PubMed Health⌕ Search

Biomedical subjects

B Falissard

Publications and source records attributed to B Falissard.

At least 19 recordsLinked to original sources

Evaluation of the nutritional and inflammatory status in cancer patients for the risk assessment of severe haematological toxicity following chemotherapy.

BACKGROUND: The toxicity outcome of cancer patients receiving chemotherapy is difficult to predict. In this study the influence of malnutrition and inflammation on acute haematological toxicity was investigated. PATIENTS AND METHODS: Between January 1999 and January 2000, 48 consecutive cancer patients experienced severe haematological toxicity (SHT), either neutropenic fever or severe thrombocytopenia, following various chemotherapy regimens. Their baseline characteristics were compared with those of 59 control patients. Previous chemotherapy regimens, type of chemotherapy, performance status (PS), calculated creatinine clearance, bilirubin, C-reactive protein (1), alpha-1 acid glycoprotein (2), albumin (3), pre-albumin (4) and the nutritional and inflammatory status (NIS) ratio [NIS = (1 x 2)/(3 x 4)] were studied. Statistical analysis was carried out using either a t-test or a chi-square test. A receiver operating characteristic (ROC) curve determined the cut-off value for NIS. RESULTS: Patients experiencing SHT had a higher PS (P <0.001), inflammatory serum protein levels (P <0.001) and NIS ratio (P <0.0001), but lower haemoglobin (P <0.05) and serum-albumin levels (P <0.0001). Using a cut-off of 0 or 1 for PS and 1 for NIS, sensitivity was 98%, 43% and 89%; specificity was 38%, 90% and 66%, respectively. In 37 patients treated with topotecan as single agent, the determinants for SHT were PS (P <0.0001) and NIS (P <0.0001). CONCLUSIONS: Altered nutritional and inflammatory status correlates with increased risk of severe haematological toxicity following anticancer chemotherapy.

Adult↗

Cytotoxic synergism of methioninase in combination with 5-fluorouracil and folinic acid.

Potentiation of the cytotoxic activity of 5-fluorouracil (FUra) by folinic acid (5-HCO-H4folate) is due to elevation of the methylene tetrahydrofolate (CH2-H4folate) level, which increases the stability of the ternary complex of thymidylate synthase (TS), fluorodeoxyuridine monophosphate, and CH2-H4folate that inactivates the TS. Methionine deprivation results in the production of tetrahydrofolate (H4folate) and, subsequently, CH2-H4folate from methyl tetrahydrofolate, as a consequence of the induction of methionine synthesis. We hypothesized that the efficacy of FUra could be augmented by the combination of high-concentration 5-HCO-H4folate and recombinant methioninase (rMETase), a methionine-cleaving enzyme. Studies in vitro were performed with the cell line CCRF-CEM. Cytotoxic synergism of FUra + rMETase and FUra + 5-HCO-H4folate + rMETase was demonstrated with the combination index throughout a broad concentration range of FUra and rMETase. A subcytotoxic concentration of rMETase reduced the IC50 of FUra by a factor of 3.6, and by a factor of 7.5, in the absence and in the presence of 5-HCO-H4folate, respectively. 5-HCO-H4folate increased the intracellular concentrations of CH2-H4folate and H4folate from their baseline levels. Concentrations of folates were not changed by exposure to rMETase. Levels of free TS in cells treated with FUra + 5-HCO-H4folate and with FUra + rMETase were lower than those in cells exposed to FUra alone. The decrease of TS was still more pronounced in cells treated with FUra + 5-HCO-H4folate + rMETase. The synergism described in this study will be a basis for further exploration of combinations of fluoropyrimidines, folates, and rMETase.

Antimetabolites, Antineoplastic↗

Impact of reminders and method of questionnaire distribution on patient response to mail-back satisfaction survey.

