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Biomedical subjects

L Fall

Publications and source records attributed to L Fall.

At least 19 recordsLinked to original sources
PubMed2006

[Low level educated community health workers training: a strategy to improve children access to acute respiratory treatment in Senegal].

BACKGROUND: Acute respiratory infections (ARI) are the leading cause of death in childhood. Most of children's deaths happen at home without health level first cares. However in Senegal only health workers are allowed to prescribe antibiotics. A competency-based training was developed to improve and assess the management of acute respiratory infections in young children aged 2 to 59 months by low level educated community health workers (CHWs) in 4 districts of Senegal. The first findings showed the CHWs capable of acquiring the skills needed to effectively manage ARI cases in accordance with the World Health Organization's ARI case management strategy. The aim of this study was to assess the quality of their management after a 1 year follow-up. METHODS: We provided to CHWs 3 days course in ARI management. After the 3-day course, a 4-month follow-up was performed. We organized a 1-day refresher course every month and in every district. In order to assess the quality of management of CHWs we analyzed the management process and compared the CHWs classification to the classification of the first level health facilities. RESULTS: Twenty-three percent (3727/15,965) of IRA cases of district were managed by CHWs. Ninety percent (2738/3042) among them were well classified, well managed and well followed-up. But 28% of severe pneumonia cases were misclassified as pneumonia. About treatment, 22.5% of 'cough or cold' got wrong treatment with cotrimoxazole and 10.3% of severe pneumonia got cotrimoxazole without referral. Less than half of severe pneumonia benefited of the first follow-up and only 18% of the second. CONCLUSIONS: The results highlight that a CHWs low-level educated in French, trained and followed-up could apply the WHO algorithm of IRA management. They could help to give proximal care related to children ARI, to the community. But it seems useful of emphasizing the recognition of danger signs and the follow-up of severe cases.

Acute Disease↗
PubMed2003

[Development of African children: influence of the home environment].

The purpose of this report was to show how special features of the African home environment affect child development. Special emphasis was placed on the traditional social structure and the roles of various players. The different stages of development are described in relation to the major social events in African families and communities. Psychomotor development in African children presents several particularities in relation to children in the industrialized world but differences tend to decrease as a result of ongoing social upheaval. Modernization or globalization has had a profound effect on family organization and child care. These changes must be taken into account by officials in charge of child-psychiatry services. Preventive initiatives should taken into account and, insofar as possible, preserve traditional familial resources.

Africa↗
PubMed2001

[Acute encephalic manifestations in Senegalese children with sickle cell disease].

The course of sickle cell disease (SCD) may be complicated by neurologic events, mainly bactérial meningitidis and stroke. We retrospectively studied all cases with acute encephalic manifestations (AEM) in a cohort of 461 children and adolescents with SCD followed at Albert Royer Children Hospital of Dakar (Senegal) from january 1991 to december 2000 (ten years). Among them 438 had sickle cell anemia (SCA), 19 SC disease and 4 S-beta thalassemia (3 S-beta+, 1 S-beta0). Seven patients, all with SCA, presented antecedents of AEM revealed by flacid and proportionnal hemiplegia evoking stroke. Prevalence of these AEM was 1.5 per cent among patients with SCD and 1.6 per cent among those with SCA. They were 4 girls and 3 boys (sex ratio = 0.75) aged 4 to 8.5 years when occurred the first accident. We observed no clinical or biological distinctive characteristic of SCA in these patients compared to those without crebrovascular accident. Recurrence was observed once in a boy after a 12 months interval and twice in a girl after 20 and 60 months intervals successively. No transfusionnal program was applied to prevent recurrent stroke because of insufficient conditions for long-term transfusion. Stroke appears to be rare in senegalese children with SCD. However it poses in our context the major problem of applicability of transfusionnal program which constitute the only therapy universally recognised to be effective to prevent recurrence. Nevertheless hydroxyurea could be a satisfactory alternative.

Anemia, Sickle Cell↗
PubMed2000

[Infections in Senegalese children and adolescents with sickle cell anemia: epidemiological aspects].

