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Biomedical subjects

F Duval

Publications and source records attributed to F Duval.

At least 19 recordsLinked to original sources

Analysis of the CAG repeats in the SCA1 and B37 genes in schizophrenic and bipolar I disorder patients: tentative association between B37 and schizophrenia.

We have genotyped unrelated French Alsatian schizophrenic and bipolar I disorder (BPD) patients and matched controls for the polymorphic CAG repeats within the genes for spinocerebellar ataxia type 1 (SCA1) and dentatorubral-pallidoluysian atrophy (B37), in order to test their possible involvement in these disorders. No alleles with abnormally expanded repeats were found in either gene in patients and controls. Differences in allele and genotype frequencies for the SCA1 CAG repeat between patients and controls were not significant, thus providing no support for its role as a possible positional candidate gene for schizophrenia and BPD in our patients. Chi square testing revealed a significant result (P = 0.019) for an association between the B37 CAG repeat on chromosome 12p and schizophrenia. This result was more significant when only schizophrenics with a positive family history were compared with controls (P = 0.0001). The frequencies of alleles with 14, 12, and 15 CAG repeats differed the most, respectively, between schizophrenics and controls. When choosing the median of the B37 allele distribution (15 CAG repeats) as a threshold, there were significantly more controls than schizophrenics in the group with longer alleles (15 or more repeats) and more schizophrenics with shorter alleles (P = 0.002 by Fisher exact test). No particular genotype was associated with schizophrenia. This result possibly indicates linkage disequilibrium with another locus on chromosome 12p and therefore deserves further attention. No association was found between the B37 CAG repeat and patients with BPD.

Adult

HPA axis dysfunction in depression: correlation with monoamine system abnormalities.

Abnormality of the hypothalamic-pituitary-adrenal (HPA) axis has been one of the most consistently demonstrated biological markers of depressive disorder. It has also been proposed that abnormality of monoamine function plays a role in the pathogenesis of the disorder. In order to examine the interrelationships of the HPA axis with the dopaminergic, noradrenergic, and serotoninergic systems, we studied, in 52 medication-free inpatients with DSM-IV nonpsychotic major depressive disorder, the relationship between dexamethasone suppression test (DST) status and a series of multihormonal responses to apomorphine (APO), clonidine (CLO), and D-fenfluramine (FEN) tests. DST nonsuppressors did not present any difference compared with suppressors in growth hormone (GH) and cortisol stimulation by APO suggesting that a chronic elevation of cortisol did not lead to an alteration of dopaminergic activity in this population of nonpsychotic depressed inpatients. Cortisol and prolactin responses to FEN were comparable in nonsuppressors and in suppressors. In contrast, GH response to CLO was lower in DST nonsuppressors than in suppressors (p < .03), suggesting that the HPA abnormality indicated by a positive DST may be related to alpha 2-adrenoreceptor dysfunction.

Adrenergic alpha-Agonists

Growth hormone response to clonidine and the cortisol response to dexamethasone in depressive patients.

The dexamethasone suppression test (DST) and the clonidine stimulation test (CST) were studied in 47 depressed patients. Issues addressed included (1) the usefulness of both tests as markers of major depression; (2) the relationship between the two tests and the pathophysiology underlying this relationship; and (3) the psychopathological correlates of both tests. The widely reported link between abnormal DST results and melancholic depression was confirmed. The DST and the CST showed extensive overlap, suggesting a relationship in major depression between the biological abnormalities indexed by each test (i.e., hypothalamic-pituitary-adrenal axis and noradrenergic system). Finally, the psychopathological correlates of various subgroups categorized on the basis of test responses (e.g., normal test results, blunted CST results, and both abnormal DST and CST results) confirmed significant differences between groups on two items of the Hamilton Rating Scale for Depression: psychic anxiety and somatic anxiety. The results suggest that particular patterns of neuroendocrine abnormalities may be associated with particular profiles of depressive symptomatology.

Adrenergic Agonists

Dopamine D3 receptor gene: organization, transcript variants, and polymorphism associated with schizophrenia.

