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Biomedical subjects

F Gay

Publications and source records attributed to F Gay.

At least 55 records · Page 3Linked to original sources
PubMed1998

Internal quality control of the malaria microscopy diagnosis for 10 laboratories on the Thai-Myanmar border.

On the Thai-Myanmar border, where multidrug resistance to anti-malaria medications is a major problem, a quality control program for diagnostic laboratories has been set up. This study examines the "passive" screening performed in 10 laboratories. Monthly evaluation of the quality of thick and thin smear practice, Giemsa staining and microscopy took place during the year 1994. Considering the general context and the methodology applied, the evaluation of performance and strategy of the malaria diagnostic test showed satisfactory results for all 10 laboratories. Performance of technics = 64% (62-66) to 96% (95-97); Sensitivity = 92.6 (91.5-95.5) to 96.6% (95.8-99.0); Specificity = 93.5% (91.4-95.5) to 98.3% (97.6-99.0); Predictive Positive Value = 92.0% (90.9-93.1) to 98.3% (97.6-99.0); Predictive Negative Value = 94.3% (93.0-95.6) to 98.5% (98.0-99.0). The study underlines the importance of a reliable quality control method for microscopy diagnosis of malaria in hyperendemic areas, with Plasmodium falciparum as the main species. A high level of input from the international laboratory technician, performing training, follow-up and evaluation was required. The need for adequate training of national technicians and supervisors, especially regarding long-term sustainability, is stressed. The type of program presented can be used as a model for similar projects in developing countries.

Clinical Laboratory Techniques↗
PubMed1997

Functional interaction between TGF-beta and IL-12 in human primary allogeneic cytotoxicity and proliferative response.

IL-12 is an important cytokine in the control of cell-mediated immunity. We have investigated the functional interaction of IL-12 with TGF-beta1, a cytokine involved in the regulation of growth and differentiation of immunocompetent cells, during human allogeneic response development. Using primary MLR, our data show that addition of exogenous TGF-beta at the sensitizing phase of the primary MLR resulted in the inhibition of both allogeneic cytotoxic and proliferative responses. The inhibitory effect of TGF-beta on allogeneic response involves an abrogation of IL-12/p70 production upon allostimulation. In contrast to its effect on IL-12 production, TGF-beta did not alter the expression of IL-12R beta1-chain (IL-12R beta) in T cells induced upon allogeneic activation. Addition of exogenous IL-12 or IFN-gamma in the MLR cultures in the presence of TGF-beta did not result in reversal of CTL generation and T cell proliferation. Interestingly, TGF-beta was efficient in down-regulating IL-12 responsiveness of alloactivated T cells as well as TCR-alphabeta or TCR-gammadelta alloreactive T cell clones. These studies suggest that the inhibitory effect of TGF-beta on the development of human allogeneic proliferation and cytotoxic responses involves an additional mechanism associated with an interference with IL-12 pathway.

Adult↗
PubMed1997

Randomised phase II study of cisplatin and 5-fluorouracil (5-FU) versus cisplatin alone in advanced squamous cell oesophageal cancer.

Patients with measurable or evaluable locally advanced or metastatic squamous cell carcinoma of the oesophagus were treated with cisplatin (CDDP), 100 mg/m2, combined with 5-fluorouracil (5-FU) at a dose of 1000 mg/m2 as a continuous infusion from days 1-5 (Arm A) or with CDDP alone (Arm B). Cycles were repeated every 3 weeks. 92 patients were randomised centrally, 88 were eligible. The response rate was 35% (95% CI (confidence interval), 20-54%) in Arm A and 19% (95% CI, 8-35%) in Arm B. One complete response was observed in each arm. The median duration of survival was 33 weeks and 28 weeks for Arm A and Arm B, respectively. Haematological and non-haematological toxicities were more frequent and more severe in Arm A. The most prominent toxicities were grade 4 aplasia and septicaemia (2), meningeal haemorrhage (1), cerebrovascular accident (3) and ischaemia of the lower limbs (1) all occurring in Arm A. Overall, seven treatment-related deaths (16%) were observed in Arm A, none in Arm B. The severe side-effects induced by the combination suggest that, currently, no standard chemotherapy can be recommended for patients with advanced squamous cell oesophageal cancer.

