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Biomedical subjects

P Levy

Publications and source records attributed to P Levy.

At least 19 recordsLinked to original sources
PubMed2006

Age and high-dose methotrexate are associated to clinical acute encephalopathy in FRALLE 93 trial for acute lymphoblastic leukemia in children.

The objective of the study was to assess acute neurotoxicity associated with triple intrathecal therapy (TIT)+/-high-dose methotrexate (HD MTX) in children with acute lymphoblastic leukemia (ALL). 1395 children were enrolled on FRALLE 93 protocol from 1993 to 1999. Lower-risk group (LR, n=182) were randomized to weekly low-dose MTX at 25 mg/m(2)/week (LD MTX, n=81) or HD MTX at 1.5 g/m(2)/2 weeks x 6 (n=77). Intermediate-risk group (IR, n=672) were randomized to LD MTX (n=290) or HD MTX at 8 g/m(2)/2 weeks x 4 (n=316). Higher-risk group (HR, n=541) prednisone-responder patients received LD MTX and cranial radiotherapy. HR group steroid resistant cases were grafted (autologous or allogenic). TIT (MTX, cytarabine and methylprednisolone) was given every 2 weeks during 16-18 weeks and every 3 months during maintenance therapy in LR and IR patients. 52 patients (3.7%) developed neurotoxicity. Isolated seizures: n=15 (1.1%), peripheral and spinal neuropathy: n=17 (1.2%) and encephalopathy: n=20 (1.4%). Age >10 years was significantly associated with neurotoxicity (P=0.01) and use of HD MTX is associated with encephalopathy (P=0.03). Sequels are reported respectively in 60 and 33% of spinal neuropathy and encephalopathy cases. Current strategies tailoring risk of neurological sequels has to be defined.

Adolescent↗
PubMed2006

Prenatal diagnosis of myopathy, encephalopathy, lactic acidosis, and stroke-like syndrome: contribution to understanding mitochondrial DNA segregation during human embryofetal development.

INTRODUCTION: Myopathy, encephalopathy, lactic acidosis, and stroke-like (MELAS) syndrome, a maternally inherited disorder that is among the most common mitochondrial DNA (mtDNA) diseases, is usually associated with the m.3242A>G mutation of the mitochondrial tRNA(leu) gene. Very few data are available with respect to prenatal diagnosis of this serious disease. The rate of mutant versus wild-type mtDNA (heteroplasmy) in fetal DNA is indeed considered to be a poor indicator of postnatal outcome. MATERIALS AND METHODS: Taking advantage of a novel semi-quantitative polymerase chain reaction test for m.3243A>G mutant load assessment, we carried out nine prenatal diagnoses in five unrelated women, using two different fetal tissues (chorionic villi v amniocytes) sampled at two or three different stages of pregnancy. RESULTS: Two of the five women, although not carrying m.3243A>G in blood or extra-blood tissues, were, however, considered at risk for transmission of the mutation, as they were closely related to MELAS-affected individuals. The absence of 3243A>G in the blood of first degree relatives was associated with no mutated mtDNA in the cardiovascular system (CVS) or amniocytes, and their three children are healthy, with a follow-up of 3 months-3 years. Among the six fetuses from the three carrier women, three were shown to be homoplasmic (0% mutant load), the remaining three being heteroplasmic, with a mutant load ranging from 23% to 63%. The fetal mutant load was fairly stable at two or three different stages of pregnancy in CVS and amniocytes. Although pregnancy was terminated in the case of the fetus with a 63% mutant load, all other children are healthy with a follow-up of 3 months-6 years. CONCLUSION: These data suggest that a prenatal diagnosis for MELAS syndrome might be helpful for at-risk families.

Acidosis, Lactic↗
PubMed2006

Non-arteritic anterior ischaemic optic neuropathy is nearly systematically associated with obstructive sleep apnoea.

AIM: To evaluate newly diagnosed non-arteritic anterior ischaemic optic neuropathy (NAION) patients for the existence of an associated sleep apnoea syndrome. METHODS: Newly identified NAION patient underwent polysomnography. The prevalence of sleep apnoea in NAION patients was compared to the prevalence previously found in the general population. Hypertension, diabetes, hyperlipidaemia, and atheromatous lesions of carotid vessels as classic risk factors associated with NAION were also identified. RESULTS: 27 consecutive newly diagnosed NAION patients (18 men and nine women, mean age 65 (SD 8) years, body mass index 27.2 (3.8) kg/m2) were included in the study. 24 of these 27 NAION patients (89%) exhibited a sleep apnoea syndrome (respiratory disturbance index: 37.2/h (SD 18.3/h). Risk ratio for a NAION patient to have sleep apnoea was 4.9 compared to the general population (p < 0.001). Sleep apnoea was 1.5-2-fold more frequent than the rate of the other identified risk factors typically associated with NAION (hypertension, diabetes). CONCLUSIONS: Sleep apnoea is the most frequent disorder associated with NAION and should be screened in this population. At least a questionnaire related to obstructive sleep apnoea symptoms and assessment of sleepiness should be systematically proposed to patients with NAION.

