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Biomedical subjects

M Meunier

Publications and source records attributed to M Meunier.

At least 19 recordsLinked to original sources

Neuroprotective effects of RPR 104632, a novel antagonist at the glycine site of the NMDA receptor, in vitro.

The NMDA antagonist and neuroprotective effects of RPR 104632 (2H-1,2,4-benzothiadiazine-1-dioxide-3-carboxylic acid), a new benzothiadiazine derivative, with affinity for the glycine site of the NMDA receptor-channel complex are described. RPR 104632 antagonized the binding of [3H]5,7-dichlorokynurenic acid to the rat cerebral cortex, with a Ki of 4.9 nM. This effect was stereospecific, since the (-)-isomer was 500-fold more potent than the (+)-isomer. The potent affinity of RPR 104632 for the glycine site was confirmed by the observation that RPR 104632 inhibited [3H]N-[1-(2-thienyl)cyclohexyl]-3,4-piperidine ([3H]TCP) binding in the presence of N-methyl-D-aspartate (NMDA) (IC50 = 55 nM), whereas it had no effect on the competitive NMDA site or on the dissociative anaesthetic site. RPR 104632 inhibited the NMDA-evoked increase in guanosine 3',5'-cyclic monophosphate (cGMP) levels of neonatal rat cerebellar slices (IC50 = 890 nM) in a non-competitive manner and markedly reduced NMDA-induced neurotoxicity in rat hippocampal slices and in cortical primary cell cultures. These results suggest that RPR 104632 is a high-affinity specific antagonist of the glycine site coupled to the NMDA receptor channel with potent neuroprotective properties in vitro.

Aminoquinolines

Cerebral ischemia: are the memory deficits associated with hippocampal cell loss?

The long-standing notion that damage restricted to the hippocampal formation is sufficient to produce a significant global memory deficit derives from clinical data. Specifically, it is based on the observation that transient global ischemia, which leads to partial cell loss within the hippocampal formation but not in other brain areas important for memory, can produce global amnesia in humans. This view is, however, challenged by a number of experimental findings. First, in both monkeys and rats, there is evidence that ischemia disrupts delayed object recognition, a memory process found to be largely intact following selective hippocampal lesions. These findings indicate that damage confined to the hippocampal formation cannot account for all aspects of the ischemia-induced memory impairments. Second, although some groups of hippocampal neurons are the most prone to degeneration following ischemia, a wide array of extra-hippocampal damage has been observed in all species, for which the precise extent and distribution may well be underestimated by conventional histological evaluations of ischemic brains. Partial neuronal degeneration reported in regions such as the rhinal areas, medial dorsal thalamic nucleus, or cingulate cortex may contribute to varying degrees to ischemia-induced memory deficits. Third, experimental studies have failed to generate a general consensus on the correlation between extent of hippocampal cell loss and memory performance. In sum, the experimental studies do not, as yet, support the view that hippocampal damage is solely responsible for ischemia-induced memory deficits. Rather, they suggest that both the intra- and extra-hippocampal damage contribute to the pattern of memory impairments observed following ischemia. Consequently, although animals with global and focal ischemia represent valuable models for neuropathological and therapeutic studies, they may not be so useful in assessing the role of the hippocampal formation and its sub-components in memory processes.

Animals

3-Nitropropionic acid exacerbates [3H]GABA release evoked by glucose deprivation in rat striatal slices.

3-Nitropropionic acid (3-NPA) is a metabolic poison that produces lesions of striatal intrinsic neurones such as gamma-aminobutyric acid (GABA) neurones. This study was carried out to determine whether 3-NPA would impair the ability of striatal GABAergic neurones to withstand hypoglycaemic stress. 3-NPA (500 microM) did not affect [3H]GABA release from striatal slices under normal (11 mM) glucose concentrations. When the glucose concentration was lowered to 0.3 mM, however, 3-NPA greatly potentiated the leakage of [3H]GABA from the slices. Blockage of N-methyl-D-aspartate (NMDA) or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors with 1 microM 5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801) or 10 microM 2,3-dihydroxy-6-nitro-7-sulpha-moylbenzo[F]quinoxaline (NBQX), respectively, or a combination of both, had no effect. However, blockade of voltage-dependent sodium channels with tetrodotoxin totally antagonized the [3H]GABA overflow induced by the combination of 3-NPA and hypoglycaemis. Riluzole (10 to 100 microM), a neuroprotective agent that stabilizes the inactivated state of the voltage-dependent sodium channel, also dose-dependently antagonized the increase in [3H]GABA release induced by the combination of the two stresses.

Animals

Effects of rhinal cortex lesions combined with hippocampectomy on visual recognition memory in rhesus monkeys.

