[SARS-CoV: 2. Modeling SARS epidemic].
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Disease Outbreaks↗
Biomedical subjects
Antoine Flahault
Publications and source records attributed to Antoine Flahault.
In vitro fertilization may increase the risk of Beckwith-Wiedemann syndrome related to the abnormal imprinting of the KCN1OT gene.
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Animals↗
Effects of postoperative, nonsteroidal, antiinflammatory drugs on bleeding risk after tonsillectomy: meta-analysis of randomized, controlled trials.
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Anti-Inflammatory Agents, Non-Steroidal↗
[Spiral CT: is it time for lung cancer screening?].
Recent studies have benefited from the progress of the scanner in order to relaunch the debate on the opportunity of screening lung cancer. Even if these initial studies have succeeded in showing that the practise of helical scan allows the screening of a considerable proportion of cases at an early stage which may have 5-year survivals of up to 70%, there is no specific indication of the diminution of lung cancer-specific mortality. Studies of cohorts of several dozen millions subjects during a period of 8 to 10 years are to be realised and an international pool will be charged of the harmonization of the protocols in order to realize the analyse of the collected information. An experimental study of 1000 subjects financed by a grant have started recently in France.
Aged↗
Risk factors for nephrolithiasis in patients with familial idiopathic hypercalciuria.
PURPOSE: About 40% of patients with nephrolithiasis have idiopathic hypercalciuria, sometimes associated with a family history of kidney stones. In these families, little is known about the frequency of, and risk factors for, stone formation among hypercalciuric patients. We therefore conducted a prospective study of 216 subjects from 33 families with idiopathic hypercalciuria. MATERIALS AND METHODS: We recorded the age, weight, and history of calcium stones in all subjects, and measured 24-hour urine volume and excretion of calcium, uric acid, sodium, magnesium, urea, citrate, phosphate, and sulfate on a nonrestricted diet. We performed a more complete metabolic evaluation in many of the hypercalciuric subjects (calciuria/weight >0.1 mmol/kg/d). Multivariate logistic regression analysis was performed to identify independent risk factors for stone formation. RESULTS: The prevalence of self-reported nephrolithiasis was 46% (61/132) in hypercalciuric subjects and 11% (7/63) in normocalciuric subjects (P <0.0001). In multivariate analysis, age (odds ratio [OR] per 10 years of age = 1.3; 95% confidence interval [CI]: 1.1 to 1.6), urine calcium excretion (OR = 1.3 per mmol/d increase; 95% CI: 1.2 to 1.5), and uric acid excretion (OR = 3.3 per mmol/d increase; 95% CI: 1.4 to 7.5) were independent risk factors for nephrolithiasis. The risk of nephrolithiasis increased progressively with greater levels of hypercalciuria. CONCLUSION: We found a significant dose-effect association between calciuria and stone disease in patients with familial hypercalciuria. Other factors associated with stone formation included higher uric acid excretion, probably reflecting higher food intake, and age, probably reflecting the length of exposure to hypercalciuria and hyperuricosuria.
Adult↗
Chronic graft dysfunction in renal transplant patients: potential role of plasminogen activator inhibitor type 1.
BACKGROUND: Chronic allograft nephropathy is the main cause of long-term kidney graft loss. The plasminogen activator inhibitor type 1 (PAI-1) is a potential fibrogenic molecule whose secretion is regulated by several metabolic, inflammatory, and genetic factors. We aimed to determine whether PAI-1 secretion in renal transplant patients is correlated with the decline in renal function after transplantation. METHODS: Renal transplant patients (145 male/71 female) were included in the study 1-27 years after transplantation (median of follow-up: 7.35 years). At inclusion, routine clinical and biological data were collected, the 4G/5G polymorphism of the recipient PAI-1 gene was determined, and the PAI-1 plasma level was measured. RESULTS: The mean rate of decline in renal function was -4.26+/-0.30 ml/min/year. By multiple linear regression analysis, the rate of decline in renal function was significantly correlated with proteinuria (P=0.0176), occurrence of late acute rejection episodes (P=0.0001), and PAI-1 plasma level (P=0.0051). In addition, PAI-1 plasma level was also significantly correlated with body mass index (P=0.038), insulin (P<0.0001), platelet count (P<0.0001), and fibrinogen (P=0.024). The PAI-1 gene polymorphism tested did not influence the rate of decline in renal function after transplantation nor the plasma level of PAI-1 antigen. CONCLUSION: We conclude that PAI-1, whose secretion is determined in large part by metabolic and inflammatory factors, may be implicated in the rate of decline in renal function after transplantation.
Adult↗
Hepatitis C virus-Epstein-Barr virus interaction in patients with AIDS.
