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Biomedical subjects

C Pichard

Publications and source records attributed to C Pichard.

At least 55 records · Page 3Linked to original sources

(133)Xe SPECT cerebral blood flow study in a healthy population: determination of T-scores.

UNLABELLED: Dementia is becoming a major health problem as the population of the Northern Hemisphere ages. Early differential diagnosis between normal cognitive decline and dementia is particularly difficult. If psychometric evaluation can contribute to the diagnosis, quantitative cerebral functional imaging would play an important role. We therefore proposed, first, to constitute a normative dataset that could later be used to identify subjects at risk for neurodegenerative processes and, second, to describe the risk of abnormal global cerebral blood flow (gCBF) by defining categories based on the standardized cutoff scores of a young, healthy population (T-score). METHODS: Of a total of 203 healthy volunteers, 187 were included in the protocol, which included evaluation of medical history, neurologic and neuropsychologic status, and body composition; analysis of blood; and measurement of gCBF by means of (133)Xe SPECT. RESULTS: With ANOVA analysis using age and sex as between-subject factors and gCBF as a within-subject factor, a significantly higher gCBF was found in women than in men. In addition, a linear reduction as a function of age was observed for both sexes (-0.3%/y). T-score was determined for the 18- to 28-y-old age group, for whom gCBF was found to be 46.7 +/- 5.1 mL/min/100 g tissue in men and 49.0 +/- 5.0 mL/min/100 g tissue in women. The age-dependent decrease could thus be expressed in T-scores and, in the 29- to 38-y-old, 39- to 48-y-old, and >48-y-old age groups, averaged -0.63, -1.29, and -1.92, respectively, in men and -0.63, -0.83, and-2.40, respectively, in women. Cognitive performance, body composition, and blood analysis revealed the expected significant effects from sex and age. CONCLUSION: The large-scale reference database of gCBF measurements constituted from a healthy, well-controlled population enabled age and sex stratification, which showed significant differences between the sexes and a significant decline as a function of age. T-scores were determined and warrant further studies on the prospective identification of early dementia by (133)Xe SPECT in elderly individuals.

Adolescent↗

[Early detection of protein-calorie malnutrition: a therapeutic asset].

In the industrialised countries, the sedentary life and the ageing process of the population, as well as the more frequent chronic diseases and heavy treatments, increase the incidence of protein-energy malnutrition (PEM). The insidious nature and harmful outcome of the PEM on the recovery process requires careful attention of the practitioner to the clinical signs of PEM. Their detection includes an anamnesis, anthropometric examinations, and assessments of the nutritional intakes and the impact of disease and medico-surgical treatments. However, the loss of muscle mass, which is the main indicator of the PEM, is often only assessed by the measurement of the body composition using bioelectrical impedance analysis. The advantage of this method is to distinguish fat-free mass, including muscle mass, from fat mass, when the loss of muscle is hidden by an increase of fat mass and/or body water. Using these different tools allows the practitioner to early detect PEM, to identify its causes, and to establish an appropriate nutritional schedule, in order to prevent from PEM or correct it.

Disease Progression↗

[Nutrition and HIV infection].

The HIV infection leads to many nutritional problems. For a long time, the Wasting Syndrome was one of the most frequent inaugural features of AIDS and still concerns many patients. The weight loss worsens the prognosis of the disease. The reduced dietary intakes, the increased digestive losses and energetic expenditure result in severe malnutrition. Therefore, the nutritional support and its association with orexigenes, anabolic agents and physical activity has to be carefully selected. The adverse events of new antiretroviral drugs influence the nutritional state and the patient's compliance towards their treatments. For lipodystrophy, whose etiology is still unknown, no treatment has yet been found. Metabolic disorders (dyslipidemia, glucose intolerance, diabetes, etc.) in this presently chronic disease require particular attention since they increase cardiovascular risks. In general they are sensitive to a dietary approach.

HIV Infections↗

[Value of prokinetics in enteral nutrition intolerance].

Malnutrition is associated with an increase in morbidity and mortality and therefore a raise in hospitalization's costs. Nevertheless, an early nutritional support can reverse this trend. Gastrointestinal dysfunctions (gastroparesis, abdominal distension, high gastric residues) in patient on enteral nutrition, may appear and very likely generate an increasing risk of regurgitations, pulmonary aspiration and infection. These symptoms represent the main factors limiting dosage in administering enteral nutrition. Prokinectics agents (metoclopramid, cisaprid and erythromycin) which improve gastric motility are often used in order to maintain enteral nutrition and to cover the energetic needs of patients. This revenue shows some way of using prokinectics in case of enteral nutrition intolerance and propose a step-by-step guideline on how to start and increase progressively enteral nutrition.