Nonresponse and methods of data collection could affect satisfaction measurement. The goal of this study was to estimate the impact of (1) nonresponse and (2) distribution method on evaluation of patient satisfaction in a mail-back study measuring patient opinion of medical and nursing care. The study was conducted in an adult hospital. Patients were pseudo-randomized according to the initial mode of questionnaire distribution (given at hospital or sent by mail). Three reminders were made at 1-week intervals to nonrespondents, regardless of the method of initial questionnaire distribution. Groups were distinguished according to the delay of response: initial (before any reminder), middle (after one or two mailed reminders), and late respondents (after mailed reminders plus telephone contact). The study included consecutively discharged patients to obtain 300 patients per arm. 482 patients returned the questionnaire (248 in the group receiving the questionnaire at the hospital and 234 in the other group). Groups were compared for satisfaction scores and delay of response. Early respondents were compared with middle and late respondents for patient characteristics, modality of hospital care, and satisfaction scores. Multivariate analyses were performed. Participation rate before any reminder was higher when the questionnaire was mailed than when it was given at the hospital (45% versus 39.7%, p = 0.03). The initial method of distribution did not influence patient satisfaction level. Satisfaction did not differ between respondents with or without reminders. Distributing questionnaires by mail may be preferred to distribution at discharge to optimize response rate. Reminders do not seem necessary to estimate satisfaction of overall potential respondents.

Adult↗

Genetic clustering of hepatitis C virus strains and severity of recurrent hepatitis after liver transplantation.

The influence of viral factors on the severity of hepatitis C virus (HCV)-related liver disease is controversial. We studied 68 liver transplant patients with recurrent hepatitis C, of whom 53 were infected by genotype 1 strains. Relationships between core sequences, serum HCV RNA levels, and fibrosis scores for each patient were analyzed in pairwise fashion 5 years after transplantation. We used Mantel's test, a matrix correlation method, to evaluate the correspondence between measured genetic distances and observed phenotypic differences. No clear relationship was found when all 68 patients were analyzed. In contrast, when the 53 patients infected by genotype 1 strains were analyzed, a strong positive relationship was found between genetic distance and differences in 5-year fibrosis scores (P = 0.001) and differences in virus load (P = 0.009). In other words, the smaller the genetic distance between two patients' viral core sequences, the smaller the difference between the two patients' fibrosis scores and viral replication levels. No relationship was found between genetic distance and differences in age, sex, or immunosuppression. In multivariate analysis, the degree of fibrosis was negatively related to the virus load (r = -0.68; P = 0.003). In the particular setting of liver transplantation, and among strains with closely related phylogenetic backgrounds (genotype 1), this study points to a correlation between the HCV genetic sequence and the variability of disease expression.

Genotype↗

Use of hormone replacement therapy: women's representations of menopause and beauty care practices.

OBJECTIVES: Hormone replacement therapy (HRT) during menopause has been shown to have beneficial effects on women's health, including preventing osteoporosis and probably reducing cardiovascular mortality and morbidity. However, these effects appear only after long use. Knowledge of factors influencing HRT use is a prerequisite for developing and assessing preventive actions. Most studies of user characteristics have focused on medical knowledge and socioeconomic characteristics, although social and cultural models of menopause may also play a role. Therefore, our study of the determinants of HRT use focused on representations of menopause and on beauty care. METHODS: Two scores, one concerning the level of beauty care and the other the representations of menopause, were calculated. In our population of 561 postmenopausal women from the GAZEL cohort in France, 409 (72.9%) had been using HRT for more than one year, and 152 (27.1%) had used it for less than three months, if ever. Associations between the study variables and HRT use were then analysed. RESULTS: No association was found between representations of menopause and HRT use. Beauty care and some beliefs about HRT (i. e. that it is useful for osteoporosis prevention, causes resumption of menstruation, and has anti-aging effects) were independently associated with HRT use. Moreover, the proportion of HRT users increased with socioeconomic status, with vasomotor symptoms in early menopause, and among hysterectomised women. CONCLUSIONS: The results suggest that the amount of attention women pay to beauty care plays a role, in determining HRT use.

Beauty↗

Performance of an automated system for quantification of hepatitis C virus RNA.

The Amplicor HCV Monitor test for quantitative determination of serum or plasma hepatitis C virus (HCV) RNA was modified recently and introduced onto the Cobas Amplicor instrument to automate fully amplification, detection and calculation of results. This new version (v2.0) was evaluated in a routine diagnostic laboratory. The sensitivity and reproducibility were assessed on well-characterized panels (Eurohep) and clinical samples. HCV RNA levels measured by the v2.0 Monitor test were about 1log(10) higher than those detected by the previous version test, and genotypes 1 and 3 were quantified with equal sensitivity. Within the linear dynamic range of 10(3) to 10(6) copies/ml, the coefficients of variation for both intra- and inter-assay reproducibility ranged from 1.9 to 2.95%. This test system was found to be a reliable and labor saving assay for the quantification of HCV RNA.

