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J F Menard

Publications and source records attributed to J F Menard.

At least 37 records · Page 2Linked to original sources

Thermodynamics of the binding of BTCP (GK 13) and related derivatives on the dopamine neuronal carrier.

We have studied the thermodynamic properties of the binding of a coherent series of uptake inhibitors derived from BTCP (GK 13 = N-[1-(2-benzo(b)thiophenyl)cyclohexyl]piperidine) to the dopamine neuronal carrier labelled with [3H]GBR 12783 (1-[2-(diphenylmethoxy)ethyl]4-(3-phenyl-2-propenyl)-piperazine). GK 13 (30 nM) and its 2-naphthyl derivative GK 189 (15 nM) competitively inhibited the specific binding of [3H]GBR 12783 to sites present in rat striatal membranes. Hill numbers calculated for the inhibition of the specific binding of [3H]GBR 12783 by BTCP derivatives were close to 1 (range 0.79-1.18). Increasing the temperature from 0 degrees to 30 degrees C induced a decrease in the affinity of [3H]GBR 12783 and GK derivatives which was generally less pronounced than that obtained when temperature was raised from 30 degrees C to 37 degrees C. Increasing the incubation temperature led to a decrease in both enthalpy (delta H degrees) and entropy (delta S degrees). We observed at 37 degrees C a large negative enthalpy change (range -48, -79 kJ/mol) and a negative, binding unfavorable, change in entropy. This indicates that the GK derivatives binding is enthalpy-driven. Furthermore, data obtained in the present study show that changes in thermodynamic parameters are not a function of the inhibitor's affinity for the dopamine neuronal carrier and this suggests that bonds involved in the inhibitor-carrier interaction are more likely related to the carrier configuration than to the chemical structure of the inhibitor.

Animals↗

Morphometric analysis of melanocytic tumors. A study of nuclear area and density.

Because the differential diagnosis of melanocytic tumors is sometimes difficult, we performed a morphometric analysis of 20 benign nevi, 20 malignant melanomas, and 10 Spitz's nevi. The nuclear pleomorphism and the maturation to the depth of the tumor were quantified by measuring nuclear area and nuclear density at serial levels of the tumor (every 220 microns of thickness). Data obtained were analyzed statistically. Linear regression was used to represent the variation of nuclear area to the depth, and the standard deviation of nuclear areas reflected nuclear pleomorphism. We attempted to separate different tumors from each other using the Jacknife procedure and morphometric data. Using the Jacknife procedure rather than the usual histological procedures, we were able to distinguish benign nevi from Spitz's nevi and malignant melanoma in as many as 92% of cases, but we distinguished Spitz's nevi from malignant melanoma in only up to 60% of cases. In conclusion, we found it difficult to distinguish between Spitz nevi and melanoma using nuclear morphometric parameters. Other studies using new morphometric parameters are needed in order to improve our ability to make this discrimination.

Adolescent↗

Does age play a role in clinical presentation of hypothyroidism?

OBJECTIVE: To determine if aging modifies the clinical presentation of hypothyroidism. DESIGN: Comparison of 24 clinical signs of hypothyroidism between elderly patients (> or = 70 years of age) and younger patients (< or = 55 years of age). SETTING: Prospective study of patients with chemically confirmed overt hypothyroidism. PATIENTS: Sixty seven elderly patients (79.3 +/- 6.7 years) and 54 younger patients (40.8 +/- 9 years) were included in the study. RESULTS: Neither mean duration of evolution nor mean thyroid-stimulating hormone (TSH) level were different between the 2 groups. Two signs were found in more than 50% of the elderly patients (fatigue and weakness). Four signs were significantly less frequent in elderly patients (chilliness, paresthesiae, weight gain, and cramps). Mean number of clinical signs in the elderly (6.6 +/- 4) was significantly smaller than in young patients (9.3 +/- 4.7) (P < 0.01). CONCLUSIONS: Our results suggest that the presentation of hypothyroidism is altered in the elderly in comparison with young patients in that there are (1) fewer signs or symptoms and (2) diminished frequency of some classical signs. Our results underline the importance of TSH measurement in the elderly.

Adult↗

[Long term evaluation of sensation sequelae of bipedicled digital advancement island flaps. Comparison of clinical and electrophysiological results. Apropos of 13 cases].