Immortalization of B cells by Epstein-Barr virus (EBV) and their subsequent proliferation leads to B-cell non-Hodgkin's lymphoma in immunocompromised patients. The role of hepatitis C virus (HCV) in B-cell non-Hodgkin's lymphoma has recently been raised, and an interaction between HCV and EBV is supported by recent in vitro experiments. The aim of this study was to investigate in vivo interactions between HCV and EBV in patients with AIDS, i.e., patients exposed to the risk of EBV-related B-cell non-Hodgkin's lymphoma. A total of 135 patients were prospectively studied. Serological and molecular markers of HCV, EBV, and human immunodeficiency virus (HIV) infection were sought. All the patients harbored latent EBV infection, and 20% had detectable HCV RNA in serum. No significant relationship was found between HIV, HCV, and EBV viral load in peripheral blood mononuclear cells or plasma. There was no difference between anti-HCV-positive and -negative patients or between HCV RNA-positive and -negative patients with regard to the prevalence of EBV markers, especially EBV replication markers. The presence of EBV replication markers was not related to HCV RNA seropositivity or to HCV viral load. Five patients subsequently developed B-cell non-Hodgkin's lymphoma, none of whom had markers of EBV or HCV replication. These results argue against an in vivo interaction between HCV and EBV in patients with AIDS, and against a role of HCV infection in the occurrence of B-cell non-Hodgkin's lymphoma in these patients.
Adult↗
Why and how post-mastectomy edema should be quantified in patients with breast cancer.
In the present study, we advocate quantifying post-mastectomy edema in patients with breast cancer in millilitres and not in centimetre, contrarily to the usual routine practice. The water displacement and perimetric quantification methods exhibited both excellent reproducibility with an intraclass correlation coefficient > 0.99 and an accuracy coefficient < 0.3%.
Anthropometry↗
Liver disease in pediatric patients with cystic fibrosis is associated with glutathione S-transferase P1 polymorphism.
Liver disease in patients with cystic fibrosis (CF) is inconstant and has not yet been clearly related to any specific risk factor. While the expression of cystic fibrosis transmembrane conductance regulator (CFTR) is restricted to the biliary epithelium in the liver, recent findings indicate that CFTR modulates reduced glutathione (GSH) transport and that CFTR dysfunction creates an imbalance in the antioxidant defense. Among liver detoxifying enzymes, the glutathione S-transferases (GSTs) play a key role in the protection against oxidative stress. Because oxidative injury contributes to the development of liver disease, we hypothesized that 2 members of the GST superfamily, GSTM1 and GSTP1, which are expressed in the biliary epithelium, could influence the hepatic status in patients with CF. The potential impact of GSTM1 and GSTP1 gene polymorphisms was assessed in 106 children with CF (mean age, 11.5 years). Based on polymerase chain reaction/restriction fragment length polymorphism analysis, we found that the frequency of GSTP1-Ile(105)/Ile(105) genotype was significantly higher in patients with CF with liver disease than in those without (P <.03). Among the youngest patients, aged 6 years, GSTP1-Ile(105)/Ile(105) genotype was associated with a 8-fold increase in the risk of liver disease compared with other GSTP1 genotypes (P =.002). No association between the GSTM1 genotype and liver status was documented. In conclusion, GSTP1-Ile(105)-encoding allele contributes to hepatic dysfunction in CF. Identification of this polymorphism may have prognostic value and prompt early treatment in patients with CF with an increased risk of liver disease.
Adolescent↗
Prospective evaluation of risk factors of cutaneous drug reactions to sulfonamides in patients with AIDS.
BACKGROUND: Persons with HIV infection have increased rates of drug eruptions. OBJECTIVE: Our aim was to evaluate the risk factors of drug eruptions in response to sulfonamides in patients with AIDS, using a case-control analysis. METHODS: One hundred thirty-six patients who were hospitalized for pneumocystosis or toxoplasmosis were evaluated at the onset of treatment for various risk factors, which were then compared among patients with (48, 36%) and without (88, 64%) a drug eruption. RESULTS: In multivariate analysis, high CD8(+) cell count and age less than 36 years indicated a risk of drug eruption (respective odds ratios: 3.5 [95% CI 1.6-7.8], P =.002, and 2.1 [95% CI 1-4.6], P =.06). Markers of viral replication for HIV, Epstein-Barr virus, cytomegalovirus, human herpesvirus 6, and parvovirus B19, slow acetylation phenotype or genotype, and glutathione level were not associated with a risk. Administration of corticosteroids had no preventive effect. CONCLUSIONS: Our results challenge several current concepts regarding drug eruptions by discarding a strong association with glutathione deficiency, slow acetylation, or active viral infections and by showing no preventive effect of corticosteroids.
AIDS-Related Opportunistic Infections↗
Adult haemolytic and uraemic syndrome: causes and prognostic factors in the last decade.