1. We assessed the visual recognition abilities, as measured by delayed nonmatching-to-sample with trial-unique objects, of rhesus monkeys with hippocampectomy (i.e., removal of the hippocampal formation plus parahippocampal gyrus) combined with ablations of the rhinal cortex (i.e., entorhinal cortex plus perirhinal cortex). 2. Relative to unoperated controls, monkeys with combined hippocampectomy and rhinal cortex ablation (H+Rh) were significantly impaired in visual recognition. 3. Comparison of the scores of the monkeys in the present H+Rh group, which sustained near-complete rhinal cortex damage, with the scores of monkeys in an earlier H+Rh group in which the rostral part of the rhinal cortex had been spared indicates that the magnitude of the impairment is greater in the group with the more complete rhinal cortex damage. This finding is consistent with the idea that the rhinal cortex is critical for visual recognition. 4. Comparison of the present results with those from an earlier study on visual recognition that employed lesions limited to the rhinal cortex (Rh group) shows, paradoxically, that adding removal of the hippocampal formation and parahippocampal gyrus to a rhinal cortex lesion significantly reduces the recognition impairment produced by rhinal cortex lesions alone. 5. Our findings do not fit the view that the hippocampal formation, parahippocampal gyrus, and rhinal cortex constitute parts of a single functional system, such that the greater the damage to the entire system, the more severe the impairment. Instead, the results are consistent with the view that there are multiple functional subdivisions within the medial temporal lobe.

Animals

[A rare cause of severe diarrhea in children: pseudomembranous colitis].

BACKGROUND: Pseudomembranous colitis is a rare and serious complication of treatment by antibiotics. The case of a patient with a protracted pseudomembranous colitis followed by two relapses is reported. CASE REPORT: A 4 year-old boy was admitted after 18 days of profuse and feverish diarrhea. He had been given amoxycillin for 10 days, one and a half months previously. His temperature was 40 degrees C; he had abdominal pain and leucocytosis was 30,000/mm3. The situation rapidly improved with digestive rest and i.v. antibiotic therapy. Relapse of diarrhea together with bilious vomiting and acute abdominal pains required readmission three days after his discharge. Search for Clostridium difficile in stools remained negative. The diagnosis of pseudomembranous colitis was confirmed by sigmoidoscopy and intestinal biopsy. The patient was given parenteral nutrition for 3 weeks and vancomycin. The disease was complicated by anasarca related to severe protein-loosing enteropathy but evolution was finally favourable after a two month period. CONCLUSION: Pseudomembranous colitis remains a serious affection in childhood; its prognosis largely depends on the precocity of diagnosis and treatment.

Anti-Bacterial Agents

Mammographic lesions suggestive of radial scars: microscopic findings in 40 cases.

PURPOSE: To analyze the histologic appearance of mammographically detected lesions suspected of being radial scars. MATERIALS AND METHODS: Mammographic and pathologic findings in 40 patients with a preoperative diagnosis of radial scar were reviewed retrospectively. RESULTS: Pathologic examination revealed 20 pure radial scars, 12 pure carcinomas, and eight malignant lesions (seven tubular carcinomas and one infiltrating ductal carcinoma) associated with a radial scar. At mammography, no difference was noted between benign and malignant lesions according to size and shape of the spicule, size of the central core, and the presence of calcifications. CONCLUSION: Because of the association of radial scars with borderline and malignant lesions, a spiculated lesion suggestive of a radial scar found at mammography must always be surgically removed. The surgeon and pathologist must be aware of the mammographic aspects of radial scar, however, to avert excessive surgery, because all cancers in this study had a good prognosis.

Adult

Ductal carcinoma in situ: MR imaging-histopathologic correlation.

PURPOSE: To correlate histopathologic and magnetic resonance (MR) imaging findings of ductal carcinoma in situ (DCIS). MATERIALS AND METHODS: Thirty-six women with DCIS underwent preoperative contrast material-enhanced subtraction dynamic MR imaging. Concomitant early contrast enhancement in the breast parenchyma with normal vessels was considered a positive finding. The size and shape of early enhancement were correlated with the size and density packing of ducts involved by DCIS. Tumor angiogenesis in the stroma that surrounded the ducts was evaluated with immunoperoxidase staining. RESULTS: Early contrast enhancement was demonstrated in 34 patients with DCIS but not in two patients with comedo-type DCIS. Tumor angiogenesis was demonstrated in the stroma. The size and morphology of contrast-enhanced lesions significantly correlated with the size (P = .0085) and density packing of ducts involved by DCIS (P = .012). CONCLUSION: Contrast enhancement on dynamic MR images of DCIS may be due to the presence of tumor angiogenesis in the stroma.

Breast

[Diagnosis of non-palpable breast lesions: contribution of cytological punctures after stereotaxic localization].