Automation↗

Hepatocellular carcinoma with lymphoid stroma: a tumour with good prognosis after liver transplantation.

AIMS: Carcinomas with lymphoid stroma arising in non-liver-organs have a better prognosis than other carcinomas and may be associated with Epstein-Barr virus. We determined the frequency, characteristics and prognosis of hepatocellular carcinomas with lymphoid stroma. METHODS AND RESULTS: Histology of the livers of 162 patients with hepatocellular carcinoma, who underwent an orthotopic liver transplantation, was reviewed independently by three pathologists. Hepatocellular carcinoma with lymphoid stroma was diagnosed when all tumour samples contained more lymphocytes than tumour cells. Epstein-Barr virus was detected by in-situ hybridization and by polymerase chain reaction. Five patients (3.6%) were classified as hepatocellular carcinomas with lymphoid stroma. All patients were males. Cirrhosis was present in four/five patients. Serum alpha-fetoprotein levels were normal. Inter-observer histological reproducibility was good. Tumour cells did not contain Epstein-Barr virus. The five patients were alive without tumour at three years, although two of them had adverse prognostic factors at the time of transplantation (more than one tumour with a diameter > or = 40 mm). Only one patient had tumour recurrence, but he survived 7.6 years post-transplantation. The 5-year survival of patients with hepatocellular carcinoma with lymphoid stroma was better than that of the patients with other types of hepatocellular carcinomas (P = 0.04). CONCLUSIONS: Hepatocellular carcinoma with lymphoid stroma should be considered as a distinct clinicopathological and prognostic entity.

Carcinoma, Hepatocellular↗

Sleep and alertness in children with ADHD.

OBJECTIVE: To evaluate sleep and alertness and to investigate the presence of possible underlying sleep/wake disorders in children with attention-deficit/hyperactivity disorder (ADHD). METHOD: After 3 nights of adaptation in a room reserved for sleep studies in the department of child psychiatry, children underwent polysomnography (PSG) followed by the Multiple Sleep Latency Test (MSLT) and reaction time tests (RT) during the daytime. Thirty boys diagnosed as having ADHD (DSM-IV), aged between 5 and 10 years, and 22 age- and sex-matched controls participated in the study. All children were medication-free and showed no clinical signs of sleep and alertness problems. RESULTS: No significant differences in sleep variables were found between boys with ADHD and controls. The mean latency period was shorter in children with ADHD. Significant differences were found for MSLT 1, 2 and 3 (p < .05). Mean reaction time was longer in children with ADHD, with significant differences in all tests (p < .05). Number and duration of sleep onsets measured by the MSLT correlated significantly with the hyperactivity-impulsivity and inattentive-passivity indices of the CTRS and CPRS. CONCLUSION: Children with ADHD were more sleepy during the day, as shown by the MSLT, and they had longer reaction times. These differences are not due to alteration in the quality of nocturnal sleep. The number of daytime sleep onsets and the rapidity of sleep-onsets measured as MSLT were found to be pertinent physiological indices to discriminate between ADHD subtypes. These results suggest that children with ADHD have a deficit in alertness. Whether this deficit is primary or not requires further studies.

Adult↗

Chlorhexidine compared with povidone-iodine as skin preparation before blood culture. A randomized, controlled trial.

BACKGROUND: Chlorhexidine is better than povidone-iodine for care of catheter sites, but it is not known whether chlorhexidine is superior in reducing blood culture contamination. OBJECTIVE: To determine whether alcoholic chlorhexidine is a more effective skin antiseptic for collection of blood cultures than aqueous povidone-iodine. DESIGN: Randomized, controlled trial. SETTING: Three adult intensive care units in a French university hospital. PATIENTS: 403 adults who had at least one blood culture drawn through a peripheral vein. INTERVENTIONS: Patients were randomly assigned to receive skin preparation with an aqueous solution of 10% povidone-iodine or an alcoholic solution of 0.5% chlorhexidine before phlebotomy. MEASUREMENTS: Contamination rates of blood cultures. RESULTS: Of 2041 blood cultures collected in 403 patients, 124 yielded pathogens. Chlorhexidine reduced the incidence of blood culture contamination more than povidone-iodine (14 of 1019 cultures [1.4%] compared with 34 of 1022 cultures [3.3%]; odds ratio, 0.40 [95% CI, 0.21 to 0.75]; P = 0.004). CONCLUSION: Skin preparation with alcoholic chlorhexidine is more efficacious than skin preparation with aqueous povidone-iodine in reducing contamination of blood cultures.