BACKGROUND: Haemolytic uraemic syndrome (HUS) is a rare and severe disease of various aetiologies in adults. The effect of fresh frozen plasma (FFP) infusion in adults suffering from HUS is not well defined. The aim of this retrospective study was to analyse the causes of HUS in adults admitted in a single renal intensive care unit (ICU) and to determine the life and renal prognosis factors, while most patients (78%) received FFP infusion. METHODS: We recorded clinical, biological, and histological data of 55 adults admitted in our renal ICU for HUS between 1990 and 1998, 49 of them having had a renal biopsy. By stepwise logistic regression analysis, we examined the parameters that were associated with the in-hospital mortality and renal function at discharge. RESULTS: HUS complicated different diseases in 40 patients (HIV infection n=18, nephropathies n=10, allotransplantation n=7, malignant diseases n=5) and appeared as a primary in 15 patients. Factors influencing the in-hospital mortality were positive HIV serology (odds ratio (OR) >20, P=0.0002) and requirement for haemodialysis (OR >35, P=0.004). A pre-existing nephropathy was a bad prognosis factor for renal function (OR >99, P=0.02), while fever was associated with better renal prognosis (OR=1/10, P=0.033). CONCLUSIONS: HUS in adults remains a severe disease, with a high mortality rate in HIV patients and in those who required haemodialysis. However, as compared with previous studies, we observed an improvement in renal outcome, particularly in patients with primary HUS, suggesting a beneficial effect of FFP infusion, at least in these forms.
Acquired Immunodeficiency Syndrome↗
A recent increase in the incidence of male urethritis in France.
BACKGROUND: At-risk sexual behaviors appear to have increased recently in France, possibly because of the reassuring efficacy of highly active antiretroviral treatments. The objective of this study was to assess the pattern of change. GOAL: The goal was to analyze trends in the incidence of male urethritis, a marker of at-risk sexual behavior, between 1989 and 2000. STUDY DESIGN: The general practitioners of the Sentinelles Network reported, through an online computer system, all cases of male urethritis they diagnosed, together with the patients' age, presence of discharge, sexual preference, history of sexually transmitted disease, prescriptions, and results of microbiologic findings. RESULTS: After falling markedly between 1989 and 1995, the incidence of urethritis increased slightly in 1996 and then stabilized. The percentage of homosexual/bisexual men was higher among the cases than in the general population. Homosexual/bisexual men were younger than heterosexual men with urethritis; they were more likely to have a discharge and a history of sexually transmitted disease and had more sex partners. The main causative organisms were chlamydiae (18%) and Neisseria gonorrhoeae (13%). CONCLUSION: The increasing incidence of urethritis in France calls for a readjustment of preventive strategies.
Adult↗
Virus diversity in a winter epidemic of acute diarrhea in France.
In France, an epidemic peak of acute diarrhea is observed each winter. Previous results suggested a viral etiology for these winter epidemics. We investigated the role of enteric viruses in acute diarrhea and their molecular diversity. One hundred sixty-one patients with acute diarrhea and 45 healthy patients (controls) from the general population were given a standardized questionnaire between December 1998 and May 1999. Stool specimens were screened for group A and C rotaviruses, human caliciviruses, astroviruses, and adenovirus types 40 and 41 by reverse transcription-PCR and/or enzyme immunoassay. Virologic analysis was positive for 63 cases (39%). Caliciviruses and group A rotaviruses were the most frequent (19 and 17% of cases, respectively). Two control stool specimens were found positive for group A rotavirus, and one was found positive for astrovirus. Molecular characterization of the strains disclosed a cocirculation of P[8],G1, P[8],G4, and P[4],G2 rotaviruses; type 1, 2, 3, 4, and 8 astroviruses; and Sapporo-like and Norwalk-like human caliciviruses. These four types of viruses accounted for an attributable risk of acute diarrhea of 34.7% for the general population, under the assumption of a causal role of these viruses.
Acute Disease↗
Prospective evaluation of genetic abnormalities and telomerase expression in exfoliated urinary cells for bladder cancer detection.