DNA fragments from a genomic library were used to establish the partial structure of the human dopamine D3 receptor gene (DRD3). Its coding sequence contains 6 exons and stretches over 40,000 base pairs. The complete DRD3 transcript and three shorter variants, in which the second and/or third exon are deleted, were detected in similar proportions in brains from four controls and three psychiatric patients. The Msp I polymorphism was localized in the fifth intron of the gene, 40,000 base pairs downstream the Bal I polymorphism and a PCR-based method was developed for genotyping this polymorphism. The distribution of the Msp I and Bal I genotypes were not independent in 297 individuals (chi 2 = 10.5, df = 4, P = 0.03), but only a weak association was found between allele 1 of the Bal I polymorphism and allele 2 of the Msp I polymorphism (chi 2 = 3.99, df = 1, P = 0.04). The previously reported association between homozygosity at both alleles of the Bal I polymorphism and schizophrenia was presently maintained in an extended sample, comprising 119 DSM-III-R chronic schizophrenics and 85 controls (chi 2 = 5.3, df = 1, P = 0.02) and found more important in mal than in females. The presence of the Bal I allele 2 is associated with an early age at onset, particularly in males (df = 35, t value = 2.6, P = 0.014). In the same sample, allelic frequencies, genotype counts, and proportion of homozygotes for the Msp I polymorphism did not differ between schizophrenics and controls (chi 2 = 0.06, df = 1, P = 0.80, chi 2 = 0.22, df = 1, P = 0.90 and chi 2 = 0.16, df = 1, P = 0.69, respectively). The large distance of the Msp I polymorphism from the Bal I polymorphism and its localization in the 3' part of the gene may explain the discrepant results obtained with the two polymorphisms.

Animals

Effect of antidepressant medication on morning and evening thyroid function tests during a major depressive episode.

BACKGROUND: This study sought to determine whether changes in thyroid function that may occur during antidepressant treatment are related to a direct effect of the drug on the thyroid axis or to a change in clinical state. METHODS: Morning and evening thyroid function was evaluated in 30 euthyroid inpatients who met DSM-IV criteria for major depressive episode, by determination of free triiodothyronine, free thyroxine, and thyrotropin levels before and after 8 AM and 11 PM protirelin challenges (200 micrograms intravenously), on the same day. Results at baseline were compared with those after 1 month of antidepressant treatment with either amitriptyline hydrochloride, fluoxetine hydrochloride, or toloxatone. RESULTS: Clinical efficacy and effects on thyroid function did not differ across the 3 antidepressant drugs. Compared with pretreatment values, significant reductions in basal serum 8 AM free thyroxine, 11 PM free thyroxine, and 8 AM free triiodothyronine levels and increases in 11 PM maximum increment in plasma thyrotropin level and the difference between 11 PM and 8 AM maximum increment in plasma thyrotropin values were observed in responders (n = 11) but not in partial responders (n = 6) or nonresponders (n = 13). Moreover, nonresponders exhibited lower pretreatment 11 PM thyrotropin values (basal and maximal increment above basal) than responders. CONCLUSIONS: The results suggest that (1) changes in thyroid function are related to clinical recovery rather than to a direct effect of the antidepressant drug and (2) patients with the lowest pretreatment evening thyrotropin secretion have the lowest rate of antidepressant response, and this may contribute to treatment resistance.

Adult

Stimulator design and subsequent stimulation parameter optimization for controlling micturition and reducing urethral resistance.

An implantable computerized electrical stimulation system designed to induce bladder evacuation in animal models (dogs) after spinal cord transection has been realized and evaluated. This fully programmable system is based on a handheld device and generates a wide range of stimuli through multichannel implantable miniaturized stimulator. Using the new bladder stimulator and inducing reversible fatigue to the external sphincter via the pudendal nerve enables us to reduce the bladder outlet resistance, resulting in the proper emptying of the bladder during stimulation without the need for sacral nerve rhizotomies and the pudendal nerve neurectomies. Four chronically affected dogs were studied to determine the optimal stimulation parameters for inducing a sphincter fatigue that would reliably empty the bladder for the duration of the experiment. These parameters were: maximum amplitude of 1.5 mA +/- 0.5 SD, stimuli composed of a high frequency signal of 200 Hz +/- 50 SD modulated by a low frequency signal of 10 Hz +/- 5 SD, pulse width controlled by a duty-cycle of 20% +/- 10 SD, sacral nerve stimulation of 50 s +/- 25 SD and fatiguing duration of 20 s +/- 5 SD.

