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Biomedical subjects

E Louis

Publications and source records attributed to E Louis.

At least 19 recordsLinked to original sources

Risk of Alzheimer's disease in relatives of Parkinson's disease patients with and without dementia.

OBJECTIVE: To determine whether first-degree relatives of PD patients with dementia were at increased risk for the development of AD compared with first-degree relatives of nondemented PD patients and nondemented normal subjects from the community. METHODS: A structured family history interview was administered to 146 nondemented PD patients, 120 patients with PD and dementia, and 903 normal subjects from the community to ascertain the presence of AD among parents and siblings of these subjects. Cox proportional hazards models with double censoring techniques for missing information were used to model the risk of AD among relatives. RESULTS: No increase in risk of AD was found among parents of patients with PD and dementia or parents of nondemented PD patients compared with parents of normal subjects. However, siblings of demented PD patients were three times as likely (relative risk [RR] = 3.2, 95% confidence interval [CI] = 1.1 to 9.4, p < 0.04) as siblings of normal subjects to develop AD. When only siblings >65 years of age were considered, there was a fivefold increase in risk of AD among siblings of demented PD patients compared with siblings of normal subjects (RR = 4.9, 95% CI = 1.1 to 21.4, p < 0.03). The risk of AD was also increased for female relatives, regardless of whether the woman was a relative of a demented PD patient, a nondemented PD patient, or a normal subject. Ethnicity and APOE genotype did not affect dementia status among relatives. CONCLUSIONS: The increased risk of AD in siblings of demented PD patients compared with siblings of normal subjects supports the possibility of familial aggregation of AD and PD with dementia.

Aged

Intraventricular cavernomas: three cases and review of the literature.

OBJECTIVE AND IMPORTANCE: Cavernomas occur very rarely in the ventricular system. We report three cases of intraventricular cavernomas and review the literature. CLINICAL PRESENTATION: A 16-year-old female patient presented with a sudden distal deficit of the left superior limb. She had a voluminous tumor involving the two lateral ventricles, with radiological evidence of recent hemorrhage. A 30-year-old man presented with generalized seizures and a right hemiplegia related to a 4-cm-diameter cavernoma in the two lateral ventricles involving the interhemispheric scissure through the corpus callosum and left centrum ovale. The radiological appearance was not typical and did not allow the diagnosis. A 42-year-old man had a cavernoma in the third ventricle, which was responsible for his short-term memory loss. This cavernoma had been revealed by computed tomography that was performed after intracerebral hemorrhage related to another cavernoma in the right parietal lobe occurred. INTERVENTION: Stereotactic biopsies allowed the diagnosis of intraventricular cavernoma in the first case. Surgical removal via a right transcortical transventricular approach and a transcallosal approach in the first and second cases, respectively, was complete, resulting in good outcomes. Surgical removal via a right transcortical transventricular approach in the third case was partial. CONCLUSION: Intraventricular cavernomas are so uncommon that only 42 well-documented cases have been previously reported in the literature. It seems that their radiological diagnosis may be difficult because of their uncommon location in the ventricular system and their voluminous size. A wrong preoperative diagnosis has sometimes been the cause of inefficient therapy, such as radiotherapy, for these surgically curable benign lesions.

Adolescent

Effects of dexamethasone on the profile of cytokine secretion in human whole blood cell cultures.

EXPERIMENTAL OBJECTIVES: The interaction between the endocrine and immune systems is a very intriguing area. Endogenous glucocorticoids, as end-effectors of the hypothalamo-pituitary-adrenal axis, inhibit the immune and inflammatory responses and are used as immunosuppressive drugs in many inflammatory, autoimmune and allergic diseases. The aims of this study were to investigate the effects of dexamethasone on the profile of cytokine secretion in whole blood cell cultures from healthy subjects and to analyse the gender-related sensitivity to dexamethasone on each cytokine secretion. RESULTS: There was a significant inhibition by dexamethasone (from 1 to 100 nM) on the secretion of monokines (IL-1beta, IL-6, IL-8 and TNF alpha) and lymphokines (IL-2, IL-4, IL-10 and IFN gamma), either after LPS or PHA stimulation (P < 0.01). Interleukin 4 and IL-10 were less inhibited than IFN gamma (P < 0.05 at 1 nM, P < 0.01 at 10 nM and P < 0.001 from 100 nM to 10 microM). No gender difference was observed in the rate of inhibition of the secretion of each cytokine. CONCLUSION: This study shows that the inhibition of cytokine secretion by dexamethasone is more marked on Th1-type cytokines than on Th2-type cytokines. These data support the idea that glucocorticoids may induce a shift from the Th1 to Th2 profile of cytokine secretion.

