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Biomedical subjects

M Dumas

Publications and source records attributed to M Dumas.

At least 55 records · Page 3Linked to original sources

Prevalence of epilepsy in rural Bolivia: a door-to-door survey.

OBJECTIVE: To carry out a door-to-door survey in rural areas of the Cordillera Province, Santa Cruz Department, Bolivia, to determine the prevalence of neurologic diseases (epilepsy, stroke, parkinsonism, and peripheral neuropathy) in a sample of approximately 10,000 inhabitants. METHODS: A team of nondoctor health workers administered a standard screening instrument for neurologic diseases-a slightly modified version of the World Health Organization protocol. All subjects found positive during the screening underwent a neurologic examination. RESULTS: On screening, the authors found 1,130 positive subjects, of whom 1,027 were then investigated by neurologists. On the basis of the definition proposed by the International League Against Epilepsy, we detected 124 epileptic patients (prevalence, 12.3/1,000), 112 of whom had active epilepsy (prevalence, 11.1/1,000) on the prevalence day (November 1, 1994). Peak age-specific prevalence occurred in the 15 to 24-year age group (20.4/1,000). Sex-specific prevalence was higher in women (13.1/1,000) than men (11.4/1,000). Eighty-nine patients (71.8%) underwent a standard EEG recording. Considering both EEG and clinical data, partial seizures were the most common type (53.2%) based on the classification of the International League Against Epilepsy. The mean age at onset was 20.7 years for partial seizures and 13.6 years for generalized seizures. Only 10.5% of patients had received specific treatment for more than 2 months of their life. CONCLUSION: This report on epilepsy prevalence in Bolivia confirms that epilepsy is a major health problem in rural areas of developing countries.

Adolescent↗

Onchocerciasis and epilepsy: a matched case-control study in the Central African Republic.

The occurrence of epileptic seizures during onchocercal infestation has been suspected. Epidemiologic studies are necessary to confirm the relation between onchocerciasis and epilepsy. A matched case-control study was conducted in dispensaries of three northwestern towns of the Central African Republic. Each epileptic case was matched against two nonepileptic controls on the six criteria of sex, age (+/-5 years), residence, treatment with ivermectin, date of last ivermectin dose, and the number of ivermectin doses. Onchocerciasis was defined as at least one microfilaria observed in iliac crest skin snip biopsy. A total of 561 subjects (187 cases and 374 controls) were included in the study. Of the epileptics, 39.6% had onchocerciasis, as did 35.8% of the controls. The mean dermal microfilarial load was 26 microfilariae per mg of skin (standard deviation, 42) in the epileptics and 24 microfilariae per mg of skin (standard deviation, 48) in the controls. This matched case-control study found some relation (odds ratio = 1.21, 95% confidence interval 0.81-1.80), although it was nonstatistically significant.

Adolescent↗

Pharmacological and biochemical study on the effects of selective phosphodiesterase inhibitors on human term myometrium.

This study was aimed at evaluating the in vitro effects of phosphodiesterase inhibitors and beta2-adrenoceptor agonists on spontaneous contractions of human term myometrium. Rolipram, RP 73401 (3-cyclopentyloxy-N-(3,5(-dichloro-4-pyridil)-4-methoxybenzamide) and Ro 20-1724 (1-4-(3-butoxy-4-methoxybenzyl)-2-imidozolidinone) (phosphodiesterase 4 inhibitors) inhibited spontaneous myometrial contractions (Emax approximately 100%; pD2 of 6.80+/-0.28, 6.84+/-0.32 and 6.31+/-0.03, respectively). Salbutamol and formoterol were less effective (Emax=40+/-6% and 35+/-12%, respectively) than phosphodiesterase 4 inhibitors to reduce myometrial contractility. Inhibitors of phosphodiesterase 3 (milrinone and siguazodan) and 5 (zaprinast) were marginally effective. Rolipram (10-30 nM) and siguazodan (0.1 microM) potentiated the response to salbutamol (Emax=75+/-12%, 88+/-8% and 73+/-12% and pD2=6.51+/-0.20, 6.93+/-0.29 and 6.48+/-0.16, respectively). Sodium nitroprusside (pD2=6.76+/-0.29) and theophylline (pD2=5.15+/-0.22) were effective inhibitors of myometrial contractions. Chromatographic separation of phosphodiesterase isoenzymes demonstrated that phosphodiesterase 4 is predominant but other phosphodiesterase isoenzymes were also identified. In conclusion, phosphodiesterase 4 inhibitors alone or combined with beta2-adrenoceptor agonists have potential interest as tocolytic agents.