Animals

Multihormonal responses to apomorphine in mental illness.

The neuroendocrine responses to subcutaneous (SC) administration of the dopamine (DA) agonist apomorphine (APO) hydrochloride (0.75 mg) were studied in a large group of subjects: 110 drug-free inpatients with either DSM-III-R schizophrenia (SCZ, n = 46), schizoaffective disorder (SAD, n = 14), or major depressive episode (MDE, n = 50), plus 18 hospitalized controls. Compared to a saline test, APO induced a significant increase of growth hormone (GH), adrenocorticotropin (ACTH), and cortisol (COR) release and a decrease in prolactin (PRL) secretion. No change in thyrotropin (TSH) levels was observed. In the total sample the extents of ACTH, COR and GH responses were correlated, but in the group of 88 subjects who exhibit a normal GH stimulation this correlation disappeared. This discrepancy suggests that APO-induced ACTH and COR stimulation may be mediated by pathways different from those mediating GH stimulation. According to diagnostical categories, we found significant lower ACTH and COR stimulation in the schizophrenic group and in patients with SAD, compared with that among controls or depressed patients. We found also a significant difference between subgroups of schizophrenic patients. These results agree with the hypothesis that different aspects of psychosis might involve different subtypes of DA-receptors with different localizations and sensitivities.

Adrenocorticotropic Hormone

Long-term effect of sphincteric fatigue during bladder neurostimulation.

Commercially available stimulators lack several features, including multiple channel capability and flexible stimulation parameters. These factors limit clinical application. A new computerized electrical stimulator system was developed by our team and evaluated for its efficacy in bladder evacuation in an animal model after spinal cord transection. The system can generate a wide range of stimulation characteristics and has the feature of being a programmable multichannel pacemaker. It has enabled us to induce a reversible fatigue to the external sphincter that results in proper bladder emptying on stimulation. Using this new bladder pacemaker, 8 dogs were studied. We applied the concept of fatiguing of the external sphincter via the pudendal nerve to avoid rhizotomy. We determined the optimal stimulation parameters that can reliably empty the dog's bladder for the duration of the experiment, which lasted for 8 months. The new computerized electrical stimulation system achieved the objective of reducing bladder outlet resistance without the need for sacral rhizotomy.

Animals

Influence of thyroid hormones on morning and evening TSH response to TRH in major depression.

The serum levels of thyroid hormones and thyrotropin (TSH) were evaluated before and after 8 PM and 11 PM thyrotropin-releasing hormone (TRH) challenges, on the same day, in 41 drug-free DSM-III-R euthyroid major depressed inpatients and 16 hospitalized controls. Depressed patients exhibited elevated circulating concentrations of thyroid hormones, which were associated with and may have contributed to the blunted TSH response to TRH. This was confirmed by: (a) higher basal levels (albeit not always statistically significant) of free triiodothyronine (FT3B) and free thyroxine (FT4B) at 8 AM and 11 PM in the depressed patient population compared with the controls; (b) lower basal levels of TSH in the depressed subjects (even though this was only statistically significant at the 11 PM sampling) compared with the controls; (c) blunted TSH response to TRH (delta TSH) in the depressed group (although this was only statistically significant at 11 PM) and blunted delta delta TSH values (differences between 11 PM-delta TSH and 8 AM-delta TSH).

Adult

A transcutaneous implantable bladder controller.

We describe a computerized experimental system to investigate the effect of early electrical stimulation of the bladder during the spinal shock phase in paraplegic dogs. This system is composed of two main devices; an external part (or controller) based on a portable microcomputer, and a versatile implant (internal) based on a multichannel CMOS microstimulator. Using a new operative technique, this system enabled us to obtain many favorable results.

Animals

Neuroendocrine profile of SDZ HDC-912 and OPC-4392, two new atypical antipsychotic drugs, in schizophrenic patients.