The authors reviewed the accuracy of stereotaxic fine-needle aspiration cytology. Two hundred-twenty-eight lesions were studied: 103 benign lesions, 125 cancers. Inadequate sample was obtained in 26% of cases. None of the cytology reports were false-positive, whereas 77% of the suspect cytologic reports were malignant on histology. In strongly suspicious lesions at mammography, the decision to perform surgical biopsy should not be postponed as false negative cytologic findings (7 cases) are possible. In patients with a low suspicious lesion, cytology found six cancers. The benign-to-malignant ratio of excisional biopsies of non palpables lesions should be reduced by stereotaxic fine-needle aspiration cytology.

Adult

Riluzole and experimental parkinsonism: antagonism of MPTP-induced decrease in central dopamine levels in mice.

We have investigated whether riluzole, a compound that interferes with glutamatergic (GLUergic) transmission, would protect central dopaminergic (DAergic) neurones from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced toxicity in the striatum in mice. MPTP decreased DA, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels. Riluzole protected against the MPTP-induced decrease in DA levels. The utilization of DA ([DOPAC+HVA]/DA) was increased after MPTP treatment, but returned to control values in mice given riluzole in combination with MPTP. Riluzole did not confer protection by inhibiting either monoamine oxidase type B activity or DA uptake. Possible mechanisms involved in the protective action of riluzole are discussed. Our results show that riluzole antagonizes the DAergic neurotoxicity of MPTP, a pro-parkinsonian neurotoxin, in mice.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Riluzole and experimental parkinsonism: partial antagonism of MPP(+)-induced increase in striatal extracellular dopamine in rats in vivo.

Superfusion of the rat striatum with 100 microM of 1-methyl-4-phenylpyridinium (MPP+) induced a 70-fold increase in dopamine (DA) release and a decrease in the extracellular levels of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). Pretreatment with riluzole (8 mg kg-1, i.p.), a compound that interferes with glutamatergic transmission, partially antagonized the effect of MPP+ on the release of DA, but did not change the effects of this toxin on the efflux of DOPAC and HVA. Riluzole did not affect the increase in DA release induced by MPP+ in vitro. The in vivo efficacy of riluzole on MPP(+)-induced DA release could be due to its central interference with glutamatergic transmission. Our data point to a protective role of riluzole with regard to DA release, a marker of the neuronal impairment induced by MPP+, a pro-parkinsonian neurotoxin.

1-Methyl-4-phenylpyridinium

Polyhedral microcalcifications at mammography: histologic correlation with calcium oxalate.

Pathologists have associated calcium oxalate dihydrate (weddellite) in breast biopsy specimens with benign or borderline lesions and rarely with malignancy. These microcalcifications may have a polyhedral shape in histologic specimens owing to their crystalline structure. A retrospective radiologic-histologic correlation study was performed on 300 clusters of microcalcifications to determine if microcalcifications with a polyhedral shape could be found at mammography. In 19 cases (6.3%), polyhedral microcalcifications (PMs) were detected by two radiologists. In 12 of these 19 cases, weddellite crystals were found in the histologic specimen under polarized light; in seven cases, no calcification was found. Although rare, PMs can be found at mammography by radiologists aware of their existence. They are due to weddellite crystals and in this series were associated with benign disease in 89% of cases. Prospective studies are required to determine the frequency of PMs on screening mammograms and to evaluate their negative predictive value.

Breast

Effects on visual recognition of combined and separate ablations of the entorhinal and perirhinal cortex in rhesus monkeys.

Performance on visual delayed nonmatching-to-sample was assessed in rhesus monkeys with combined and separate ablations of the perirhinal and entorhinal cortex, as well as in unoperated controls. Combined (i.e., rhinal cortex) lesions yielded a striking impairment on this task, one almost as severe as that seen after combined amygdalohippocampal removals that included some of this subjacent cortex (Mishkin, 1978; Murray and Mishkin, 1984). Ablations of the perirhinal cortex alone produced a deficit nearly as severe as that found after rhinal cortex lesions, whereas ablations of the entorhinal cortex alone produced only a mild deficit. Contrary to the conclusion from an earlier study (Murray and Mishkin, 1986), the present results demonstrate not only that damage limited to the rhinal cortex is sufficient to produce a severe loss in visual recognition, but also that such damage leads to a far greater loss than damage to any other single structure in the medial part of the temporal lobe.

Animals

Mammographic features of 455 invasive lobular carcinomas.