Adult↗
PubMed1997

The place of upper gastrointestinal tract endoscopy before and after vertical banded gastroplasty for morbid obesity.

In industrialized countries, surgical gastroplasty is performed more and more frequently in patients with morbid obesity. The aims of this prospective study were to determine the incidence of upper gastrointestinal lesions in obese patients and to assess the place of digestive endoscopy in symptomatic patients after gastroplasty. A consecutive group of 159 obese patients were studied before and after vertical banded gastroplasty. In the preoperative evaluation, reflux esophagitis and gastroduodenal lesions were endoscopically observed in 31% and 37% of the patients, respectively. Interestingly, the majority of the obese patients with upper gastrointestinal lesions were asymptomatic. In the postoperative follow-up period, 55 of the 159 patients complained of upper gastrointestinal symptoms such as vomiting (72%), esophageal reflux (17%), and epigastric pain (3%). Stenosis of the outlet of the gastric pouch was described in 40 of the 55 symptomatic patients. Esophagitis was observed in 60% of these patients. Endoscopic dilation using Savary bougies or TTS balloon was successfully performed in all the patients with symptomatic stenosis of the gastric outlet. Food impaction was endoscopically removed in four patients. Thus, we recommend performing an upper gastrointestinal endoscopy in obese patients who are candidates for surgical gastroplasty because of the high incidence of upper gastrointestinal peptic lesions. Endoscopy is also helpful in patients with digestive disorders occurring after gastroplasty in order to define and to treat the lesions.

Adult↗
PubMed1997

A bioassay for evaluating antimalarial activity and for measuring concentration in plasma.

Our objective was to develop a bioassay method based on the isotopic microtest of Desjardins and to validate it by comparing the results with high performance liquid chromatograph (HPLC). The bioassay was developed using a continuous culture of P. falciparum, and the test material consisted of 32 human serum samples from 22 Filipino patients treated only with chloroquine (CQ) for noncomplicated malaria. A blind assay of the serum was done using the Desjardins method and HPLC. A good correlation (r2 = 0.90, n = 32) was observed between the CQ plus monodesethylchloroquine (DCQ) concentrations obtained by HPLC and the equivalent CQ by bioassay. It was also shown that the antimalarial activity of CQ is practically identical to that of its main metabolite DCQ, the activity of DCQ being 0.9 times the activity of CQ. The bioassay is reliable, semi-automated, and reproducible. This method may be used as a complementary technique to HPLC for determining biological activity in serum and for measuring the kinetics of this activity, as well as to indicate the existence of new metabolites. The bioassay can be applied to other protozoans for which an in vitro model is available.

Adolescent↗
PubMed1997

Evidence for an inducible repair-recombination system in the female germ line of Drosophila melanogaster. III. Correlation between reactivity levels, crossover frequency and repair efficiency.

We previously reported evidence that the so-called reactivity level, a peculiar cellular state of oocytes that regulates the frequency of transposition of I factor, a LINE element-like retrotransposon, might be one manifestation of a DNA repair system. In this article, we report data showing that the reactivity level is correlated with the frequency of crossing over, at least on the X chromosome and on the pericentromeric region of the third chromosome. Moreover, a check for X-chromosome losses and recessive lethals produced after gamma irradiation in flies with different reactivity levels, but common genetic backgrounds, brings more precise evidence for the relationship between reactivity levels and DNA repair. Those results support the existence of a repair-recombination system whose efficiency is modulated by endogenous and environmental factors. The implications of this biological system in connecting genomic variability and environment may shed new lights on adaptative mechanisms. We propose to call it VAMOS for variability modulation system.

Aging↗
PubMed1997

In vitro response of Plasmodium falciparum to atovaquone and correlation with other antimalarials: comparison between African and Asian strains.