Clinical Trials as Topic↗

Human prolactin (hPRL) antagonists inhibit hPRL-activated signaling pathways involved in breast cancer cell proliferation.

The involvement of human prolactin (hPRL) in breast cancer has been recently reconsidered based on its autocrine/paracrine proliferative effect described in human mammary tumor epithelial cells. Therefore, there is growing interest in the development of potent hPRL antagonists that may inhibit this effect. We previously designed hPRL analogs displaying antagonistic properties in a human transcriptional bioassay. We now report that the most potent of those analogs, G129R-hPRL, antagonizes all hPRL-induced effects analysed in various breast cancer cell lines, including cell proliferation. The analog per se lacks intrinsic agonistic activity on PRL receptor-activated signaling cascades, cell proliferation and apoptosis, indicating that its mode of action only occurs through competitive inhibition of hPRL. We provide some molecular basis of this antagonistic effect by demonstrating that G129R-hPRL competitively inhibits hPRL-activation of the JAK-STAT and MAPK pathways, two signaling cascades involved in the mitogenic effect of hPRL in mammary epithelial cells. This competitive inhibition persists for at least 48 h, as evidenced by long term analysis of STAT5b activation or of progression through cell cycle. These results are the first demonstration at the molecular level that hPRL antagonists interfering with receptor dimerization disrupt signaling events in breast cancer cells, which prevents hPRL-induced cell proliferation.

Autocrine Communication↗

Reference values of fat-free and fat masses by bioelectrical impedance analysis in 3393 healthy subjects.

Determination of fat-free mass (FFM) and fat mass (FM) is of considerable interest in the evaluation of nutritional status. In recent years, bioelectrical impedance analysis (BIA) has emerged as a simple, reproducible method used for the evaluation of FFM and FM, but the lack of reference values reduces its utility to evaluate nutritional status. The aim of this study was to determine reference values for FFM, FM, and %FM by BIA in a white population of healthy subjects, to observe the changes in these values with age, and to develop percentile distributions for these parameters. Whole-body resistance of 1838 healthy white men and 1555 women, aged 15-64 y, was determined by using four skin electrodes on the right hand and foot. FFM and FM were calculated according to formulas validated for the subject groups and analyzed for age decades. This is the first study to present BIA-determined age- and sex-specific percentiles for FFM, FM, and %FM for healthy subjects, aged 15-64 y. Mean FM and %FM increased progressively in men and after age 45 y in women. The results suggest that any weight gain noted with age is due to a gain in FM. In conclusion, the data presented as percentiles can serve as reference to evaluate the normality of body composition of healthy and ill subject groups at a given age.

Adipose Tissue↗

Economic investigation of the use of three-compartment total parenteral nutrition bag: prospective randomized unblinded controlled study.

Optimal strategy for total parenteral nutrition (TPN) administration is essential both in terms of clinical effectiveness and economic efficiency. The aim of the present economic analysis was to provide a systematic and comprehensive cost comparison of the application of three currently available TPN systems: Separate Bottles (SB), Hospital-Compounded Bags (HCB) and Three-Compartment Bags (TCB). Sixty patients, admitted to the Geneva University Hospital and requiring TPN, were randomly assigned to one of the three systems. Three standard TPN formulas were prescribed to meet the patients' protein energy needs. TPN-related activities of medical, nursing and pharmacy staff were timed for the 24 hours of TPN administration. Manpower, nutrient solutions and medical supplies costs were calculated on the basis of mean Swiss salaries and hospital prices. TCB was the least expensive TPN system. SB and HCB systems' application costs were 120 and 150% of TCB cost, respectively. All intersystems cost comparisons were statistically significant (ANOVA p < or = 0.01). SB system required more items and manipulations, resulting in higher nurses manpower cost. Pharmacy overhead cost due to compounding was responsible for the higher cost of HCB system. Detailed manpower data presented in this study allow for an estimation of TPN application costs in other hospitals, using local salaries, specific product prices and compounding costs.

Cost-Benefit Analysis↗

Dynamic assessment of fat-free mass during catabolism and recovery.

