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Biomedical subjects

M Primeau

Publications and source records attributed to M Primeau.

12 recordsLinked to original sources
PubMed2005

Combining several polymorphisms of thymidylate synthase gene for pharmacogenetic analysis.

Thymidylate synthase (TS) is an essential enzyme in proliferating cells and an important target for several chemotherapeutics. Several TS gene polymorphisms correlate with variable TS expression: a double (2R) and triple (3R) 28-bp repeat element, a G to C substitution of the 3R allele and a 6 bp variation in 3'UTR. We have previously shown that childhood acute lymphoblastic leukemia (ALL) patients who are homozygous for the 3R allele had reduced event-free survival (EFS) probabilities. Here, we analyzed all three polymorphisms in an extended group of ALL patients (n=259). The effect of the 3R homozygosity on ALL outcome was confirmed (P=0.006), whereas 6 bp polymorphism did not influence EFS when analyzed separately. No significant difference among 3R3R genotype subgroups, as defined by a G to C substitution, was observed. The haplotype analysis revealed the higher frequency of the 3RC/6 bp+ haplotype (P=0.04) and the protective role of the 2R/6b p- (P=0.04). Consequently, homozygosity for the 6 bp- allele appeared to reduce an event-predisposing effect of 3R variant. Although of importance for translation into the clinical practice, these findings need confirmation in larger studies.

Child↗
PubMed2004

Role of polymorphisms in MTHFR and MTHFD1 genes in the outcome of childhood acute lymphoblastic leukemia.

The central role of 5,10-methylenetetrahydrofolate reductase (MTHFR) and methylenetetrahydrofolate dehydrogenase (MTHFD1) in folate metabolism renders polymorphisms in genes encoding these enzymes potential modulators of therapeutic response to antifolate chemotherapeutics. The analysis of 201 children treated with methotrexate for childhood acute lymphoblastic leukemia (ALL) showed that patients with either the MTHFR T677A1298 haplotype or MTHFD1 A1958 variant had a lower probability of event-free survival (EFS) in univariate analysis (hazard ratio (HR)=2.2, 95% confidence interval (CI), 1.0-4.7 and 2.8, 95% CI, 1.1-7.3, respectively). Multivariate analysis supported only the role of the MTHFR variant (HR=2.2, 95% CI, 0.9-5.6). However, the association of both genes with ALL outcome appears to be more obvious in the presence of another event-predisposing variant belonging to the same path of drug action. The combined effect of a thymidylate synthase (TS) triple repeat associated with increased TS levels, with either the MTHFR T677A1298 haplotype or MTHFD1 A1958 allele, resulted in a highly significant reduction of EFS (multivariate HR=9.0, 95% CI, 1.9-42.8 and 8.9, 95% CI, 1.8-44.6, respectively). These results reveal the role of gene-gene interactions within a folate pathway, and how they can correlate with relapse probabilities in ALL patients.

Child↗
PubMed2001

A battery-powered notebook thermal cycler for rapid multiplex real-time PCR analysis.

A compact, real-time PCR instrument was developed for rapid, multiplex analysis of nucleic acids in an inexpensive, portable format. The instrument consists of a notebook computer, two reaction modules with integrated optics for four-color fluorescence detection, batteries, and a battery-charging system. The instrument weighs 3.3 kg, measures 26 x 22 x 7.5 cm, and can run continuously on the internal batteries for 4 h. Independent control of the modules allows differing temperature profiles and detection schemes to be run simultaneously. Results are presented that demonstrate rapid (1) detection and identification of Bacillus subtilis and Bacillus thuringensis spores and (2) characterization of a single nucleotide polymorphism for the hereditary hemochromatosis gene.

Bacillus subtilis↗
PubMed1999

Global-local processing in schizophrenia: hemispheric asymmetry and symptom-specific interference.

