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Biomedical subjects

M Dumas

Publications and source records attributed to M Dumas.

At least 73 records · Page 4Linked to original sources

Intrafamilial clustering and 4-year follow-up of asymptomatic human T-cell leukaemia virus type I (HTLV-I) infection in Benin (West Africa).

BACKGROUND: Few data exist concerning familial human T-cell leukaemia virus type I (HTLV-I) carrier states and transmission in African countries. Two previous surveys performed in Benin in 1989 and 1990 using a three-level cluster sampling method allowed us to identify HTLV-I positive subjects. The evolution of HTLV-I within the families of these subjects is described over a 4-year period, 1991-1995. METHODS: Since 1991, 37 HTLV-I seropositive subjects, six subjects with indeterminate Western-Blot pattern, and their relatives have been followed up once a year clinically and biologically. RESULTS: Twenty-three mothers in the study group gave birth to 27 children between 1991 and 1995. Among the 13 infants born to the 12 seropositive mothers, two seroconverted before their second birthday. One adult woman whose husband was seropositive developed seropositivity 4 years after marriage. In March 1992, a family case-control study (proband study) was conducted. A seroprevalence of 27.5% was found among 138 relatives of 32 infected subjects and 1.4% among 142 relatives of 32 control subjects. CONCLUSIONS: There is clearly an intrafamilial clustering of HTLV-I in Benin. The annual incidence density of HTLV-I in this cohort is estimated at 6 per thousand.

Adolescent↗

Plasma melatonin rhythm is maintained in human African trypanosomiasis.

In human African trypanosomiasis (sleeping sickness), sleep and wake episodes are sporadically distributed throughout the day and the night. Plasma melatonin, sleep-wakefulness and rectal temperature rhythms were studied in 9 Congolese patients suffering from sleeping sickness compared to 6 healthy controls submitted to the same light/dark regime. The circadian distribution of the sleep-wake cycle was disturbed in relation to the severity of the disease. As controls, patients maintained a very distinct plasma melatonin nyctohemeral rhythm which displayed a significant phase advance (1:08 +/- 0:43 and 2:34 +/- 0:31 mean +/- SD, in patients and controls respectively; p < 0.01, U test), as well as a persistent rectal temperature rhythm (mesor 36.67 +/- 0.29 and 36.74 +/- 0.13 degrees C, amplitude 0.29 +/- 0.16 and 0.32 +/- 0.13 degrees C, acrophase 13:53 +/- 2:47 and 15:32 +/- 0:36 for patients and controls respectively). No alteration of these rhythms was observed after treatment. In African controls we observed plasma melatonin characteristics similar to those of European controls, especially for the onset and the duration of the secretion and the stability of the rhythm, despite a different light/dark regime. The dissociation observed between the 3 rhythms (melatonin, temperature and sleep-wake cycle) is discussed, taking into consideration a functional compartmentalization of the suprachiasmatic nuclei or more likely a disruption of the neural pathway between the circadian clock and structures involved in the regulation of the sleep-wake cycle, related to the activity of compounds released by the parasites or host cells.

Adolescent↗

Multicenter phase II trial of interleukin-2, interferon-alpha, and 13-cis-retinoic acid in patients with metastatic renal-cell carcinoma.

PURPOSE: To determine the response rate and toxicity of oral 13-cis-retinoic acid (CRA) added to an outpatient regimen of subcutaneous interleukin-2 (IL2) and interferon-alpha (IFNA) in previously untreated patients with metastatic renal-cell carcinoma (RCC). PATIENTS AND METHODS: Eligibility included a performance status of 2 or better, no significant end-organ dysfunction, and written informed consent. Characteristics of 47 of 48 assessable patients included a median performance status of 0, prior nephrectomy in 68% of patients, one metastatic site in 30% of patients, and lung-only metastatic disease in 21% of patients. Therapy consisted of IL2 11 x 10(6) IU 4 days per week for 4 weeks, IFNA 9 x 10(6) IU 2 days per week for 4 weeks, and CRA 1 mg/kg daily on a 6-week cycle. RESULTS: Eight of 47 patients (17%) responded (one complete response, seven partial responses). Three partial responders were rendered disease free by subsequent surgical resection. Four additional patients experienced a minor response in lung or soft tissue metastases. The median duration of response, which included minor responses, was 42 weeks, and median survival was 74 weeks (17 months). Grades 3 or greater toxicities during the first cycle included flu-like symptoms (21% of patients), fatigue (6% of patients), and nausea and vomiting (15% of patients). Significant cumulative toxicities were hyperlipidemia (four of 18 patients), and cardiomyopathy (one of 18 patients). There was one therapy-related death. CONCLUSION: Outpatient CRA plus IL2 and IFNA is feasible and modestly effective in metastatic RCC. The prolonged median survival is encouraging, but randomized trials are required to show that the combination represents an improvement over single-agent immunotherapy.