Thirteen homodigital bipedicle island flaps for digital pulp amputation were reviewed to allow a better evaluation of sensory sequelae. A clinical and electrophysiological study of the sensory score of the pulp were compared to the contralateral normal digit and expressed in relative values. Sensory sequelae, even minor, are constant. The summated scores of dynamic and static 2 point discrimination test, appeared correlated to the electrophysiological amplitude modulations. This result seems particularly interesting as it adds another test for the objective evaluation of sensitivity.

Adolescent↗

Relationship between depressive and positive symptoms in schizophrenia.

The aim of this study was to investigate the relationship between depressive and positive symptoms, two positive symptom using scales (PANSS and SAPS) in samples defined by three schizophrenic diagnostic systems (DSMIII-R, ICD9 and Langfeldt) at difference phases of the illness and in taking into account the negative and extrapyramidal symptoms and the doses of neuroleptics. With both scales, correlations between depressive and positive symptoms were significantly negative in two diagnostic subgroups (DSMIII-R and Langfeldt) in the acute phase. These correlations were also significant when negative symptoms, subjective extrapyramidal signs and the doses of neuroleptics were partialled out. Only the extrapyramidal physician's score was intercorrelated with positive and negative symptoms. Among the positive symptoms, 'conceptual disorganization' (or 'positive formal thought disorder') and 'suspiciousness/persecution' were especially correlated negatively with depression. At the post-acute phase or at the residual phase, no significant correlation between depressive and positive symptoms was found in any diagnostic subgroup. These results show the necessity of taking into account the phase of illness and the diagnostic criteria in order to study depression in schizophrenia.

Adult↗

The Centre H. Becquerel studies in inflammatory non metastatic breast cancer. Combined modality approach in 178 patients.

One hundred and seventy-eight patients with non metastatic inflammatory breast cancer (IBC) have been treated at the Centre H. Becquerel. Median follow up is 67 months (6-178). Every patient received neoadjuvant chemotherapy (mean number of cycles = 4; range: 2-8), followed by a loco regional treatment (radiotherapy = XRT or modified radical mastectomy = S), followed by adjuvant chemotherapy. During this period, the types of chemotherapy and locoregional treatment have been the following: Study I: 64 patients treated with CMF or AVCF and XRT; Study II: 83 patients, treated with either AVCF, FAC or VAC followed by S (n = 38) or XRT (n = 22) in case of complete or partial response, or followed by XRT (23) in case of initial supraclavicular lymph node involvement or lack of response after chemotherapy; Study III: 31 patients treated with FEC-HD + Estrogenic recruitment followed by S and XRT after adjuvant chemotherapy, except seven patients who received XRT (refusal of surgery). Although objective response rates (= 56.2, 73.5 and 93.5% for study I, II and III respectively) are statistically better in the 3rd study, this does not translate in dramatically different disease free survival (median = 16.7, 19 and 22.2 months respectively for study I, II and III) or overall survival (median = 25, 45.7 and 32.6 months respectively for study I, II and III). Analysis of subset of patients without supra clavicular lymph node involvement where neoadjuvant chemotherapy obtained at least a 50% response reveals a median disease free survival and median overall survival of respectively 38.3 and 60.1 months for patients who underwent S vs 19 and 38.3 months for those who received XRT (P = 0.15). These studies suggest that surgery has no deleterious effect on outcome of IBC. Advantage on disease free survival or overall survival from intensive chemotherapy in IBC remains to be proven with appropriate randomised trials.

Adult↗

Caffeine decreases glial cell number and increases hyaluronan secretion in newborn rat brain cultures.