Atovaquone (dihydroxynaphthoquinone 566C80) is a broad-spectrum antiprotozoal compound demonstrating potent antimalarial activity against multidrug-resistant malaria. We present the results of in vitro drug sensitivity tests of 142 Plasmodium falciparum isolates, 108 from 14 countries of West and Central Africa, 32 from the Philippines, and one each from Laos and Myanmar. These were tested in vitro against nine drugs: the classic antimalarials chloroquine, quinine, mefloquine and halofantrine, the four qinghaosu derivatives, artemisinin, artemether, artesunate, and arteether, and the new compound atovaquone. Results showed the Asian strains have a higher median 50% inhibitory concentration (IC50) to almost all drugs compared with those from Africa. This was significantly different for chloroquine, halofantrine, and artemisinin. We used three different approaches to estimate the threshold for resistance of atovaquone to be approximately 5-7 nmol/L. The global median of 96 pooled strains is 1.4 nmol/L and the 90th percentile is 5.5 nmol/L for atovaquone. There were no correlations of atovaquone with the eight other antimalarials among African strains, but significant correlations, except for halofantrine, were observed among Asian strains. The absence of a correlation between atovaquone and the other available drugs indicates the potential of atovaquone as an alternative antimalarial in Africa. The correlation observed among Asian strains, however, suggests that atovaquone has to be used cautiously in Asia. Nevertheless, the association with proguanil in recently concluded clinical trials in Europe, South America, Asia, and Africa has demonstrated its antimalarial efficacy.

Africa↗
PubMed1997

[Note on imported malaria in metropolitan France from 1993 to 1995].

Concerning malaria, the role of the Reference National Centre on the Imported Diseases is to observe the cases that occur on the continent in order to describe their characteristics, assess their annual incidence and objectify the secular trend. The aim is to provide annual indicators to help to advise travellers. This surveillance is based on a voluntary network providing standardised informations on the epidemiologic, prophylactic, clinical, parasitologic and therapeutic data. After a noticeable increase between 1987 and 1988, the occurrence of the imported malaria cases in France decreased since 1989 then became stable since 1991, between 3,500 and 4,000 cases per year. From one year to another the characteristics of the cases are stable for most of the parameters. However, it is interesting to note: a progressive increase in the ratio of foreigners with a decrease of the median age, the average five days delay between the first symptoms and the diagnostic, the same ratio of severe cases for French people and foreigners, the average time of the stay at the hospital of 4.5 days for non severe malaria cases and the preferential use of halofantrine in first line treatment. The delay of the diagnostic and more precisely the delay of treatment turn-out to be the main factors leading to severe malaria sometimes leading to death. The limited interpretation of data is due to the lack of corresponding denominators required for measuring the rates and density of the incidence as well as the identification of risk factors.

Adult↗
PubMed1996

Laparoscopic treatment of a sigmoid perforation after colonoscopy. Case report and review of literature.

The authors report a case of sigmoid colon perforation post colonoscopic polypectomy. Such perforation is rare and has been estimated to occur between 0.1 and 3% of the time. Surgical treatment is necessary when there is deterioration of the clinical state. In this reported case, surgical closure of the perforation was achieved by laparoscopy. We believe that this approach is effective for colonic suture, peritoneal lavage, and drainage.

Aged↗
PubMed1996

Diagnostic efficacy of push-enteroscopy and long-term follow-up of patients with small bowel angiodysplasias.

Gastrointestinal angiodysplasias are the most common cause of obscure chronic digestive blood loss. Push-enteroscopy is likely to detect and to treat vascular lesions. Push-enteroscopy was performed in 83 patients (mean age 62 years) presenting with iron deficiency anemia of obscure origin. A nonrevealing preliminary evaluation included esophagogastroduodenoscopy, colonoscopy and, in 50% of the patients, small bowel barium studies. We employed a 240-cm Olympus push-enteroscope (XSIF-100), 11.3 mm in diameter. A potential bleeding lesion was observed in 49 patients (59%). Gastrointestinal angiodysplasias were the most common lesion (33 patients). Electrocoagulation (bicap) of angiodysplasias was performed when accessible and not diffuse (<20). If not contraindicated, hormonal treatment was proposed for patients who had at least five AD. Some patients had both treatments. Long-term follow-up (mean, 12.2 months) was obtained in 25 patients with small bowel angiodysplasias. A good outcome (neither recurrence of anemia nor blood transfusion requirements) was observed in 12 patients. The diagnostic efficacy of push-enteroscopy is high. Despite available and recommended therapeutic modalities, the long-term outcome was considered to be good in only 50% of the patients.

