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Biomedical subjects

J P Soucy

Publications and source records attributed to J P Soucy.

At least 19 recordsLinked to original sources
PubMed2006

Acute prefrontal cortex TMS in healthy volunteers: effects on brain 11C-alphaMtrp trapping.

High-frequency repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (LDLPFC) is a technique with purported efficacy as a treatment for major depression. Here, we assessed in vivo, in healthy volunteers, the effect of acute rTMS of the LDLPFC, relative to the stimulation of the left occipital cortex (LOC), on brain regional serotonin synthesis capacity, using the [(11)C]-alpha-methyl-tryptophan ((11)C-alphaMtrp)/PET method. Ten subjects were studied twice, once following rTMS of the LDLPFC and once following rTMS of the LOC in a randomized counterbalanced order. Three blocks of 15 trains of 10 Hz rTMS were delivered 10 min apart. Behavioural and autonomic measures were recorded before and after each rTMS session. Comparisons of TMS-related changes in regional normalized brain uptake and trapping of (11)C-alphaMtrp (K*) values were carried out using SPM99. Statistically significant regional differences were identified on the basis of an extent threshold of 50 voxels, with a peak threshold of p=0.005 uncorrected. Behavioural and autonomic measures were unaffected by rTMS. Relative to LOC stimulation, LDLPFC rTMS was associated with marked changes in normalized K* in limbic areas, with significantly lower values in the left parahippocampal gyrus (BA 28) and the right insula (BA 13), and higher values in the right cingulate gyrus (BA 31) and cuneus (BA 18). These findings indicate that acute rTMS of the LDLPFC in healthy volunteers modulates aspects of tryptophan/5-HT metabolism in limbic areas. Such adaptive changes may contribute to the mechanism of action of prefrontal rTMS in major depression.

Adult↗
PubMed2006

Assessing whole brain perfusion changes in patients with REM sleep behavior disorder.

OBJECTIVE: To investigate the regional cerebral perfusion in patients with idiopathic REM behavior disorder (RBD) in order to establish the topography of networks involved. METHODS: We performed cerebral blood flow evaluation using (99m)Tc-Ethylene Cysteinate Dimer (ECD) SPECT on eight patients with polysomnographically confirmed RBD and nine age-matched controls. Comparisons were made using SPM2. RESULTS: We found increased perfusion in the pons and putamen bilaterally and in the right hippocampus. In addition, we observed a decreased perfusion in frontal (Brodmann area [BA] 4, 6, 10, 43, 44, 47 bilaterally and left BA 9, 46) and temporo-parietal (BA 13, 22, 43 bilaterally and left BA 7, 19, 20, 21, 39, 40, 41, 42) cortices. CONCLUSION: Perfusional abnormalities in patients with REM behavior disorder were located in the brainstem, striatum, and cortex. These abnormalities are consistent with the anatomic metabolic profile of Parkinson disease.

Aged↗
PubMed2004

Comparison between olanzapine and haloperidol on procedural learning and the relationship with striatal D2 receptor occupancy in schizophrenia.

The striatum is known to play a primary role in procedural learning. In this study, the authors simultaneously assessed the effects of two antipsychotic drugs on procedural learning and on striatal dopamine (D2) receptor occupancy. Twenty-seven patients receiving either olanzapine or haloperidol as antipsychotic medication were assessed with the Computed Visual Tracking Task (CVTT) and Single Photon Emission Computed Tomography (SPECT) following the administration of Iodine 123-IBZM (123I-IBZM), a radioligand with a high affinity and specificity for the D2 receptors. The results showed poorer procedural learning in the haloperidol-treated patients than in normal control subjects, while no difference could be found between olanzapine-treated patients and normal control subjects. In the haloperidol but not the olanzapine group, significant correlations were found between procedural learning deficits and striatal D2 receptor occupancy. However, there was no significant difference in D2 receptor occupancy between olanzapine- and haloperidol-treated patients, and this may be related to the high doses of olanzapine and low doses of haloperidol administered. The authors concluded that: 1) striatal D2 receptor blockade may alter procedural learning in humans; and 2) olanzapine may have a protective effect on procedural learning, even at doses that produce striatal D2 receptor occupancy as high as that found with haloperidol. This protective effect of olanzapine may be related to its atypical pharmacological properties.

Adult↗
PubMed2001

Lack of associations between occlusal and cephalometric measures, side imbalance in striatal D2 receptor binding, and sleep-related oromotor activities.