Newborn rat brain astrocytes (type 1 astrocytes, O-2A progenitor cells, and O-2A progenitor-derived cells, i.e. oligodendrocytes and type 2 astrocytes) were cultivated to investigate the effect of addition of caffeine to the culture medium on glial cell development and secretion of hyaluronan (hyaluronic acid, HA). HA is a glycosaminoglycan, secreted by type 1 astrocytes especially, which is a major component of the extracellular matrix of immature brain involved in morphogenesis and differentiation. Caffeine was added to the culture medium of primary glial cell cultures at concentrations of 102 microM (20 mg/L) or 255 microM (50 mg/L), considered therapeutic and toxic levels, respectively, in human newborns. HA was measured in the culture medium by immunoenzyme assay using sheep brain hyaluronectin, a glycoprotein that exhibits a strong affinity for HA, as probe. In primary glial cell cultures, 102 microM (20 mg/L) caffeine had no visible effect on cell number or on HA secretion. At 255 microM (50 mg/L), there was a significant reduction of cell number (i.e. type 1 astrocytes, O-2A progenitor cells, and progenitor-derived cells) and a significant increase of HA secretion per cell. These results suggest that caffeine at a high concentration in brain could have a prejudicial effect on the number of proliferating glial cells (astrocytes and oligodendrocytes) and on the composition of the extracellular matrix, which could affect myelination onset.

Animals↗

Amisulpride versus bromocriptine in infantile autism: a controlled crossover comparative study of two drugs with opposite effects on dopaminergic function.

An alteration of dopaminergic (DA) function much more complex than simple hyperactivity has been evoked in infantile autism. We therefore compared the clinical efficacy of a DA antagonist (amisulpride) and a DA agonist (bromocriptine) in a randomized, double-blind, crossover trial in 9 children with autism, likely severely mentally retarded. Amisulpride acts preferentially on specific autistic symptoms whereas bromocriptine acts more on motor hyperactivity and attention symptoms. These findings raise the specificity of these two drugs which appear to act preferentially on some target symptoms and are consistent with some clinical and pharmacological observations showing a sedative effect with low doses of DA agonists and a stimulant effect with low doses of DA antagonists such as the benzamides.

Adolescent↗

VAD or VMBCP in severe multiple myeloma. The Groupe d'Etudes et de Recherche sur le Myélome (GERM).

A randomized trial has been performed in which 91 patients with stage III myeloma and additional severe criteria were randomly allocated to either VAD or VMBCP. No significant difference was noted between these two groups using the following criteria: response rate (VMBCP: 54%; VAD: 39%), impact on symptoms, median survival (VMBCP: 14 months, VAD: 17 months). However, toxic effects and refusal to pursue treatment were more frequent with VAD than with VMBCP (12 v 6). Therefore, in this trial, VMBCP appears to be more useful than VAD.

Adult↗

[An aid to the electrophysiological diagnosis of diabetic peripheral neuropathy].

The electrophysiological diagnosis of peripheral neuropathy in diabetics becomes increasingly difficult with the increase in number of parameters measured. We have examined 102 subjects: 60 diabetics, 32 control subjects and 10 with impaired glucose tolerance. From the 37 recorded parameters during 8 examinations, a linear discriminant analysis allowed us to separate the 19 diabetics with clinical neuropathy and the control subjects with only 5 parameters, with a good concordance (96%): the motor conduction velocities (MCV) of the peroneal and median nerves, the amplitude of the action potential (AP) of the sural nerve, the Hmax/Mmax ratio and the M latency of the Hoffman reflex. These parameters, weighted with a coefficient, constitute a score of discrimination. This score has been tested by the Jackknife method on the same sample (94% of well-classified patients), then validated on the other patients. Thus we propose a method to aid the diagnosis of diabetic peripheral neuropathy, without the arbitrary character of the classical single parameter method, and allowing easy repetition.

Adult↗

Hypothermic effect of neuromedin N in mice and its potentiation by peptidase inhibitors.

The intracerebroventricular administration of neuromedin N (from 50 ng to 5 micrograms) elicited a dose- and time-dependent hypothermia in mice. Two aminopeptidase inhibitors, bestatin (50 micrograms) and puromycin (50 micrograms), the endopeptidase 24.11 inhibitor, thiorphan (10 micrograms), and the angiotensin-converting enzyme inhibitor, captopril (50 micrograms), were tested for their ability to potentiate the neuromedin N-induced hypothermia. Only bestatin significantly increased the response to the peptide. In addition, thiorphan, though devoid of effect on the neuromedin N-induced hypothermia when given alone, further potentiated the response elicited by neuromedin N and bestatin. The combinations of puromycin/thiorphan and bestatin/captopril did not potentiate the neuromedin N-induced hypothermia.

Animals↗

Susceptibility of Mycobacterium avium complex to various two-drug combinations of antituberculosis agents.

