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Biomedical subjects

C Lejeune

Publications and source records attributed to C Lejeune.

At least 55 records · Page 3Linked to original sources
PubMed1996

Carboplatin plus paclitaxel in the first-line treatment of advanced ovarian cancer: preliminary results of a phase I study.

This phase I trial was designed to determine the maximum tolerated dose of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) given as a 3-hour infusion in combination with carboplatin (400 mg/m2) as first-line chemotherapy for stage IIIC/IV ovarian adenocarcinoma. After premedication, paclitaxel was infused over 3 hours, followed by carboplatin infused over 30 minutes on day 1 of a 28-day cycle (group 1, with 28 patients accrued and 150 evaluable cycles) or on day 1 of a 21-day cycle (group 2, with 16 patients accrued and 55 evaluable cycles). Dose-limiting toxicities assessed after the first course included grade 4 neutropenia lasting longer than 7 days, febrile grade 4 neutropenia requiring intravenous antibiotics, grade 4 thrombocytopenia, mucositis greater than grade 2 for more than 7 days, grade > or = 3 nonhematologic toxicity (excluding alopecia, vomiting, and muscular pain), no hematologic recovery on day 42 (for group 1) or on day 35 (for group 2), neurotoxicity above grade 2, and persistence of nonhematologic toxicity (excluding alopecia, nausea/vomiting, and musculoskeletal pain) grade > or = 2 at scheduled re-treatment. If any of the events occurred during the first cycle in three or more of six patients, maximum tolerated dose was considered to have been reached. The hematologic toxicity associated with the two treatment schedules was mainly neutropenia, but it was of short duration. Very few dose reductions or dose delays were necessary. Until now, the six planned courses have been administered without colony-stimulating factors. No toxic death has occurred. Grade 2 or 3 peripheral neuropathy has occurred in 12% of patients, mainly with high doses of paclitaxel. At this time, the maximum tolerated dose has not been reached at paclitaxel 275 mg/m2 every 4 weeks or 225 mg/m2 every 3 weeks, and enrollment continues.

Adolescent↗
PubMed1995

Inflammatory carcinomas of the breast: a clinical, pathological, or a clinical and pathological definition?

Some controversy remains about the clinical or pathological definition of the different types of inflammatory breast cancer (IBC) and especially the diagnostic and prognostic value of dermal lymphatic involvement. Our purpose was to classify the different types of IBC for which diagnosis was confirmed intraoperatively and ascertain features allowing reliable diagnosis. We studied clinical findings, biological data, and treatment outcome in a series of 144 successive patients. Our results suggest that there are 2 biologically different entities i.e., true IBC and pseudo-IBC. True IBC, whose course is currently fatal in all cases, can be divided into 2 sub-categories i.e., common true IBC (75.7% of cases), in which inflammatory signs occur primarily or secondarily, and occult true IBC (13.2% of cases). Dermal emboli have been observed in 61% of common true IBC, but their absence did not alter the rapidly unfavourable outcome. Extensive lymph-node involvement, other biological features and survival were the same in the 2 sub-categories. Pseudo-IBC (11.1% of cases) can easily be confused with common true IBC. The biological characteristics of pseudo-IBC differ from those of true IBC: no dermal lymphatic involvement and little or no lymph-node involvement. Despite large tumour size, outcome was particularly favourable. It is of great importance to differentiate true and pseudo-IBC, for which the treatments are different. Confirmation of true IBC requires pathological demonstration of dermal lymphatic emboli or extensive lymph-node involvement. Occult IBC must be identified for patients presenting rapidly growing tumours.

Adenocarcinoma↗
PubMed1995

Age as a prognostic factor in breast cancer: relationship to pathologic and biologic features.

The relationship of age with prognostic factors and outcome of breast cancer has long been controversial due to numerous confounding factors. In order to clarify the prognostic value of age, we analyzed a homogeneous population of 1,266 patients treated for breast cancer at the same institution (mean follow-up: 62 months). Three groups were compared: patients under 35 years of age, non-menopausal patients over 35 years of age, and post-menopausal patients under the age of 70 years. A higher frequency of undifferentiated tumors, histoprognostic grade-3 cancer, microscopic lymph-node involvement and negative hormonal receptor status was observed in patients under 35 years. In addition, clinical but not anatomical tumor size was greater in young patients, suggesting higher stromal activity. Metastasis-free survival and overall survival were significantly poorer before 35 years. Differences were observed when patients were matched with regard to stage, anatomic size, histoprognostic grade, microscopic lymph-node involvement and receptor status. Multivariate analysis of both overall and metastasis-free survival demonstrated that age younger than 35 years was an independent risk factor. Younger women had a higher risk of local recurrence but, unlike older women, they did not experience any worsening of the already unfavorable outcome due to recurrence.