The hypothesis of atypical functional hemispheric asymmetry in schizophrenia is tested using the directed global-local paradigm, a lateralizing measure of visual perception. Results indicate low error rates (< 2%) for schizophrenia and normal control groups, but longer response times for the schizophrenia group. In the normal group, detection speed of global and local forms did not differ. In contrast, the schizophrenia group responded significantly faster to local relative to global forms, which supports the asymmetry hypotheses of left hemisphere overactivity-right hemisphere underactivity in schizophrenia. The normal group exhibited a global interference effect (slowed response latency to the local target in the presence of a dissimilar global distractor). When the schizophrenia group was examined according to symptom type and severity, high positive symptom severity was associated with local interference (slowed response latency to the global target in the presence of dissimilar local distractors). Negative symptoms were not associated with interference from the competing local or global forms. Patients with a combination of high positive and low negative symptoms showed significantly greater local interference than patients with high negative and low positive symptoms. Interconnected temporal and frontal systems are postulated to contribute to this pattern of perceptual processing efficiency and distractibility in schizophrenia.

Adolescent↗
PubMed1999

Neuropsychological functioning in migraine headache, nonheadache chronic pain, and mild traumatic brain injury patients.

There are conflicting reports in the literature concerning the neuropsychological functioning of migraine headache patients. The finding in some studies that migraineurs performed more poorly than healthy controls led to the hypothesis that chronic migraine may result in subtle but persistent cerebral dysfunction. Reports describing acute and between-headache neurophysiological disturbances in migraineurs lent support to this hypothesis. To elucidate the cognitive status of these patients, we administered a brief neuropsychological battery to 60 individuals with migraine headache (HA), nonheadache chronic pain (PAIN), or mild traumatic brain injury (MTBI). The PAIN group was included to test the hypothesis that cognitive difficulty in migraineurs might result from the discomfort, depression, medications, etc. often associated with chronic pain, rather than from brain dysfunction. The MTBI patients were considered a useful comparison for the migraineurs because their level of impairment was also expected to be mild, at worst. A MANOVA, with three cognitive index scores as the dependent variables, revealed that the three groups differed significantly. Follow-up contrasts demonstrated that the MTBI group was significantly more impaired on the memory index compared to the HA and PAIN groups, which did not differ from each other. The use of two different normative-based cutoffs to identify individuals who were impaired on the test battery revealed that the frequency of impairment within the two groups of pain patients, but not the MTBI patients, was within normal limits. Thus, the results did not support a link between migraine headache and cognitive impairment.

Journal Article↗
PubMed1998

Dissociation of affect recognition and mood state from blunting in patients with schizophrenia.

The present study was designed to investigate the relationships between expression, perception, and experience of emotion in schizophrenic patients with and without affective blunting. Cognitive processing speed, emotional perception, and emotional experience were assessed in 25 schizophrenic patients grouped according to scores on a measure of overt emotional expression (Rating Scale for Emotional Blunting). Results showed dissociation of emotional expression from emotional perception and emotional experience. Blunted schizophrenic patients were no more impaired in the perception of emotion (Profile of Nonverbal Sensitivity) than non-blunted schizophrenic patients. In addition, groups did not differ in intensity of emotional experience as quantified on the self-report of arousal state (Positive and Negative Affect Scales). Accuracy of perception and reported experience of emotion did not differ between groups as a function of emotional valence. Cognitive processing speed (Symbol Digit Modalities Test; SDMT) was related to blunting score and to perception accuracy, although the SDMT did not differ between groups. Results are discussed in terms of a neuropathological basis for impairment of emotional expression.

Adult↗
PubMed1996

Memory functioning in Lyme borreliosis.

BACKGROUND: To objectively measure memory functioning in patients with Lyme borreliosis and examine the relationship between subjective reports of memory dysfunction and actual impairment. METHOD: A prospective pretreatment study of patients with Lyme borreliosis (N = 21), a patient control group (osteomyelitis, N = 21), and healthy controls (N = 21) was conducted by using tests of verbal memory functioning (California Verbal Learning Test) and self-reported depression (Beck Depression Inventory-Cognitive Index), fatigue (Fatigue Severity Scale), and subjective ratings of memory abilities (Self-Rating Scale of Memory Functions). RESULTS: Patients with Lyme borreliosis performed worse than healthy controls on verbal memory testing, but did not perform significantly differently from patient controls. Lyme borreliosis patients reported increased fatigue, which was correlated with poorer memory performance. Although the Lyme borreliosis patients rated their memory as more impaired, subjective complaints were not correlated with objective memory scores. CONCLUSION: These findings suggest impaired memory performance is not specific to Lyme borreliosis and may be a result of evaluating cognitive functioning in patients with physical illness and somatic complaints. Fatigue is a prominent presenting complaint in patients with Lyme borreliosis and needs to be controlled for since it is known to influence neuropsychological performance. Subjective complaints are not correlated with objective memory assessment, so self-report of memory impairment should not be the criterion for inclusion in studies investigating cognitive manifestations of Lyme borreliosis.