Adult↗

[Human African trypanosomiasis, contributions of experimental models].

Melarsoprol has remained the chosen drug for the late-stage treatment of human African trypanosomiasis (HAT) due both to Trypanosoma brucei (T.b.) gambiense and T.b. rhodesiense; however, arsenical encephalopathies, which are often fatal, occur in 5-10% of the treated cases. To date, two major problems have not been solved. The first one is the precise diagnosis of early involvement of the central nervous system (CNS) which determines the therapeutics to be administered. The second one is linked to the lack of data on in vivo efficacy of products which are effective in vitro against trypanosomes. Answers have to be provided by experimental animal models of HAT. Such models would allow for better studies of the pathology and pathogenesis of the disease, as well as therapeutic trials of potentially effective new drugs or combinations. We have developed acute and chronic murine and sheep experimental animal models of HAT infected by T. b. brucei. Meningoencephalitis and neurological signs are relatively difficult to obtain in murine models and require artificial means, such as suramin treatment on day 21 after-infection. The chronic murine model has demonstrated CNS involvement with meningitis, followed by meningoencephalitis with progressive astrocytosis. The sheep model develops a disease with CNS complications and cerebrospinal fluid can be collected. In the sheep model, we have described anti-galactocerebrosides antibodies, which represent major components of myelin, which may indicate an autoimmune process in the CNS. We then described these antibodies in the cerebrospinal fluids and sera from patients at a late-stage of the disease. From a therapeutic point of view, we have cured mice or sheep with low doses of melarsoprol, or with the nitroimidazole derivatives Ro 15-0216 and megazol, alone or combined with suramin. Further studies of these nitroimidazole compounds, which could be proposed for human use, have to be carried out on a-primate model infected by T.b. gambiense. To our knowledge, this primate model is not available. This is why we have recently developed a T. b. gambiense primate model of HAT on Cercopithecus aethiops.

Animals↗

[Comparison of the results of the Etest and the method for determining minimum inhibitory concentrations in solid media for penicillin G, amoxicillin, and cefotaxime for S. pneumoniae. A multicenter study].

In 1996-1997 a multicentre study was carried out on 450 Streptococcus pneumoniae strains to compare the MICs and susceptibility categories obtained with the Etest (AB Biodisk) used under routine conditions in 22 hospital laboratories in the Rhône-Alpes region, France, with those obtained by the reference technique of agar dilution performed in a single coordinating centre. Each laboratory detected penicillin resistant pneumococci (PRP) by the oxacillin disk method (1 microgram and 5 micrograms) and determined the MICs of penicillin G (PG), amoxycillin (AMX) and cefotaxime (CTX) by the Etest. All the PRP strains were collected in the coordinating centre where MICs were carried out. The strains were classified as susceptible (S), intermediate (I) and resistant (R) according to the CASFM criteria (Comité de l'Antibiogramme de la Société Française de Microbiologie). The concordance results based on susceptibility categories are as follows: PG = 67.6%, AMX = 63.6%, CTX = 71.5%. Minor errors are as follows: PG = 31.2%, AMX = 36%, CTX = 28.5%. Major and very major errors are rare (0% to 0.6%). Agreement within 1 log2 dilution was obtained for about 80% of the strains. The minor errors results from strains clustering near the breakpoints 1 mg/l (PG) and 0.5 mg/l (AMX, CTX), and from practical difficulties in routine use of the Etest. These discrepancies may result in severe therapeutic problems. This study confirms the limits of the Etest. The authors insist on standardization and rigorous use of the Etest under routine conditions.

Amoxicillin↗

Simple high-performance liquid chromatographic method to analyse megazol in human and rat plasma.