Adrenergic beta-Agonists↗

Hypoxic pulmonary vasoconstriction.

Hypoxic vasoconstriction is unique to pulmonary circulation. The pulmonary response is part of a self-regulatory mechanism by which pulmonary capillary blood flow is automatically adjusted to alveolar ventilation for maintaining the optimal balance of ventilation and perfusion. In pathological conditions, hypoxic pulmonary vasoconstriction may occur as an acute episode or as a sustained response with pulmonary hypertension and vascular remodeling. Vasoactive substances produced from the endothelial cells (prostanoids, nitric oxide, or endothelin) or other mediators such as 5 hydroxytryptamine have been examined as possible mediators of hypoxic vasoconstriction. These appear more likely to be modulators than mediators of the vasoconstrictor response to hypoxia. Recent hypotheses have emerged indicating that O2 levels per se can regulate ion channel activity. The modulation of both K+ and Ca2+ channels differs according to the conduit or resistance pulmonary vessel type, tending to extend the former and contract the latter, thereby opposing the ventilation to perfusion mismatching. In the absence of drugs that act selectively on pulmonary circulation, inhaled therapy is an alternative in the treatment of pulmonary hypertension. According to its short half-life and to its potential cytotoxicity, nitric oxide is only of value in the management of patients with acute respiratory disease. Aerosolized prostacyclin and iloprost result in a sustained efficacy of the inhaled vasodilator regimen in patients with severe pulmonary hypertension and offer a new strategy for treatment of this disease. At the moment, therapy aimed at reversing the structural remodeling and matrix deposition in pulmonary arteries remains experimental. New drugs such as potassium channel openers or endothelin receptor antagonists warrant further investigations as possible therapeutic candidates in the treatment of pulmonary hypertension.

Animals↗

Trigeminal sensory neuropathy: a study of 35 cases.

OBJECTIVE: Trigeminal sensory neuropathy includes a wide variety of conditions sharing a common symptom described as sensory disturbance of the face--usually numbness. STUDY DESIGN: This 10-year retrospective study included 35 patients referred for investigation of trigeminal sensory neuropathy. RESULTS: The most common causes of trigeminal sensory neuropathy were nonneoplastic cerebral disorders, mainly represented by multiple sclerosis and idiopathic trigeminal sensory neuropathy. Furthermore, when only mandibular trigeminal sensory neuropathy was considered, metastatic neoplasia was the most frequent cause, often afflicting men over the age of 60 years. CONCLUSIONS: This overview will orient clinicians in their diagnosis when they are faced with patients consulting for trigeminal sensory neuropathy.

Adolescent↗

Role of potassium channels and nitric oxide in the relaxant effects elicited by beta-adrenoceptor agonists on hypoxic vasoconstriction in the isolated perfused lung of the rat.