Adult

Tumour necrosis factor (TNF) gene polymorphism influences TNF-alpha production in lipopolysaccharide (LPS)-stimulated whole blood cell culture in healthy humans.

TNF-alpha is involved in infectious and immuno-inflammatory diseases. Different individuals may have different capacities for TNF-alpha production. This might determine a predisposition to develop some complications or phenotypes of these diseases. The aims of our study were to assess the inter-individual variability of TNF-alpha production and to correlate this variability to a single base pair polymorphism located at position -308 in TNF gene. We studied 62 healthy individuals. TNF-alpha production after LPS stimulation was evaluated using a whole blood cell culture model. The TNF gene polymorphism was studied by an allele-specific polymerase chain reaction. Other cytokines produced in the culture, soluble CD14 concentrations and expression of CD14 on blood cells were also measured. Among the 62 individuals, 57 were successfully genotyped. There were 41 TNF1 homozygotes and 16 TNF1/TNF2 heterozygotes. TNF-alpha production after LPS stimulation of whole blood cell culture was higher among TNF2 carriers than among TNFI homozygotes (929pg/ml (480-1473pg/ml) versus 521 pg/ ml (178-1307 pg/ml); P<0.05). This difference was even more significant after correction of TNF-alpha production for CD14 expression on blood cells. In conclusion, the single base pair polymorphism at position -308 in the TNF gene may influence TNF-alpha production in healthy individuals.

Adult

Clinical pattern of corticosteroid dependent Crohn's disease.

OBJECTIVES: Corticosteroid dependency in Crohn's disease (CD) is characterized by the need for chronic use of corticosteroids to maintain clinical remission. Several definitions have been used. Depending on the definition, 10-30% of the patients are considered as corticosteroid dependent. The aim of the study was to define a clinical pattern of corticosteroid dependent CD patients. PATIENTS AND METHODS: Epidemiological and clinical characteristics were retrospectively compared between 20 corticosteroid dependent CD patients and 248 non-corticosteroid dependent CD patients by using univariate and multivariate analyses. Corticosteroid dependency was defined either by two successive relapses during the 2 months after discontinuing glucocorticoids (n=5) or by two successive relapses at dose tapering, after successful treatment of a flare-up by using glucocorticoids (n=15). RESULTS: Corticosteroid dependent CD patients were younger at diagnosis (P < 0.001), and were characterized by a higher frequency of colonic location (P< 0.05), but lower frequency of ileal location (P < 0.01), and higher ano-perineal location (P < 0.05). They were also more frequently smokers (P< 0.05) and users of contraceptive pills (P< 0.01). The inflammatory type of the disease was increased (P < 0.01), while the fibrostenotic type was decreased (P < 0.001) in corticosteroid dependent CD patients. By multivariate analysis, a smoking habit (P < 0.01), a colonic location (P < 0.05), a non-fibrostenotic type (P< 0.05) and a younger age at diagnosis (P< 0.05) were shown to be independently associated with corticosteroid dependency. CONCLUSIONS: This study suggests a clinical pattern associated with corticosteroid dependency. Whether this clinical pattern is simply associated with the dependency, or whether a primary decrease of corticosensitivity produces this clinical pattern, is not known. Further prospective studies will have to determine whether the presence of these clinical characteristics is predictive of corticosteroid dependency and whether this prediction will be useful for the management of this condition.

Adolescent

Environmental risk factors for Parkinson's disease in an urban multiethnic community.

Environmental risk factors were examined using univariate and multivariate unconditional logistic regression models in 89 nondemented patients with Parkinson's disease (PD) and 188 control subjects in a multiethnic urban community. Rural living, area farming, and drinking well water were associated with PD only in African-Americans. In Hispanics, area farming was protective, whereas drinking unfiltered water was a risk factor for PD. Consideration of ethnic and cultural origin may add to the epidemiologic study of PD.

Aged

Systemic iron metabolism and mortality from Parkinson's disease.