Adult↗
PubMed2006

A new large CFTR rearrangement illustrates the importance of searching for complex alleles.

The p.Val754Met variant, described in 1996 in a CF patient, has been considered a CF mutation. However, biochemical aspects, results of functional studies and, finally, the identification of a complex deletion removing exons 3 to 10 and 14b to 16 in cis of p.Val754Met in a CF patient, argue against a strong deleterious effect. An inventory through the French CF network of patients carrying p.Val754Met led to the registration of seven patients (CF: n=4; idiopathic chronic pancreatitis: n=3) and six healthy individuals, all heterozygous for the variation. Extensive CFTR gene analysis was carried out, including the search for large rearrangements and other possible mutations. The complex deletion, whose breakpoints are described here, was found only in the four CF patients, in association with the same haplotype. This data, added to the fact that the p.[Phe508del]+[Val754Met] genotype was found in a healthy individual, bring further arguments against the association of p.Val754Met with CF. We thus suggest looking for a possible complex allele whenever p.Val754Met is detected and considering it neutral regarding genetic counseling when found in isolation.

Adolescent↗
PubMed2005

Deoxyguanosine kinase mutations and combined deficiencies of the mitochondrial respiratory chain in patients with hepatic involvement.

The activity of deoxyguanosine kinase (DGUOK), a mitochondrial enzyme involved in the anabolism of mitochondrial (mt) deoxyribonucleotides, governs the maintenance of the mtDNA. Deleterious mutations of the DGUOK gene are thus associated with mtDNA depletion and result in combined deficiencies of mtDNA-encoded respiratory chain enzymes. With the aim to estimate the prevalence of DGUOK mutations in a cohort of 30 patients with hepatocerebral disease and combined respiratory chain deficiencies, we studied the DGUOK gene and identified previously unreported mutations in five families. Two patients and their affected sibs, born to non-consanguineous parents, were homozygous for a missense mutation (M1T, and L250S, respectively). One patient presented a homozygous 4 pb insertion (796 insTGAT) and two other patients, and their affected sibs, were compound heterozygous (E165V/L266R and E211G/L266R, respectively). These findings allowed us to propose prenatal diagnosis in two families. In conclusion, we observed a high prevalence of DGUOK mutations (17%) in patients with hepatic involvement and combined respiratory chain deficiencies with hepatic involvement.

Amino Acid Sequence↗
PubMed2002

Novel dynamical effects and persistent memory in phase separated manganites.

The time dependent response of the magnetic and transport properties of Fe-doped phase separated (PS) manganite La(0.5)Ca(0.5)MnO3 is reported. The nontrivial coexistence of ferromagnetic (FM) and non-FM regions induces a slow dynamics which leads to time relaxation and cooling rate dependence within the PS regime. This dynamics influences physical properties drastically. On one hand, metalliclike behavior, assumed to be a fingerprint of percolation, can be also observed before the FM phase percolates as a result of dynamical contributions. On the other hand, two novel effects for the manganites are reported, namely, the rejuvenation of the resistivity after aging and a persistent memory of low magnetic fields (<1 T), imprinted in the amount of the FM phase.

Journal Article↗
PubMed2002

The cost of osteoporosis in men: the French situation.

The objective of this study was to estimate the annual direct medical costs of osteoporosis and osteoporotic fractures incurred by French men > or =50 years of age. Costs were assessed from a societal perspective for 1999 and expressed in Euros. An expert panel was consulted to identify fractures attributable to osteoporosis according to International Classification of Diseases (ICD)-10 codes. Available age- and gender-specific osteoporosis attribution probabilities (OAP) were used to derive the proportion of health-care utilization for fractures resulting from osteoporosis. Hospital and ambulatory care costs due to fractures were obtained from French databases. A total of 23,260 acute hospitalizations were found to be caused by osteoporosis, 52% of which are for hip fractures. Mean cost per stay varied widely according to the site of fracture, from 1300 (wrist fracture) to 5900 (hip fracture). Consequently, the total cost of acute hospitalization amounts to 97.6 million, with hip fractures accounting for 73.2% of the expenditures. Rehabilitation and convalescence costs were estimated to be 90.8 million, generating a total hospital cost of 188.4 million. The total outpatient costs were estimated to be 9.1 million. Thus, the total medical costs of male osteoporosis amount to 197.5 million. A sensitivity analysis was performed to test the robustness of this figure. We estimate the number of fractures by applying international incidence rates from the literature to the French male population aged > or =50 years, whereas the OAP and unit costs were kept constant. This approach yielded an estimate of 21,857 fractures, which is only 6% below the base case. When compared with values from other countries, our study results appear very conservative.

Aged↗
PubMed2002

Identification of quality of life concerns of patients with obstructive sleep apnoea at the time of initiation of continuous positive airway pressure: a discourse analysis.