Adult↗
PubMed1995

[Modality and causes of 259 deaths in a pediatric intensive care unit].

BACKGROUND: There are few data available from European pediatric intensive care units (PICU) regarding the modes of death and their causes. POPULATION AND METHODS: Two hundred and fifty nine children, not including neonates, died in the PICU over a 7-year period (1987-1993). Data were obtained from a computerized data base and the retrospective review of medical records by two intensivists. Deaths were classified into three groups according to the terminal event: brain death (BD), unsuccessful resuscitation (UR), do-not-resuscitate order and limitation and/or withdrawal of therapy (LWT). RESULTS: BD was the most common mode of death (38%); UR accounted for 34% and LWT for 28% of deaths. There was no significant annual variation in the proportion of BD, UR and LWT. Age and sex were similar in the three groups. The predominant organ system failure involved upon admission was the central nervous system (52%) in the LWT group, and the cardiovascular system (54%) in the UR group. Severe chronic disease (37%) and immunosuppression (19%) were more prevalent in the LWT group than in the BD group. Time from admission to death was longer in the LWT group (median = 119 hours) as compared to the UR group (10 hours) and the BD group (54 hours). Ten percent of the BD patients became organ transplant donors. Sixty-seven per cent of BD patients had medical contraindication for organ donation: parents did not accept organ donation in 61% of potential cases. Thirty deaths (12%) seemed to be avoidable; dehydration from acute infectious gastroenteritis (n = 7) was the most common cause of avoidable death. CONCLUSIONS: The modes of death in our PICU were statistically not different from those seen in two of four North-American PICUs; LWT was less prevalent than in the two other PICUs, but the patient populations were very different (presence of neonates and many cardiovascular surgery patients). Assessment of the severity of illness at admission and of functional outcome in the survivors are mandatory in future studies.

Adolescent↗
PubMed1995

[Early, severe, neonatal infections due to streptococcus group B. Multicenter retrospective study on the incidence and risk factors].

UNLABELLED: Streptococcus group B is often the causal agent in maternofetal infections occurring early. The prevention of fatal fulminant forms is much controversial. POPULATION AND METHODS: A retrospective multicentric study (10 maternity wards, 5 years, 96.243 live births) was conducted. All cases of early (<48 th) infection due to Streptococcus group B were collected and divided into two groups for comparison: group 1: infant death, and group 2: surviving infants requiring ventilatory assistance for > or = 12 hours. The aim of this study was to determine the incidence of fatal infections and to ascertain he clinical features and laboratory data correlated with death. RESULTS: The incidence of fatal early maternofetal infection due to Streptococcus group B (group 1) was 14 cases in 96,243 live births (0.14%) or 1 case in 7,143 live births. All newborns who died were symptomatic at 8 hours of life. The factors significantly correlated with death were: lack of antibiotics per partum, which did not [correction of no] altogether prevent severe forms (2/14 deaths and 14/28 survivals had had antibiotic per partum); prematurity; impaired adaptation to birth, early clinical signs and sudden aggravation; lack of an inflammatory syndrome at first work-up; a chest X-ray suggesting hyalin membrane disease; and major non-infectious associated disease. CONCLUSION: These findings underscore the importance of antibiotic prophylaxy per partum and the need for immediate paediatric care in case of risk factors.

Cross Infection↗
PubMed1994

Pharmacokinetics of folinic acid and 5-methyltetrahydrofolic metabolite after repeated oral administration of calcium folinate following methotrexate treatment.

The pharmacokinetic profiles of folinic acid (FA) and its active metabolite, 5-methyltetrahydrofolic acid, were studied after oral administration of decreasing doses of calcium folinate during 37 courses of high and intermediate dose methotrexate treatment in 25 lymphoma patients. FA was administered at a dose of 6 x 50 mg in 15 courses, 6 x 25 mg in seven courses, 6 x 15 mg in 10 courses and 6 x 7.5 mg in 5 courses. FA, 5-methyltetrahydrofolic acid, methotrexate and 70H-methotrexate were assayed simultaneously by high performance liquid chromatography. When FA was administered at doses between 50 and 15 mg, maximum concentrations of both the drug and its metabolite were always obtained after 1 to 2 h and remained stable. The same was true for the equilibrium concentration of the two products at doses over 15 mg. These findings suggest saturation of absorption and metabolism of folinic acid at doses over 15 mg.

Administration, Oral↗
PubMed1994

Relative contribution of phosphoinositides and phosphatidylcholine hydrolysis to the actions of carbamylcholine, thyrotropin (TSH), and phorbol esters on dog thyroid slices: regulation of cytidine monophosphate-phosphatidic acid accumulation and phospholipase-D activity. I. Actions of carbamylcholine, calcium ionophores, and TSH.