Infection is the main factor of morbidity and mortality in children with sickle cell disease (SCD). The objective of this study is to determine it's epidemiologic outline in senegalese children and adolescents with SCD. We retrospectively studied infection data in all the charts of a cohort of 323 patients with SCD (307 SS, 13 SC and 3 s beta + thalassemia) followed at Albert Royer children hospital from january 1991 to december 1997. Serum sampling was systematically made for HIV and antigen HBs serology in all patients we received in the last 3 months (october to december 1997). Patients were aged from 5 months to 22 years (medium age = 8 years). 813 infection episodes were diagnosed, concerning 184 patients (56 per cent). SS patients were more affected (59 per cent) than the others (23 per cent, p = 0.04). ENT and broncho-pulmonary onsets were more frequent but had a generally benign course. Menigitidis, septicemia and osteomyelitis were exclusively diagnosed in SS patients. Their prevalences in this group were respectively: 1.0 per cent, 4.9 per cent and 9.8 per cent. HIV serology was determined in 155 patients, including 41 per cent with blood transfusion antecedents. All tests were negative. HBs antigen was determined in 104 patients and seroprevalence was 7.7 per cent in the whole group and 6.0 per cent in patients with transfusion antecedents and 7.7 per cent for the others. Plasmodium falciparum malaria onset was observed in 9.6 per cent of our patients and there was no case of cerebral malaria. Infection was involved in 9 of the 11 cases of death. Then infection constitute the major problem in children and adolescents with SCD in Dakar. However prevalences of severe onsets are comparable to data in Europe despite our poor follow up conditions. Senegal haplotype may lead to a good tolerance of SCD. Negative HIV serology and low HBs antigen seroprevalence in transfused patients are attributed to a relatively low level of HIV prevalence in the general population and a good transfusion security in Senegal.

Adolescent↗
PubMed1998

[Hyperthyroidism in people over 50 years of age in Senegal. Study of 31 cases observed over a 14-year period].

PURPOSE: Though common in elderly, with poor and masked symptomatology, hyperthyroidism has never been studied in people older than 50 years of age in African countries. METHODS: Of the 300 cases of hyperthyroidism that were observed during this study, 31 belonged to this category. We analyzed the frequency of various parameters, demographic characteristics, motivation for consulting, thyrotoxic syndrome, non thyrotoxic signs, cardiac manifestations, hormonal and scintigraphic characteristics, etiology and etiologic factors, and treatment. RESULTS: The frequency of hyperthyroidism in this population was 10%. Housewives were more numerous, with 20 cases observed in the 31 patients. The main group (13/31) was of rural origin. Signs that predominantly led to consultation were weight loss (23/31), cervical tumor (17/31), and palpitations (12/31). Three major signs were associated with the thyrotoxic syndrome: weight loss (29 cases), tachycardia (27/31), and the existence of tremors in the extremities (22/31). Hormone assays showed that thyroxine (T4) was about 265 +/- 74 nmol/L and triiodothyronine (T3) about 6 +/- 2 nmol/L, at immunoradiometric assay; thyroid-stimulating hormone (TSH) was about 0.17 +/- 0.23 muIU/mL. Eye protrusion predominated in the nonthyrotoxic syndrome, with 25 cases in the 31 patients. Etiologic forms of the disease were composed of 25 Grave's disease, with 22 typical cases. Etiologic factors were various, however without any case of neoplasia. Cardiac complications included two cases of atrial fibrillation. No iatrogenic form of the disease was observed. Mean initial carbimazole dosage was about 34 +/- 8 mg/d. Of the 23 patients, 15 had a favourable outcome. CONCLUSIONS: In this series, the high number of housewives and the patients' rural origin were less characteristic of hyperthyroidism than the Grave's disease etiology. This might be due to the young age of this African population.

Age Factors↗
PubMed1994

Lovastatin inhibits HIV-1 expression in H9 human T lymphocytes cultured in cholesterol-poor medium.

The effects of the HMG-Coenzyme A reductase inhibitor lovastatin on HIV-1 expression and sterol synthesis have been investigated in the human H9 lymphocytic cell line. To this purpose, sterol synthesis from 14C-acetate, cell multiplication and reverse transcriptase activity have been measured in parallel at various times after cell infection by HIV-1. It was found that nine days after viral loading, lovastatin inhibited both sterol synthesis and viral multiplication as assessed by the reverse transcriptase activity. Since HIV infection has been shown to induce alterations in membrane cholesterol content, suggesting that the virus cycle may be partially dependent upon cellular cholesterol, inhibitors of cholesterol synthesis could be an interesting way of research in order to slower HIV propagation.

