Small babies receive the cardiovascular protective apolipoprotein epsilon 2 allele less frequently than expected.
Explore the source record for details and available documents.
Alleles↗
Biomedical subjects
E Lévy
Publications and source records attributed to E Lévy.
Manic episodes: the direct cost of a three-month period following hospitalisation.
INTRODUCTION: Few data exist to estimate the burden of manic episodes on healthcare systems or the therapeutic strategies used. This study was undertaken to identify treatment strategies chosen, and to assess the "real-world" direct medical cost of treating manic episodes necessitating hospitalisation. METHOD: Case record data were reviewed during the three months following hospitalisation for a manic episode in France. Healthcare resource utilisation was assessed, direct costs calculated, and treatment strategies analysed. A total of 137 patients files (51.8% female; mean age: 35 years) were reviewed and data on 185 hospitalisations collected. RESULTS: The mean duration of hospitalisation was 47 days over the study period. The most common treatment strategy during hospitalisation was the combination of a mood stabilizer with a neuroleptic drug (64% of patients at day 30). Anticonvulsants including valproate (39%) and carbamazepine (20%) were more common than lithium (42%). Treatment received during hospitalisation was generally continued after discharge, with a trend away from neuroleptics and towards mood stabilizers. The mean direct costs incurred over the three-month study period was Euro 22297, with 98.6% of those costs due to hospitalisation. CONCLUSION: These results confirm that the costs of treating a manic episode are high, and overwhelmingly due to the cost of hospitalisation.
Adult↗
Sim1 haploinsufficiency causes hyperphagia, obesity and reduction of the paraventricular nucleus of the hypothalamus.
The bHLH-PAS transcription factor SIM1 is required for the development of the paraventricular nucleus (PVN) of the hypothalamus. Mice homozygous for a null allele of Sim1 (Sim1(-/-)) lack a PVN and die perinatally. In contrast, we show here that Sim1 heterozygous mice are viable but develop early-onset obesity, with increased linear growth, hyperinsulinemia and hyperleptinemia. Sim1(+/-) mice are hyperphagic but their energy expenditure is not decreased, distinguishing them from other mouse models of early-onset obesity such as deficiencies in leptin and melanocortin receptor 4. Quantitative histological comparison with normal littermates showed that the PVN of Sim1(+/-) mice contains on average 24% fewer cells without a selective loss of any identifiable major cell type. Since acquired lesions in the PVN also induce increased appetite without a decrease in energy expenditure, we propose that abnormalities of PVN development cause the obesity of Sim1(+/-) mice. Severe obesity was described recently in a patient with a balanced translocation disrupting SIM1. Pathways controlling the development of the PVN thus have the potential to cause obesity in both mice and humans.
Adipose Tissue↗
Determinants of lipid level variability in French-Canadian children with familial hypercholesterolemia.
The wide variability in the biochemical expression of familial hypercholesterolemia (FH) is only partly explained by mutational heterogeneity in the low density lipoprotein receptor (LDLR) gene. In the current study, we measured this biochemical variability in a group of children heterozygous for the >15-kb LDLR gene deletion (n=67) and examined the contribution of apolipoprotein (apo) E and B allelic variations to this phenotypic variability. Variances of total cholesterol (TC), LDL-C, and apoB concentrations and of the ratio of TC to high density lipoprotein cholesterol (HDL-C) were increased in FH subjects compared with controls. However, after taking the means into account, the coefficients of variation showed that the variability of LDL-C and apoB concentrations was smaller for FH than for controls and that the variability of TC and of the ratio TC to HDL-C was similar between both groups. The epsilon2/3 genotype was associated with lower mean TC, LDL-C, and apoB concentrations in FH. The magnitude of this effect was smaller in controls than in FH. Indeed, the percentages of total variance of TC, LDL-C, and apoB attributable to the apoE locus were 19.9%, 18.1%, and 11.8%, respectively, in FH cases and 5.9%, 7.4%, and 6.0%, respectively, in controls. We did not detect any effect of the apoB insertion/deletion polymorphism on lipid traits in FH children. However, in controls, we observed a strong interaction between apoE and apoB genotypes on apoB concentrations and on TC to HDL-C ratios. Our study reemphasizes the important role of apoE in lipid metabolism and illustrates that the effects of allelic variations on lipid traits are context dependent.
