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Biomedical subjects

F Gay

Publications and source records attributed to F Gay.

At least 37 records · Page 2Linked to original sources

[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↗

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↗

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↗

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↗

[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↗

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↗

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↗

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↗

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↗

Interleukin 12 induces the differentiation of major histocompatibility complex class I-primed cytotoxic T-lymphocyte precursors into allospecific cytotoxic effectors.

The production of interleukin 12 (IL-12) following allogeneic stimulation and its involvement in the differentiation of allospecific cytotoxic T lymphocytes (CTLs) have been investigated. Supernatants of mixed lymphocyte cultures had detectable levels of IL-12 p40 which were completely abrogated after depletion of responder cells from monocytes. While addition to the culture of anti-IL-12 neutralizing antibodies partially inhibited the allogeneic proliferative response and the subsequent CTL activity, addition of IL-12 stimulated both responses, suggesting that endogenously produced IL-12 plays a role in the development of alloreactivity. Furthermore, using primary mixed cultures of lymphocytes from major histocompatibility complex-recombinant siblings identical for class II antigens and displaying class I disparity, we demonstrated that addition of recombinant IL-12 at the sensitizing phase of the primary mixed lymphocyte culture induced CTL activity. Under these stimulation conditions, addition of recombinant IL-12 also triggered cell proliferation, indicating that IL-12 provides both growth and differentiation signals. The mechanism underlying this process does not appear to require IL-2, since IL-12-mediated CTL generation was not abrogated by anti-IL-2 alpha-chain antibodies. IL-12 increased granzyme B and perforin mRNA accumulation in major histocompatibility complex class I-primed lymphocytes, suggesting that this cytokine activates these two genes in CTL precursors. We conclude that IL-12 can stimulate the generation of alloreactive CTLs. We suggest that IL-12 may play a role in helper cell-independent CTL generation.

Adult↗

[Color Doppler ultrasonography in urology].

Due to the development of the duplex mode, combining ultrasound images with Doppler recording, and especially the development of flow colour coding. Doppler is now increasingly used to investigate the kidney and male genital tract. It is now the technique of choice in the initial diagnosis of certain renal diseases: primary renal vein thrombosis, iatrogenic and malformative arteriovenous anomalies, vascular complications of renal transplantation, and for examination of the scrotal contents in a context of acute scrotum or investigation of the cavernosal arteries in the case of erection disorders. It allows a rapid diagnosis and guides the subsequent radiological assessment. Doppler can also provide useful or even essential additional information in the case of a known abnormality such as renal cancer, in which it defines the venous extension when CT scan is technically insufficient. In certain fields, such as diagnosis of renovascular hypertension or exploration of the prostate, the place of Doppler is still poorly defined and remains controversial, except in a few specialised centres equipped with sophisticated apparatuses used by experienced operators. After briefly reviewing Doppler techniques and the basic steps in interpretation, the authors define the contribution and limitations of colour Doppler in the investigation of the urinary tract and male genital tract. Normal appearances and the results of Doppler-ultrasound in nephrourological disease are illustrated.

Genital Diseases, Male↗

The pharmacokinetics and electrocardiographic effects of chloroquine in healthy subjects.

Chloroquine prophylaxis was administered to 3 healthy male volunteers at 100 mg base/day for 25 days, followed by the curative dose at 25 mg base/kg for 3 days. Subjects attained effective chloroquine (mean = 50 micrograms/l) and desethylchloroquine (mean = 17 micrograms/l) concentrations by the 3rd week of prophylaxis, underlining the need to start chloroquine prophylaxis two weeks before travel. On the second day of the treatment period, hourly electrocardiographic monitoring showed a diminution of the T wave and prolongation of the QTc interval, manifesting cumulatively during the 3 days' curative dose, but with no cardiac symptoms. A dose-dependent cumulative effect of chloroquine was demonstrated with higher blood concentrations during the treatment period. Electrocardiographic readings spontaneously normalized after the treatment period as drug concentrations diminished progressively.

Adult↗

In-vitro tests on Philippine isolates of Plasmodium falciparum against four standard antimalarials and four qinghaosu derivatives.

In-vitro drug sensitivity tests were performed on Philippine isolates of Plasmodium falciparum between 1991 and 1993, using the radioisotope microdilution method. The success of the tests varied significantly with the level of parasitaemia, the source of the strains, the period that elapsed before culturing, and the detectable concentrations of antimalarials in the blood. There was a significant positive correlation between the IC50 values for chloroquine and artesunate and the level of chloroquine in the blood before testing. In the Philippines the sensitivity profiles of the standard antimalarials (chloroquine, quinine, mefloquine, and halofantrine) were less severe than those in other south-east Asian countries. Fairly low IC50 values were obtained for the qinghaosu derivatives artemisinin, artemether, arteether and artesunate. There was a positive correlation between quinine, mefloquine, halofantrine and some of the qinghaosu derivatives, and between the qinghaosu compounds themselves, raising the possibility of either cross-resistance or possible drug associations.

Adolescent↗

[Subacute Plasmodium falciparum malaria in 43 patients returning from areas with chloroquine in Africa].

PURPOSE: To identify clinical and biological features of subacute falciparum malaria, risk factors, and to evaluate the efficacy of curative treatment. PATIENTS AND METHODS: Diagnostic criteria were the association of apyrexia, anemia, little or no parasitemia and a high titer of anti-Plasmodium antibodies. Forty-three cases were observed in subjects returning from chloroquine-resistant areas in Africa. They were matched with controls for age, country of residence and duration of stay. Controls were missionaries who attended our unit for a routine medical check-up during the study period. RESULTS: The clinical presentation and biological features were similar to "malarial cachexia", a condition mainly described in non-immune children in endemic areas. Splenomegaly was present in 58% of the patients. Biological features included little or no parasitemia, an overall decrease in the blood cell count, an increased erythrocyte sedimentation rate and a high titer of anti-Plasmodium antibodies. This syndrome was not correlated with the frequency of chloroquine resistance, the area of stay (urban or rural) or to the kind of chemoprophylaxis. CONCLUSIONS: This study describes subacute resistant falciparum malaria in patients who had prolonged stay in chloroquine-resistant areas of Africa associating splenomegaly, cytopenia and a low or absent parasitemia. Subacute chloroquine-resistant malaria could be due to host factors which remained to be determined by prospective immunological studies. Curative treatment with mefloquine is effective.

Adult↗