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Biomedical subjects

G Lasfargues

Publications and source records attributed to G Lasfargues.

At least 37 records · Page 2Linked to original sources
PubMed1996

Characterization of human immunodeficiency virus type 1 p17 matrix protein motifs associated with mother-to-child transmission.

In order to determine if viral selection occurs during mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1), we used a direct solid-phase sequencing method to sequence the p17 matrix protein-encoding regions of viral isolates from 12 HIV-1-infected mother-and-child pairs, 4 infected infants, 4 transmitting mothers, and 22 nontransmitting mothers and compared the sequences. The blood samples were collected during the delivery period for the mothers and during the first month of life for most of the children. The p17 nucleic sequences were distributed among several clades corresponding to the HIV-1 A, B, and G subtypes. At the amino acid level, no significant differences within the known p17 functional regions were observed among the subtypes. Statistical analyses could be performed with the B subtype. Within the major p17 antibody binding site, a constant KIEEEQN motif (amino acids 103 to 109) was found in all mother-and-child isolates from the B subtype. On the other hand, 9 of 17 nontransmitting mother isolates were variable in this 103 to 109 region. Thus, this motif was significantly associated with the transmitting status (chi square, P = 0.0034). A valine residue at position 104 was significantly associated with the nontransmitting phenotype (chi square, P = 0.014), suggesting that it has a protective role during vertical transmission. The C-terminal end of p17 was globally conserved among nontransmitting mother isolates (chi square, P = 0.0037). These results might improve the understanding of the pathogenesis of HIV-1 vertical transmission and might allow the screening of seropositive mothers by a rapid molecular or peptide test.

Amino Acid Sequence↗
PubMed1996

Relations among night work, dietary habits, biological measure, and health status.

A cross-sectional study was conducted to investigate dietary intake, behavioral habits, and clinical and metabolic differences in night workers compared to day workers and to evaluate the metabolic differences associated with diet and body habits that occur between these two groups. Dietary habits, biological parameters, and health status were collected in 1,200 night workers and in an equal number of day workers, matched for gender, age, and socioeconomic status. Our findings demonstrated that night workers had poorer dietary habits and metabolic profile compared to day workers with a similar overall health status. These differences were associated with a higher prevalence of some cardiovascular risk factors such as smoking and obesity.

Journal Article↗
PubMed1995

The delayed lung responses to single and repeated intratracheal administration of pure cobalt and hard metal powder in the rat.

Epidemiological and clinical studies suggest that inhalation of cobalt metal dust (Co) mixed with tungsten carbide particles (WC), but not of cobalt dust alone, may cause interstitial pulmonary lesions (hard metal disease). In previous experimental studies in the rat, we have demonstrated the greater acute pulmonary toxicity of a WC-Co mixture compared to Co or WC alone. The present study was undertaken to compare in the same animal model the delayed lung response after intratracheal administration of Co or WC-Co particles (cobalt particle 6.3 wt%). The responses were also compared with those obtained after treatment with arsenic trioxide and crystalline silica used a reference materials producing an acute toxic insult and a progressive fibrogenic response, respectively. Cellular (total and differential counts) and biochemical parameters (LDH, N-acetyl-beta-D-glucosaminidase, total protein, albumin, fibronectin, and hyaluronic acid) were measured in bronchoalveolar lavage fluid following single and repeated intratracheal instillations. The results indicate that the delayed lung response observed after WC-Co is different from that after cobalt metal alone. A single intratracheal dose of WC-Co (1, 5, or 10 mg/100 g body wt) induced an acute alveolitis which persisted for at least 1 month. Four months after a single instillation of WC-Co, no clear histological lung fibrosis could however be evidenced, indicating a reversibility of the lesions. The effects of cobalt (0.06, 0.3, or 0.6 mg/100 g body wt) or tungsten carbide alone (1, 5, 10 mg/ 100 g body wt) were very modest, if any. Following repeated intratracheal instillations (four administrations at 1-month interval), increased lung hydroxyproline content and histopathological evidence of interstitial fibrosis were observed after WC-Co (4 x 1 mg/100 g body wt), but not after administration of each component separately, i.e., Co (4 x 0.06 mg/100 g body wt) or WC (4 x 1 mg/100 g body wt). The mechanism of the fibrotic reaction induced by WC-Co seems different from the progressive inflammatory reaction induced by crystalline silica. We suggest that it might result from a scarring reaction elicited by repeated acute insults as observed after repeated administration of arsenic trioxide.