AIMS: First, to evaluate possible orofacial morphologic differences between sleep bruxers and non-bruxers, and second, to determine possible correlations between morphologic factors and striatal D2 receptor expression in persons with sleep-related oromotor activities. METHODS: Twenty subjects were included in this study; half of them had polysomnographically confirmed oromotor values above the cutoff points for sleep bruxism. For all participants, 26 standard occlusal measures were recorded clinically and from dental study casts. In addition, 25 standard angular and linear measures were taken from standardized cephalometric films, and variables were derived to evaluate dental and skeletal relationships. Fourteen of the 20 participants had also participated in a previous study that included iodine-123-iodobenzamide (I-123-IBZM) and single-photon emission-computed tomography (SPECT). For them, the side-to-side difference in striatal D2 receptor binding was determined as the neurochemical outcome measure. RESULTS: Following the classical Bonferroni adjustment for multiple testing, no morphologic differences were found between the sleep bruxers and the non-bruxers. In addition, none of the morphologic variables were significantly associated with the neuroimaging data. CONCLUSION: Taking into account the low power of this retrospective, exploratory study, the results suggest that the orofacial morphology of sleep bruxers does not differ from that of non-bruxers. In addition, morphologic factors are probably not involved in the asymmetry in striatal D2 receptor distribution that was previously observed in association with sleep bruxism.

Adult↗
PubMed1999

Absence of correlation between amobarbital distribution as assessed with SPECT brain perfusion imaging and behavioral manifestations during the intracarotid amobarbital procedure (Wada test).

1. The IAP is used presurgically in patients with temporal lobe epilepsy to predict the effects on LTM and language of the planned temporal lobectomy. This prognosis presumes that a similar pattern of perfusion will result in anesthesia of the same cerebral regions in most patients. 2. Coinjection of Tc-99m HMPAO with the barbiturate during the IAP has been used to ascertain whether this actually is true, with variable results. Moreover, most studies document only unilateral IAPs and do not report on behavioral performance. 3. The authors coinjected Tc-99m HMPAO and amobarbital in 33 IAPs from 18 patients (15 injected bilaterally, 3 unilaterally) to clarify this and to evaluate the relationship of the perfusion pattern to behavioral performance; SPECT results were also compared to angiographic evaluation obtained at the time of catheter placement. 4. SPECT perfusion data was rated for presence/absence and intensity of perfusion to the ACA, MCA, PCA territories and to H, i or c to the injection site. V, STM and LTM were graded according to a standardized protocol. 5. MCAi was perfused in 100% of cases, ACAi in 91%, PCAi in 21% and Hi in only 6%. Cross-over flow was shown in 9 studies; 50% of the patients in whom both sides were injected (on different days) had crossover, involving the ACAc territory in 80% of cases. As expected, injection on the non-ES was associated with a significantly worse LTM performance than on the ES (p = 0.006). There was no relationship between the perfusion pattern and the V level of the patients (a potential confounding variable in memory/language evaluation) during IAP, nor between perfusion pattern and LTM. STM was significantly adversely affected by the presence of crossover perfusion. Angiography in general overestimated the extent of cerebral perfusion demonstrated by SPECT, most probably because of the markedly different injection conditions. 6. Despite the best efforts to standardize injections, the perfusion pattern has been mostly unpredictable in the patients. Moreover, it has little bearing on their behavioral performance, except for the prediction of poor STM performance (the clinical implications of this remaining dubious). Marked LTM alterations after non-ES injections confirm remote hippocampal effects in the presence of only rare direct perfusion of that region. Tc-99m HMPAO/Amobarbital coinjection was unhelpful from a clinical perspective, most probably because a large part of the effects of amobarbital arise from deafferentation of regions not directly perfused by the anesthetic agent.

Adult↗
PubMed1997

Comparative evaluation of [3H]WIN 35428 and [3H]GBR 12935 as markers of dopamine innervation density in brain.

