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Biomedical subjects

G Carles

Publications and source records attributed to G Carles.

At least 37 records · Page 2Linked to original sources

Effects of dengue fever during pregnancy in French Guiana.

To determine the effects of dengue fever (DF) during pregnancy, pregnant women presenting with a dengue-like syndrome at a hospital in Saint-Laurent du Maroni, French Guiana, from 1 January 1992 to 1 April 1998 were studied. The diagnosis of DF was made by serological tests, virus isolation on AP 61 mosquito cells, and/or reverse transcriptase polymerase chain reaction analysis. Twenty-two women had either probable or confirmed DF. Dengue virus serotype 2 was detected in four cases, and dengue virus serotype 1 was detected in one. Three fetuses died following the onset of the disease, and three cases of prematurity occurred. All infants appeared normal during physical examination, and no neonatal DF was diagnosed. In conclusion, DF in pregnant women did not cause any infant abnormality, but it may have been responsible for fetal death. The rate of fetal death associated with DF (13.6%) was much higher than the mean rate for the gynecology unit at the hospital (1.9%). However, these differences were not significant, and consequently these preliminary results need to be confirmed.

Dengue↗

Convergent effects of growth factors, hormones, and fibronectin are necessary for the enterocyte differentiation of a colon adenocarcinoma cell line (HT29-D4).

The aim of this work was to show in serum-free medium a convergent effect of physiological factors and extracellular matrix proteins on the differentiation process of enterocytes by taking as a model the HT29-D4 clone that has the feature of differentiating when subcultured in fetal bovine serum glucose-free medium. We show that triiodothyronine (T3) as well as insulin promotes limited cell growth and differentiation, whereas fibronectin or bovine serum albumin (BSA) induces cell growth and a low level of differentiation. However, insulin, T3, fibronectin, and BSA together with epidermal growth factor and transferrin promoted satisfactory growth and enterocyte morphology with epithelial electrophysiological properties in HT29-D4 cells. With these factors adequate protein targeting was achieved since cells apically expressed the carcinoembryonic antigen, and basolaterally transferrin and insulin receptors, beta 1 and alpha v beta 6 integrins, talin, vinculin, and focal adhesion kinase (FAK). Talin, vinculin, FAK, and alpha v beta 6 integrin, the fibronectin receptor, were clustered in focal contacts, which agrees with a possible role of fibronectin in final cell growth, the latter process mediating the final phase of differentiation. This level of differentiation can be maintained for a long time. Thus HT29-D4 cells appear to be a suitable model to study the implication of integrins in the differentiation process of human enterocytes.

Adenocarcinoma↗

The effect of combining antitubulin agents on differentiated and undifferentiated human colon cancer cells.

The cytotoxicity of sequential combinations of a taxoid [paclitaxel (TAX) or docetaxel (TXT)] with a vinca alkaloid [vinorelbine (NVB)] was compared in differentiated and undifferentiated HT29-D4 cells. Agents were titrated from low doses inducing no modification of microtubule network to high doses corresponding to the clinically relevant concentrations that block mitosis. For undifferentiated cells, the sequential combination NVB/TAX was more efficient than TAX/NVB (22% cell survival versus 37% for 5 nM TAX and NVB). Surprisingly, we successively obtained synergism for low doses of both compounds [NVB (1-5 nM) and TAX (1-15 nM)], then additivity and finally antagonism when one of the compounds was at the concentration inducing mitotic block. The three patterns of results were also obtained with NVB/TXT combinations. For the synergistic combinations at the lowest concentrations, cytotoxicity occurred by apoptosis following mitosis. For differentiated cells, the most cytotoxic combinations were 1 microM TAX or TXT for 3 days followed by 1 microM NVB for 3 days, and 0.75 nM TAX or TXT for 9 days followed by 1 microM NVB for 3 days, the latter producing synergistic effects. Cytotoxicity occurred by apoptosis for the two states of differentiation. Major differences depending on cell phenotype were demonstrated: low sensitivity of differentiated cells to antitubulin agents and the difference in apoptotic pathways since mitosis is not involved in differentiated cells.

Antineoplastic Agents, Phytogenic↗

Fetal cerebral and umbilical artery blood flow changes during pregnancy complicated by malaria.