Adolescent↗
PubMed1996

Induction of tumor necrosis factor alpha expression in human T lymphocytes following ionizing gamma irradiation.

In this work, we present evidence that enriched human peripheral blood T lymphocytes, depleted of contaminating monocytes, rapidly express tumor necrosis factor alpha (TNF-alpha) mRNA when exposed to low doses of gamma-irradiation. In total PBL, TNF-alpha mRNA accumulation increased threefold as early as 30 minutes following exposure to 4 Gy and then declined to the baseline level by 3-5 h, as measured by the reverse transcriptase-polymerase chain reaction (RT-PCR). The increase in TNF-alpha mRNA was also observed in populations of enriched T cells and decreased when the dose of irradiation was increased to 10 Gy, strongly suggesting that T lymphocytes, the most radiosensitive cells of the body, contributed directly to the increase of TNF-alpha mRNA. A good correlation was found between mRNA expression and TNF-alpha protein secretion. Interestingly, a eightfold increase in glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA accumulation was also detected in both PBL and enriched T cells irradiated at 4 Gy for 3 h compared with unirradiated cells. This irradiation effect was almost completely abolished, however, following exposure to 10 Gy. Together these data suggest that T cells are responsible for the irradiation-induced expression of TNF-alpha and GAPDH.

Base Sequence↗
PubMed1996

[Contribution of enteroscopy in the diagnosis of digestive hemorrhages of unknown origin].

In this work we report our experience with enteroscopy and its contribution in the diagnosis of anaemia of unknown digestive origin. 90 enteroscopies had been performed in 83 anaemic patients with positive blood stool. 37 of the patients experienced episodes of melena. Preliminary minimal routine investigations including gastroscopy and coloscopy were not contributive. Potentially haemorrhagic lesions were diagnosed in 49 patients (59%), and 7 of these lesions were located in the small bowel. A small bowel lesion has been found in 17 patients with melena and in 19 patients without melena (p > 0.10). The most frequent lesions were angiodysplasias (AD). The mean age of patients with AD was 71.4 years old, vs. 57.2 years (p < 0.00001). Endoscopic bipolar electrocoagulation was performed in 22 patients. Enteroscopy is an efficient technique in the evaluation of patients suffering from obscure digestive bleeding, regardless the presence or absence of melena.

Adolescent↗
PubMed1995

Isolation and characterization of brain microvascular endothelial cells from Saimiri monkeys. An in vitro model for sequestration of Plasmodium falciparum-infected erythrocytes.

The adhesion of parasitized red blood cells (PRBC) to the endothelium (sequestration) may contribute to the pathogenic events in severe human malaria caused by P. falciparum. However, the factors involved in the pathophysiology, especially cerebral malaria are poorly understood. Previously, we have shown that the squirrel monkey Saimiri sciureus is a potential model for human cerebral malaria. In this paper we describe five stable clones of endothelial cell lines isolated immediately postmortem from different regions of the brain of Saimiri monkeys. The endothelial cell characteristics of these clones were confirmed by analyzing their ultrastructural aspects by transmission electron microscopy and by immunodetection of various endothelial cell markers. The Saimiri brain endothelial cell clones (SBEC) varied in their expression of different surface molecules. For example, various combinations of receptors involved in P. falciparum PRBC adherence such as CD36, ICAM-1 and E-selectin, were expressed at baseline values and could be up-regulated by human srTNF-alpha and human srIFN-gamma. One of the SBEC clones showed a strong cytoadherence for various laboratory strains of P. falciparum despite the absence of surface expression of any of the known endothelial receptors implicated in PRBC adherence. This finding suggests the existence of a new and uncharacterized PRBC binding receptor. The use of target organ specific endothelial cell lines expressing a number of different potential P. falciparum PRBC cytoadherence receptors, will be a useful in vitro system for the evaluation of strategies for the development of vaccine and antimalarial drugs to prevent human cerebral malaria.