Adult↗

"Silent" presentation of veno-occlusive disease after liver transplantation as part of the process of cellular rejection with endothelial predilection.

Hemorrhagic centrilobular necrosis and fibrous stenosis of hepatic venules, suggesting veno-occlusive disease (VOD) have rarely been observed after orthotopic liver transplantation (OLT). The aim of this study was to determine the prevalence of this syndrome after OLT in relation to the course with particular reference to acute rejection and to azathioprine administration. VOD was identified in 19 of 1,023 patients transplanted over a 9-year period. VOD occurred at a median of 30 days posttransplantation, without clear cut clinical evidence for hepatic vein outlet obstruction. Seventeen of the 19 patients had an episode of acute rejection before or at the time of VOD. These episodes were compared with that of patients without VOD. In patients with VOD, portal inflammation and endothelialitis were enhanced (P =.014 and P =.048) and endothelialitis was also higher than bile duct damage (P =.03). The incidence of a centrilobular endothelialitis for both groups was not different although an increased trend was observed in the study group (64% vs. 46%; P =.18). The incidence of persistent rejection was similar between both groups (47% vs. 41%). The incidence of chronic rejection was higher in the study group (29% vs. 10%; P =. 04). All patients with VOD received azathioprine as part of immunosuppressive regimen. Despite azathioprine withdrawal, zone 3 changes persisted in 57% of patients. In conclusion, the incidence of VOD was 1.9% after OLT. The association of prominent endothelial involvement and VOD with acute rejection in most cases suggests an immunological phenomenon.

Adult↗

Abnormal psychosocial situations among inpatients from a child and adolescent psychiatric department in a teaching hospital in France.

In order to examine the relationships between Associated Abnormal PsychoSocial Situations and psychiatric disorders in children and adolescents, an exploratory analysis using Axis V of the ICD-10 was performed on 1050 child and adolescent psychiatric inpatients. A logistic regression analysis was completed with respect to four groups of DSM-III-R diagnostic categories (Emotional Disorders, Disruptive Behavior Disorders, Specific Developmental Disorders, Non Specific Developmental Disorders). AAPSS were more frequently found in children and adolescents with Emotional Disorders or Disruptive Behavior Disorders than in those with Developmental Disorders but there was no diagnostic specificity in the distribution of AAPSS.

Adolescent↗

Further epidemiological evidence for anticipation in schizophrenia.

Anticipation describes an inheritance pattern within a pedigree in which disease severity increases, and/or age at onset decreases, in successive generations. This phenomenon has been described in different samples of schizophrenic subjects, and could explain many inconsistencies in the inheritability of schizophrenia. Anticipation is, however, subject to numerous and significant biases, partially controlled by different methodologies used in different studies. We analyzed the anticipation effect on an original sample of schizophrenic patients (n = 57) who had at least one other schizophrenic in their family belonging to another generation (father/mother, uncle/aunt, son/daughter). We tested the anticipation effect according to previously published methodologies, such as percentages of parent-child pairs showing negative versus positive anticipation, comparison of anticipation limited to parent-child or uncle-nephew pairs, anticipation analysis on the basis of families with unilineal origins only, and comparison of the age at onset-survival distribution of the two generations. The 31 schizophrenic subjects who belonged to the younger generation had a significantly earlier age at onset (24.58 years) than the 26 schizophrenic subjects who belonged to the older generation (36.46 years). Whatever the method used to control biases, we significantly found earlier age at onset for schizophrenic patients from the younger generation. There is strong evidence for the existence of the anticipation effect in schizophrenia in our sample, as well as in various others, which may elucidate numerous inconsistencies in clinical and epidemiological data which characterize schizophrenia. Looking for expanded trinucleotide repeats is thus the next step to detect the gene(s) that are potentially involved.