1. The aims of this study were to compare, in the rat isolated perfused lung preparation, the antagonist effects of a nonselective beta-adrenoceptor agonist (isoprenaline), a selective beta2-adrenoceptor agonist (salbutamol) and a selective beta3-adrenoceptor agonist (SR 59104A) on the hypoxic pulmonary pressure response, and to investigate the role of K+ channels, endothelium derived relaxing factor and prostaglandins in these effects. K+ channels were inhibited by glibenclamide, charybdotoxin or apamin, NO synthase and cyclo-oxygenase were inhibited by N(G)-nitro-L-arginine methyl ester (L-NAME) and indomethacin, respectively. 2. Hypoxic ventilation produced a significant increase in perfusion pressure (+65%, P<0.001) and L-NAME significantly increased this response further (+123%, P<0.01). After apamin, L-NAME, indomethacin, post-hypoxic basal pressure did not return to baseline values (P<0.001). 3. Glibenclamide partially inhibited the relaxant effects of isoprenaline (P<0.05) and salbutamol (P<0.001) but not that of SR 59104A. In contrast, charybdotoxin and apamin partially inhibited the relaxant effects of SR 59104A (P=0.053 and <0.01, respectively) but did not modify the effects of isoprenaline and salbutamol. L-NAME partially inhibited the dilator response of salbutamol (P<0.01) and SR 59104A (P<0.05) but not that of isoprenaline. 4. We conclude that (a) EDRF exerts a significant inhibition of the hypoxic pulmonary response, (b) SK(Ca) channel activation, EDRF and prostaglandins contribute to the reversal of the hypoxic pressure response, (c) the vasodilation induced by isoprenaline is mediated in part by activation of K(ATP) channels, that of salbutamol by activation of K(ATP) channels and EDRF. In contrast, SR 59104A partly operates through BK(Ca), SK(Ca), channels and EDRF activation, differing in this from the beta1 and beta2-adrenoceptor agonists.

Adrenergic beta-Agonists↗

Pharmacokinetics, metabolism and excretion of megazol, a new potent trypanocidal drug in animals.

The pharmacokinetics of megazol (CAS 19622-55-0) was investigated after intraperitoneal and oral administration of the drug (80 mg/kg) to mice. The plasma levels were significantly higher after oral administration of drug than after intraperitoneal route (33.8 micrograms/ml compared with 19.0 micrograms/ml for Cmax, 158714 micrograms.h/l compared with 96057 micrograms.h/l for AUC). When suramin (CAS 145-63-1) was administered 24 h before oral administration of megazol, megazol absorption was accelerated (2 h compared with 4 h for Tmax) but the amount absorbed was lower (19.9 micrograms/ml compared with 33.8 micrograms/ml for Cmax and 95547 micrograms.h/l vs 158714 micrograms.h/l for AUC). In the infected mice previously treated with suramin, all estimated pharmacokinetic parameters of plasma megazol were significantly modified, in particularly an increase in the apparent volume of distribution (5.6 l/kg compared with 0.9 l/kg) with a prolongation of the elimination half-life (3 h compared with 0.7 h) of megazol. Excretion of the total radioactivity of megazol was also evaluated after oral administration of 3H-megazol to rats. Total radioactivity was eliminated predominantly via the urinary route (80%) vs. 10.5% in the faeces, 9.5% remaining in the body 8 days after dosing. When unlabelled megazol was orally administered to rats with absence or presence of suramin, megazol recovered in urine and faeces 72 h dosing was: 55.7%/2% vs 20.6%/1.6%, respectively. In the urine, unchanged megazol was present as characterized by LC-MS/MS as well as 4 unknown metabolites. This study indicates that suramin significantly affects the pharmacokinetics of megazol and its elimination.

Administration, Oral↗

Epilepsy and neurocysticercosis in an Andean community.