Acetylglucosaminidase↗
PubMed1995

Lung toxicity of hard metal particles and production of interleukin-1, tumor necrosis factor-alpha, fibronectin, and cystatin-c by lung phagocytes.

Hard metal alloys (WC-Co) are made of a mixture of cobalt (Co; 6%) and tungsten carbide (WC; 94%) particles. Chronic inhalation of hard metal dust can lead to the development of a fibrosing alveolitis, the pathogenesis of which is still undefined. The present investigation was undertaken to assess the effect of Co, WC, and WC-Co particles on the release by lung phagocytes of interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), fibronectin, and cystatin-c. The responses were compared with those induced by two other lung toxicants, i.e., crystalline silica (DQ12) and arsenic trioxide (As2O3). IL-1 and TNF-alpha activities produced in the presence and absence of LPS stimulation were measured with the aid of bioassays while fibronectin and cystatin-c were determined by latex immunoassays. In vitro, maximal noncytotoxic doses of As2O3, Co, WC, or WC-Co did not significantly affect the production of these mediators by rat alveolar macrophages. In contrast, DQ12 enhanced the production of TNF-alpha (with and without LPS stimulation) and IL-1 (after LPS stimulation) and decreased cystatin-c release (in the absence of LPS). Following a single intratracheal instillation of the different test preparations in the rat, the response of the lung phagocytes obtained by bronchoalveolar lavage (BAL) 24 hr later was examined. We were unable to detect any consistent effect of Co (0.06 mg/100 g body wt), WC (1 mg/100 g body wt), or WC-Co treatment (1 mg/100 g body wt) on the production of the above mediators. In contrast, after LPS stimulation, As2O3 (0.5 mg/100 g body wt) and DQ12 (1 mg/100 g body wt) stimulated the production of TNF-alpha and IL-1. In the absence of LPS, As2O3 stimulated fibronectin and cystatin-c production and DQ12 stimulated cystatin-c release. Since the dose of WC-Co used in vivo (1 mg/100 g body wt) caused pronounced lung inflammation (increased LDH, protein, and albumin levels in BAL fluid), we conclude that the acute lung toxicity of WC-Co particles is not mediated through enhanced production of the examined mediators by lung phagocytes.

Alloys↗
PubMed1995

Outcome of elderly patients requiring ventilatory support in intensive care.

The objectives of the study were: 1) to evaluate mortality in elderly patients requiring ventilatory support in Intensive Care Unit (ICU) and at 6, 12 and 18 months after discharge from ICU; 2) (main objective) to determine predictors of mortality in ICU and after discharge; and 3) to assess the life-style of survivors. One hundred and ten consecutive hospitalized patients > or = 70 years were included in this retrospective study. Follow-up evaluation was conducted by telephone interview. Mortality in ICU and after discharge was the outcome variable. Fifteen parameters were recorded at admission and during hospitalization. Residence, health status, and self-sufficiency were evaluated after discharge. 1) Mortality in ICU and at 6, 12 and 18 months after discharge was 38%, 60%, 63% and 67% respectively. 2) The predictors of mortality in ICU were admission in shock, and use of major therapeutic interventions. Predictors of mortality at 6 months were admission in shock, previous impaired health status and marital status. 3) Eighteen months after discharge 92% of the surviving patients (N = 33) had the same residence, 75% had the same health status, and 78% had the same autonomy compared with pre-admission status. We concluded that shock and previous health status but not age are predictors of short- and long-term prognoses in elderly patients hospitalized in ICU for mechanical ventilation.

Aged↗
PubMed1995

[Hemophagocytic syndrome in children infected by HIV. Apropos of 3 cases].

BACKGROUND: The hemophagocytic syndrome has previously been reported in different infectious diseases (EBV, CMV, tuberculosis...) but rarely in adults with AIDS and never in children suffering from AIDS. CASE REPORTS: A hemophagocytic syndrome was recognized during the follow-up of 3 children with AIDS. The first, a 9-year-old girl developed an acute EBV coinfection and was treated with shots of corticosteroids and vepesid but died shortly afterwards. The second patient, a 3-year-old girl was infected with Aspergillus fumigatus for which she was given amphotericin B with a rapid improvement. The third patient, an 8-year-old boy had multi-resistant Streptococcus pneumoniae otitis and pneumonitis; his condition improved rapidly with adapted antibiotherapy. DISCUSSION: The HIV-hemophagocytic syndrome is not exceptional in HIV infection because of the association of immunodeficiency and resulting superinfections. Its diagnosis and treatment should be etiologic. Severe cases without etiology could benefit from chemotherapy. CONCLUSION: Management and outcome of this potentially lethal syndrome might depend on the identification of a curable infectious cause.