The objectives of our study were to quantify the fetal cerebral artery and umbilical artery blood flow changes daily during a malaria crisis in a pregnant patient and evaluate the sensitivity and the specificity of Doppler indices for the prediction of acute fetal distress at the end of the pregnancy. The study, designed as a prospective and observational one, was carried out in the obstetric department of a government hospital in French Guiana, on 23 women with pregnancies complicated by malaria (age range, 23 +/- 5 years; primiparas, 30%); crisis date: 30.8 +/- 2.5 weeks of gestation; start of treatment: 3.7 +/- 1.3 days after crisis started). The main measures of outcome consisted of daily determinations of fetal Doppler indices during the crisis, evidence of fetal distress (fetal heart rate decelerations) during labor, Apgar scores after birth, gestational age at birth, mode of delivery, and birth weight. During the crisis umbilical artery resistance index increased by 5 to 20% (P < 0.05), cerebral artery resistance index decreased by 5 to 20% (P < 0.05), and CURR decreased by 10 to 35% (P < 0.01), indicating flow redistribution toward the brain. No relationship was found between the CURR value and the following data: parasitemia grade, parity, gestational age of the crisis, date and mode of delivery, and fetal weight. A change in the hypoxia index (% change in CURR during the crisis x number of days of crisis) greater than 150 was associated with abnormal fetal heart rate in 75% of the cases, and a hypoxia index lower than 150 was associated with normal fetal heart rate in 90% of the cases (sensitivity, 89%; specificity, 77%). Lastly, the combination (hypoxia index > 150 and CURR < 1) was associated with abnormal fetal heart rate in 80% of the cases, and one or two of these normal parameters were associated with normal fetal heart rate in 84.6% of the cases (sensitivity, 80%; specificity, 84%). The CURR and the hypoxia index during the malaria crisis can be used to predict acute fetal distress at delivery.

Acute Disease↗

[Pregnancy and malaria. Study of 143 cases in French Guyana].

Malaria is the most frequent infection world wide affecting pregnant women. The association of malaria and pregnancy sometimes has serious repercussions on the foetus and increases maternal morbidity. We report 143 cases of pregnant women infected by Plasmodium falciparum in French Guyana. The consequences on the fetus in this area, where the maternal premunition rate is low, are serious: the rates of prematurity, hypotrophy and stillbirth are 3 times higher among pregnant women infected by malaria. The consequences for the fetus are all more serious if the infestation is repeated or prolonged, the closer one is to delivery, and if the parity is low. The histologic study of the placenta shows a significant correlation between the placental infection and the fetal hypotrophy. We tried to detect in utero the consequences malaria infection has on the fetus: the presence of an echographic oligoamnios and alterations of the Doppler ratings would be predictive of deleterious consequences of malaria on the fetus. We emphasize the need for rapid treatment as soon as the attack begins, before serious placental lesions occur.

Female↗

[Pregnancy and childbirth in adolescents under 16. Study of 150 cases in French Guyana].

We studied 150 cases of adolescents under 16 having delivered at the maternity of Saint Laurent du Maroni hospital in French Guyana. These pregnancies were compared with those of 150 parturient women aged between 18 and 25. Significant differences were found between the two groups in terms of vaginal infectious diseases, premature birth rate and perinatal mortality. There was a significantly higher rate of assisted deliveries. These results are in concordance with the literature, except for the percentage of pre-eclampsia, which is not higher in our series. We point out the very high adolescent pregnancy prevalence in French Guyana and the need for setting up of a suitable prevention policy.

Adolescent↗

[Fetal circulation and malaria].

OBJECTIVE: To quantity the fetal vascular changes during flare-up, and to evaluate the sensitivity and the specificity of Doppler indices for the prediction of acute fetal distress at the end of the pregnancy. METHOD: Every day of flare-up the umbilical resistance (Rp), cerebral resistance (Rc), cerebro-placental ratio (CPR = Rc/Rp), and hypoxia index (HI = delta % CPR x crisis duration) were calculated. RESULTS: Twenty-three pregnancies were investigated at St Laurent du Maroni Hospital (French Guiana). During flare-ups the Doppler placental resistance increased (placental disorder), cerebral resistance decreased (vasodilation), CPR decreased (flow redistribution toward the brain), and HI increased. An abnormal CPR (< 1) was associated with abnormal fetal heart rate (FHR) in 61.5% of the cases, a CPR > 1 was associated with a normal FHR in 80% of the cases. (sensitivity: 80%, specificity 61%). A CPR < 1 was associated with one of the abnormalities (abnormal FHR, cesarean section, abnormal Apgar) in 71% of the cases, a CPR > 1 was associated with normal delivery in 55% of the cases (sensitivity: 71.4%, Specificity 55%). A HI higher than 150 was associated with abnormal FHR in 75% of the cases, a HI < 150 was associated with normal FHR in 90% of the cases (sensitivity: 89%, specificity: 77%). Lastly the combination (HI > 150 + CPR < 1) was associated with abnormal FHR in 80% of the cases, 1 or 2 of these parameters were associated with normal FHR in 84.6% of the cases (sensitivity: 80%, specificity: 84%). The minimum CPR and the HI during malaria flare-up can be used to predict acute fetal distress at delivery.