WIN 35428 and GBR 12935, two uptake blocker ligands of the membrane transporter for dopamine (DA), were evaluated as quantitative markers of DA innervation density in CNS tissue. From alternate rat brain slices respectively processed for either light microscope or film autoradiography, counts of DA axon terminals (varicosities) labeled by uptake/storage of [3H]DA were matched with densitometric measurements of the specific binding of [3H]WIN 35428 and [3H]GBR 12935 in the same anatomical areas. The relation between the two parameters was examined in 1) the normal cingulate cortex; 2) the neostriatum severely DA-denervated by unilateral intramesencephalic injections of 6-hydroxydopamine; and 3) the neostriatum, partly DA-reinnervated by an intrastriatal graft of fetal mesencephalic neurons after prior 6-hydroxydopamine lesion. For technical reasons, the hyperdense DA innervation of normal striatum was not amenable to such correlative testing. Data were subjected to multilevel analysis. Specific [3H]WIN binding at 37 degrees C was tightly and linearly correlated with the number of DA varicosities over the full range of DA innervation densities tested. The regression lines for intact cortex and for DA-denervated as well as DA-reinnervated neostriatum had the same slope and crossed the ordinate near zero. In contrast, [3H]GBR 12935 binding at 37 degrees C showed no correlation with the number of DA varicosities. A linear correlation could be obtained after incubation with [3H]GBR 12935 at 4 degrees C in the presence of ZnSO4, but the intercept of this regression line remained significantly above zero at origin, indicating extraneous binding to non-DA transporter sites. Providing that the hyperdense DA innervation of the normal neostriatum does not generate a particular problem in vivo as it does in vitro. WIN 35428, but not GBR 12935, might satisfy the selectivity and sensitivity requirements of a quantitative marker of DA innervation density for eventual use in positron emission tomographic studies.

Animals↗
PubMed1997

Effects of the D2 receptor agonist bromocriptine on sleep bruxism: report of two single-patient clinical trials.

An altered dopamine receptor status has been associated with sleep bruxism. Evidence from a functional neuro-imaging study has implicated an abnormal side imbalance in striatal D2 receptor expression in its pathophysiology. To assess the significance of this finding, we studied the effects of short-term administration of the preferential dopamine D2 receptor agonist bromocriptine on sleep bruxism in a double-blind, placebo-controlled polysomnographic and neuro-imaging study with a single crossover design. Six otherwise healthy and drug-free patients with sleep bruxism were entered into the trial. One of the patients dropped out due to an intercurrent illness, while three others were discontinued from the study due to severe adverse reactions to bromocriptine. Because of the high frequency and intensity of the side-effects, the trial was interrupted. Two patients, however, completed the trial without any adverse reactions. Their outcome measures are presented as single-patient clinical trials. Following a two-week administration of bromocriptine, both patients showed a decrease in the number of bruxism episodes per hour of sleep of about 20% to 30% with respect to the placebo. WHile no significant differences between both conditions (i.e., placebo and bromocriptine) were found for the number of bruxism bursts per episode, significantly lower root-mean-squared EMG levels per bruxism burst occurred during bromocriptine use. In association with this polysomnographically established attenuation of sleep bruxism, bromocriptine afforded a decreased normal side distribution of striatal D2 receptor binding, as was evidenced by single-photon-emission computed tomography using the radioactive D2 receptor antagonist iodine-123-iodobenzamide. This study supports previous suggestions that the central dopaminergic system may be involved in the modulation of sleep bruxism. To see if the present findings apply across a population, investigators should use a peripheral D-2 antagonist to prevent side-effects.

Adult↗
PubMed1996

Striatal D2 receptor binding in sleep bruxism: a controlled study with iodine-123-iodobenzamide and single-photon-emission computed tomography.

The neurochemical mechanisms underlying sleep bruxism are little understood at present. However, recent pharmacologic evidence suggests that the central dopaminergic system may be involved in the pathophysiology of sleep bruxism. This possibility was further assessed by means of functional neuroimaging of dopamine D2 receptors with single-photon-emission computed tomography (SPECT). Ten controls and ten patients with polysomnographically confirmed sleep bruxism were injected intravenously with 185 MBq (5 mCi) iodine-123-iodobenzamide, a specific D2 receptor antagonist radioligand, and data acquisition was performed 90 min post-injection. Following image reconstruction, it was found that striatal D2 receptor binding potential (basal ganglia/background ratio) did not differ significantly between bruxism patients and controls. However, side-to-side differences between unilateral values of the striatal D2 binding potential ("highest side" values minus "lowest side" values) were significantly larger for the bruxism patients (p < 0.001, by two-independent-samples t test with pooled variances). It was concluded that an abnormal side imbalance in striatal D2 receptor expression can be associated with sleep bruxism. This reinforces the possibility that the central dopaminergic system plays a role in the pathophysiology of this disorder.

Adult↗
PubMed1996

Autosplenectomy in systemic lupus erythematosus.