The aim of this study was to evaluate the effect on the activity of the hypothalamic-pituitary dopaminergic system of two new atypical antipsychotic drugs: the ergoline derivative SDZ HDC-912, which is a dopamine (DA) D2 receptor partial agonist; and the quinolinone derivative OPC-4392, which acts as an agonist at presynaptic DA autoreceptors and as an antagonist at post-synaptic D2 receptors. The effects of both compounds were compared to the effects of the benzamide derivative amisulpride. Prolactin (PRL) and growth hormone (GH) levels before and after challenge with apomorphine (Apo), a dopaminergic agonist, were determined after at least 2 weeks washout and again after 1 month of treatment in DSM-III-R schizophrenic inpatients. SDZ HDC-912 significantly decreased Apo-induced PRL inhibition, and tended to decrease PRL secretion and Apo-induced GH stimulation. OPC-4392 induced a significant decrease in baseline PRL and in Apo-induced PRL suppression, and a non-significant decrease in Apo-induced GH stimulation. The neuroendocrine profiles of these two compounds agree with their dopaminergic properties; however, the decrease in PRL basal level differentiates the two drugs from neuroleptic agents.

Adult

[In vitro pharmacological study of fluconazole. Evaluation of an antifungal assay].

Fluconazole is a new antifungal drug which is now very often used for the treatment of yeasts infections: mucocutaneous candidosis, systemic candidosis and cryptococcosis. Some resistance seems to occur in clinical practice. It turns out now that it must be necessary to test the drug susceptibility in vitro of the yeast strains isolated from patients. Unfortunately, a current laboratory technique to test this agent doesn't exist. In this work a useful method for Minimal inhibitory concentration (MIC) evaluation in a commercial available broth medium, and a technique for testing fluconazole disks on an agar medium are studied. 150 strains of different yeasts species are tested. A regression curve is performed to correlate the two methods.

Antifungal Agents

Effect of early bladder stimulation on spinal shock: experimental approach.

The period of spinal shock which frequently follows spinal cord injury is associated with bladder areflexia and urinary retention. We studied the effect of early bladder electric stimulation on detrusor activity during the spinal shock phase in the dog. The animals had a spinal cord section at T10 vertebra, and their bladder management was assigned to one of the three following groups: intermittent catheterization, indwelling catheterization, and electric bladder stimulation. The parameters for evaluating each treatment included: blood chemistry, and radiographic and urodynamic tests. The most important finding was the early return of detrusor activity in the group of animals treated by early electric stimulation of the bladder.

Animals

Electrical stimulation induced sphincter fatigue during voiding.

The stimulation of the sacral nerves to induce voiding is often associated with simultaneous contraction of the striated sphincter rendering micturition difficult or impossible. Rhizotomy of some sacral nerves was found to be necessary to facilitate voiding with stimulation. An main objective in the present experiment was to evaluate the feasibility of achieving the same result using electrical stimulation to fatigue the sphincter. In order to compare the effect of rhizotomy and fatiguing striated sphincter, the bladder outlet resistance was measured. S2 nerves were stimulated with 3 V, 35 Hz and 100 microseconds duration for 5 to 10 sec. Following S2 nerves stimulation the pudendal nerve was stimulated till we obtained sphincteric fatigue. The optimal parameter to induce sphincter fatigue were 3 V, 100-500 Hz and 100 microseconds. for 15-20 sec. The combined pressure-flow studies showed that fatiguing the sphincter via the pudendal nerve using these parameters was as good as cutting it in achieving bladder emptying with stimulation.

Animals

Role of electric stimulation in bladder evacuation following spinal cord transection.

Neural stimulation is potentially a valuable therapeutic tool in the treatment of neurogenic bladder with detrusor areflexia. We studied 20 dogs in different groups, up to eight months, and compared the effect of electric stimulation with intermittent catheterization, specially during spinal shock phase. We found that early stimulation hastened the return of detrusor activity. When stimulation was delayed, the bladder could still regain its activity, and when the pace-maker was turned off, the detrusor activity was gradually decreased. Neurostimulation can completely empty bladder up to eight months. The lowest A.Ch. content in detrusor muscle was found in intermittent catheterization group and in this group the detrusor strips showed marked supersensitivity to urecholine stimulation than the bladders managed by electric stimulation. Also, we found that electric stimulation reduced the complications caused by intermittent catheterization and protected kidney function.

Animals