A simple and sensitive high-performance liquid chromatographic method has been developed to measure megazol in human plasma. The method was optimized and validated according to the Washington Concensus Conference on the Validation of Analytical Methods (V.P. Shah et al., Eur. J. Drug Metab. Pharmacokinet., 15 (1991) 249). The criteria of complete validation were specificity, linearity, precision, analytical recovery, dilution and stability. It involved extraction of the plasma with dichloromethane, followed by reversed-phase high-performance liquid chromatography using a Kromasil C8 column and UV detection at 360 nm. The retention times of the internal standard (tinidazol) and megazol were 6.10 and 9.60 min, respectively. The standard curve was linear from 2 ng ml-1 (limit of quantification) to 2000 ng ml-1. The coefficients of variation for all the criteria of validation were less than 6%; 85 to 92% extraction efficiencies were obtained. Megazol was stable during the storage period (one month at -20 degrees C) in plasma and for two months at 25 degrees C in standard solution. The method was tested by measuring the plasma concentration following oral administration to rat and was shown to be suitable for pharmacokinetic studies.

Animals↗

Effect of melarsoprol treatment on circulating IL-10 and TNF-alpha levels in human African trypanosomiasis.

The pathogenesis of human African trypanosomiasis (HAT) has been the object of considerable research interest but has remained incompletely understood. The importance of cytokines in the pathophysiology of this protozoan infection is now widely recognized, but the full spectrum of cytokines involved has yet to be determined. In the present investigation we compared the plasma concentrations of TNF-alpha and IL-10 in normal African controls and patients suffering from advanced meningocephalic (late-stage) Trypanosomiasis brucei (T.b.) gambiense infections, before and after treatment with the arsenical trypanocide melarsoprol. We found that patients with late-stage T. b. gambiense exhibit chronically elevated circulating levels of both of these cytokines, and that these levels quickly decline following melarsoprol treatment. These findings confirm that TNF-alpha is involved in the immunopathogenesis of late-stage African trypanosomiasis and suggest that IL-10 may also play an important regulatory role in this disease.

Adolescent↗

Trypanosoma brucei brucei: a long-term model of human African trypanosomiasis in mice, meningo-encephalitis, astrocytosis, and neurological disorders.

The search for a chronic experimental model for human African trypanosomiasis (HAT) in animals with cerebral lesions and neurological disorders has been difficult. Models with meningo-encephalitis have been proposed using Trypanosoma brucei gambiense or T. b. rhodesiense. Meningo-encephalitis is rare in infection with T. b. brucei. It has been shown that the treatment of mice infected with T. b. brucei with diminazene aceturate (Berenyl) led to development of a rapid meningo-encephalitis. In this study, we report the development of a chronic experimental model of HAT in mice infected with T. b. brucei AnTat 1.1E. To obtain a chronic evolution of the infection, on Day 21 postinfection, mice were treated with a dose of suramin (Moranyl) at 20 mg x kg(-1) body weight, a dose which failed to eliminate trypanosomes in the central nervous system (CNS). This treatment, repeated after each parasitemic relapse in the blood, allowed animals to survive more than 300 days postinfection. After a few weeks of infection, mice displayed neurological signs. Histological studies showed the appearance of increasing inflammatory lesions, from meningitis to meningo-encephalitis, with progression of lesions throughout the perivascular spaces in cerebral and cerebellum parenchyma. No demyelination or neuronal alteration were observed except in the necrotic spaces. Trypanosomes were observed in different structures in CNS. An immunohistochemical study of glial fibrillary acidic protein (GFAP) showed an increasing astrocytosis according to the duration of the infection. This model reproduces neurological and histological pathology observed in the human disease and can be useful for further immunopathological, neurohistological and therapeutic studies on this condition.

Animals↗

Parenchymal neurocysticercosis: follow-up and staging by MRI.