Six measures of systemic iron metabolism were used to predict mortality among 103 patients with Parkinson's disease and 353 controls followed in a longitudinal study. Adjusting for gender, education, ethnicity, presence of dementia, and extrapyramidal signs, transferrin receptor concentration was strongly associated with mortality in patients with PD but not controls. This increase in serum transferrin receptor concentration before death suggests that the previously observed perturbation in iron metabolism continues throughout the disease course.

Aged

Anatomic basis for auditory brainstem implant.

Profound bilateral retrocochlear deafness cannot respond to a cochlear implant. For such patients only electrical stimulation of the cochlear nucleus complex can achieve, at best, a partial restoration of hearing. Based on the experience of the W.F. House group at the House Ear Institute in Los Angeles, we have developed an implantable device with many surface electrodes. A personal study has enabled us to establish the main relationships of the nucleus with the aim of inserting the device in contact with it, and to verify its effectiveness in the region. Histological study of anatomic specimens has shown the presence of spheroid neurone, considered to be the secondary neurone of the auditory pathway, at the level of the area of implantation.

Brain Stem

Genetic markers may predict disease behavior in patients with ulcerative colitis.

BACKGROUND & AIMS: Recent studies have suggested that HLA DRB1*0103 and allele 2 of the interleukin 1 receptor antagonist (IL-1RA) gene predict severe and extensive ulcerative colitis, respectively. The aim of this study was to test these hypotheses in patients undergoing surgery for their colitis. METHODS: HLA DRB1 and DQB1 genotyping was performed in 99 patients and 472 controls. Genotyping for polymorphisms of genes encoding tumor necrosis factor alpha and IL-1RA was performed in 107 patients and 89 controls. Measurement of antineutrophil cytoplasmic antibody (ANCA) was performed in 72 patients and 58 healthy subjects by fixed neutrophil enzyme-linked immunosorbent assay and indirect immunofluorescence. RESULTS: The DRB1*0103 allele was increased in patients (14.1% vs. 3.2% in controls; P < 1 x 10[-5]). This association was greatest in patients with extensive disease (15.8%; P < 0.0001) or extraintestinal manifestations (22.8%; P < 0.0001): mouth ulcers (25.8%; P < 0.0001), arthritis (27.2%; P < 0.0001), and uveitis (35.7%; P < 0.0001). The DRB1*04 alleles were reduced in patients (P = 0.005). Differences were noted between extensive and distal disease in the frequency of allele 2 of IL-1RA (10.9% in distal vs. 28.6% in extensive; P = 0.01) and allele 2 homozygosity. ANCA was detected in 76.4% of patients. Carriage of IL-1RA allele 2 and tumor necrosis factor 2 allele was increased in ANCA-positive patients. CONCLUSIONS: Genetic markers may predict disease behavior in ulcerative colitis.

Adolescent

A high serum concentration of interleukin-6 is predictive of relapse in quiescent Crohn's disease.

BACKGROUND/AIMS: Relapses of Crohn's disease are difficult to predict. We assessed the value of serum level of interleukin-6, tumour necrosis factor alpha (TNF-alpha) and soluble TNF receptors as predictors of relapse in quiescent Crohn's disease. PATIENTS/METHODS: Thirty-six patients with inactive Crohn's disease, treated or not, were included. Various clinical and biological parameters, including interleukin-6, TNF-alpha and soluble TNF receptors serum levels were measured at inclusion in the study and the patients were followed clinically for 1 year. The relapse was defined as a Crohn's Disease Activity Index (CDAI) greater than 150 with an increase greater than 100 compared to the inclusion value. We analysed the ability of these parameters to predict relapse in parallel to clinical characteristics and other laboratory parameters. RESULTS: Among the 32 variables tested, interleukin-6 serum level had the greatest ability to predict the time-to-relapse, with 17-fold chance of relapse over a 1-year period for patients with an interleukin-6 serum level greater than 20 pg/ml than for patients with a lower level (P < 0.001). A high serum level of the soluble TNF receptors p55 and p75 also had significant predictive value, in contrast to TNF-alpha serum levels. An interleukin-6 serum level greater than 20 pg/ml and either an acid alpha-1-glycoprotein level greater than 1.1 g/l or a soluble interleukin-2 receptor serum level greater than 95 pM/l were risk factors selected by a stepwise multivariate analysis. In both models a good prognosis group was defined by the absence of the two risk factors, a bad prognostic group by the presence of the two risk factors and an intermediate in between. With both models, the good prognosis group included 17 patients who experienced no relapse over the 1-year follow-up, whereas all patients (seven with the first model and six with the second) in the bad prognosis group had a relapse during the follow-up. Looking specifically at two homogeneous subgroups including either naturally/5-aminosalicylic acid (5-ASA) quiescent or corticoid quiescent patients, a very good predictive value for interleukin-6 serum concentration was also found. CONCLUSION: Interleukin-6 serum level alone or in association with other biological parameters such as acid alpha-1-glycoprotein or the soluble interleukin-2 receptor serum level may be useful for predicting the course of the disease in patients with quiescent Crohn's disease.