Cells, Cultured↗
PubMed1993

Identification of CD4 and major histocompatibility complex functional peptide sites and their homology with oligopeptides from human immunodeficiency virus type 1 glycoprotein gp120: role in AIDS pathogenesis.

CD4 molecules interact with class II major histocompatibility complex molecules as a critical costimulatory signal in CD4+ cell immune activation. CD4 also recognizes a specific region of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 forming a binding site for early stages of HIV-1 infection. We designed two software packages, AUTOMAT and CRITIC, which allowed us to identify similarities between regions of HIV-1 proteins and immunoregulatory protein sequences stored in data banks. In this report we have characterized (i) a pentapeptide, SLWDQ, found in both CD4 and HIV-1 gp120, which surprisingly had remained undetected in these two well-studied molecules until now, and (ii) an HLA sequence corresponding to the putative functional site of H2 I-A. We found that a region of gp120 (residues 254-263) known to be similar to a sequence in HLA class II beta chain overlaps this functional region. We showed experimentally that these two CD4 and HLA peptide segments inhibit CD4+ cell immune activation. There is strong inhibition (50% up to 80%) of immune activation by SLWDQ-containing gp120 segments and a lesser inhibition by the gp120 HLA-homologous segment. In addition, we found that SLWDQ induced in HIV-1-infected individuals a humoral (antibody) and cellular (cytotoxic T lymphocyte) immune reaction. We propose that these HIV-1 gp120 segments, together with the known CD4-binding region, may contribute to the HIV-1-induced immunosuppression by two mechanisms affecting CD4-HLA interaction during T-cell immune activation: autoimmune reaction toward CD4 and direct interference with the CD4-HLA costimulatory signal inducing CD4+ cell anergy with, as a consequence, generation of immunosuppression.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Striking similarities between HIV-1 Env protein and the apoptosis mediating cell surface antigen Fas. Role in the pathogenesis of AIDS.

We have designed a computer strategy in order to detect systematically peptidic sites with the potential of interfering with the immune regulatory processes. Applying this software to HIV-1 proteins has led us to unravel a few peptidic sites which could either act directly or be the targets of an auto-immune reaction during HIV-1 infection. We previously reported that the SLWDQ pentapeptide identity with a critical site of CD4 could trigger in HIV-1 infected individuals both an humoral and a cellular autoimmune reaction. In this study, we focused on surprising similitudes unravelled by our software Automat, between HIV-1/2 and another immunoregulatory molecule, the Fas protein which is also called the apoptosis-mediating cell-surface antigen.

Acquired Immunodeficiency Syndrome↗
PubMed1993

HIV-1-induced immune suppression may result from autoimmune disorders including anti-SLWDQ autoantibodies.

We have previously unravelled the striking SLWDQ pentapeptide identity between HIV-1 env gp120 and the CD4 molecule. We show here that this pentapeptide is required for the functioning of the co-stimulatory MHC-CD4 signal in T4-cell activation since it suppresses antigen-induced T-cell proliferation. Moreover, concerning the MHC class II counterpart, the LNGQEETGVVSTN sequence which strongly inhibits T-cell immune activation is likely to be part of the functional site of the molecule. Interestingly the MHC/gp120 homology described by Young overlaps this MHC region. We further report that the gp120 SLWDQ peptide triggers an immune reaction which is both humoral (anti-SLWDQ antibodies) and cellular (CTLs against autologous targets carrying the pentapeptide) in HIV-1 infected individuals. Finally, anti-SLWDQ antibodies from patients sera purified by column chromatography strongly inhibit antigen-induced immune T-cell activation. This result led us to postulate that these antibodies found in high titers in HIV-1 infected individuals could contribute to set up the progressive systemic immune T-cell suppression characterizing AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Critical sites: a semantic approach to protein sequences. Application to the HIV-1 envelope molecule.

We have designed two software systems allowing the study of proteins through a comparison to those stored in data banks. The first one, "Automat", locates in a systematic manner all identities shared by a given protein and the proteins in a data bank. The second, "Critic" enables the selection of specific segments in a given molecule by comparing them with those gathered in a data bank. These sites were termed "critical" since they mostly correspond to functional sites (active sites) of the well-known proteins which were studied with the aid of this program (somatostatin, insulin, IL2, etc). Automat allowed us to reveal homologies between HIV-1 and the CD4, which have remained unsolved until now. These similitudes proved to be critical sites (according to Critic). The putative involvement of these sites in the physiopathological processes as induced by HIV-1 are worth considering since the results of our experiments are consistent with this assumption.