AIDS-Related Opportunistic Infections↗
PubMed1995

Relationships between humoral factors in HIV-1-infected mothers and the occurrence of HIV infection in their infants.

Based on what is known about the biology of HIV-1 vertical transmission, the HIV burden of the mother, maternal immune factors and the integrity of the placental barrier are likely to play major roles. We therefore sought to determine whether the presence of antibodies in sera from 47 HIV-1-infected mothers, including 30 non-transmitting and 17 transmitting mothers, affected the risk of HIV-1 transmission to infants. Our findings showed no significant correlation between the capacity of antibodies to mediate antibody-dependent cell-mediated cytotoxicity (ADCC) and their capacity to induce protection of the child from HIV-1 infection (P = 0.14). Furthermore, no correlation was found between the capacity of maternal antibodies to neutralize in vitro lymphocyte or macrophage heterologous viral infection and the occurrence of in vivo HIV-1 infection in the infant. Sera recovered from five of 12 transmitting mothers and from five of 11 non-transmitting mothers were compared in their capacity to neutralize the viruses drawn from the same individuals. Four out of five maternal isolates from transmitting mothers and all maternal isolates from non-transmitting mothers were sensitive to enhancement of infection mediated by the maternal serum.

Acquired Immunodeficiency Syndrome↗
PubMed1995

[Value of the analysis of cellular chimerism following bone marrow graft by amplification of minisatellite sequences or specific of the Y chromosome].

We used polymerase chain reaction amplification of minisatellites sequences (33.6.3, G3, PMS51, YNZ22) and of a Y chromosome specific sequence (DYZ1) to document chimaerism in 50 patients. Indications for bone marrow transplantation (BMT) was acute leukemia (n = 23). Aplastic anemia (n = 18) and inherited newborn disease, SCID and familial hemophagocytic lymphohistiocytosis (n = 9). The method was informative in all cases. We were able to demonstrate engraftment in 23/23 leukemia patients, 15/18 in aplastic patients and 8/9 in the last group of patients. HLA mismatching BMT was significantly less efficient. Analysis with DYZ1 probe in case of sex mismatched. BMT revealed the frequency of host residual cells after Bott. Their detection in a 0.01-1% range does not seem to influence the outcome of the transplantation procedure.

Base Sequence↗
PubMed1995

[Chronic course of reactive bronchial dysfunction syndrome. Apropos of 6 further cases].

The reactive airways dysfunction syndrome (RADS) occurs as a persistent bronchial hyper-reactivity with asthmatic-type dyspnoea and occurs after a single and massive inhalation of irritant gases, smoke or vapours, in subjects who had previously had no respiratory disease. We report six cases in patients without any previous asthmatic history or history of atopy who had developed RADS after being exposed to different irritants. The symptoms evolved over 5-84 months after the initial accident. Only moderate airflow obstruction was found, but all subjects had bronchial hyper-reactivity to methacholine. A bronchial biopsy was performed in a patient and this showed moderate sub-epithelial mononuclear inflammatory infiltrate. A specific feature of this syndrome is the facility to inaugurate a susceptibility to asthma after the initial accident and for this to progress of its own accord with secondary aggravation, even in the absence of new exposure to the irritating agent. Its frequency is probably under-estimated because it remains little known in France. It is very important both to recognise and notify inhalational accidents at work to be able, should the nedd arise, to identify the worker and to enable a move to a different job if necessary.

Adult↗
PubMed1995

Clearance of HIV infection in 12 perinatally infected children: clinical, virological and immunological data.