BACKGROUND: Taenia solium neurocysticercosis (NCC) has been documented as one of the major causes of epilepsy in developing countries. However, methodological limitations have hindered the evaluation of the epidemiological relationship between cysticercosis and epilepsy at the community level. METHODS: We used the WHO protocol for epidemiological evaluation of neurological disorders to conduct a door-to-door survey among 2723 residents of San Pablo del Lago, an Ecuadorean rural community in which T. solium taeniasis/cysticercosis was known to be endemic. The WHO protocol was complemented by neuroimaging and immunological tests to confirm the diagnosis of this infection. RESULTS: In all 31 people suffering from active epilepsy were detected (prevalence 11.4 per 1000, 95% CI:7.7-15.4); 26 agreed to undergo a computer tomography (CT) examination, and 28 agreed to have blood drawn for serodiagnosis. Fourteen of the 26 (53.8%) had CT changes compatible with NCC and six of the 28 (21.4%) tested positive in the enzyme-linked immunoelectro-transfer blot (EITB) assay. In a seizure-free random sample of this population, 17 of 118 (144 per 1000) subjects examined by CT and 10 out of 96 (104 per 1000) examined by EITB had evidence of this infection. The differences between the epilepsy group and the random sample of the population were statistically significant (OR = 6.93, 95% CI: 2.7-17.5, P < 0.001) for CT diagnosis, but not for EITB results (OR = 2.75, 95% CI: 0.8-7.1, P > 0.12, NS). CONCLUSIONS: These findings confirm that T. solium NCC is a significant cause of epilepsy at the community level in Andean villages of Ecuador. It is important to initiate effective public health interventions to eliminate this infection, which may be responsible for at least half of the cases of reported epilepsy in Ecuador.

Adolescent↗

[Epidemiology of cerebral cysticercosis in an Andean community in Ecuador].

Taenia solium neurocysticercosis (NCC) has been documented to be an underlying cause of epilepsy, intractable headaches, hydrocephalus, dementia and other serious neurological conditions in many countries of Central and South America. However, methodological limitations had prevented the assessment of the true prevalence of this condition at the community level. We conducted a house-to-house neuroepidemiological survey of 6,118 residents of an Andean community. This information was used to target neuroimaging (CT-scan) and immunodiagnosis (enzyme-linked immunoelectrotransfer blot assay, EITB) tests in individuals suspected of harbouring Taenia solium NCC. In the rural population, NCC was confirmed in 8 out of 47 examined by CT-scan (17%) and in 6 of 42 examined by EITB (14%). In the urban population, NCC was confirmed in 35 of 147 examined by CT-scan (23.8%) and in 28 of 124 examined by EITB (22.6%). In a sample of relatives of patients with documented cerebral cysticercosis, 20 out of 81 examined by CT-scan (25%) and 12 of 79 (15%) examined by EITB had NCC. Finally, CT scans were performed for 83 school children from urban areas, and 9 (11%) were diagnosed as harbouring NCC. In a community-based study, cysticercosis appears to be much more frequent than initially thought, when CT examination is used as the "gold standard" for diagnosis.

Adolescent↗

[Cerebral miliary granulomatosis with Histoplasma capsulatum in an HIV seronegative patient].

A 51 year old patient who worked in Africa for eight years, presented twelve years later a progressive ataxia associated with headaches. Neuroimaging studies done after a partial complex seizure demonstrated multiple supra and sub-tentorial cortical ring enhancing lesions. Histoplasma capsulatum histoplasmosis was found on histological examination of brain biopsy and confirmed by isolation of the fungus. Medical treatment with intravenous amphotericin B followed by oral itraconazole (400 mg per day) improved both clinical and radiological status. This observation of cerebral histoplasmosis is rather unusual for a seronegative HIV patient in a non endemic area.

Amphotericin B↗

[Epidemiological observations on the first case of human paragonimiasis and potential intermediate hosts of Paragonimus sp. in Benin].

Parasitological investigations were carried out for four months in 1998 in two Beninese centres of pneumo-phtisiology (Akpakpa, at Cotonou, and Akron, at Porto-Novo) to detect the patients harbouring eggs of Paragonimus sp. amongst the persons consulting for tuberculosis and showing a broncho-pneumopathy without mycobacteria. Eggs of Paragonimus sp. were detected in the sputum of a single patient out of 369 persons examined (prevalence, 0.2%). This patient had eaten crabs in the months preceding the date of diagnosis. A treatment using praziquantel has improved clinical symptomatology and biological signs found in this patient. These studies have been completed by visiting markets located in the coastal plain of Benin to identify the crabs that were sold and to find metacercariae of Paragonimus sp. Negative results were obtained when 126 Cardisoma armatum ("hole crab") were dissected. In contrast, the dissection of 176 Callinectes marginatus ("swimming crab") was successful, with 5% of crabs harbouring metacercariae of probably Paragonimus sp. Further studies are necessary to confirm these first results and to determine the global prevalence of Paragonimus infection in these definitive and intermediary hosts.