Catabolism of fat-free mass affects both the quality of life and survival of patients. Because of variations in fluid status during acute illness, changes in body weight are difficult to evaluate and interpret during treatment. Nutritional assessment should therefore evaluate fat-free and fat mass changes during metabolic stress and catabolism. We have chosen to discuss bioelectrical impedance analysis, including the various bioelectrical impedance analysis techniques (i.e. multi-frequency and bioimpedance spectroscopy), as an easy, non-invasive, portable bedside technique that is operator-independent for evaluating fat-free and fat mass compartments and their changes during treatment. Clinical examples of the determination of fat-free mass in healthy and ill individuals are also presented.

Acquired Immunodeficiency Syndrome↗

[Assessment of nutritional status].

Malnutrition is an important factor which influences both the morbidity and the recovery. Assessment of the initial nutritional status, then its evolution during the disease and/or treatment, plays an important role for tailoring the nutritional support. This assessment allows to specify the nutritional needs and body reserves, as well as the metabolic and immunologic functions. The global nutritional assessment is aimed at defining if the patient is: well nourished, slightly or severely malnourished, and if the aetiologies of the existing malnutrition will disappear, increase or decrease. This conclusion correlates the nutritional assessment to the dynamic of the pathology and highlights if the nutritional support has to be immediate or delayed, maximal or partial. No single method allows to detect PCM, except in very severe cases. The diagnosis of PCM results of various clinical, biological and functional informations. This review describes the main methods and suggests practical modalities for nutritional assessment.

Absorptiometry, Photon↗

Should prolactin be reconsidered as a therapeutic target in human breast cancer?

Although prolactin (PRL) has been long suspected to be involved in the progression of human breast cancer, the failure of clinical improvement by treatment with dopamine agonists, which lower circulating levels of PRL, rapidly reduced the interest of oncologists concerning a potential role of this pituitary hormone in the development of breast cancer. Within the last few years, however, several studies reported first, that PRL is also synthesized in the mammary gland, and second that it exerts its proliferative action in an autocrine/paracrine manner. These observations have led to a reconsideration of the role of PRL as an active participant in breast cancer and are an impetus to search for alternative strategies aimed at inhibiting the proliferative effects of PRL on tumor mammary cells. In this report, we discuss the three possible levels that can be targeted for this purpose: the mammary synthesis of PRL, the interaction of the hormone with its receptor at the surface of mammary cells, and the intracellular signaling cascades triggered by the activated receptor. For each of these steps, we discuss the molecular event(s) that can be targeted, our understanding of the mechanisms involving these putative targets as well as the tools currently available for their inhibition. Besides its proliferative effect, PRL is also involved in the control of angiogenesis through one of its cleaved fragments, named PRL 16K, which has been shown to inhibit the angiogenic process. In view of this biological activity, we discuss first the cleavage of PRL with respect to the human mammary gland and, second, the hypothesis speculating that a balance between the proliferative effect of intact PRL and the anti-angiogenic activity of its 16K-like fragments might be physiologically relevant in the evolution of mammary tumors. If true, our hypothesis would suggest that the enzymatic cleavage of PRL could represent a new molecular target in the search for alternative strategies in the treatment of breast cancer.

Breast Neoplasms↗

Management of nutrition in European intensive care units: results of a questionnaire. Working Group on Metabolism and Nutrition of the European Society of Intensive Care Medicine.

OBJECTIVE: To describe the practical aspects of nutritional management in intensive care units (ICUs). DESIGN: A 49-item questionnaire was sent to the physician members of the European Society for Intensive Care Medicine. The issues addressed included: medical environment, assessment of nutritional status and current practice for enteral and parenteral nutrition. SETTING: 1608 questionnaires were sent in 35 European countries. ANALYSIS: The answers were pooled and stratified by country. RESULTS: 271 questionnaires were answered (response rate 17%). Assessment of nutritional status was generally based on clinical (99%) and biochemical (82%) parameters rather than on functional (24%), anthropometric (23%), immunological (18%) or questionnaire-based (11%) data. Two thirds of 2774 patients hospitalised in the corresponding ICUs at the time the questionnaire was answered were receiving nutritional support; 58% of those were fed by the enteral route, 23% by the parenteral route and 19% by combined enteral and parenteral. The preferred modality was enteral nutrition, instituted before the 48th h after admission, at a rate based on estimated caloric requirements. Specific and modified solutions were rarely used. Parenteral nutrition was less commonly used than enteral, although the practices differed between countries. It was mainly administered as hospital-made all-in-one solutions, at a rate based on calculated caloric requirements. CONCLUSIONS: European intensivists are concerned by the nutritional management of their patients. The use of nutritional support is common, essentially as early enteral feeding.