Acute Disease↗

[Modification of the response to paclitaxel of human differentiated colon cancer line after long-term treatment at very low dose].

Taxoids (paclitaxel, Taxol and docetaxel, Taxotere), drugs which stabilize microtubules, demonstrate marked activity against ovarian, brain and lung cancer. We investigated, on the human colon adenocarcinoma HT29-D4 cell line, firstly the effects of taxoids in function of the differentiation state and secondly the effects of a low dose of paclitaxel on the differentiation process. The cellular parameters studied were microtubular network, cell cycle and cell tubulin content. Undifferentiated cells treated with paclitaxel or docetaxel (10-100 nM) classically induced bundles in interphasic cells and pseudoasters in mitotic cells, arrest in cell cycle in G2M and increase in tubulin content. Inversely, no modification was observed in differentiated cells after similar taxoid treatment. Long-term low-dose pretreatment of differentiated cells restitutes some sensitivity to taxoids since these cells become responsive to further taxoid treatment, as reflected by modifications of the microtubule network.

Adenocarcinoma↗

Risk factors for maternal HTLV-I infection in French Guiana: high HTLV-I prevalence in the Noir Marron population.

The aim of this study was to compare rates of human T-cell lymphotropic virus type I (HTLV-I) seroprevalence in pregnant women belonging to different ethnic groups in French Guiana and to determine the risk factors associated with HTLV-I seropositivity. All 1,873 deliveries between 1 July 1991 and 30 June 1993 in the only gynecologic and obstetric unit at Saint Laurent du Maroni were enrolled. Serologic status could be established for 1,727 women, with 75 (4.3%) being HTLV-I seropositive. The HTLV-I seroprevalence rate differed significantly between ethnic groups: 5.7% for Noir-Marron (70/1,302), 6.3% for Haitian (3/50), and 0% for Creole (126), Amerindians (166), and Hmong (64). In Noir-Marron pregnant women, HTLV-I seropositivity was associated with a maternal age of > 35 years [odds ratio (OR), 3.3; 95% confidence interval (CI), 1.4-7.6], prior miscarriage (OR, 1.7; CI, 1-2.8), prior cesarean section (OR, 2.1; CI, 1.1-4.0), a parity > 4 (OR, 4.0; CI, 1.8-8.8), a gravidity > 6 (OR, 4.2; CI, 2.0-7.2), and a negative Rhesus factor (OR, 2.2; CI, 1.1-4.5). Two separate stepwise logistic regressions were done because gravidity and parity were highly correlated. HTLV-I seropositivity remained associated with a gravidity > 6 (OR, 3.9; CI, 2.1-7.4) and a negative Rhesus factor (OR, 2.6; CI, 1.2-5.3) for the first model and with a parity > 4 (OR, 4.1; CI, 1.9-9.0) and a negative Rhesus factor (OR, 2.5; CI, 1.2-5.1) for the second model.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Simultaneous combination of microtubule depolymerizing and stabilizing agents acts at low doses.

The combined activity of a stabilizing and a depolymerizing agent was studied on microtubule formation in vitro and on cellular parameters related to the cytoskeleton. New compounds in each class of microtubular drugs, docetaxel, as stabilizing agent, and CI 980, as colchicine analog, currently in clinical trials, were tested at high and low concentrations. Simultaneous combination of docetaxel and CI 980, both in vitro and in cell lines, induced microtubule structures resulting from the association of the effects of the two drugs: short and numerous microtubules in vitro, abnormal asters or short bundles in cells depolymerized in their periphery. Moreover, combining the two drugs at low concentrations inducing neither modification of the microtubular network nor variation in cell polymerized tubulin content showed synergistic effects in mitotic cell block and, at lower concentrations, in inhibition of proliferation in the KB 3-1 cell line. Similar qualitative results were obtained with paclitaxel and colcemid, used in the place of docetaxel and CI 980, respectively. At low doses, the taxoid/colchine analog combination seems to induce some degree of mitotic inhibition, resulting from a subtle effect on the inhibition of microtubule dynamics.

Antineoplastic Agents↗

[Leptospirosis and pregnancy. Eleven cases in French Guyana].

The incidence of leptospirosis, a widespread antropozoonosis, is underestimated due to variable clinical presentations. The abortive effect of this disease, well known in animals, is only reported rarely in humans although transplacental transmission has been demonstrated. We report 11 cases of leptospirosis in pregnant women in French Guiana. The diagnosis was made on identification of the germ in maternal urine samples and/or on specific serology tests. Fetal death occurred in more than 50% of the cases due to premature abortion or in utero death. The rate of maternal-fetal transmissions is not known, but leptospirosis could be a not uncommon cause of perinatal deaths in endemic zones.