Amino Acid Sequence↗
PubMed1992

Removal of gp160 induced bio-hazards for a safe AIDS vaccine candidate.

In the first AIDS vaccine trial, immunizing preparations were based on HIV-1 Env protein (gp160). Immunogenic properties of gp160 which trigger both a humoral and cellular immune response have since justified its use in various vaccine programs, both past and present. Many reports however have underlined deleterious effects on the immune system--anti-HIV-1 enhanced antibodies, anti-CD4 autoantibodies, and inhibition of T cell activation by HIV-1--particularly associated with the Env protein. The present study shows that gp160 presented in a biologically inactivated but immunogenic form, as used in our trial, could avoid these complications. Bio-hazards associated with gp160 which indeed could be removed by appropriate treatment of the native protein, should be taken into consideration in AIDS vaccine programs.

AIDS Vaccines↗
PubMed1988

Linkage of organic phosphates to oxygen binding in human hemoglobin at high concentrations.

We have performed high-precision oxygen binding studies on human hemoglobin tetramers in the presence of a series of limited, subsaturating amounts of the effector compounds 2,3-diphosphoglycerate (DPG) and inositol hexaphosphate (IHP). The use of thin-layer optical methods enabled the use of high hemoglobin concentrations, preventing complications arising from the dissociation of the tetramer into dimers. Model-independent, simultaneous analysis of all data for each effector demonstrated that the intrinsic oxygen binding characteristics of the molecule are in agreement with those determined in earlier high-precision studies [e.g., Gill, S. J., Di Cera, E., Doyle, M. L., Bishop, G. A., & Robert, C. H. (1987) Biochemistry 26, 3995-4002] and that the affinity of the tetramer for the tightly binding effector IHP changes most markedly between the second and fourth oxygen binding steps, perhaps indicating a large conformational change. The data were then analyzed by using the truncated allosteric model [Di Cera, E., Robert, C. H., & Gill, S. J. (1987) Biochemistry 26, 4003-4008], which is based on the hypothesis that a quaternary conformational change occurs in the hemoglobin tetramer before the third and fourth oxygen molecules bind.

2,3-Diphosphoglycerate↗
PubMed1984

A twin titration microcalorimeter for the study of biochemical reactions.

A small-volume (200 microliter) titration calorimeter of high sensitivity (1 mu cal ) has been developed for the purpose of studying biochemical reactions where the amounts of material are limited to a few nanomoles. High sensitivity is achieved by calorimetric twining , use of glass cells, elimination of vapor space, effective low-energy stirring, and reduction of measurement time. The calorimeter operates using the heat conduction principal with computer-controlled electrical compensation, which reduces the measurement time of each point from 10 to 3 min. This reduction in time is accompanied by a corresponding increase in the precision of measurement. The use of the calorimeter is demonstrated by a measurement of the heat of oxygenation of hemocyanin.

Biochemistry↗
PubMed1981

The effect of non-binding molecules on the gelation of HbS.

The influence of an inert globular macromolecule upon the solubility of sickle cell hemoglobin has been determined as a function of the degree of oxygenation. The thermodynamic theory required to treat this and related problems is derived starting with the Gibbs-Duhem equation and introducing the effect of specific binding (oxygen) by use of the binding partition function. The treatment includes non-ideal solution behaviour as measured by osmotic pressure of highly concentrated macromolecular solutions. Application of the theoretical equation demonstrates how the solubility of hemoglobin is influenced by the presence of the binding ligand (oxygen) and the inert macromolecule, bovine serum albumin (BSA). Good agreement is obtained between experimentally determined and theoretically calculated solubilities using 1) oxygen binding curves to solution and gel phases, 2) activity coefficients from osmotic pressure data, 3) one solubility under the condition where oxygen and BSA are absent, and 4) the value of the water content of the gel phase. Examination of theoretical equations suggests that inert molecules of intermediate size, that are partially excluded from crystalline or gel phases, have the potential of generally increasing the solubility when non-ideal solution effects are small.

Gels↗