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Biomedical subjects

M Le Bras

Publications and source records attributed to M Le Bras.

At least 19 recordsLinked to original sources
PubMed2006

GAPDH, a novel regulator of the pro-apoptotic mitochondrial membrane permeabilization.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a pleiotropic enzyme that is overexpressed in apoptosis and in several human chronic pathologies. Here, we report that the protein accumulates in mitochondria during apoptosis, and induces the pro-apoptotic mitochondrial membrane permeabilization, a decisive event of the intrinsic pathway of apoptosis. GAPDH was localized by immunogold labeling and identified by matrix-assisted laser desorption/ionization-time of flight and nano liquid chromatography mass spectroscopy/mass spectroscopy in the mitochondrion of various tissues and origins. In isolated mitochondria, GAPDH can be imported and interact with the voltage-dependent anion channel (VDAC1), but not the adenine nucleotide translocase (ANT). The protein mediates a cyclosporin A-inhibitable permeability transition, characterized by a loss of the inner transmembrane potential, matrix swelling, permeabilization of the inner mitochondrial membrane and the release of two pro-apoptotic proteins, cytochrome c and apoptosis-inducing factor (AIF). This novel function of GAPDH might have implications for the understanding of mitochondrial biology, oncogenesis and apoptosis.

Amino Acid Sequence↗
PubMed2005

Reactive oxygen species and the mitochondrial signaling pathway of cell death.

Reactive oxygen species (ROS) are produced as a by-product of cellular metabolic pathways and function as a critical second messenger in a variety of intracellular signaling pathways. Thus, a defect or deficiency in the anti-oxidant defense system on the one hand and/or the excessive intracellular generation of ROS on the other renders a cell oxidatively stressed. As a consequence, direct or indirect involvement of ROS in numerous diseases has been documented. In most of these cases, the deleterious effect of ROS is a function of activation of intracellular cell-death circuitry. To that end, involvement of ROS at different phases of the apoptotic pathway, such as induction of mitochondrial permeability transition and release of mitochondrial death amplification factors, activation of intracellular caspases and DNA damage, has been clearly established. For instance, the ROS-induced alteration of constitutive mitochondrial proteins, such as the voltage-dependent anion channel (VDAC) and/or the adenine nucleotide translocase (ANT) can induce the pro-apoptotic mitochondrial membrane permabilization. Not only do these observations provide insight into the intricate mechanisms underlying a variety of disease states, but they also present novel opportunities for the design and development of more effective therapeutic strategies.

Aging↗
PubMed2004

[Malaria at the time of "Roll Back Malaria"].

Only within the last 4 years has worldwide political awareness of the impact of malaria made it possible to envision significant initiatives in malaria control and research within the framework of an ambitions and sustained program called the "Role Back Malaria (RBM) Partnership" coordinated by the WHO. The purpose of this article is to describe the current main objectives of the RBM partnership. This program implies a transfer of responsibilities and research technologies, which will require adaptation. Up to now French expertise has played little part.

Biomedical Research↗
PubMed2004

[The tropical pathogenic complex: a new look at an old concept].

The failure of programs implemented to improve public health in the world, the poor performance of health care systems, and the difficulty in anticipating and reacting to emerging disease suggest that a more global approach to individual and community health problems is needed. Risk and disease must be correlated in space and time based on precise identification of their respective determinants, predictive factors, preventive targets, and diagnostic and prognostic indicators. For this purpose it could be useful to revive the pathogenic complex concept defined by the geographer Maximillien Sorre in 1933 in the light of new tools allowing better identification of biologic determinants (molecular genetics), of environmental factors (geographic information systems), and of behavior related to health care service activities. This concept could be used to place disease threats in a global context and to assess the consequences of current upheavals such as globalization of populations and products, exploding demographics, rapid urbanization, deforestations, rapid changes in behavior, and health care systems that can lead to both good and bad effects.

Communicable Diseases↗
PubMed2003

[Amoebic liver abscess. Study of 20 cases with literature review].