PURPOSE: To evaluate alternative procedures to cytoscopic examination we prospectively compared noninvasive procedures for detecting bladder cancer namely cytology, loss of heterozygosity (LOH), microsatellite instability and human telomerase catalytic subunit reverse transcriptase (hTERT) messenger (m) RNA detection. MATERIALS AND METHODS: Specificity and cutoff values were established in the blood and urine sediment of 50 controls. Sensitivity was analyzed in the urine and tissue samples of 50 patients with bladder cancer. The diagnosis was established by cystoscopic and histological examination. Genomic alterations were studied using a panel of 24 microsatellite markers to detect LOH events, while 3 additional mononucleotide repeats were analyzed for microsatellite instability detection. Telomerase expression was detected in urinary cells by nested RT-polymerase chain reaction amplification of hTERT mRNA. All techniques were compared by cytological examination. RESULTS: Sensitivity and specificity were 31% and 100% for cytological testing, 96% and 100% for LOH, and 75% and 69% for RT-polymerase chain reaction of hTERT, respectively. No alteration was detected on microsatellite instability analysis in urine or tumor tissue cells. Using only the 5 markers most strongly associated with bladder cancer selected by logistic regression analysis, namely ABL1, IFNa, D9S12, MJD58 and D18S364, LOH test sensitivity slightly decreased to 90%. CONCLUSIONS: Urinary LOH analysis was the most sensitive and specific method for bladder cancer detection and it appeared less dependent on urine sediment quality. The logistic regression score may be an interesting complement to cystoscopy. The specificity of hTERT mRNA detection was incomplete since false-positives were observed in 31% of cases. Absent microsatellite instability in our cohort showed that these genomic alterations are not present at the early step of bladder cancer.
Catalytic Domain↗
Automated analysis of mature red blood cells and reticulocytes in SS and SC disease.
Phenotypic expression of sickle cell disease (SCD) is highly variable. We investigated red blood cells (RBCs) and reticulocytes using a laser light scattering method (ADVIA120, Bayer Diagnostics, Tarrytown, NY) in a series of patients with either sickle cell anemia (SS) or compound SC heterozygosity (SC), both groups with or without alpha thalassemia. Results were compared with those of a series of patients without hematological disease. Known data were consistently confirmed, namely heterogeneity in cell volume and hemoglobin (Hb) concentration, as well as the premature exit of "stress" reticulocytes from the bone marrow, mostly in SS patients. Specific changes were observed during maturation, including decreases in macrocytic and hypodense cells. Simultaneous viewing of the indices of the different RBC populations provided information on erythropoietic maturation by a rapid, reproducible, and cost-effective method.
Anemia, Sickle Cell↗
Modeling spatial and temporal transmission of foot-and-mouth disease in France: identification of high-risk areas.
Foot-and-mouth disease is one of the most contagious diseases of animal livestock. We used statistical tools to explore the dynamics of epidemics and to evaluate the consequences of virus reintroduction in France. We developed a stochastic farm-based model adapted to the French farm structure from previous modeling works following the 2001 epidemic in the United Kingdom. This model depends upon the distance between the 280,000 French farms and on species type (e.g. cows and sheep) and it tracks each animal's farm status at any given day. Since data were only available at the town scale, the farm location and the number of animals in each farm were simulated over the surface area of each French town, as well as the number of mixed farms. Based on 200 simulations of the model, our results allowed for the study of local disease transmission, since it begins simulations once limitation of movement is put into place. On average, the same 50 randomly chosen initially infected farms would lead to 1,110 infected farms (610; 1,590) when two control strategies (culling within 0.5 km from an infected farm and vaccination within 3 km) are put into place. Regions with high densities of cows and sheep (e.g. Pays-de-la-Loire) are high-risk zones, confirming that the epidemic process depends upon the location and the type of initially infected farms (size, species type). The results of this model highlight the importance of Geographical Information Systems (GIS) to obtain more precise data concerning herds.
Animals↗
Disclosure of diagnosis of Alzheimer's disease in French general practice.
Most practitioners find disclosing the diagnosis of Alzheimer s disease (AD) to an individual with dementia very difficult. Literature results show a wide variability in attitudes and clinicalpractice, and diagnosis seems to be more often disclosed to caregivers than to patients. The objective of this study was to examine whether and how diagnosis of AD is disclosed in French general practice and which issues are addressed with the patient. A questionnaire was sent via mail to 1,629 general practitioners (GPs), 1,105 belonging to the Sentinel's network and 524 specially recruited doctors practicing in the Rhône-Alpes region. A total of 631 questionnaires were returned (response rate, 39 percent), of which 616 were eligible for analysis. Twenty-eight percent of GPs reported having disclosed diagnosis to the patient (25 percent mentioned "Alzheimer's disease"), whereas 88 percent considered it their role to announce the diagnosis to the patient. Regarding the type of information provided to the patient, only 25 percent discussed the nature of the illness, 23 percent behavioral problems, and 47 percent depression, mainly for psychological reasons (63 percent). Stress was discussed with 79 percent of the caregivers. We concluded that GPs do not discuss the consquences of AD and symptoms (e.g., behavioral disorders) with patients, mainly for psychological reasons, whereas they have a less-reluctant attitude toward caregivers. As the GP has the weighty task of providing ropriate community care and psychological support to the patient, it is of utmost importance to reflect on how disclosure of diagnosis can be facilitated.
Alzheimer Disease↗