Aged↗

[Pneumococcus observatory data in the Rhône-Alps region. Results from 1996].

Throughout 1996, 22 hospital-based laboratories in the Rhône-Alpes region of France collected pneumococcal strains and used a standardized protocol to record the following data; patient age and sex; type of specimen; and determination of susceptibility to at least the following antibiotics: oxacillin 1 microgram and 5 micrograms, erythromycin (Ery), tetracycline (Tet), chloramphenicol (Chl), rifampin (Rmp), and loracarbef. For penicillin-nonsusceptible strains (PNSSs), which were identified based on results with oxacillin, MICs for penicillin G, amoxicillin (Amx), and cefotaxime (Ctx) were determined using the E Test, at the study site and agar dilution at the coordinating center. Of the 1153 strains, 65.5% were from adults and 31.8% from children; patient age was unknown in 2.7% of cases. PNSPs (MIC > 0.06 mg/l) contributed 32.9% of strains (I: 23.3%; R: 9.6%) and were more common in children (41.1%) than in adults (28.1%). The frequency of PNSSs varied across specimen types: 27.9% in blood cultures (305 strains), 15.6% in cerebrospinal fluid (32), 38.7% in protected bronchopulmonary specimens (31), 31.5% in unprotected bronchopulmonary specimens (434), 50.8% in acute otitis media (118), and 34.4% in other specimens (221). Among PNSSs, nonsusceptibility (I + R) to other antibiotics was variable: Ery, 62.1%; Tet, 41.5%; Chl, 40.4%; Rmp, 1.1%. Corresponding figures for the overall strain population were Ery, 33.3%; Tet, 22.7%; Chl, 22.8%; Rmp, 0.9%. In addition, 56.5% of PNSSs exhibited multiple drug resistance. Resistance to amoxicillin (MIC > 2 mg/l) was demonstrated for only 5 strains. No strains were resistant to loracarbef or cefotaxime. Serotypes of the 379 PNSSs were as follows: 23F, 26.6%; 14 (25.6%); 9V (18.2%), 6 (8.7%), 15 (5%), 19 (4.5%).

Adult↗

Influence of beta-adrenoceptor agonists on the pulmonary circulation. Effects of a beta3-adrenoceptor antagonist, SR 59230A.

The aims of this study were (a) to compare in the rat isolated perfused lung preparation, the effects of isoprenaline and of three beta3-adrenoceptors agonists, SR 59104A, (N-[(6hydroxy-1,2,3,4-tetrahydronaphtalen-(2 R)-2yl)methyl]-(2R)-2-hydroxy-2-(3-chlorophenyl)ethanamine hydrochloride), SR 59119A (N[(7-methoxy-1,2,3,4-tetrahydronaphtalen-(2R)-2yl)methyl]-( 2R)-2-hydroxy-2-(3-chlorophenyl)ethanamine hydrochloride) and SR 58611A (ethyl¿(7S)-7-[(2R)-2-(3-chlorophenyl)-2-hydroxyethylamino]-5,6,7, 8-tetrahydronaphtalen-2-yloxy¿acetate hydrochloride) on hypoxia-induced pulmonary vasoconstriction, and (b) to investigate the potential existence of atypical beta-adrenoceptors in these effects. Propranolol (0.1 microM) was used to antagonize beta1- and beta2-adrenoceptors whereas SR 59230A, 3-(2-ethylphenoxy)-1-[(1S)-1,2,3,4-tetrahydronapht-1-ylam ino]-(2S)-2-propanol oxalate) (0.3 microM) was used to block beta3-adrenoceptors. Isoprenaline and the three beta3-adrenoceptors agonists caused concentration-dependent relaxations during the pulmonary pressure response. Propranolol and SR 59230A inhibited the relaxant effects of isoprenaline. SR 59230A but not propranolol inhibited those of SR 59104A. Finally, propranolol and SR 59230A failed to oppose SR 59119A- and SR 58611A-induced relaxant effects. In concentrations > or = 1 microM, SR 59230A caused per se a relaxation of the hypoxic vasoconstricted lung. These results suggest the existence of atypical beta-adrenoceptors in the rat pulmonary vessels.