PURPOSE: The management of amoebic liver abscess includes antiamoebic drugs combined or not with percutaneous puncture or surgical drainage. This study was to suggest a decision tree for the therapeutic approach of such feature. METHODS: We report a retrospective analysis of 20 imported cases with amoebic liver abscesses admitted at the Department of Tropical Diseases during 1995-1999 at the Bordeaux University Hospital Centre, France, and a review of the literature. RESULTS: The twenty patients were 14 males and 6 females, mainly 20 to 40 years old. The clinical presentation was mainly accounting a painful liver enlargement with hyperthermia. The echographic picture was mostly represented by a unique liver element located at the liver right lobe. They were numerous in an HIV infected patient. Thirteen patients have been treated using a medical therapeutic approach. A percutaneous puncture has been necessary for 4 cases. A percutaneous drainage has been realised for two patients as regard to the persistence of the hepatalgia occurrence. A surgical drainage has been experienced by two patients after a lack of efficacy of a percutaneous drainage, after rupture of an abscess treated medically, respectively. A review of the literature and the analysis of the 20 cases history have been used to determine a therapeutic algorithm. CONCLUSION: The occurrence of immediate complications at onset must indicate a first line surgical drainage procedure. Beside this situation, risk factors for rupture must be assessed (high size abscess, pejorative localization), as well as poor prognosis feature (liver failure, bacteraemia). If no pejorative condition occurs, a first-line exclusive medical approach can be undertaken with a clinical efficacy evaluation at H72. Otherwise, the indication of the percutaneous drainage must be discussed.

Adult↗
PubMed2003

[Why a graduate diploma specializing in the management of health projects in Cote d'Ivoire?].

The achievement of the "health for all" objectives represents a particular challenge for developing countries where the morbidity rates and the number of deaths are increasing on an annual basis. In order the face this situation in Côte d'Ivoire, health action programmes were initiated on the one hand, and on the other, a type of decentralised responsibility was established for the coverage of the population's health at the health district level where these programmes are administered. However, serious insufficiencies were noted in the management of health projects as well as a lack of follow-up and evaluation by trained staff. Furthermore, it is imperative to have personnel qualified in managing health projects. In fact, this specialised training will allow for the attainment of knowledge and competencies necessary for the effective conception, development, planning, implementation and management of health action programmes at the national level as much as the district level. In addition, these health project specialists will be able to get involved at several levels in positions such as managers of national projects, technical advisors for national health directives, district managers, etc. Such training would contribute to the improvement of the population's health status and thus address the challenge of health for all.

Cote d'Ivoire↗
PubMed2002

[Experience with the combination atovaquone-proguanil in the treatment of uncomplicated Plasmodium falciparum malaria--report of 112 cases].

The purpose of this open non-comparative retrospective study was to evaluate the efficacy and tolerance of Malarone for management of uncomplicated imported Plasmodium falciparum malaria. A total of 112 non-immune adult patients were included between 1999 and 2001. Excellent responses in terms of both clinical symptoms and parasite control were achieved within 4 days after the beginning of treatment in all cases. No recurrence was observed after 28 days of individual followup. Tolerance was satisfactory with no adverse events except for occasional, minor gastrointestinal upset. Based on our experience, Malarone appears to be effective, well-tolerated, and suitable for routine management of uncomplicated imported Plasmodium falciparum malaria.

Adolescent↗
PubMed2001

[Cutaneous pyoderma gangrenosum with hepatosplenic localization and monoclonal gammapathy. A case report].

Pyoderma gangrenosum is an ulcerative disease of the skin. The histopathological lesions are nonspecific, characterized by a diffuse neutrophilic infiltrate in the dermis. Pyoderma gangrenosum is associated with inflammatory, digestive or articular disease, or acute or chronic hemotology disorders in 50% of the cases, more rarely with monoclonal gammapathy. A visceral localization of pyoderma gangrenosum is rare, simulating a systemic disease or an underlying neoplasia. We report a case of cutaneous pyoderma gangrenosum with splenic and hepatic localizatios associated with an IgG monoclonal gammapathy. We emphasize the efficacy of immunosuppressor treatment and the importance of long-term monitoring of these patients.

Drug Monitoring↗
PubMed2001

Clinical and laboratory findings of cytomegalovirus infection in 115 hospitalized non-immunocompromised adults.