The drug susceptibility of two untypable strains of Mycobacterium avium complex were studied in 7H10 agar plates containing ethambutol (EMB), isoniazid (INH), rifampicin (RMP), ethionamide (ETH), and streptomycin (SM) alone and in two-drug combinations. The effective dose inhibiting 75% of the mycobacterial population (ED 75) was estimated by a regression analysis on the probit transformed inhibition percentages and plotted on an isobologram for each combination. No major discrepancies were found between strains. Five combinations (RMP plus INH, RMP plus EMB, EMB plus SM, INH plus EMB, and ETH plus INH) showed synergistic effect, whereas five other combinations (ETH plus EMB, ETH plus RMP, ETH plus SM, SM plus RMP, and SM plus INH) showed antagonistic effect. These in vitro results are not in combination with the known results of treatment of the M. avium diseases. We conclude that the effect of drug combinations against M. avium may be strain dependent and that it is important to determine this effect in vitro before setting up a treatment protocol.

Aged↗

Prognostic value of response after three MOPP cycles in Hodgkin's disease--stage III and IV.

Sixty-eight patients with Hodgkin's disease stage III and IV were evaluated after three out of six MOPP cycles. At that time, 46 (68%) were classified as early responders and 22 as slow responders. The criteria of response were: disappearance of B symptoms, decrease in the size of the largest lymph nodes (by more than 50%) and significant reduction (more than 20%) of mediastinal enlargement. Out of 43 early responders, 38 were in complete remission after six MOPP cycles and only five out of 22 slow responders. Such an early response is only related to the absence of B symptoms at the time of diagnosis (p less than 0.05). The survival curves of early responders and slow responders were significantly different (p less than 0.02). A rapid erythrocyte sedimentation rate (ESR) (greater than 50 mm) was the most frequently abnormal sign found in the group not responding after three MOPP cycles (p less than 0.0001). Such a significant prognostic value of early response is observed for stage III but not for stage IV patients. We conclude that early clinical response after three MOPP cycles is a good prognostic factor which must be kept in mind in the formulation of the therapeutic regimen for Hodgkin's disease stage III and IV.

Antineoplastic Combined Chemotherapy Protocols↗

In situ versus reversed saphenous vein for femoropopliteal bypass: a prospective randomized study of 100 cases.

With the purpose of comparing results using the greater saphenous vein in situ or as a reversed conduit, 100 femoropopliteal bypasses, performed in 91 patients between October 1980 and January 1985, were randomized into two statistically comparable groups of 50 procedures of each type. Seventy-five percent of patients had cutaneous signs of ischemia and 20% had isolated rest pain. Average follow-up was 32 months for the in situ group and 33.4 months in the reversed bypass group. The quality of the vein was statistically better in the in situ group (p less than 0.01). There were six cases of early thrombosis in the in situ group compared to four in the reversed bypass group. In the in situ group, half of the thromboses could be attributed to inadequate valvular destruction. Seven delayed thromboses were noted in the in situ group whereas there were two in the reversed saphenous vein bypass group. The actuarial rates of bypass patency at three years in the reversed and in situ groups were 88.2 and 70.8%, respectively (chi 2 = 2.62; NS). Analysis of results suggests that: 1) the reversed saphenous vein bypass provides excellent results if vein harvest and preparation are as atraumatic as possible; 2) expertise in rendering the valves incompetent markedly increases patency in the in situ technique; 3) during the first 12 months, Doppler follow-up of measured distal pressures is necessary in order to detect pathologic changes of the bypass and adjacent arterial tree.

Aged↗

Naloxone-insensitive potentiation of neurotensin hypothermic effect by the enkephalinase inhibitor thiorphan.

The hypothermic effect of neurotensin (0.1 microgram) injected i.c.v. in mice is potentiated by the enkephalinase inhibitor thiorphan (10 micrograms, i.c.v.). This potentiation is not reversed by systemic naloxone. The hypothermic effect of neurotensin is not modified by the amino-peptidase inhibitor bestatin (50 micrograms, i.c.v.) nor by the angiotensin-converting enzyme inhibitor captopril (50 micrograms, i.c.v.). These data indicate the involvement of enkephalinase in the inactivation of neurotensin, at least when it is injected i.c.v.

Amino Acids, Sulfur↗