We describe the evolution of parenchymal cerebral cysticerci on MRI, to assess signs of early cyst degeneration. We studied 15 lesions in four treated and one untreated patient. MRI was performed before therapy and repeated in the 1st month after each course of anticysticercus drugs, every 4 months during the 1st year and then annually; the follow-up period was 8-48 months. Lesions were classified according to changes in four features: cyst content and capsule signal, gadolinium enhancement and oedema signal. We were able to recognise each of the pathological phases; five MRI stages were identified. Stage 1 showed oedema and/or nodular gadolinium enhancement in the tissue invasion phase; stage 2 was cerebrospinal fluid-like signal within a cyst in the vesicular phase; stage 3 showed a thick capsule with an impure liquid content signal and surrounding oedema, in the cystic phase; stage 4 showed the disappearance of the cyst fluid content signal in the degenerative phase; stage 5 showed a calcified lesion in the residual phase. Stage 1 lesions disappeared after therapy; the other progressed from one stage to another. Stage 4 indicated the end of viability of the parasite and determined the point after which treatment was useless. On T2-weighted images changes in the cyst content differed according to the history of the lesion; nodular low intensity followed the natural degeneration of the parasite and a mixed fluid signal with punctate low signal seemed to represent the specific result of therapy. MRI staging can help in the evaluation of indications for treatment and facilitate clinical therapeutic trials.

Adolescent↗

Role of potassium channels and nitric oxide in the effects of iloprost and prostaglandin E1 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 iloprost, a stable analogue of prostacyclin, and prostaglandin E1 (PGE1) on the hypoxic pulmonary pressure response, and to investigate the possible involvement of KATP and KCa channels and of EDRF (NO) in the effects. In addition, iloprost and PGE1 effects were compared to those of adenosine and forskolin. 2. Isolated lungs from male Wistar rats (260-320 g) were ventilated with 21% O2 + 5% CO2 + 74% N2 (normoxia) or 5% CO2 + 95% N2 (hypoxia) and perfused with a salt solution supplemented with ficoll. Glibenclamide (1 microM), charybdotoxin (0.1 microM), NG-nitro-L-arginine methyl ester (L-NAME, 100 microM) were used to block KATP, KCa channels and NO synthesis, respectively. 3. Iloprost, PGE1, adenosine and forskolin caused relaxation during the hypoxic pressure response. The order of potency was: iloprost > PGE1 = forskolin > adenosine. EC50 values were 1.91 +/- 0.52 10(-9) M, 3.31 +/- 0.58 10(-7) M, 3.24 +/- 0.78 10(-7) M and 7.70 +/- 1.68 10(-5) M, respectively. Glibenclamide, charybdotoxin and L-NAME inhibited partially the relaxant effects of iloprost and forskolin but not those of PGE1. 4. It is concluded that in the rat isolated lung preparation, iloprost and forskolin but not PGE1 dilate pulmonary vessels partly through KATP channels, KCa and nitric oxide release. Furthermore our results suggest that the role of cycli AMP in these effects is not unequivocal.

Adenosine↗

Ergonomic risk exposure and upper-extremity cumulative trauma disorders in a maquiladora medical devices manufacturing plant.

Workers at a Nogales, Mexico, maquiladora plant that assembles medical devices were studied to determine the prevalence of upper-extremity cumulative trauma disorders (CTD). Subjects included production workers employed 6 months or longer; of the 148 eligible workers, 145 (98%) participated. Subjects had a mean age of 24.6 years (SD = 5.2; range, 17 to 45) and the mean length of employment was 3.5 years (SD = 2.5; range, 0.5 to 14). Job tasks were videotaped and analyzed for ergonomic risk factors, using pre-defined criteria. All jobs performed by study subjects were found to involve one or more ergonomic risk factors associated with the development of CTD. A CTD questionnaire and screening physical examination format, similar to that used by the National Institute of Occupational Safety and Health (NIOSH) in a chicken processing plant study, were administered. Period prevalence of CTD within the previous year, as reported on the questionnaire, was 28%. Prevalence of CTD was 17%, using data from the screening physical examination. Point prevalence (current pain data from the questionnaire plus positive symptoms on the screening physical examination) was 15%. CTD was reported more frequently in women than men (46% and 25%, respectively; P < 0.05) and in subjects who had worked at the plant less than one year (50%; P < 0.05). Workforce turnover (3% monthly) may have resulted in those affected by CTD leaving employment, reducing the apparent CTD rate in experienced workers.

Adolescent↗

Improved management of invasive pulmonary aspergillosis in neutropenic patients using early thoracic computed tomographic scan and surgery.