Adrenergic beta-Agonists↗

[Waiting for the end of poliomyelitis. Setting of the last phase of the eradication program. National Commission for the Certification of the Eradication of Poliomyelitis].

The worldwide eradication of poliomyelitis is expected within a few years. A reinforcement of epidemiological, clinical and viral supervision is necessary. Besides a sustained immunization effort, particular attention is required from all clinicians concerning the cases of non-traumatic acute flacid palsy that they may observe. In these cases it is asked to clinicians to perform a search for enterovirus in stool and spinal fluid, and a poliomyelitis serology.

Cerebrospinal Fluid↗

Age-related functional and structural changes in human dermo-epidermal junction components.

Cultured normal human keratinocytes obtained from 14 facial skin biopsies of donors aged 9-79 y were used to study the influence of donor age on the integrin receptors, cell adhesive properties in vitro, and type VII collagen synthesis. Immuno-spectrofluorimetric quantitation of integrins showed a decrease in the beta1- and beta4-subunits in low (0.08 mM) and high (1.8 mM) calcium conditions with aging. Calcium ions decreased the fluorescence intensity by relocating integrins at cell boundaries. Measurements of adhering cells showed that adhesion to bovine serum albumin-, type IV collagen- or laminin 1-coated plastic surfaces initially increased until donor age reached 30 y and then decreased. Specific adhesion to type IV collagen and laminin 1 did not vary with age, but the increase in adhesion to type IV collagen produced by manganese ions increased with age, suggesting an age-dependent feature of beta1 integrin. Synthesis of type VII collagen, increased or not by TGFbeta1 (10 ng per ml), did not vary with the donor age. Global normalized principal component analysis showed that variables related to integrins were strongly correlated, as were those of adhesion. Pre-embedding immunoelectron microscopy of freshly isolated keratinocytes showed that certain hemidesmosomes from aged cells had little or no reaction with anti-beta4-chain antibody. Post-embedding type IV collagen immunostaining and image analysis showed less type IV collagen in adult dermo-epidermal junctions. These findings indicate that there are structural and functional changes in the dermo-epidermal junction components with aging, probably giving a less effective epidermal anchoring system.

Adolescent↗

Megazol combined with suramin: a chemotherapy regimen which reversed the CNS pathology in a model of human African trypanosomiasis in mice.

Chemotherapy for human African trypanosomiasis (HAT), or sleeping sickness, is unreliable because of resistance, refraction and toxic and adverse side-effects. Using a long-term experimental model of HAT with involvement of the central nervous system (CNS), we tested the ability of a megazol and suramin combination treatment to eliminate CNS trypanosomes. This consisted of 20 mg suramin per kg body weight administered intraperitoneally (i.p.), followed 24 h later by 4 daily doses (80 mg/kg) of megazol given either i.p. or per os. One week post-treatment, neurological disorders had disappeared. One of 15 mice relapsed in each application group at 81 and 98 days after treatment, respectively. At six months, no signs of relapse were seen in remaining mice, indicating that this chemotherapy regimen was curative. Immunohistochemical (astrocytosis) and histological (inflammatory lesions) examinations of brain tissues showed that animals returned to normal from 2 months post-treatment. These results suggest that the megazol-suramin combination reversed the CNS pathology in this model.

Animals↗