Apolipoproteins B↗
The 1999 French Venous Disease Survey: epidemiology, management, and patient profiles.
A recent (1999) Sofres survey of representative samples of the adult French population aged 15 and over showed that almost half this population suffered from lower limb venous complaints and that 43% of them were untreated. Of those treated, 24.2% received venotropics, including 21.5% by prescription, while 6.0% practiced self-medication. Venous disease sufferers form a relatively underprivileged sector of the population in terms not only of age, income, work and living conditions, but also of general health and medical history. Despite its clinical efficacy and potential social utility, venotropic treatment is possible only if backed by adequate state health insurance coverage supplemented by mutual and private insurance schemes. Any restriction to such coverage will only decrease access to prescription venotropics.
Adolescent↗
[Management of venous leg ulcer by French physicians, diversity and related costs: a prospective medicoeconomic observational study].
OBJECTIVES: The purpose of this study was to better ascertain how French physicians manage venous ulcers of the lower limbs. We explored the various therapeutic approaches used and their respective costs. Particular attention was focused on dressing prescriptions. MATERIAL AND METHODS: A prospective medicoeconomic study was conducted. Eight hundred general practitioners and specialists throughout France were included and followed two patients each, one with a "new ulcer" (less than two weeks) and another with a "longstanding ulcer" (more than six weeks). Patients were followed to healing or for up to six months. An observation chart was completed at each visit. Data collected were characteristics of the ulcer at inclusion, assessment of the clinical course, and the nature and the volume of medical care prescribed. Corresponding costs (total cost for the society) were calculated on the basis of 1996 public prices for drugs and the French national health insurance quotations for ambulatory care. For hospital care, cost was calculated from the cost of stay for homogeneous patient groups. RESULTS: Files established for 1,098 patients by 652 physicians could be assessed. Elderly female patients predominated in this population (mean age 72 years, 74% women). The length of the ulcer at inclusion was significantly correlated with its duration: 2.82 cm for new ulcers (52.6% of the cases) versus 5.03 cm for longstanding ulcers (47.3%). The mean number of consultations for all patients was 4.8 over a 29-day period. Mean cost resulting from these consultations was 5,827 FF per patient: 48% for care, 33 for drugs, 16% for hospitalizations, and 3% for work lay-off ). Cure was achieved in 77% of the cases within a mean delay of 3 months. Older ulcer was significantly associated with longer treatment (117 days for longstanding ulcers versus 80 days for new ulcers), lower cure rate (67% versus 86%) and higher cost (7 078 FF versus 4 669 FF). Dividing care methods between those using cleaning with compression or not showed that compression was prescribed in 76% of the cases at the inclusion consultation. This predominance of compression therapy did not preclude use of a variety of other therapeutic methods depending on the clinical and demographic situation of the patient. Cost varied accordingly with a mean ranging from 3 160 FF to 6 697 FF depending on the therapeutic attitude. The study also focused on the type and amount of dressings used. Dressings were prescribed for 56 patients in this series. It can be hypothesized that these patients already had dressings. Different indicators show that the absence of prescriptions for dressings concerned less severe and less costly ulcers (4 130 FF versus 5 918 FF for those with dressing prescriptions). Among the 1 042 patients for whom dressings were prescribed, 35% were for occlusive dressings, 29% for ointment dressings and also 24% for both occlusive and ointment dressings. The type was not specified in 55% of the cases. Mean cost for these different categories ranged from 4 921 to 7 019 FF.
Absenteeism↗
[Economic study of carvedilol in heart failure. A cost effectiveness study in France].
A programme of four phase III clinical trials carried out in the USA on 1094 patients showed that Carvedilol, associated with the usual bitherapy and eventually with digitalis, reduced the mortality and number of hospital admissions of patients with cardiac failure. These results, transposed to the French population, may be used to evaluate the economic advantages of Carvedilol by developing a cost-effectiveness study which consists in relating the direct expenses (drugs and hospital admissions) of each of the two strategies, with or without Carvedilol, to their respective mortalities. Hospital expenses were estimated with respect to the H.M.G. corresponding to each hospital stay at 1997-1998 values. The cost in the Carvedilol group was 2,823 FF per patient (including 1,491 FF for the drug itself) but 2,056 FF were economised in hospital expenses. With an increased cost of 767 FF but a 50% reduction in mortality corresponding to a difference in mortality of 45@1000, the cost-effectiveness of Carvedilol was 17,040 per life saved and 2,130 FF per additional year of life expectancy. A study of the sensitivity produced even more favourable results of Carvedilol. An evaluation of hospital expenses on the basis of AP-HP data indicates that the addition of Carvedilol is associated with a 4,425 FF reduction in hospital expenses, which makes it a cost saving strategy.