Adult↗

TCR alpha beta gene usage for myelin basic protein recognition in healthy monozygous twins.

The pathogenic role of myelin basic protein (MBP)-specific T lymphocytes in multiple sclerosis (MS) has been suggested by the encephalitogenicity of MBP-specific T cells in experimental allergic encephalomyelitis (EAE). In humans, extensive analysis of TCRs involved in MBP recognition has led to conflicting results, varying from an intra- and/or interindividual restriction to high diversity in TCRAV/TCRBV gene usage. We previously established MBP-specific T cell lines (TCLs) from healthy monozygous twins and characterized their fine epitope specificity. In this study, we report on the TCR alpha beta gene usage of 52 of these MBP TCLs that are specific for epitopes recognized by both co-twins within the same pair. High overall diversity in the TCR alpha and TCR beta genes used for recognition of this self-Ag, MBP, was observed. Variable genes belonging to 19 different TCRAV and 16 different TCRBV subfamilies are expressed by the 52 TCLs herein studied. In co-twins, TCLs utilized genes belonging to common TCRAV and/or TCRBV gene subfamilies in 7 of 13 instances of shared epitope recognition. Statistical analysis of intrapair concordance for TCR gene usage for the recognition of a given peptide did not show any significant deviation from values that would be anticipated in the absence of genetic background effect.

Amino Acid Sequence↗

Anticipation in schizophrenia: new light on a controversial problem.

OBJECTIVE: Anticipation, recently found in several neuropsychiatric disorders, is an inheritance pattern within a pedigree in which disease severity increases or age at onset decreases in successive generations. Demonstration of genetic anticipation in schizophrenia could be of heuristic value, since unstable trinucleotide repeat DNA is known to be the biological basis of anticipation. However, to overcome one of the major ascertainment biases that might mimic anticipation--namely, the fact that patients in different generations are not interviewed at the same age, resulting in a greater chance of finding a later age at onset in the older generation--a new method of investigating anticipation was used. METHOD: The study subjects were 97 systematically ascertained schizophrenic patients belonging to 24 families with at least two generations affected who were identified during a 1-year prevalence study in a limited geographical area of Reunion Island (Indian Ocean). A method of calculating expected age at onset according to age at interview was used in the analyses. RESULTS: In the younger generation of patients, the observed age at onset (21.80 years) was earlier than the expected age at onset (24.95 years), demonstrating anticipation, even when five additional biases that can mimic this genetic effect--the proband effect, the presence of an affected father or mother, the bilineality of the illness, the fertility effect, and the cohort effect--were taken into account. CONCLUSIONS: Evidence for anticipation was demonstrated in this group of schizophrenic patients. This may help the search for pathological genes implicated in the genesis of schizophrenia.

Adult↗

[The center effect in multicenter studies: fixed or random?].

The multiplication of multicentric clinical studies leads to a generalization of the use of a center effect in statistical analyses. In the simple situation where the dependent variable is quantitative and there is only a simple factor of interest, the formalisation of such a protocol corresponds to a two way ANOVA (with the factor of interest and the center factor) with generally a term of interaction. Even such a simple situation leads to interrogations, one of them being to determine whether the centre effect is fixed or random. In the first situation, the conclusion of the study will concern only the centres evaluated in the study, while in the second, the conclusion will concern the whole population from which the centers have been randomly selected. Such a generalizability has a cost: a loss of power in determining the effect of the factor of interest (the loss being as important as the interaction factor of interest x centre factor is large) and the necessity of sophisticated statistical software. This paper will focus on successively: the notion of ANOVA, of fixed or random effect (with the conceptual, formal and numerical differences that distinguish these two approaches). A numerical example is proposed.

Analysis of Variance↗

The succession procedure for interim analysis: extensions for early acceptance of Ho and for flexible times of analysis.

The succession procedure is a new method for group sequential analysis based on a succession of significant tests. In this paper, the procedure is extended by the addition of a lower boundary, which allows the early acceptance of the null hypothesis Ho according to the stochastic curtailing approach. The succession procedure is also adapted to the type I error spending rate function alpha *(t), leading to the method of semisequential analysis for which the times of analysis need not be specified in advance.

Algorithms↗