PURPOSE: The prognosis of invasive pulmonary aspergillosis (IPA) occurring in neutropenic patients remains poor. We studied whether new strategies for early diagnosis could improve outcome in these patients. PATIENTS AND METHODS: Twenty-three histologically proven and 14 highly probable IPAs in 37 hematologic patients (neutropenic in 36) were analyzed retrospectively. RESULTS: The most frequent clinical signs associated with IPA were cough (92%), chest pain (76%), and hemoptysis (54%). Bronchoalveolar lavage (BAL) was positive in 22 of 32 cases. Aspergillus antigen test was positive in 83% of cases when tested on BAL fluid. Since October 1991, early thoracic computed tomographic (CT) scans were systematically performed in febrile neutropenic patients with pulmonary x-ray infiltrates. This approach allowed us to recognize suggestive CT halo signs in 92% of patients, compared with 13% before this date, and the mean time to IPA diagnosis was reduced dramatically from 7 to 1.9 days. Among 36 assessable patients, 10 failed to respond (amphotericin B [AmB] plus fluorocytosyne, n = 2; itraconazole + AmB, n = 8) and died of aspergillosis. Twenty-six patients were cured or improved by antifungal treatment (itraconazole with or without AmB, n = 22; voriconazole, n = 4). In 15 of 16 cases, surgical resection was combined successfully with medical treatment. Achievement of hematologic response, early diagnosis, unilateral pulmonary involvement, and highest level of fibrinogen value < 9 g/L were associated with better outcome. CONCLUSION: In febrile neutropenic patients, systematic CT scan allows earlier diagnosis of IPA. Early antifungal treatment, combined with surgical resection if necessary, improves IPA prognosis dramatically in these patients.

Antigens, Fungal↗

Detection and characterization of autoantibodies directed against neurofilament proteins in human African trypanosomiasis.

In serum and in cerebrospinal fluid (CSF) from patients with human African trypanosomiasis (HAT) with central nervous system involvement, we detected autoantibodies directed to some proteins from these tissues. The characterization of antigenic proteins by Western blotting showed that the antibodies recognized the 200-kD and 160-kD proteins of neurofilament (NF). Serum anti-NF antibodies were more frequent in HAT patients than in control subjects (86% versus 24%; P < 10[-9]) and they belonged predominantly to the IgM class (anti-NF IgM = 86% versus anti-NF IgG = 4%; P < 10[-9]) in the patients with stage II (central nervous system involvement) HAT. The CSF antibodies to NF were IgM in 88% (22 of 25) of the cases and IgG in 32% (8 of 25) of the cases. Epitopes shared by NF and trypanosomes were detected by indirect immunofluorescence and this was confirmed by the disappearance of anti-NF reactivity after adsorption with trypanosome antigens (Trypanosoma brucei brucei or T. b. gambiense). Anti-NF antibodies were undetectable in the CSF from stage I HAT patients.

Animals↗

Expression of Bcl-2 and Bax in cultured normal human keratinocytes and melanocytes: relationship to differentiation and melanogenesis.

Keratinocyte differentiation and melanogenesis are two major cellular processes by which the epidermal compartment of the skin acquires its protective properties. Bcl-2; an oncoprotein involved in the regulation of apoptosis, has been shown to be expressed by keratinocytes and melanocytes. To determine whether Bcl-2 and Bax, a protein which heterodimerizes with Bcl-2, may control these epidermal functions, we investigated the expression of these two oncogenes in cultivated human keratinocytes and melanocytes from the same donors, respectively induced to differentiate and to produce melanin. As determined by cytometry, we observed that these two cell types constitutively express the two proto-oncogenes. Quantification of Bcl-2 antigen sites per cell showed that Bcl-2 expression is higher in keratinocytes than in melanocytes. An increase in transglutaminase activity, a marker of keratinocyte terminal differentiation initiating cornified envelope formation, was accompanied by a decrease in Bcl-2 levels without significant modification of Bax expression. In melanocyte cultures, stimulation of the dopa-oxidase pool, a key enzyme in melanin synthesis, paralleled Bcl-2 down-regulation and Bax up-regulation. This led us to conclude that the expression of these two oncogenes and their cellular ratio are closely involved in keratinocyte differentiation and melanogenesis.