Adrenergic beta-Antagonists↗
[Anaplastic cancers of the thyroid. Is healing possible?].
OBJECTIVE: Thyroid anaplastic carcinoma is associated with a very poor prognosis. The goal of this study was to determine whether an aggressive treatment is worthwhile. PATIENTS AND METHODS: Of 22 thyroid anaplastic carcinomas confirmed with immunohistochemistry, 17 were judged eligible for surgery. Total thyroidectomy was planned in all patients. Frozen section of the lower lateral lymph nodes was routinely performed and in case of involvement (n = 9), a modified radical neck dissection was carried out. Fractionated radiotherapy was started within 5 weeks following surgery: 6,000 cGy was delivered on the thyroid area and all involved areas while 4,500 cGy was delivered on the lymph nodes of the neck and of the superior mediastinum when non involved. RESULTS: The three patients without distant metastasis, with thyroid removal considered as complete, were still free of disease 10, 12 and 13 years later. One of these patients had been initially considered inoperable and was operated later when a combination of radiotherapy and chemotherapy obtained a decrease of the tumor. All other patients, 13 with incomplete removal and one with pulmonary metastasis died from their cancer; the median of the survival was 7 months. CONCLUSION: When anaplastic carcinoma is suspected on clinical appearance, the diagnosis should be rapidly confirmed with percutaneous biopsy and immunohistochemistry. If a lymphoma is found, surgery is not indicated. Our results demonstrate that except for widely infiltrating tumors or distant metastasis, a complete removal of the tumor should be attempted as soon as possible. Surgery should be followed with hyperfractionated radiotherapy. Multimodal therapy may result in long-term survival. A patient free of disease at 5 years may be considered as definitively cured.
Adult↗
Apolipoproteins in human fetal colon: immunolocalization, biogenesis, and hormonal regulation.
The present investigation aimed at defining the localization of apolipoproteins (apo) A-I, A-IV, B-48, and B-100 along the crypt-villus axis of the human fetal colon, their biogenesis during gestation, and their hormonal regulation. Using immunofluorescence, the distribution of apo A-I and A-IV appeared as a gradient, increasing from the developing crypt to the tip of the villus. On the other hand, apo B-100 staining was found in the crypt and the lower mid-villus region with varying intensities in the upper villus cells, while the 2D8 antibody which recognizes both apo B-100 and B-48, revealed uniform staining along the crypt-villus axis. Apolipoprotein synthesis, determined by [35S] methionine labeling, immunoprecipitation, and SDS-PAGE showed a predominance of apo A-IV (53%), followed by apo A-I (23.9%), apo B-48 (13.4%), and apo B-100 (9.7%). The synthesis of each apolipoprotein was significantly modulated by hydrocortisone, insulin and epidermal growth factor (EGF). Apart from a decrease in apo B-100 exerted by EGF and a reduction in apo A-I resulting from the addition of insulin, the other apolipoproteins were all enhanced. Our data confirm that the fetal colon has the capacity to synthesize apolipoprotein A-I, A-IV, B-48, and B-100 and establish that their synthesis are modulated by hormonal and growth factors known to be involved in the regulatory mechanism of the functional development of human jejunum.
Antibodies, Monoclonal↗
The role of dietary choline in the beneficial effects of lecithin on the secretion of biliary lipids in rats.