Autosplenectomy in systemic lupus erythematosus (SLE) is associated with a high mortality rate due to Streptococcus pneumoniae sepsis. We describe 2 patients who developed autosplenectomy in the setting of an acute SLE exacerbation. Followup of both patients 12 and 5.5 years after the initial diagnosis of autosplenectomy revealed persistent absence of the spleen. Pneumococcal vaccine was given to both patients. In contrast with reports describing life threatening infections in 46.7% of asplenic patients with SLE, none developed during prolonged followup of our patients. Our data and review of 13 other patients with SLE with autosplenectomy suggest that the 23-valent pneumococcal vaccine should be given promptly to patients with SLE when a diagnosis of autosplenectomy is established.

Adult↗
PubMed1995

Quantification of the serotonin hyperinnervation in adult rat neostriatum after neonatal 6-hydroxydopamine lesion of nigral dopamine neurons.

Light microscope autoradiography after uptake and storage of tritiated serotonin (5-HT) in brain slices was used to count 5-HT axon terminals (varicosities) in the 5-HT-hyperinnervated neostriatum of adult rats subjected to neonatal 6-hydroxydopamine treatment and age-matched, normal controls. After correction for incomplete autoradiographic exposure and for section thickness, the results were expressed in millions of varicosities per mm3 of tissue. Control values ranged from 4.8 in the rostral to 6.3 in the caudal neostriatum (5.8 at intermediate level), for an average of 5.6. The corresponding values in 5-HT-hyperinnervated tissue ranged from 9.7 to 7.7 (8.8 at intermediate level), for an average of 8.7 and increases of 102%, 52% and 22% above control in the rostral, intermediate and caudal neostriatum, respectively (average increase of 55%). These data confirmed the predilection of the 5-HT hyperinnervation for the rostral neostriatum and demonstrated its presence in the caudal neostriatum also.

Animals↗
PubMed1995

Evaluation of three transporter ligands as quantitative markers of serotonin innervation density in rat brain.

Direct counting of axon terminals (varicosities) labeled by uptake/storage of a tritiated monoamine provides a means to test radioligands of the corresponding membrane transporter as quantitative markers of regional monoamine innervation density in brain tissue. In autoradiographs from alternate rat brain slices, counts of [3H]5-HT-labeled axon terminals were matched with densitometric measurements of the specific binding of tritiated cyanoimipramine (CYI), citalopram (CITAL), and 6-nitroquipazine (6-NTQ), under conditions of hypo-, normo-, or hyper-5-HT innervation of the neostriatum. A total of 267 pairs of data were subjected to a multilevel analysis (iterative generalized least square procedure). With all three ligands, there was a linear relationship between the density of 5-HT innervation and the density of specific binding and no change in the slope of the regression lines as a function of 5-HT innervation density. Thus, none of these ligands gave any sign of down- or up-regulation of the 5-HT transporter consequent to 5-HT hypo- or hyper-innervation. The regression lines for CYI and CITAL were not significantly different from one another and crossed the ordinate near zero, whereas the regression line for 6-NTQ was less steep and had a higher intercept with the ordinate. In addition, the dispersion of values around the regression line (residuals) was lower with CYI and CITAL than 6-NTQ. It was concluded that both CYI and CITAL may serve as quantitative markers of 5-HT innervation density, at least in vitro, whereas 6-NTQ demonstrates a certain lack of specificity and sensitivity. Further work will be needed to assess the potential of CYI and CITAL for positron emission tomographic studies of living brain. Such empirical testing should also be applicable for screening radioligands of the dopamine or the noradrenaline transporters.

Animals↗
PubMed1994

Validation of the transporter ligand cyanoimipramine as a marker of serotonin innervation density in brain.

UNLABELLED: Radiolabeled ligands of monoamine transporters have already been used to visualize cerebral monoamine innervation by tissue autoradiography and by PET or SPECT in vivo. METHODS: A sampling technique was developed to allow for both the autoradiographic counting of serotonin (5-HT) axonal varicosities, labeled by uptake and storage of [3H]5-HT, and the measurement of the binding of [3H]cyanoimipramine ([3H]CYI), a specific 5-HT transporter ligand, in adjacent slices of adult rat neostriatum. The experiments were conducted in normal, decreased (after 5,7-dihydroxytryptamine lesions in adults) or increased (after 6-hydroxydopamine lesions in neonates) states of neostriatal 5-HT innervation. RESULTS: In normal tissue, the regional density of [3H]CYI binding faithfully reproduced rostrocaudal variations in the number of [3H]5-HT-labeled axonal varicosities. Pairs of values from all three experimental groups showed a highly significant linear correlation (r = 0.93) between the density of [3H]CYI binding and the number of 5-HT varicosities per cubic millimeter of tissue. The intercept of the regression line was close to zero; this confirmed the selectivity of the ligand. CONCLUSION: Under drug-free conditions, specific [3H]CYI binding is a good quantitative index of 5-HT innervation density in brain tissue and is not significantly up- or downregulated on 5-HT denervation or hyperinnervation. When it is adequately labeled, such a ligand might therefore be appropriate to quantify regional 5-HT innervation in vivo by PET or SPECT. The present approach should also be useful to select ligands to quantify 5-HT and monoamine systems.