The actions of carbamylcholine (Cchol), the ionophores A23187 and thapsigargin, and TSH on [3H]cytidine monophosphate-phosphatidic acid ([3H]CAMP-PA) accumulation were studied in prelabeled dog thyroid slices to evaluate phosphatidic acid (PA) generation and inositol recycling by phosphatidylinositol (PtdIns) synthesis. The effects of the same agonists were also measured on phosphatidylbutanol generation in [3H]palmitate- or [3H]myristate-prelabeled slices to assess the activity of phospholipase-D (PLD) and on the effluxes of myo-[3H]inositol and [3H]choline induced by these agents from prelabeled slices. Cchol (10(-6)-10(-4) M) increased inositol phosphate (InsP) generation, with no change in inositol efflux, and contracted the intracellular inositol pool. This suggests a stimulation of PtdIns synthesis as well as hydrolysis. The muscarinic agonist provoked a dramatic accumulation of CMP-PA in the presence of lithium chloride (10 mM), which suggests that when InsP hydrolysis is inhibited, inositol limits the rate of CMP-PA incorporation into PtdIns. Cchol also increased phosphatidylbutanol formation. The latter two actions of Cchol were reproduced by A23187 (10(-5) M) and thapsigargin (2 x 10(-6) M) and were inhibited by calphostin-C, an inhibitor of the regulatory site of protein kinase-C. Cchol also induced increased free choline efflux, with a decreased choline phosphate relative content of the medium. TSH (10 mU/ml) stimulated free inositol efflux and induced a slight and proportional increase in [3H]inositol incorporation in phosphoinositides and InsP. The hormone also increased PA and CMP-PA accumulation exclusively in the presence of the PA phosphatase inhibitor propranolol (10(-4) M), but had no detectable action on PLD activity. None of these effects of TSH was reproduced by forskolin or potentiated by lithium chloride (10 mM). The data demonstrate the existence in thyroid tissue of a PLD-hydrolyzing phosphatidylcholine that was stimulated by Cchol and increased intracellular Ca2+, but not by TSH. The results obtained, besides confirming that TSH does not stimulate PtdInsP2-PLC or affect phosphatidylcholine hydrolysis, suggest that the hormone, instead, stimulates de novo PtdIns synthesis and/or inositol transport. The physiological relevance of these actions of Cchol, increased intracellular Ca2+, and TSH in thyroid metabolism could be related to their divergent effects on thyroid cell metabolism.

Animals↗
PubMed1994

Relative contribution of phosphoinositides and phosphatidylcholine hydrolysis to the actions of carbamylcholine, thyrotropin, and phorbol esters on dog thyroid slices: regulation of cytidine monophosphate-phosphatidic acid accumulation and phospholipase-D activity. II. Actions of phorbol esters.

The effects of phorbol dibutyrate (PDBu) on phosphatidylbutanol (PtdBut) generation in [3H]palmitate- or [3H]myristate-prelabeled dog thyroid slices were measured to assess the activity of phospholipase-D (PLD) in the presence or absence of the two inhibitors of protein kinase-C (PKC), staurosporine (STSP) and calphostin-C. The actions of the same agents on [3H]cytidine monophosphate-phosphatidic acid accumulation were also determined to evaluate phosphatidic (PA) generation and inositol recycling to phosphatidylinositol. The effluxes of [3H]choline and [3H]ethanolamine induced by the phorbol ester from prelabeled slices were also evaluated. PDBu (5 x 10(-9) to 5 x 10(-6) M) potently stimulated PLD activity, with a concomitant increase in fatty acids incorporation in phosphatidylcholine (PtdCho). However, under no condition did the phorbol ester result in cytidine monophosphate-phosphatidic acid accumulation. It stimulated the efflux of choline and ethanolamine while decreasing choline and ethanolamine phosphates in the slices and incubation medium. Calphostin-C, inhibiting PKC, decreased PtdBut and PtdCho formation induced by the phorbol ester, as opposed to STSP (5 x 10(-6) M), which did not affect these actions of PDBu and, moreover, reproduced by itself the effects of the phorbol ester on choline efflux and PtdBut generation despite efficient inhibition of other effects of PKC. These data demonstrate the existence in thyroid tissue of a PLD-hydrolyzing PtdCho, which was stimulated by phorbol esters and STSP. They also suggest that the PA formed after PKC stimulation and subsequent PLD activation is channeled toward PtdCho resynthesis when intracellular Ca2+ is not increased, whereas the PA accumulated with a concomitant increase in intracellular Ca2+ is diverted toward phosphatidylinositol synthesis. The physiological relevance of this Ca-independent stimulation of a PKC-coupled PLD in thyroid metabolism could be related to the growth-inducing and dedifferentiating effects of the phorbol esters.