Earlier studies showed that dietary soybean lecithin increases biliary lipid secretion, which mainly comes from the contribution of high density lipoprotein (HDL) and hepatic microsomal pools of phosphatidylcholine and cholesterol. In addition, a lecithin diet enhances bile secretion and prevents bile acid-induced cholestasis. This study evaluated the contribution of choline, a component of lecithin, to the observed effect of lecithin on biliary secretory function. Rats were fed either a control diet (CD), a choline diet (ChD) or a lecithin-enriched diet (LD) for 2 weeks. Results showed that like LD, ChD induced an increase in bile flow and bile acid secretion rate when compared with the control diet. However, unlike LD, ChD did not significantly increase biliary phospholipids and cholesterol output. An increase of hydrophilic bile acids (i.e. ursodeoxycholic and muricholic acids) in bile of rats fed choline could explain why the biliary phospholipid and cholesterol secretion was not increased. During taurocholic acid infusion, both experimental diets increased bile flow and the bile acid secretion rate maximum (BASRm). The cholestasis usually observed after the BASRm is reached was inhibited by ChD and LD. Both diets induced a decrease in plasma cholesterol (total and HDL), however, only LD induced statistically significant changes. Analysis of total cholesterol and phospholipid content of microsomes and canalicular membranes indicated no statistically significant difference between control and experimental groups either under basal conditions or after bile acid infusion. Similarly, the phospholipid classes and fatty acid composition of biliary phosphatidylcholine were not altered by feeding ChD and LD. We conclude that choline contributes to the beneficial effect of a lecithin diet on bile secretion. It is postulated that this effect may be attributed to modulation of HDL and an enhancement of the cholesterol and phospholipid pools destined for biliary secretion.
Animals↗
Familial lipoprotein lipase deficiency in infancy: clinical, biochemical, and molecular study.
OBJECTIVES: To describe the characteristics of lipoprotein lipase (LPL)-deficient patients seen in infancy and to evaluate the safety and efficacy of severe fat restriction. METHODS: Children <1 year old presenting with chylomicronemia between 1972 and 1995 were identified, and their clinical courses were reviewed retrospectively. RESULTS: LPL deficiency was demonstrated in 16 infants who presented with irritability (n = 7), lower intestinal bleeding (n = 2), pallor, anemia, or splenomegaly (n = 5), and a family history or fortuitous discovery (n = 2). All plasma samples were lactescent at presentation. Chylomicronemia responded rapidly to dietary fat restriction, and it was possible to maintain satisfactory metabolic control for a prolonged period of time. Only 1 adolescent girl had an episode of pancreatitis associated with the use of oral contraceptives. No persistent adverse effects on growth were seen. We obtained abnormal values for serum iron, alkaline phosphatase, and total calcium. CONCLUSIONS: The presentation of LPL deficiency is heterogeneous during infancy. Close dietary monitoring is required to avoid nutritional deficiencies. Estrogen therapy should be avoided in LPL-deficient patients.
Adolescent↗
"Specific" scale compared with "generic" scale: a double measurement of the quality of life in a French community sample of obese subjects.
STUDY OBJECTIVE: To determine the aspects of quality of life that are affected by weight in the general population, to develop a specific questionnaire (OSQOL) that can measure with reliability and validity the impact of overweight and obesity on well being, and to compare the results with those obtained using a well known generic tool (the "SF 36" scale). DESIGN: Cross sectional survey with matched control group. SETTING: Community. PATIENTS: A permanent survey base of approximately 10,000 representative ordinary households were screened for weight and height. Five hundred subjects were randomly drawn from the sub-sample of adult people with a body mass index equal or greater than 27. A control sample of 500 subjects matched for sex, age, and employment status was drawn from the non-obese population. MAIN RESULTS: A short specific Quality Of Life scale, the OSQOL, was produced that comprises 11 items belonging to four independent dimensions. Using this scale and the SF36, it was found that: (1) moderately obese subjects (27 < or = BMI < 30) did not significantly differ from the control group except for physical capacity; (2) in the group of obese subjects with a BMI > 30, quality of life seemed to be impaired for five of nine dimensions of the SF36 compared with the control population, all related to physical consequences of obesity. This population essentially perceived itself in terms of poor general health. (3) No significant difference was observed between the samples for the psychological and social dimensions of the SF36. CONCLUSION: The quality of life of patients with severe obesity is impaired, but it mainly affects the physical consequences of the disease. The psychological and social repercussions that could have been expected to affect this population were not demonstrated. The hypothesis of a process of adaptation of the person and their social environment cannot therefore be excluded. Methodologically, comparison of the specific OSQOL with the generic SF3 shows clearly that the two kinds of scales correspond to different objectives and should be considered as complementary.
Adolescent↗
Toxicity of fluorouracil in patients with advanced colorectal cancer: effect of administration schedule and prognostic factors.