Female↗

Comparative effects of taxol and Taxotere on two different human carcinoma cell lines.

The effects of taxoids (taxol and Taxotere) were followed on two human cancerous cell lines (bladder carcinoma J82 cells and epidermoid carcinoma KB 3-1 cells). Three cellular parameters were studied, viz., the qualitative effect on cellular microtubules, the quantitation of tubulin, and the antimitotic action, using two-parametric flow-cytometric analyses in treated cells. In both of the cell lines the tubulin content increased after taxoid treatment before the accumulation of cells in the G2/M phase. The effects of taxoids on tubulin appeared at about a 10-fold lower concentration on KB cells than on J82 cells. After drug exposure, the microtubule network showed a striking difference between the two cell lines: microtubule bundles were predominant in the J82 cell line, whereas multiple asters were prevalent in the KB cell line. The formation of these structures was dose- and time-dependent. Asters were observed in mitotic cells and bundles were seen in interphase cells. The reversibility of these structures in both cell lines varied with the duration of exposure to drug. Some differences were shown between taxol and Taxotere: the effects of Taxotere as compared with taxol appeared at a 2-fold lower concentration and their reversibility was slower.

Antineoplastic Agents, Phytogenic↗

Intravenous immunoglobulin treatment in patients with motor neuron syndromes associated with anti-GM1 antibodies: a double-blind, placebo-controlled study.

We studied the effects of intravenous immunoglobulin (IVIg) in 12 patients with motor neuron syndromes associated with high titers of anti-GM1 antibodies. Five of the patients had conduction blocks. The study design was a double-blind, placebo-controlled, crossover trial with IVIg (0.4 g/kg body weight per day injected for 5 consecutive days). We evaluated the patients before and 5, 28, and 56 days after drug administration using a computerized analyzer for muscle strength, the Norris scale for disability, motor nerve conduction velocities for patients with conduction blocks, and measurements of immunologic markers. Compared with placebo, IVIg induced a significant increase in muscle strength only in the patients with conduction blocks.

Adult↗

[Retrospective study of 45 cases of congenital syphilis in French Guiana from 1980 to 1990].

From 1980 through 1990, 45 cases of congenital syphilis, i.e., 15.5/10,000 births, were reported in French Guyana. Epidemiological and clinical characteristics of these cases were analyzed retrospectively. Most mothers were immigrants (32%) or members of the traditional Maroni community (60%). Congenital infections were often severe (symptomatic in 85% of cases and fatal in 33%). Treatment should be especially aggressive in patients infected with the human immunodeficiency virus.

Causality↗

[Labor and delivery in grand multipara. Retrospective study of 419 cases in 2 1/2 years].

Grand multiparity was long considered to be an obstetric risk factor. Is this still the case in 1990? Four hundred and nineteen deliveries of grand multipara (defined as six deliveries or more) were studied and compared with deliveries of patients of lower parity. There was no evidence of significantly more difficulties in the grand multipara. Age and general condition appear to have more influence than parity on the prognosis of labour and delivery.

Adult↗

[Efficacy of halofantrine in Plasmodium falciparum or Plasmodium vivax malaria in a resistance area (French Guiana)].

Halofantrine (WR 171.669) is a phenanthrene methanol derivative effective against the multidrug resistant strains of Plasmodium falciparum. One hundred and one patients, 48 men and 53 women, 53 adults and 48 children (less than or equal to 12 years old) aged from 1.5 to 57 years were treated. Fifty-one patients received a single 16 mg/kg dose and 50 patients received 24 mg/kg/day in 3 doses at 6-hour intervals. Parasite counts with examination of both thin and thick smears were performed twice daily for 5 to 6 days following treatment, or until smears were negative for parasites for 24 hours, and then weekly for 4 weeks. Thirteen patients reported clinical side effects. Six treated patients had no parasites. One patient had mixed parasitemia. Eighty three patients had P. falciparum malaria, with mean parasitemias between 26,850 +/- 36,679 and 35,412 +/- 50,527 per cubic millimeter. Halofantrine was very effective in the two doses tested from 87.5 to 100 p. 100. Eleven patients had in vivo resistant strains; ten in vitro tests were successful and nine were resistant to chloroquine. Thirteen patients with P. vivax and a mean parasitemia of 13,858 +/- 10,835 per cubic millimeter were cured but 3 had a relapse 3 to 4 weeks after treatment. At the 2 dosage levels tested halofantrine proved highly effective in the treatment of malaria caused by resistant and sensitive strains to P. falciparum.

Adolescent↗