We report a retrospective study of 115 hospitalized non-immunocompromised adults with proved or presumed diagnosis of cytomegalovirus infection. Clinical symptoms were fever (95%), constitutive symptoms (80%), joint and muscle pain (41%), shivering (32%), abdominal pain (26%), non-productive cough (20%), cutaneous eruption (20%), and diarrhea (10%). Examination found hepatomegaly (25%), splenomegaly (23%), cutaneous rash (20%), adenopathy (19%), pharyngitis (9%), jaundice (3%) or signs of meningeal irritation (1%). Seventeen patients had a gastrointestinal form (hepatitis, jaundice, colitis, antral gastritis or cholecystitis), eight had a pattern of hemopathy, two interstitial pneumonitis, two pericarditis, two immune thrombocytopenic purpura, two a polymyalgia rheumatica-like pattern, one thrombotic thrombocytopenic purpura, one cutaneous vasculitis and one meningoencephalitis. Sixty-four percent of the patients had atypical lymphocytosis. Hepatocellular injury occurred in 90% of the patients. Nineteen of the patients had biological immune abnormalities. Cytomegalovirus infection should be mainly suspected in any patient with persistent fever, isolated or associated with signs of poor specificity, or in some patients with visceral manifestations of initially unknown origin.

Adolescent↗
PubMed2001

[Human African trypanosomiasis from Trypanosoma brucei gambiense with inoculation chancre in a French expatriate].

This report describes a case of West African trypanosomiasis involving a Caucasian Frenchman living in Conackry, Guinea. The patient presented with fever and two skin chancres highly suggestive of very early lymphatic stage trypanosomiasis. Examination of peripheral blood smears confirmed diagnosis of west African trypanosomiasis. Further immunologic evaluation showed elevated serum levels of specific IgM and IgG. The patient was treated by intravenous perfusion Pentacarinat at dose 5 x 4 mg/kg/day over a period of ten days. Clinical signs improved and parisitemia decreased within two days. The remarkable feature of this case was the presence of two chancres in association with the Gambian form. Since this finding allowed early diagnosis, treatment was well-tolerated and effective. This case also demonstrates the important role of travellers or expatriate workers as sentinels for emerging/re-emerging infectious diseases.

Animals↗
PubMed2000

[Hematologic and immunologic manifestations of primary cytomegalovirus infections in non-immunocompromised hospitalized adults].

PURPOSE: Cytomegalovirus (CMV) infection in non-immunocompromised adults can sometimes induce hematological and immunological disorders that may mislead diagnosis. METHODS: Case reports of hospitalized non-immunocompromised adults with positive serology for CMV including the presence of immunoglobulin M or seroconversion were assessed in a retrospective study (1981-1998). We focused on clinical and biological abnormalities showing the role of CMV in disruption of functioning of hematological and immunological systems. RESULTS: Among 115 patients, lymphoma-like syndrome with large adenopathies and/or splenomegaly was diagnosed in eight patients, uncovering underlying CMV infection. Lymphoma was accompanied by hematoma in two patients. Three patients presented leg purpura (with thrombotic thrombocytopenic purpura in one case), one patient had cutaneous vasculitis and on other a Still's disease. Blood abnormalities were mononucleosis (64%), anemia (20%), and thrombopenia (25%) often of peripheral or hemolytic origin or due to hypersplenia. Electrophoresis of serum proteins showed an increase in immune globulins in 56% of the cases and monoclonal abnormality in nine cases. Immunological assessment was conducted in 18 patients. At least one abnormality was depicted in ten patients, consisting of either antinuclear, anti-platelet or anti smooth muscle antibodies, cryoglobulinemia, rheumatoid factor, or reduced complement fixation. CONCLUSION: Testing for CMV infection can be of value in case of blood or immunological disorders associated with clinical or biological signs. Although hematological disorders occur early, they are rarely severe. Immunological disorders are rarely symptomatic, but often raise issues regarding the potential genesis of immune diseases in at-risk patients.

Adolescent↗
PubMed2000

[Schnitzler syndrome: a rare cause of systemic urticaria].