Adolescent

[Results of hearing preservation in surgery of vestibular schwannoma. Value of combined retrosigmoid and middle fossa approaches].

We report our experience of hearing preservation in acoustic neurinoma surgery, using combined retrosigmoid and middle fossa approaches. Fifty neurinomas operated on between 1987 and 1994 were included in this retrospective study. Hearing preservation surgery was performed for patients with grade II or grade III tumors (mean average tumor diameter: 14.4 mm), presenting with normal or serviceable pre-operative hearing (pure tonal average decrease less than 50 dB, speech discrimination score better than 50%). Isolated middle fossa approach was used in 3 cases, isolated retrosigmoid approach in 2 cases. The 45 other cases were operated on using both routes during the same procedure. Total removal of the tumor with anatomic facial preservation was performed in all cases. No death occurred. The facial function assessed 3 months after surgery was good in 84% of cases (House-Brackmann grades I or II). The mean follow-up was 42 months. Post-operative hearing was measurable in 48% of cases and serviceable in 30% of cases. The size of the tumor and the level of preoperative hearing appear to be the most important predictive criteria for successful hearing preservation.

Adolescent

Extensive ulcerative colitis and extraintestinal manifestations in a patient with HIV infection and significant CD4 T-cell lymphopenia.

We report a heterosexual patient with HIV infection and a CD4 T-cell count of 0.45 x 10(9)/L who developed mild ulcerative proctitis, sacroileitis and oligoarthiritis. While he was treated with 5-aminosalicylic enemas, the patient rapidly developed severe pancolitis. An emergency colectomy without procetectomy was performed. A few months later, he suffered recurrence of ulcerative proctitis, aggravation of arthritic pain and developed anterior uveitis. All symptoms disappeared after proctectomy. There was no evidence for opportunistic infection or Kaposi's sarcoma. Antineutrophil cytoplasmic antibodies were positive and the HLA-B27 antigen was present. CD4 counts were lower during the phases of active disease than during remission. This case demonstrates that severe ulcerative colitis can occur in the presence of moderate T-cell defects. In view of a recent report of remission of Crohn's disease under comparable circumstances, it is possible that the extent of T-cell involvement in both diseases is radically different.

Acquired Immunodeficiency Syndrome

Two stage genome-wide search in inflammatory bowel disease provides evidence for susceptibility loci on chromosomes 3, 7 and 12.

Crohn's disease (CD) and ulcerative colitis (UC), the chronic inflammatory bowel diseases (CIBD), are common causes of gastro-intestinal disease in the Western world, with a combined prevalence of 100-200/100,000 (ref. 1). Epidemiological studies, particularly concordance rates in twin pairs and siblings, strongly implicate genetic susceptibility in the pathogenesis of CIBD. In fact, the relative contribution of genetic factors to the pathogenesis of CD may be greater than in schizophrenia, asthma or hypertension, and at least equivalent to that in insulin-dependent diabetes. Systematic screening of the entire human genome now provides a strategy for the identification of susceptibility genes in complex polygenic disorders. We undertook a two-stage genome search for susceptibility genes in inflammatory bowel disease involving 186 affected sibling pairs from 160 nuclear families. We provide strong evidence for the presence of susceptibility loci for both CD and UC on chromosome 3, 7 and 12. We obtained the highest lod score (5.47; P = 2.66 x 10(-7) with the marker D12S83 and lod scores of 3.08 and 2.69 for D7S669 and D3S1573, respectively. Our data suggest that CD and UC are closely related, but distinct, polygenic disorders that share some, but not all, susceptibility genes.

Chromosome Mapping

Cytokine gene polymorphisms in inflammatory bowel disease.