Animals↗
PubMed1992

Increase in T3 levels during hypocorticism in patients with chronic secondary adrenocortical insufficiency.

The clinical and biochemical manifestations of secondary adrenocortical insufficiency are not well defined in the medical literature. This study was designed to determine the clinical and laboratory features suggesting the diagnosis of adrenal insufficiency in 15 chronic ACTH deficiency patients during low and normal cortisol states. Except for fatigue and weakness, the characteristic clinical manifestations of primary adrenal insufficiency occurred rarely. ACTH deficiency did not significantly modify blood glucose, serum calcium, sodium, potassium and differential white blood cell count. However, serum T4 was lower (65 +/- 19 vs 95 +/- 21 nmol/l, p less than 0.001) during cortisol deficiency, while T3 was higher (2.4 +/- 0.67 vs 2.0 +/- 0.60 nmol/l, p less than 0.001). Furthermore, rT3 decreased significantly during hypocorticism (0.27 +/- 0.07 vs 0.18 +/- 0.07 nmol/l, p less than 0.001). The T4/T3 ratio was significantly lower than the normal in 15 out of the 17 episodes of ACTH deficiency (29 +/- 12.5 vs 57 +/- 9.4, p less than 0.0001). We conclude that the increase in T3 and decrease in T4 levels are associated with chronic secondary adrenocortical insufficiency. This laboratory feature could be due, at least in part, to the increased peripheral conversion of T4 to T3 during cortisol deficiency.

Adrenal Cortex Diseases↗
PubMed1991

Reversible hypertriiodothyroninaemia due to adrenal insufficiency.

It is well known that an excess of glucocorticoids affects thyroid tests. The effect of adrenal deficiency on thyroid hormones is less well defined. We here describe the case of a 33-year-old woman with Cushing's disease who was cured by trans-sphenoidal surgery. During the postoperative period, a secondary adrenal insufficiency developed. The thyroid blood tests then revealed elevated L-triiodothyronine (T3) levels and a decrease in reverse T3. These findings suggest that secondary adrenal deficiency may be associated with high T3 levels, which may be due to an increase in the peripheral conversion of thyroxine (T4) to T3.

Adrenal Insufficiency↗
PubMed1990

Technetium-99m HMPAO imaging in Sturge-Weber syndrome.

The Tc-99m HMPAO brain imaging confirmed marked hypoperfusion secondary to anomalous cerebral venous drainage of the Sturge-Weber syndrome. Until now, this had been a hypothesis suggested by results obtained from conventional brain scans and cerebral arteriography.

Angiomatosis↗
PubMed1990

Evaluation of vasospasm secondary to subarachnoid hemorrhage with technetium-99m-hexamethyl-propyleneamine oxime (HM-PAO) tomoscintigraphy.

Vasospasm of intracranial vessels is difficult to diagnose on clinical ground alone. Still, a clear diagnosis is important because it can impact on surgical timing; and also because it can help evaluate new treatments. Fifteen patients with sub-arachnoid hemorrhage secondary to aneurysm rupture were submitted to a total of 26 tomographic technetium-99m-hexamethyl-propyleneamine oxime (99mTc-HM-PAO) brain examinations that were correlated with temporally close (generally less than 24 hr) angiography or transmission computed tomography (TCT). Nine of 10 angiographically confirmed episodes of spasm and 6 of 6 infarcts seen on angiography or TCT were correctly diagnosed with 99mTc-HM-PAO. One normal scintigraphic exam was angiographically doubtful, one positive 99mTc-HM-PAO study was normal on angiography (sub-radiologic spasm?), one technically poor scintigraphy was positive for spasm on angiograms, and eight exams were normal for spasm with all modalities. We had agreement between tests in 23 of 26 series of exams (88%) obtained in 15 patients. We think that 99mTc-HM-PAO tomography should be useful for the evaluation of patients with suspected vasospasm.

Adult↗