Of 6,009 cases of breast cancer studied, 455 (7.6%) were invasive lobular carcinoma (ILC); 341 of these (75%) were pure ILC and 114 (25%) were ILC mixed with ductal forms. The mammographic features were compared with those of the 5,554 other breast carcinomas. Pure ILCs were less frequently round (1% vs 11%) and more frequently spicular (28% vs 23%) or with architectural distortion (18% vs 6%) than the other breast carcinomas. Microcalcifications were less common (24% vs 41%) and retraction of the skin (25% vs 21%) and nipple (26% vs 17%) was more common in pure ILC than in the other breast carcinomas. When complementary magnification views were obtained, only 50% were helpful in diagnosis of ILC while 75% were helpful in diagnosis of other breast carcinomas. Malignancy was less frequently diagnosed in ILC (57%) than in the other breast carcinomas (64%). The results were intermediate in the mixed ILC group.

Adult

Influence of season of birth on onset of gonadotrophic and ovarian functions in young doe hares (Lepus europaeus).

The pituitary and ovarian responses to a monthly i.v. injection of 5 micrograms luteinizing-hormone-releasing hormone (LHRH) were studied in three groups of young doe hares, born in January-February (group I), in April (group II) or at the end of the breeding season (August-September, group III). The LHRH injection was always followed by a release of LH and progesterone, which did not differ among the three groups at 3 months of age. The pituitary and ovarian responses to LHRH increased gradually from the age of 3 months in groups I and III and from the age of 9 months in group II. One female of the ten born in January-February ovulated and reached puberty in June, at the age of 4 months, but with a weak pituitary response. The females born in April displayed a seasonally delayed puberty, at 9 months of age (two of five females ovulated in the next January). Four of the five females born at the end of the breeding season ovulated after LHRH when 5 months old (in February), with a full pituitary-ovarian response. The low pituitary response of group I in June-August, even if 10-20% of females ovulated after LHRH, suggests a need for a period of short days. Then, the most favourable conditions for the hare to reach puberty would be a period of short decreasing daylengths during the fall, followed by increasing daylengths after the winter solstice.

Age Factors

[Therapeutic evaluation of Mormoiron attapulgite in acute diarrheas of infants and children. A multicenter study in controlled liberal practice versus placebo in 113 patients].

A placebo-controlled multicenter study was carried out to evaluate the effectiveness and safety of Actapulgite in infants and children with acute diarrhea. One hundred and thirteen patients, with a mean age of 28 months, were enrolled by pediatricians in the office. As recommended during acute diarrhea, the dosage of Actapulgite was doubled during the first three treatment days (2 to 4 packets a day according to the patient's weight), and reduced by half thereafter. The main effectiveness criteria was passage of the first normally formed stool, which denotes normalization of intestinal transit time. The first normally formed stool was recorded after two days of treatment with Actapulgite and was followed, on the next day, by a second normal stool, denoting complete recovery. The greater effectiveness of Actapulgite as compared with the placebo was demonstrated by the fact that both the first and the second normally formed stools were passed one day earlier with the active treatment (p = 0.01 and p = 0.002, respectively). In addition, resumption of a normal diet occurred significantly earlier with Actapulgite (4.4 days) than with the placebo (5.1 days). In addition to being effective, the study drug proved remarkably well tolerated. This study is especially valuable because of its office setting and the use of exclusively clinical criteria with a strict methodology.

Acute Disease

Differential involvement of anterior and posterior cingulate cortices in spatial discriminative learning in a T-maze in mice.

The contribution of the anterior and posterior cingulate cortical areas to spatial learning and memory was examined in mice using a behavioral paradigm based on a spatial discrimination task in a T-maze. Multiple injections of small amounts of ibotenic acid were used to produce fiber-sparing lesions of either the anterior (ACC) or the posterior (PCC) cingulate area. Mice with ACC lesions, though learning the initial acquisition and first reversal of the discrimination at about the normal rate, were impaired during the subsequent four reversal sessions. In contrast to control mice, they failed to improve their performance from the first to the last session. Nevertheless, when later required to repeatedly learn the same discrimination over several days (repetitive testing), animals with ACC lesions no longer exhibited any learning deficit. The converse pattern of results was found in mice with PCC lesions. These animals performed much more poorly than control animals during the acquisition and first reversal of the discrimination, but displayed remarkable improvement over the subsequent four reversal sessions, gradually overcoming their initial impairment. However, when later submitted to repetitive testing, these animals again showed a substantial learning deficit. Neither ACC nor PCC cingulate lesions significantly affected the animals' retention capacities as measured by single test-trials over a 24-h interval. Yet, mice with PCC lesions were retarded in reversal learning after a long intersession interval (10 days), indicating that PCC, but not ACC, lesions did interfere with some long-term retention processes. These results imply that the ACC, as a part of the medial frontal cortex, may play a crucial role in temporally ordering a series of spatial responses, whereas the PCC seems to contribute to the formation and retention of each individual spatial response, probably by transmitting information from limbic structures such as the anterior thalamus and hippocampal formation to posterior neocortical association areas.

Adaptation, Psychological