BACKGROUND: Obstructive sleep apnoea syndrome (OSAS) is a common condition with multiple symptoms dominated by daytime somnolence. Thus many worries and concerns of patients remain hidden. Treatment by nasal continuous positive airway pressure (CPAP) can be imposing for the individual. An analysis of the freely expressed concerns of such patients is required. OBJECTIVE: To seek an in-depth analysis of how patients live with sleep apnoea by allowing them an open discourse and analysing the text of their statements. DESIGN: A trained psychologist conducted semi-directive interviews with patients attending a pulmonary rehabilitation and convalescent unit around the themes of sleep, health and treatment. An analysis of content and of discourse was carried out by textual analysis and by propositional analysis of discourse (PAD) with the aid of dedicated computer programs (Tropes, Sphinx Lexica). RESULTS: Thirty patients with severe sleep apnoea were interviewed of whom 15 were initiating treatment with CPAP. Patients spoke of abnormal fatigue (22 mentions) and somnolence (21 times). Many have problems with obesity (25 instances), snoring related problems (12). There were 30 mentions of depression with a relationship to alcohol and anti-depressives. Twenty six times the theme of nocturnal waking was raised. There were many instances of problems with CPAP (nasal mask and noise problems raised 21 times). Patients have problems with relationships and sex because of OSAS. Other concerns were loss of memory and fear of dying. CONCLUSION: In a non-directed conversation OSAS patients express concerns not revealed in the standard medical paradigm and such concerns should be addressed in assessing treatment or evaluating quality of life (QOL).

Adult↗
PubMed2001

Enteral compared with parenteral nutrition: a meta-analysis.

BACKGROUND: The difference in outcomes in patients is unclear when 2 types of enteral nutrition, ie, tube feeding and conventional oral diets with intravenous dextrose (standard care), are compared with parenteral nutrition. OBJECTIVE: We reviewed systematically and aggregated statistically the results of prospective randomized clinical trials (PRCTs) to examine the relations among the nutrition interventions, complications, and mortality rates. DESIGN: We conducted a MEDLINE search for PRCTs comparing the effects of enteral and parenteral nutrition in adults. Two different people abstracted data for the method and outcomes separately. We used fixed-effects meta-analysis technique to combine the relative risks (RRs) of the outcomes of infection, nutrition support complications, other complications, and mortality. RESULTS: Twenty-seven studies in 1828 patients met the study criteria. Aggregated results showed a significantly lower RR of infection with tube feeding (0.64; 95% CI: 0.54, 0.76) and standard care (0.77; 95% CI: 0.65, 0.91). A priori hypotheses showed a lower RR of infection with tube feeding than with parenteral nutrition, regardless of nutritional status, presence of cancer, year of study publication, or quality of the study method. In studies in which participants had high rates of protein-energy malnutrition, there was a significantly higher risk of mortality (3.0; 95% CI: 10.9, 8.56) and a trend toward a higher risk of infection with standard care than with parenteral nutrition (1.17; 95% CI: 0.88, 1.56). CONCLUSIONS: Tube feeding and standard care are associated with a lower risk of infection than is parenteral nutrition; however, mortality is higher and the risk of infection tends to be higher with standard care than with parenteral nutrition in malnourished populations.

Enteral Nutrition↗
PubMed2001

A general model of the effects of sleep medications on the risk and cost of motor vehicle accidents and its application to France.

BACKGROUND: Although various prescription drugs may be equally effective in promoting sleep, some may lead to substantial impairment in psychomotor functioning and an increased risk of motor vehicle accidents. OBJECTIVE: To develop a general model to evaluate the potential effects of sleep medications on motor vehicle accidents and costs, and apply the model to the French setting. METHODS: Impairment in driving performance, as evaluated by randomised controlled open-road studies using the standard deviation of a vehicle's lateral position (SDLP), a measure of weaving, was expressed in terms of equivalent blood alcohol (ethanol) concentration (BAC). Epidemiological data were then used to relate BAC to the excess risk of motor vehicle accidents. Although a non-impairing medication would not increase risk, a medication that produces mild impairment in driving performance (a change of 2.5 cm in SDLP, equivalent to 0.05% BAC) would increase motor vehicle accident risk by 25%. One that leads to moderate impairment (an SDLP change of 4.5 cm, equivalent to 0.08% BAC) would roughly double this risk, and a severely impairing medication (an SDLP change of 7 cm, equivalent to 0.12% BAC) would result in up to a 5-fold increase in motor vehicle accident risk. For application to the French setting, a hypothetical cohort of 100,000 adult drivers with insomnia was assumed to be treated for 14 days either with zaleplon 10 mg, a new sleep medication that has been shown not to significantly impair driving performance, or zopiclone 7.5 mg, which has been shown to cause moderate impairment. RESULTS: Compared with zaleplon, use of zopiclone over 14 days in France would be expected to result in 503 excess accidents per 100,000 drivers at an additional cost of 158 French francs (31 US dollars) per person (1996 values). CONCLUSIONS: Our model illustrates the extent to which non-impairing sleep medications could reduce the burden posed by motor vehicle accidents. Our model is designed to be general, and thus can serve as the basis for similar investigations.

Accidents, Traffic↗