Cell Culture Techniques↗

[Contribution of biochemical tests in the diagnosis of the nervous phase of human African trypanosomiasis].

The stage of human African trypanosomiasis (HAT) is important to define precisely as far as it is directly related to the type of treatment used. The beginning of the neurological involvement is difficult to find out because there is no known specific clinical or biological sign. This study is trying to look for a precise marker and has been realized in Congo. 70 subjects with parasitologically confirmed HAT and 70 controls are included. The stage of HAT is determined according to the classical definition on the field using the cerebrospinal fluid (CSF) cell count: less than 5 cells/microliters for the first stage (P1), more than 5 cells/microliters for the second stage (P2). The blood analysis has included: glucose, urea, creatinine, sodium, potassium, calcium, chloride, phosphorus, uric acid, total bilirubin, unconjugated bilirubin, total cholesterol, triglycerides, total proteins, aspartate aminotransferase, alanine aminotransferase, creatinine phosphokinase, alkaline phosphatase, gamma-glutamyltransferase, immunoglobulins M and G, C3c fraction of complement, transferrin, seromucoid alpha 1, haptoglobin and albumin. In CSF we have analyzed IgM, IgG, protein levels and the bloodbrain barrier (BBB) impairment. The comparison between the subjects and their controls, the subjects in P1 and in P2, the CSF cell count and the other CSF alterations show the interest of the IgM level in CSF and the BBB impairment to identify subjects in P2. However there is a low gradation in the biological disturbances and not a precise threshold point. Nevertheless it seems reasonable to raise the CSF cell count level to 20 cells/microliters to define the beginning of the nervous involvement.

Blood Chemical Analysis↗

[Current status of trypanosomiasis].

Sleeping sickness is presently undergoing a recrudescence mainly as a result of major socioeconomic problems in Africa. Despite the reigning pessimism due to the currently unfavorable context (increasing incidence, lack of rapid diagnostic criteria, and unavailability of active non-toxic therapeutic agents), research data hold the promise of more effective control of this disease in the future. Mapping of infected households is now necessary to allow better early identification and follow-up of patients. Great advances have been made in the study of the pathogenesis of nervous involvement and it has been demonstrated that the characteristic symptoms of sleeping sickness are due to penetration of trypanosomes into the central nervous system (CNS) through the blood-brain barrier. However an unsolved problem is determining whether the blood-brain barrier has been broken and CNS involvement has occurred. This determination is important because neurologic involvement is a prerequisite for deciding when to undertake treatment using highly toxic melarsoprol. Research to identify new criteria for staging blood/lymph and nervous involvement is under way and encouraging results have been obtained using auto-antibodies against nervous system components. Although there is now greater hope that a vaccine will be developed in the future, treatment has not advanced greatly in the last 50 years. Pentamidine can be effective in some patients with "early-stage" nervous involvement. Melarsoprol is fatal in about 5% of patients treated. New drugs (e.g. nitroimidazoles) may become available one day but development is slow because most research is being done in a few university laboratories.

Africa↗

[Epilepsy and its impact in northwest region of the Central African Republic].

In African countries, epilepsy is an important public health problem with major medical, socio-cultural, and economic implications. This study was carried out to evaluate attitudes towards epilepsy in the Central African Republic. A total of 187 epileptic patients were included. Only 20.9% of the study population were married. School attendance never exceeded the elementary level. Epilepsy was active in 98.4% of patients who continued to present attacks despite extensive treatment which was either poorly complied with or inadequate. Attitudes towards epilepsy remain rooted in belief in supernatural phenomenon and evil spirits with use of traditional therapies involving abstinence from certain foods and use of laxative agents to drive out evil forces. Epileptics are excluded from their families and not allowed to attend school but, in our study, they were not prevented from the work place since 70% held jobs. In this study, 54% of epileptics believed that the disease was contagious, 55.6% that it was incurable, and 20.9% that it was due occult or supernatural causes. While precise quantification is impossible, our experience based on interviews with patients and frequent observation of burn wounds suggests that moral and physical suffering is immense among epileptics in the Central African Republic. Epilepsy in Black Africa is a major public health problem requiring serious attention from government officials, health care specialists, and the families of patients. Better information to promote awareness of the non-contagious nature of the disease, greater support for families of patients, and improvement in treatment compliance are essential.

Adolescent↗