Animals↗
PubMed1993

[Massive fetomaternal hemorrhage and prevention of fetomaternal Rhesus incompatibility. The failure of our present system of prevention].

We had a case where risk of rhesus D feto-maternal immunisation occurred following failure to diagnose feto-maternal haemorrhage (HFM); and it was shown up by rhesus negative mother with a rhesus positive fetus being diagnosed as having has a massive HFM only three days after delivery. Giving the mother the standard dose of Anti-D immunoglobulin without a previous test to find out how serious the HFM was showed that we do not test for this normally. So it seems to us necessary when considering prophylaxis of rhesus D immunisation to go back to first principles and carry out Kleihauer's test particularly when neonatal anaemia is found in the child.

Adult↗
PubMed1992

Thyroid stimulating immunoglobulins, like thyrotropin activate both the cyclic AMP and the PIP2 cascades in CHO cells expressing the TSH receptor.

In human thyrocytes and in a permanent CHO cell line expressing the human thyroid stimulating hormone (TSH) receptor cDNA (JP09 cells), TSH activates both the cyclic AMP and the phosphatidylinositol 4,5-bisphosphate (PIP2) cascade, although the latter effect requires higher TSH concentrations. Thyroid stimulating autoantibodies (TSAb) activate also the human thyroid leading to the hyperthyroidism of Graves' disease. They bind to the TSH receptor and mimic the TSH stimulation of the gland by increasing intracellular cyclic AMP, but they do not enhance PIP2 hydrolysis in human thyroid slices. We show in this study that TSAb are able to activate the PIP2 cascade in JP09 cells, a cell line expressing high levels of TSH receptor. This suggests that the mechanism of action of TSAb on the TSH receptor is qualitatively similar to that of TSH.

Animals↗
PubMed1992

Inflammatory carcinoma of the breast.

Inflammatory breast carcinoma has to be defined by accurate clinical and pathological criteria. The prognosis is very poor and improvements made by chemotherapy are limited to the increase in the disease-free period and overall survival for a few months.

Adult↗
PubMed1992

[Neonatal digestive implantation of streptococcus group B. Influence of antibiotic therapy].

Group B streptococcus (GBS) is an important cause of neonatal infection. Early-onset diseases are due to perinatal contamination. The epidemiology of late-onset infections is poorly known. Maternal colonization may be responsible for some of them. The relationships between neonatal colonization and late disease could be a colonization of the gut. The purpose of this 3 year-prospective study was to analyse the kinetics of gut colonization in neonates and the influence of antibiotherapy. One hundred and nineteen infants less than one month of age were included because of the presence of GBS in their gastric aspirates or GBS infection. Depending on the therapeutic strategy, the infants were separated into 3 groups: 1) amoxicillin plus aminoside greater than or equal to 10 days because of neonatal infection (28 infants), 2) same combination less than or equal to 5 days because a GBS infection was suspected but not confirmed (17 infants), 3) no antibiotics (77 infants). Fecal flora was regularly analysed by differential count. Antibiotics caused rapid disappearance of GBS from the gut. However, the same strain reappeared after stopping the antibiotics at a rate of 13.5%. Without antibiotics, GBS was implanted in 33% of cases. This difference of implantation rate is statistically significant (p less than 0.05). No GBS infection was observed in any infant after a follow-up examination of 6 months to 2 years. Among the clinical and bacteriological factors studied, adhesion only was correlated with the GBS implantation. These results allow to discuss therapeutic abstention in colonized infants without any signs of infection.

Ampicillin↗
PubMed1991

[Epidemiology and prevention of perinatal group B streptococcal infections].

Neonatal group B streptococcal infection is frequent and may be responsible for lethal neonatal septicaemia. Its preventive treatment is still hotly debated. Digestive and genital tracts colonization is frequent in mother (15-20% of the cases) but it is unstable. About one out of two infants born of a colonized woman becomes colonized or infected. Neonates can also be colonized during their stay in maternity hospitals. Colonization is much more frequent than infection which strikes 0.2 to 0.6 per cent of neonates (at a very early period in two-thirds of the cases), but it jeopardizes their prognosis for life and later their functional prognosis. Prematurity and chorioamnionitis are the two main infection facilitating factors. Some of the various measures proposed to prevent infection in neonates, such as antibiotic therapy of colonized mothers during pregnancy and of symptomatic colonized neonates, do not seem to be effective, but others are interesting, including administration of antibiotics to mothers during delivery in high-risk situations, combined with early detection and immediate bactericidal treatment of neonatal infections.

Anti-Bacterial Agents↗