BACKGROUND: Concordance rates in siblings and twins provide strong evidence that genetic susceptibility is important in the pathogenesis of inflammatory bowel disease. The number and identity of susceptibility genes is largely uncertain. Cytokine genes are attractive candidate loci. AIMS: To study allelic frequencies of polymorphisms of the interleukin-1 receptor antagonist (IL-1RA) gene and the tumour necrosis factor alpha gene in patients with inflammatory bowel disease. SUBJECTS: One hundred and twenty nine North European caucasoid patients with ulcerative colitis, 120 patients with Crohn's disease, and 89 healthy controls. METHODS: Genotyping was performed by polymerase chain reaction. A variable number of tandem repeats (VNTR) in the IL-1RA gene and a single base pair polymorphism in the TNF alpha gene promoter region (TNF-308) were analysed. RESULTS: No significant differences in IL-1RA VNTR allelic frequencies were noted between Crohn's disease (allele 1: 72.6%, allele 2: 24.7%, allele 3: 2.6%), ulcerative colitis (72.6%, 24.3%, 3.1%, respectively), and controls (76.9%, 20.8% and 2.3%). Some 42.4% of patients with ulcerative colitis and 43.4% patients with Crohn's disease were carriers of allele 2, compared with 34.8% healthy subjects. The TNF2 allele was modestly reduced in Crohn's disease (13.2%), compared with healthy subjects (21.3%; p = 0.04), and ulcerative colitis (21.6%). CONCLUSIONS: The associations demonstrated are modest: these polymorphisms are unlikely to be important determinants of overall disease susceptibility.

Adult

Decrease in systemic tolerance to fed ovalbumin in indomethacin-treated mice.

The oral administration of non-steroidal anti-inflammatory drugs (NSAID) to animals induces a quick increase in intestinal permeability and secondary inflammatory lesions of the intestine. The mechanisms leading to the inflammatory lesions are hypothetical. The increased intestinal permeability could allow a greater mucosal and systemic penetration of fed antigens and bacterial products leading to an abnormal mucosal and systemic immune and inflammatory response toward these materials. We examined the effect of oral dosing with indomethacin on ovalbumin serum levels and the systemic immune response to ovalbumin in mice fed with ovalbumin. The ovalbumin serum level was higher in indomethacin-treated mice and the increase was proportional to the dose of indomethacin. It was associated with epithelial and subepithelial lesions. Moreover, the systemic humoral and, to a lesser extent, the cellular tolerance were partially abrogated in the treated mice. These findings suggest that the oral administration of indomethacin in mice induces an increased passage of fed antigen through the intestinal epithelium associated with a decrease in systemic tolerance to this antigen. The reason for this decrease remains unclear. Besides a disequilibrium between systemic and mucosal immune responses, a loss of integrity of the intestinal epithelial cells and a direct immunomodulating effect of indomethacin may also be involved. This decrease in systemic tolerance to luminal antigen could be involved in the development of NSAID enteropathy.

Administration, Oral

Risk of Parkinson's disease among first-degree relatives: A community-based study.

OBJECTIVE: To determine the relative risk (RR) and cumulative incidence of idiopathic Parkinson's disease (PD) in first-degree relatives of PD patients compared with relatives of controls from the same geographic region. DESIGN: A family history questionnaire was used to obtain information on all first-degree relatives of cases and controls. A subset of these first-degree relative was also examined. A Cox proportional hazards model with double-censoring techniques for missing information was used to model the RR for PD, adjusting for gender, ethnicity, and relationship to proband. RESULTS: A total of 1,458 first-degree relatives of 233 PD patients were 2.3 times as likely (95% CI = 1.3 to 4.0) as 7,834 relatives of 1,172 controls to develop PD. The cumulative incidence of PD to age 75 among first-degree relatives of PD patients was 2% compared with 1% among first-degree relatives of controls. The risk in male first-degree relatives was higher than in female relatives (RR = 2.0, 95% CI = 1.1 to 3.4) and the risk in relatives of Caucasians was higher than in African-Americans and Hispanics (RR = 2.4, 95% CI = 1.4 to 4.1). Risk for siblings and parents of probands was similar. CONCLUSIONS: Susceptibility to PD is increased in first-degree relatives of both sporadic and familial cases. The pattern of inheritance and the relationship between genetic and environmental risk factors warrant further study.

Aged