OBJECTIVE: A case of HIV infection clearance in a perinatally infected infant has been recently reported. We report here on the molecular, biological and clinical features of such virus clearance in 12 children. DESIGN AND METHODS: We performed a retrospective analysis of the diagnosis in our 6-year cohort of 188 children born to HIV-seropositive mothers. HIV-1 was detected by coculture of infant peripheral blood mononuclear cells (PBMC) with cord blood cells, direct culture of infant cells, and DNA polymerase chain reaction (PCR). The children were diagnosed three times during the first 3 months of life and then followed up over a postnatal period of 18-36 months. RESULTS: The 12 reverted children had at least two positive PCR in at least two amplified regions. Among them, six were tested positive in culture/coculture assay, and five were treated long-term with zidovudine. Thus, seven out of 12 reversions cannot be attributed to antiretroviral therapy. All the virological results became negative during the first year of life, and serology lowered to negative values between 9 and 23 months. We could not find any correlation between either neutralizing or antibody-dependent cellular cytotoxicity-mediating antibodies and HIV clearance. CONCLUSION: In our cohort, we showed that an unexpected number of children born to HIV-seropositive mothers (6.7%) cleared HIV infection during the first year of life, and subsequently became seronegative. Interestingly, most of these children exhibited unspecified clinical signs during the first months of life. Five of these children were tested positive only by PCR, which suggests a low virus load and could, at least partly, explain spontaneous clearance. However, 4 years later, among the seven remaining infants, two seronegative children presented recurrent hepatosplenomegaly, which may indicate the presence of hidden virus not detectable by peripheral blood testing.

CD4-CD8 Ratio↗
PubMed1994

Lung cancer mortality in a French cohort of hard-metal workers.

A cohort mortality study was carried out among workers of a plant producing hard metals using cobalt as a binder. This study was aimed at assessing possible lung cancer risks in relation with cobalt exposure. Seven hundred nine male workers with at least 1 year of employment were included in the cohort and followed for mortality from 1956 to 1989. Job histories were provided by the administration of the plant, whereas smoking habits were collected from medical records and by interview. The causes of deaths were ascertained from hospital and general practitioner records. The observed numbers of deaths (obs) were compared with the expected based on national rates with adjustment for age, sex, and calendar time (standardized mortality ratio; SMR). The overall mortality did not differ from that expected (obs = 75, SMR = 1.05), whereas mortality due to lung cancer was in significant excess (obs = 10, SMR = 2.13). This excess was higher among workers employed in the areas with the highest exposure (obs = 6, SMR = 5.03). No trend was observed, however, with duration of employment or time since first employment. Smoking data were available for 81% of the workers and 69% of the deceased and showed that smoking alone does not account for these lung cancer excesses, yet, because of the small numbers involved, no firm conclusion should be drawn from this study.

Adult↗
PubMed1993

[Role of neutralizing antibodies in protection of the fetal from an HIV positive mother].

The goal of this study is to compare serum Titers of Neutralizing antibodies in HIV 1 infected mothers to the virological status of their newborns. 38 infant-mothers couples were tested. Serum Neutralizing antibodies Titers of the mothers were tested the day of birth. Virological status of new borns was determined by peripheric blood mononuclear cells culture and PCR. 18 Newborns were HIV 1 infected. In 9 cases mothers had no neutralizing antibodies: 7 newborns were HIV 1 infected. In 4 cases mothers had high level of neutralizing antibodies (< 640): none of the newborns was infected. In 25 cases mothers had intermediate value of neutralizing antibodies (between 80 and 320): 11 newborns were HIV 1 infected. Women with neutralizing antibodies to HIV 1, were less likely to transmit HIV 1 to their infants than pregnant women without neutralizing antibodies. Serum neutralizing antibodies titers of pregnant women might be of predictive value in vertical transmission of HIV 1. Further investigations are needed.

Acquired Immunodeficiency Syndrome↗
PubMed1993

[Management of HIV-seropositive newborn infants. Personal experience apropos of 179 cases].

A follow-up study of 179 cases of human immunodeficiency virus (HIV) seropositive neonates born from HIV seropositive mothers is reported. At the time of the present study, HIV infection resulting from maternofetal transmission was found in 50 cases, while 108 infants were not infected; HIV infection remained uncertain in 16 cases; 5 infants were lost for follow-up. Out of the 50 infected cases, 20 were less than two-year old, 17 were 2-5 year old and 13 were older than 5 years. Very few remained asymptomatic after the age of 6 months, the most common symptoms being adenopathies and/or hepatomegaly and/or splenomegaly. Twenty-six had an acquired immunodeficiency syndrome (AIDS). Six died, from pneumocystosis (3), cytomegalovirus infection (1) and septicemia (2). Virus culture and polymerase chain reaction were the most efficient laboratory methods for early diagnosis of HIV infection, both being positive in more than 95% of the infected cases after the age of 3 months. A close clinical and biological supervision is recommended in these infants and children because of the permanent threat of infectious diseases in relation to their immunodeficiency. Treatment associates: 1) antiviral therapy with AZT as soon as the HIV infection is diagnosed; 2) primary prophylaxis against pneumocystosis with trimethoprim-sulfamethoxazol; 3) IV immunoglobulins in the case of repeated bacterial infection; 4) regular evaluation of the nutritional status and psychological assistance.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Opportunistic Infections↗
PubMed1992

Comparative study of the acute lung toxicity of pure cobalt powder and cobalt-tungsten carbide mixture in rat.

