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Biomedical subjects

F Gay

Publications and source records attributed to F Gay.

At least 73 records · Page 4Linked to original sources

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↗

Hyperammoniemic coma in a patient with ureterosigmoidostomy and normal liver function.

Hyperammoniemic encephalopathy has been reported after ureterosigmoidostomy. Its development is related to a problem of bacterial overgrowth and, most often, is favored by the presence of an underlying liver dysfunction. We report the case of a 43-year-old woman with a ureterosigmoidostomy done 28 years earlier who developed hyperammoniemic coma induced by an acute rectocolitis and in the absence of any detectable liver dysfunction. Neither administration of Lactilol and neomycin nor rectal tube drainage were effective; systemic antimicrobial therapy effective against the urease-producing gram-negative bacilli was required and led to a decrease in serum ammonia levels and a dramatic clinical improvement.

Acute Disease↗

Serum levels and receptor expression of tumor necrosis factor-alpha following human allogeneic and autologous bone marrow transplantation.

We have investigated tumor necrosis factor-alpha levels in serum samples of patients before and after allogenic (16 patients) or autologous (8 patients) bone marrow transplantation. A sensitive immunoradiometric assay for monitoring levels of endogenous tumor necrosis factor-alpha was used. The serum levels of tumor necrosis factor-alpha were found to be relatively low (ranging from less than 15 to 77 pg/ml). Among 13 patients having graft-versus-host disease following allogeneic bone marrow transplantation 8 patients did not have detectable tumor necrosis factor-alpha (less than 15 pg/ml) while 4 out of 8 patients undergoing autologous bone marrow transplantation had detectable tumor necrosis factor-alpha levels (15 pg/ml), indicating a lack of correlation between tumor necrosis factor-alpha serum levels and the occurrence of graft-versus-host disease. Because the tumor necrosis factor-alpha levels detected in patient sera could be regulated by TNF-receptor expression, the presence of TNF-receptor on patients' peripheral blood mononuclear cells was also studied using fluorescent liposome-conjugated tumor necrosis factor-alpha and immunofluorescence analysis. Our data indicate that peripheral blood mononuclear cells of some patients receiving either autologous or allogeneic bone marrow transplantation expressed significant levels of TNF-receptors, suggesting a lack of correlation between TNF-receptor expression and graft-versus-host disease development.

Bone Marrow Transplantation↗

Mefloquine-halofantrine cross-resistance in Plasmodium falciparum induced by intermittent mefloquine pressure.

The study was designed to evaluate how exposure of Plasmodium falciparum to mefloquine modifies the sensitivity of the parasite to four major antimalarial drugs. A recently culture-adapted strain of P. falciparum was subjected to intermittent drug pressure at three different mefloquine concentrations (2.34, 4.68, and 9.37 ng/ml). Growth was monitored by daily evaluation of parasitemia on thin smears. Drug sensitivity tests were done weekly, using a radioisotope microdilution method. Mefloquine was removed from culture media when decreasing parasitemia was observed, and reintroduced when multiplication reoccurred. Parasite survival was inversely proportional to drug concentrations. The parasites tolerated progressively higher concentrations of mefloquine with prolonged exposure to the drug. Throughout this adaptation, the 50% inhibitory concentration for chloroquine and quinine showed no modification, but it increased considerably for mefloquine, exceeding known levels of resistance. Furthermore, a parallel increased resistance to halofantrine was observed, surpassing the normal range of sensitivity. Cross-resistance between mefloquine and halofantrine shown in this study has now been confirmed by epidemiologic in vitro surveys and clone analysis. These findings may have important in vivo consequences and eventually affect the choice of antimalarial therapy.

Animals↗

Mycoplasma hominis infection of perihepatic hematomas in a liver transplant recipient.

We report the case of a recipient of liver transplantation in whom postoperative perihepatic hematomas were infected by Mycoplasma hominis. Etiologic diagnosis was delayed because this organism is a rare cause of postoperative infection and usually does not grow on standard bacteriologic media. The role of M. hominis in postoperative infections and the diagnostic problems of this organism are discussed.

Hematoma↗

Widespread in vitro resistance to chloroquine of Plasmodium falciparum in the Congo, 1987.

The drug sensitivity of 184 Plasmodium falciparum isolates was studied in vitro in three areas of the Congo in January 1987. Results show that parasites resistant to chloroquine but not to quinine or mefloquine were prevalent in the three investigated regions, but the drug response pattern varied widely. In Brazzaville, after the outburst of chloroquine resistance in 1985, prevalence of chloroquine resistant isolates seemed to have stabilized around 60%. The phenomenon more recently reached the North where about 30% isolates could be considered as drug resistant. As in Cameroon, wide variations in the prevalence and the level of resistance were observed within a very limited area emphasizing the role of drug pressure in market places where chloroquine is easily available.

Adolescent↗

[Comparative efficacy of chloroquine and amodiaquine (25 and 35 mg/kg) in school children infected with P. falciparum (Brazzaville, March 1990)].

The efficacy of 4 therapeutic schedules was compared in March and April 1990 in Brazzaville school children, aged between 6 and 8 years, with parasitaemia of at least 1,000 trophozoites of Plasmodium falciparum per mm3. It was possible to interpret 125 simplified in vivo tests. The results showed that the activity of amodiaquine is still relatively satisfactory. The activity of chloroquine was slightly lower with the schedule of 25 mg/kg but was good at 35 mg/kg. Although these results were obtained in children who were mostly asymptomatic, they show that the use of amino-4-quinolines is still justified, at least in the initial treatment of uncomplicated malaria in semi-immune congolese subjects.

Amodiaquine↗