PURPOSE: Fluorouracil (5-FU) continuous infusion is superior to 5-FU bolus in patients with advanced colorectal cancer, but the survival difference between the two treatments is small and, therefore, the difference in toxicity profile is crucial in choosing a treatment for individual patients. MATERIALS AND METHODS: We conducted a meta-analysis of all randomized trials that compared 5-FU bolus with 5-FU CI, based on individual data from 1,219 patients, to compare the toxicity of the two schedules of 5-FU administration and to identify predictive factors for toxicity. The toxicities considered were World Health Organization (WHO) grade 3 to 4 anemia, thrombopenia, leukopenia, neutropenia, nausea/vomiting, diarrhea, mucositis, and hand-foot syndrome. RESULTS: Hematologic toxicity, mainly neutropenia, was more frequent with 5-FU bolus than with 5-FU CI (31% and 4%, respectively; P < .0001). Hand-foot syndrome was less frequent with 5-FU bolus than with 5-FU CI (13% and 34%, respectively; P < .0001). There was no difference between the two treatment groups in terms of other nonhematologic toxicities. Independent prognostic factors were age, sex, and performance status for nonhematologic toxicities, performance status, and treatment for hematologic toxicities, and age, sex, and treatment for hand-foot syndrome. CONCLUSION: Based on a large data set, this study confirmed and quantified the toxicity profile of the two schedules of administration of 5-FU and allowed the identification of clinical predictors of toxicity.
Colorectal Neoplasms↗
From cost of illness to cost-effectiveness in heart failure.
Congestive heart failure is a severe condition responsible for 1%-2% of total health expenditure. In France, three-quarters of the medical cost of congestive heart failure, i.e. FF7 billion, is attributed to 150000 annual hospital admissions. But new treatments, especially ACE inhibitors and beta-blockers, have demonstrated, through large controlled trials (SAVE, AIRE, US trials on carvedilol and CIBIS I) that these drugs can reduce mortality and hospitalization. These results, translated in terms of cost per life year saved, show that they are all very cost effective and could be cost saving, under some conditions.
Adrenergic beta-Antagonists↗
[Non-surgical treatment of cancers of the stomach].
In western countries, most gastric cancers are diagnosed at locally advanced stages. Surgery is the only curative treatment, but the risk of locoregional relapses and of distant metastases is very high. This is the rationale for adjuvant treatments. However, currently available data do not allow a definitive conclusion as to whether chemotherapy or radiation therapy are of value as adjuvant treatments for poor-prognosis gastric cancers. Further randomized clinical trials are still needed. By contrast, it is admitted that these treatments have a palliative role in the management of patients with metastases.
Adenocarcinoma↗
[Adjuvant chemotherapy of soft tissue sarcoma].
The rôle of chemotherapy in the treatment of operable soft tissue sarcomas is still debatable. In high-grade tumors, randomized trials using adjuvant chemotherapy have resulted in controversial results. A recent meta-analysis showed a higher median disease-free survival in groups with chemotherapy compared to controls. Doxorubicin, ifosfamide and dacarbazine are the majors drugs. Their combination in adjuvant treatment is currently being investigated. Neoadjuvant chemotherapy has allowed conservative surgery in initially unoperable tumors, but its role in primarily operable tumors remains to be defined.
Antineoplastic Combined Chemotherapy Protocols↗
Calcitriol differentially modulates mRNA encoding calcitriol receptors and calcium-binding protein 9 kDa in human fetal jejunum.
Human intestinal mucosa consists of highly active epithelial cells in continual renewal and differentiation processes anatomically located at different portions of the villi. Besides its well recognized role in bone cell homeostasis, calcitriol has been attributed a role in cellular differentiation and proliferation in normal and cancerous cells. In this report, we show that in human fetal jejunum, depending upon the stage of gestation, calcitriol either enhances or decreases the levels of mRNA coding for its receptor. However, it up-regulates at all times those coding for the Vitamin D-dependent Calcium Binding Protein 9kDa. The present observations open interesting possibilities as to the role of calcitriol in the in utero human gut development and the control of colorectal cancers.
Base Sequence↗
[Effects of calcitriol on the development of the human fetal intestine].
Explore the source record for details and available documents.
Calcitriol↗