothers) were detected in the serum of about 50% of the mice in both groups. The lack of major differences in behavior in the premorbid period suggests that appearance of previously reported behavioral dysfunction in the disease state reflects the presence of autoimmunity, time-determined genetic activation, or both.

Age Factors↗

Spatial learning during the course of autoimmune disease in MRL mice.

The present study examines whether autoimmune MRL-lpr mice develop impairments in learning and memory that correlate with changing severity of lupus-like disease. MRL-lpr mice (n = 20) were tested in the Morris water-maze at 12, 14, 16 and 18 weeks of age. Age-matched controls were congenic MRL +/+ mice (n = 20) that develop the disease much later. Immune status was assessed by the presence of anti-nuclear antibodies (ANA), brain-reactive antibodies, proteinuria, and haematocrit. Learning rates and memory retention did not differ between the substrains, and did not correlate or deteriorate with advancing age and autoimmunity. However, the baseline performance level in autoimmune MRL-lpr mice was shifted, as evidenced by a consistently longer task-solving latencies. Thigmotaxic swimming (along the pool wall) was pronounced in the MRL-lpr group, and was associated with the observed difference in performance. The present study does not support the notion that learning/memory abilities of autoimmune MRL-lpr mice are impaired per se, but may support the hypothesis that the rapid progress of humoral autoimmunity affects the emotionality of lupus-prone mice.

Animals↗

Brain-reactive antibodies and behavior of autoimmune MRL-lpr mice.

The hypothesis that brain-reactive autoantibodies (BRA) impair behavior was examined in MRL-lpr mice, which develop spontaneous autoimmune disease. Circulating BRA were measured as in vitro serum reactivity to Neuro-2A neuroblastoma cell line, and behavioral competence was assessed in activity monitors, open field, beam walking, and Morris water maze task. Mice with BRA in serum (BRA positive) exhibited slower spontaneous locomotion in a novel environment, shorter grooming episodes, and less exploration of the open field centre when compared to age-matched 7-11-week-old BRA-negative cagemates. Moreover, when initially exposed to the large swimming pool, BRA-positive mice showed increased swimming along the wall, but had no difficulty in learning the water maze task or in traversing a narrow beam. Brain-reactive autoantibodies titre and behavioral measures were not correlated, suggesting that the concentration of serum BRA is not reflective of the magnitude of behavioral impairment. Nevertheless, the present study suggests that the presence of circulating BRA is associated with impaired exploration and/or enhanced emotional reactivity in MRL-lpr mice. It also supports the hypothesis of a pathogenic role of BRA in various mental disorders.

Animals↗

Reduced striatal glucose consumption and prolonged reaction time are early features in Huntington's disease.

Striatal glucose consumption was measured by positron emission tomography in 4 male patients, aged 16-27, suffering from Huntington's disease and in 3 age-matched control subjects. Symptoms had been present for 3 years or less; they were mainly psychiatric. Two of the patients had no chorea although the time taken to initiate a movement was prolonged and there was some reduction in the speed at which movements could be executed. Caudate atrophy was absent or minimal by CAT scan yet striatal glucose consumption was markedly reduced in all of the patients. It is suggested that striatal glucose consumption is largely determined by the functional integrity of spiny neurones in the striatum.

Adolescent↗

Serum lymphocytotoxic antibodies in neuropsychiatric lupus: a serial study.

The pathogenesis of neuropsychiatric (NP) SLE remains speculative. A relationship between circulating brain cross-reactive lymphocyte antibodies (LCA) and NP-SLE has been postulated but serial, prospective study of LCA in individual patients with SLE has rarely been performed. In the current study a group of 34 patients with SLE was analyzed using clinical, neurologic, psychiatric, and neuropsychological examinations, together with routine serological tests, to define NP-SLE. Previous history of alloimmunization was also recorded. LCA were measured by a two-stage microcytotoxicity assay against a panel of 25 normal donor B and T cells, at both 40 and 37 degrees C. LCA by this method were found in the serum of 20/34 (58%) SLE, 2/22 (9%) rheumatoid arthritis, and 3/24 (12%) antinuclear-antibody-positive chronic psychiatric patients (P less than 0.01). Analysis of LCA serially in individual SLE patients revealed: (1) No difference in B- or T-cell reactivity at either 4 or 37 degrees C, (2) no significant correlation between previous alloimmunization and the presence of LCA, (3) fluctuations in LCA associated with NP-SLE relapses or remissions, but not with therapy, in 10 patients prospectively studied. A significant positive association was found between the occurrence of single neuropsychiatric events and serial LCA determinations in 180 sera (P less than 0.000001). LCA as measured in this study appear more frequently in SLE than in controls and may indicate active NP-SLE in some patients. Further study of the pathogenic role and diagnostic value of LCA in NP-SLE, including their relationship to subtle neurocognitive changes, is proposed.

Adolescent↗

Neurobehavioral outcomes among farm and nonfarm rural Ecuadorians.

International researchers have urged greater use of simple neurobehavioral batteries in developing country settings where higher levels of exposure and a variety of cultural and demographic factors may both occur. We conducted a cross-sectional survey of 144 farm members and 72 age and education frequency-matched controls from rural Ecuador, using an amplified Neurobehavioral Core Test Battery. Farm members ranged from those with only indirect pesticide contact to applicators regularly applying organophosphate and carbamate insecticides by backpack sprayer. The distributors of scores showed those with less than 4 years of formal education and at the extremes of age (< 16 or > 65 years old) contributed sufficiently to nonnormality that they had to be excluded from subsequent analyses (resultant n = 170). After adjustment for age and education, language-based IQ test scores and farm membership were the most consistent determinants of neurobehavioral outcomes. Visual-spatial tasks were the most sensitive to the effects of farm membership. Gender (women better than men), alcohol problems, and solvent use were also important for some neurobehavioral tests.

Adolescent↗