Critical Care↗

Fat-free mass in chronic illness: comparison of bioelectrical impedance and dual-energy x-ray absorptiometry in 480 chronically ill and healthy subjects.

Assessment of fat-free mass (FFM) and fat mass in ambulatory and hospitalized patients permits optimal adaptation of nutrition support. Recent methods for the determination of FFM are dual-energy x-ray absorptiometry (DXA) and bioelectrical impedance analysis (BIA). The purpose of this study was to determine if the BIA-determined FFM as estimated by the formula by Kotler et al. and the Geneva formula could be validated when compared to DXA-determined FFM in subjects with various diagnoses. Body composition was measured by BIA and DXA in 480 subjects including healthy young men and women, elite female runners, and patients with various pathologies (including chronic obstructive and restrictive pulmonary disease patients; cystic fibrosis patients; lung, heart, and liver transplantation patients [both pre- and post-], and hemiplegic and AIDS patients). The present results suggest that BIA is relevant in the clinical assessment of body composition, but BIA formulas appropriate to the subject pool must be used for evaluation of FFM and fat mass. The BIA formula by Kotler et al. is appropriate for healthy subjects and patients with AIDS, cystic fibrosis, and pre- or postliver transplantation. The Geneva formula is more appropriate in pulmonary diseases and hemiplegic subjects with normal weight.

Absorptiometry, Photon↗

From the molecular biology of prolactin and its receptor to the lessons learned from knockout mice models.

Prolactin (PRL), a polypeptide hormone secreted mainly by the pituitary and, to a lesser extent, by peripheral tissues, affects more physiological processes than all other pituitary hormones combined since it is involved in > 300 separate functions in vertebrates. Its main actions are related to lactation and reproduction. The initial step of PRL action is the binding to a specific membrane receptor, the PRLR, which belongs to the class 1 cytokine receptor superfamily. PRL-binding sites have been identified in a number of tissues and cell types in adult animals. Signal transduction by this receptor is mediated, at least in part, by two families of signaling molecules: Janus tyrosine kinases and signal transducers and activators of transcription (STATs). Disruption of the PRLR gene has provided a new mouse model with which to identify actions directly associated with PRL or any other PRLR ligands, such as placental lactogens. To date, several different phenotypes have been analyzed and are briefly described in this review. Coupled with the SAGE technique, this PRLR knockout model is being used to qualitatively and quantitatively evaluate the expression pattern of hepatic genes in two physiological situations: transcriptomes corresponding to livers from both wild type and PRLR KO mice are being compared, and following statistical analyses, candidate genes presenting a differential profile will be further characterized. Such a new approach will undoubtedly open future avenues of research for PRL targets. To date, no pathology linked to any mutation in the genes encoding PRL or its receptor have been identified. The development of genetic models provides new opportunities to understand how PRL can participate to the development of pathologies throughout life, as for example the initiation and progression of breast cancer.

Adult↗

Relation of BMI to a dual-energy X-ray absorptiometry measure of fatness.

Dual-energy X-ray absorptiometry (DXA) is a valid technique for measuring the fat, bone and lean (muscle, organs and water) masses of the body. We evaluated relationships of BMI (kg/m2) with independent measurements of fat and lean masses using DXA in 226 adult volunteers. The evaluation was an application of a general approach to compositional data which has not previously been used for describing body composition. Using traditional regression analyses, when lean mass was held constant, BMI varied with fat mass (men r 0.75, P < 0.05; women r 0.85, P < 0.05); when fat mass was held constant, BMI varied with lean mass (men r 0.63, P < 0.05; women r 0.47, P < 0.05). In contrast, a regression model for compositional data revealed that BMI was: (a) strongly associated with log fat mass in both sexes (b1 4.86, P < 0.001 for all women and b1 5.96, P < 0.001 for all men); (b) not associated with bone mass, except in older men; (c) related to lean mass in women but not in men (b3 -4.04, P < 0.001 for all women and b1 -2.59, P < 0.15 for all men). Women with higher BMI tended to have more fat mass and more lean mass than women with lower BMI. Men with higher BMI had more fat mass but similar lean mass to men with lower BMI. Investigators need to be alert to the inaccuracy of BMI to assign a fatness risk factor to individuals, especially among women.

Absorptiometry, Photon↗