Animals↗
PubMed1995

Evidence for the binding of a biologically active interleukin-2 to human alpha 2-macroglobulin.

Human alpha 2-macroglobulin (alpha 2M), which irreversibly entraps proteinases through a drastic conformational change, has also been reported to bind various cytokines. The meaning of cytokine binding to native and/or transformed alpha 2M molecules is, however, not understood. In an attempt to elucidate this question, we have studied the interaction of radioiodinated recombinant human interleukin-2 (125I-rhIL-2) with native and chymotrypsin (alpha 2M-C)- or methylamine-transformed (alpha 2M-MA) alpha 2M. Our results show that native and alpha 2M-MA are able to bind 125I-rhIL-2, with binding occurring only with the latter in a covalent manner, whereas the labeled cytokine is proteolyzed when incubated with alpha 2M-entrapped chymotrypsin. The degradation of uncomplexed 125I-rhIL-2 has also been observed in the presence of trypsin, whereas 125I-rhIL-2 bound to alpha 2M-MA is protected. Moreover, the proliferative activity of this cytokine on responsive cells is still maintained either with native alpha 2M- or alpha 2M-MA-complexed rhIL-2 in comparison with that observed with the cytokine alone. Our results, which lead us to consider alpha 2M molecules as IL-2-binding proteins, emphasize the possible role of these molecules as immune response regulators.

Cells, Cultured↗
PubMed1995

Karyotype analysis of virulent Plasmodium falciparum strains propagated in Saimiri sciureus: strain adaptation leads to deletion of the RESA gene.

The squirrel monkey, Saimiri sciureus, is an important experimental model for the study of the human malaria parasite Plasmodium falciparum. A detailed karyotype analysis of four different P. falciparum strains propagated in S. sciureus was done using various subtelomeric antigen gene probes. We observed deletion of the complete RESA gene from chromosome 1 in all four strains. Interestingly, a loss of RESA was observed immediately upon adaptation to the squirrel monkey, suggesting that this DNA rearrangement is fundamental for the P. falciparum infection of S. sciureus erythrocytes. However, a RESA-specific gene probe hybridized with chromosome 1 of wild isolates from 28 different patients, indicating that this gene is maintained during infection of humans.

Animals↗
PubMed1995

In vitro drug sensitivity and clinical aspects of Plasmodium falciparum malaria in African children.

In vitro Plasmodium falciparum drug sensitivity was investigated in 115 brazzavillians children, between 1 year and 10 years of age. On the basis of clinical aspects, four groups were constituted: Group 1: 39 asymptomatic school children, Group 2: 16 children with uncomplicated malaria, Group 3: 40 with severe but not pernicious malaria and Group 4: 20 with pernicious malaria. The drugs tested were chloroquine (CQ), quinine (QN) and mefloquine (MQ). The sensitivity level was assessed by a 48-hour in vitro maturation test involving the uptake of tritiated hypoxanthine, the initial blood level of parasite being > or = 0.1% in all cases. For QN and MQ, the median IC50 values showed no significant difference related to clinical status, age or parasitaemia levels. For CQ, the proportion of resistant strains and the 50 inhibitory concentration (IC50) values were greater in the cases of children hospitalised for malaria but there were no differences related to clinical severity of these hospitalised children nor, within each group, to the age or parasitaemia levels. The percentage of subjects with an IC50 value greater than the 90 percentile of the IC50 of the asymptomatic group, which we propose as the severity index related to chemoresistance, was 15% for uncomplicated malaria, 38% for severe but non-pernicious forms and 35% for pernicious malaria. The IC50 for QN was significantly higher in CQ-resistant strains and there was a positive correlation for CQ vs QN and for QN vs MQ.

Animals↗