Alveolitis progressing to lung fibrosis has been reported in workers exposed to cobalt containing dust (e.g., tungsten carbide-cobalt mixture as produced by the hard metal industry) but rarely following exposure to pure cobalt dust (e.g., in cobalt-producing factories). We have previously demonstrated that tungsten carbide-cobalt mixture is more toxic toward rat alveolar macrophages in vitro than pure cobalt metal powder. The present study was undertaken to compare in female rats the acute pulmonary response (lung weight, lung histology, cellular and biochemical analyses of bronchoalveolar lavage fluid, and mortality) following the intratracheal instillation of pure cobalt (Co) particles (median particle size, d50:4 microns), pure tungsten carbide (WC) particles (d50:2 microns), tungsten carbide-cobalt (WC-Co) powder (d50:2 microns; cobalt 6.3%, tungsten 84%, carbon 5.4%) and crystalline silica (d50 less than 5 micron) used as pneumotoxic reference material. WC alone (15.67 mg/100 g body wt) behaves as an inert dust producing only a mild accumulation of macrophages in the alveolar duct walls. Co alone (1.0 mg/100 g) only causes a moderate inflammatory response. An identical amount of Co given as WC-Co mixture (16.67 mg/100 g; corresponding to 1.0 mg Co/100 g) produces a severe alveolitis and fatal pulmonary edema. Cellular and biochemical characteristics of bronchoalveolar lavage fluid collected 24 hr after the intratracheal instillation of WC (1.0 mg/100 g) or Co (0.06 mg/100 g) are not significantly different from those of control animals instilled with sterile saline. On the contrary, bronchoalveolar lavage fluid changes following administration of the WC-Co mixture (1.0 mg/100 g; corresponding to 0.06 mg Co/100 g) are very similar to those induced by crystalline silica (1.0 mg/100 g). The amount of cobalt excreted in urine is significantly higher when the animals are exposed to WC-Co powder as compared to an equivalent amount of pure cobalt particles, suggesting an increased bioavailability of cobalt metal when combined with tungsten carbide. This study demonstrates that the acute lung toxicity of tungsten carbide-cobalt mixture is much higher than that of each individual component and may explain why lung fibrosis is rarely if ever induced by exposure to pure cobalt dust.

Animals↗
PubMed1992

Scintigraphy with J001X, a Klebsiella membrane glycolipid, for the early diagnosis of chronic berylliosis: results from an experimental model.

A glycolipid (J001X) isolated from the membrane proteoglycans of a non-pathogenic strain of Klebsiella pneumoniae was developed to bind selectively to macrophages. A scintigraphic technique could thus be developed and applied to an experimental model of lung berylliosis. Six baboons were injected intratracheally with a beryllium metal suspension. Three to 24 months later, they were submitted to both an anatomical and a functional respiratory evaluation. Two baboons were explored at the early stage of alveolitis and four baboons at a more advanced stage characterised by a granulomatous disorder. Scintigraphy was performed using J001X labelled with 99mtechnetium administered as an aerosol. In the six baboons, conventional imaging techniques (chest x ray film, computed tomography scan, gallium scintigraphy), failed to show either any lung abnormality or mediastinal lymph nodes consistent with beryllium disease. In the two recently contaminated baboons, J001X scintigraphy showed a well defined parenchymal fixation facing the contaminated lobe. In the four baboons who were at a more advanced stage of berylliosis, J001X fixation was always focused paratracheally without any significant involvement of the lung parenchyma. The subcarinal and laterotracheal lymph nodes seen at necropsy corresponded to J001X scintigraphic fixations. In conclusion, when compared with conventional techniques such as chest x ray film, computed tomography scan, magnetic resonance imaging, and gallium scintigraphy, J001X scintigraphy has proved its ability to detect occult lesions in experimental berylliosis in baboons. By comparison with gallium scintigraphy, scintigraphy with J001X appears to have superior sensitivity and can be performed in four hours.

Animals↗