Adult↗
PubMed1991

Technetium 99m SESTAMIBI myocardial perfusion imaging: comparison between treadmill, dipyridamole and trans-oesophageal atrial pacing "stress" tests in normal subjects.

The purpose of this study was to determine the blood clearance, myocardial uptake and heart/lung and heart/liver ratios of technetium 99m methoxyisobutylisonitrile (99mTc-SESTAMIBI) following 3 different types of cardiac stimulation in normal subjects: treadmill stress (STRESS), intravenous administration of dipyridamole (DIP) and trans-oesophageal atrial pacing (TAP). Ten normal volunteers were submitted to 3 injections of 99mTc-SESTAMIBI (10 mCi/70 kg, separated by an interval of 7 days) following STRESS (standard Bruce protocol), DIP (0.142 mg/kg.min during 4 min) and TAP procedures. Blood samples were collected from 1 to 60 min after each 99mTc-SESTAMIBI injection. Planar imaging was performed at 5, 30 and 60 min. Blood retention (percentage of injected dose at 1 min) was 56% +/- 4%, 24% +/- 4% and 38% +/- 6% for STRESS, DIP and TAP, respectively (P less than 0.001). Myocardial uptake was similar for the 3 procedures while the heart lung ratio at 60 min was 3.1 +/- 0.5, 3.8 +/- 0.6 and 3.2 +/- 0.5 for STRESS, DIP and TAP, respectively. Heart/liver ratio at 60 min was 1.9 +/- 0.5, 1.3 +/- 0.3 and 1.1 +/- 0.2 for STRESS, DIP and TAP, respectively (P less than 0.001). These results demonstrated that the 3 types of cardiac stimulation show good imaging parameters with 99mTc-SESTA-MIBI.

Adult↗
PubMed1991

Technetium-99m-sestamibi myocardial perfusion imaging in detection of coronary artery disease: comparison between initial (1-hour) and delayed (3-hour) postexercise images.

Technetium-99m-sestamibi, a new myocardial perfusion imaging agent, does not show significant or rapid myocardial redistribution following its intravenous injection at stress. The purpose of this study was to evaluate the myocardial clearance of 99mTc-sestamibi and ischemic/normal wall ratios at 1 hr and at 3 hr after injection at stress in patients with significant coronary artery disease. Twenty-five patients with ischemic defects on 201Tl scans (n = 15) and/or significant disease on coronary angiogram (n = 18) were prospectively studied. Planar images were obtained at 65 and at 190 min after an injection at stress of 20-25 mCi of 99mTc-sestamibi. A rest study was performed 1-6 days later. Ischemic/normal wall ratios were 0.73 +/- 0.10 and 0.83 +/- 0.12 (p less than 0.05) at 1 and 3 hr, respectively (0.98 +/- 0.15 at rest). Myocardial washout was 26% +/- 12% for normal walls and 15% +/- 8% for ischemic walls (p less than 0.001). Segmental analysis showed 48 and 46 ischemic segments at 1 and 3 hr, respectively. In conclusion, although only a few ischemic segments were missed at 3 hr, significantly lower ischemic/normal wall ratios were found at 1 hr. Faster myocardial washout from normal walls is responsible for the partial reduction of this ratio.

Coronary Disease↗
PubMed1988

Spinal cerebrospinal fluid leak demonstrated by radioisotopic cisternography.

Many conditions are known to cause a cerebrospinal fluid (CSF) fistula; one of them is lumbar puncture for contrast myelography. Reported here is the case of a man who underwent contrast myelography at the L2-L3 level and who presented with postural headaches and lumbalgia with radiation to the legs three weeks after the procedure. Tc-99m albumin isotopic cisternography at the L5-S1 level was performed and clearly depicted a functional CSF leak through the dura at the L2-L3 level and CSF suffusion along several rachidian roots. Scinticisternography may thus be used to localize accurately a CSF leak.

Adult↗