INTRODUCTION: The Schnitzler's syndrome first described in 1972, associates urticaria, bone pain, and monoclonal IgM gammapathy. EXEGESIS: A 50-year-old man presented symptoms of urticaria restricted to the trunk and lower members, with episodes of fever accompanied by inflammatory pain in the knees and legs. Slight deterioration of his general condition was also observed. Biological findings showed the existence of an inflammatory syndrome. Electrophoresis and immunoelectrophoresis provided evidence for the existence of underlying IgM gammapathy. Bone X-ray demonstrated the presence of tibial and peroneal metaphysis thickening, with hyperfixation on bone scintigraphy. The patient's condition improved after cortisone and colchicine treatment, allowing decrease in coricosteroid doses. Two years later, except for urticaria, clinical features have disappeared and no hematological disorder has been observed.

Aftercare↗
PubMed2000

[Malaria in Vietnam: what is the awareness of risk for travel in 2000?].

Increasing numbers of people are travelling to Vietnam. From december 1st 1998 to april 31 1999, we surveyed by questionnaire 191 travellers who consulted at health centres attached to French diplomatic representations (Hanoi, Ho-Chi-Minh Ville) in order to evaluate their prophylaxis practices with regard to malaria; 59% of these travellers were taking no preventive measures whatsoever, while the rest were following an often ill-adapted treatment.

Awareness↗
PubMed2000

[Upper extremity deep venous thrombosis. 40 hospitalized patients].

Deep venous thrombosis is 50 times less frequent in upper than in lower limbs. Data remain poor in the literature. Forty consecutive patients (24 males, 16 females, mean age: 54.5 years) were retrospectively analysed from 161 subjects who underwent venous explorations of the upper extremity for a 3.5 year period in the same center. Diagnosis of thrombosis was made by duplex ultrasonography (n =37) or phlebography (n =3). Main clinical manifestations were edema (n =36) and pain (n =29). Location of thrombosis was humeral (n =1), axillary (n =2), or sub-clavian (n =37, 2 bilateral). The majority of thrombosis (n =29) were secondary to cancer and venous catheter (n =19, 15 implanted ports), to central catheter alone (n =3) or cancer alone (n =7). The 11 others were associated with thoracic outlet syndrome (n =6) or apparent primary thrombosis (n =5). Thrombophilia was identified in 6 out of these 11. During follow up [mean of 9 months (0,5-36)], two patients developed pulmonary embolism, 14 a post-thrombotic syndrome and 16 patients died. Initial therapy included heparin (n =36) or fibrinolysis (n =4). Upper extremity deep venous thrombosis are mostly associated with cancers and venous catheters. Thrombophilia is frequent in the other cases. Heparin followed by oral anticoagulation is the optimal therapy whose duration depends upon underlying condition. Fibrinolysis has not been useful for preventing post-thrombotic syndrome in our study.

Adult↗
PubMed1999

[Kidney transplantation and travel in the tropics].

About 1600 kidney transplants are performed each year in France. The quality of life of grafted patients has therefore improved, to the extent that such patients are now envisaging professional or other activity and stays in tropical or sub-tropical regions. However, this is not without some degree of risk or difficulty. Anti-malarial drugs may interfere with other medication, particularly ciclosporin in kidney grafted patients. Moreover, other vaccinations such as anti-amaril immunization are recommended or even required by certain countries. Yet the immunodepression induced by this in grafted patients is a contraindication for such vaccination. For the other types of immunization, the risk/benefit ratio is not always obvious.

Antimalarials↗
PubMed1999

[Hemorrhagic complications of antivitamin K. Report of 75 hospitalized patients].

Hemorrhagic complications are the most frequent complications of antivitamin K (AVK) treatments and can be life-threatening. We report 75 patients from a University Hospital. They were 40 males and 35 females (median age 74 years, 20-94), and were classified into 3 grades according to clinical picture: grade 1 (no surgery or transfusion, grade 2: surgery or blood transfusion needed, grade 3: death). 43 patients had grade 1 complications, 27 grade 2, and 5 grade 3 complications. The most frequent complications were muscular hematomas (36 patients), sub-cutaneous hematomas (14 patients), digestive bleeding (13 patients), hematuria (12 subjects). Eight patients had intracerebral bleeding, of whom 3 died. The treatment time was very variable (1 to 988 weeks). Only half patients had a prothrombin rate (PR) below 20% but two thirds had an INR above 5. This study showed that PR was a poor predictor of hemorrhagic complications. INR was a better parameter. For 15 patients, we considered that the indication was unadapted or questionable, among whom 2 died. This work suggests that the promotion of AVK prescription rules should go on.

Adult↗