Selection of Single Nucleotide Polymorphisms for Association Studies in Candidate Genes

Comparison of polymorphic sites such as single nucleotide polymorphisms (SNPs) within a gene between cases and controls may be useful for establishing a role of this gene in disease susceptibility. The approach includes two steps: the first step is the discovery of the different SNPs within the candidate gene and the second step is the association testing per se that can be done on the entire set of sites discovered or on a subset of these sites only. Selecting a subset of sites may increase the power to detect the association with the candidate gene since a smaller number of tests would then be performed. We proposed a strategy to select sites within a candidate gene and applied it on the Genetic Analysis Workshop 12 candidate gene data. Using these selected sites, we detected an association with candidate genes 1 and 6. © 2001 Wiley‐Liss, Inc.     

Coping with mild inflammatory catamenial acne

BACKGROUND: Acne is a multifactorial disease exhibiting distinct clinical presentations. Among them, the catamenial type is a matter of concern for young women. Some oral contraceptives may help without, however, clearing the skin condition. AIM: The present open study aimed at evaluating the effect of overnight applications of a paste made of petrolatum,15% zinc oxide and 0.25% miconazole nitrate. METHOD: The split-face trial was conducted in 35 women. A non-medicated cream was used as control. Clinical evaluations and biometrological assessments on cyanoacrylate follicular biopsies were performed monthly for 3 months. Comedometry and the density in autofluorescent follicular casts were used as analytical parameters. In addition, the five most severe cases at inclusion were tested at the completion of the study for follicular bacterial viability using dual flow cytometry. RESULTS: Compared with baseline and to the control hemi-face, the medicated paste brought significant improvement of acne. The number of papules and their redness were reduced beginning with the first treatment phase. A reduction in the follicular fluorescence was yielded beginning with the second treatment phase. The ratios between injured and dead bacteria, on the one hand, and live bacteria, on the other hand were significantly increased at completion of the study. CONCLUSION: A miconazole paste applied for 1 week at the end of the ovarian cycle has a beneficial effect on catamenial acne.     

Life events exposure before a treated major depressive episode depends on the number of past episodes.

A cross-sectional survey investigated the relationship between the number of previous depressive episodes and life events, testing the kindling hypothesis, in a sample of 13,377 treated patients with unipolar depression. A linear decline of average life events exposure is observed for more frequent past episodes, even when age, gender and severity are taken into account.     

Biodistribution study of 99mTc-labeled LDL in B16-melanoma-bearing mice. Visualization of a preferential uptake by the tumor

Since there is strong evidence of a preferential LDL accumulation in tumor cells, LDL might be of interest for tumor imaging. We have tested the ability of ^99mTc-LDL in tumor imaging with B16-melanoma-bearing mice as a model for further applications in human studies. The LDL fixation rate was higher with 99^mTc-labeled LDL than with ¹²⁵I labeled LDL. Since technetium-99m remains trapped in the cells, ^99mTc-LDL is a well-adapted radioligand because of information given by this radiotracer on the receptor metabolism. We observed that, at early growth stages, the tumor took up the LDL at a maximal rate, suggesting differences in cholesterol metabolism as a function of tumor growth. Accumulation of label in the tumor area was perfectly observable in tumor-bearing mice on scintigraphic images. Computerized quantification of the regions of interest (as well as biodistribution studies including killing of the animals) showed a 1.81 -fold increase in uptake by the tumor as compared to the liver and a 28-fold increase as compared with corresponding normal tissue (muscle of the left leg) at day 8 of tumor growth. These data give strong support to the value of this non-invasive method in visualizing and quantifying the tissue LDL uptake in vivo, including the precise information provided by nuclear scintigraphy on the distribution of the radiolabeled LDL in the different tissues. ^99mTc-LDL could be an efficient tool for further diagnostic or therapeutic exploration in cancer patients.     

Progressive myelopathy due to meningeal thickening in shunted patients: description of a novel entity and the role of surgery

INTRODUCTION: Spinal cord compression due to meningeal thickening is a rare occurrence in shunted patients. Because of the long delay to clinical onset, this complication has not been identified as yet. AIMS: We report on nine cases of shunt-related progressive myelopathy due to meningeal thickening (SPMMT). MATERIALS AND METHODS: We reviewed our database of shunted children, for cases having developed progressive tetraparesis due to cervical meningeal thickening. RESULTS: We identified nine observations of SPMMT, eight of these with hydrocephalus due to neonatal meningitis; the last case had Dandy-Walker malformation shunted at birth and suffered postoperative meningitis. The age of clinical onset of myelopathy was between 6 and 20 years (median 12.8). All patients presented with slowly progressive walking difficulties with falls and no spinal pain. Magnetic resonance imaging (MRI) showed typically a thickened dura mater with collapse of the arachnoid space, compensatory expansion of the epidural fat, and T2 hyperintensity in the spinal cord. We operated on seven patients for surgical decompression and arachnoidolysis: One died postoperatively because of shunt malfunction, and two others died later of complications of tetraplegia. Three patients were aggravated after surgery, three experienced partial improvement, but one of these subsequently deteriorated again. CONCLUSION: SPMMT appears to be a novel and well-defined clinical and pathological entity; its pathological and radiological features are stereotyped; however, the diagnosis is delayed because of the slow pace of the disease. Although surgical decompression may be the only option, its results were poor in our experience; earlier surgery might improve this grim prognosis.     

Propriospinal myoclonus: utility of magnetic resonance diffusion tensor imaging and fiber tracking.

Propriospinal myoclonus (PSM) is a rare movement disorder characterized by involuntary spinal-generated muscular jerks that spread rostrally and caudally to other spinally innervated muscles. Most patients have no clear etiology, and conventional MRI of the spinal cord is generally normal. Here we report the use of magnetic resonance diffusion tensor imaging (DTI) and fiber tracking to detect tract-specific abnormalities in a patient with propriospinal myoclonus. As the patient had the fragile-X premutation and antithyroid antibodies, spinal cord DTI abnormalities may be related to these conditions. Tract-specific analysis may provide new insights into the pathophysiology of propriospinal myoclonus.     

Atypical forms of isolated partial atrioventricular septal defect increase the risk of initial valve replacement and reoperation.

OBJECTIVE: We consider the short- and long-term outcomes of the repair of the isolated partial atrioventricular (AV) septal defect to determine the role played by the atypical forms on the initial AV valve replacement and on the risk of reoperation. METHODS: Two hundred and eight patients underwent an operation for this malformation between 1974 and 2001. Clinical and echocardiographic examinations were performed on all patients, the AV valve regurgitation was graded from 1 to 4 and a residual interatrial shunt was sought. Median age at the intervention was 5.8 years (3 months to 67 years). RESULTS: Median follow-up time was 7.5 years (range 0-22.6 years). The cumulative 30-day, 5- and 20-year survival rates were 96.5, 95.4 and 94.6%, respectively. AV valve replacement was associated with a high mortality (P<0.001). A reoperation was performed on 12 patients (5.7%) including six patients within less than a 30-day period, especially to repair residual AV valve regurgitation. We performed four AV valve repairs by annuloplasty and six AV valve replacements. Two patients who had initially undergone an AV valve replacement underwent a reoperation for valve thrombosis. The cumulative 30-day, 5- and 20-year rates of freedom from reoperation were 96.5, 93.6 and 83%, respectively. An atypical form was present in 24 patients (11.5%) and was a risk factor for initial AV valve replacement (P<0.001) and for reoperation (P<0.001). A complete AV block occurred in 13 patients (6.2%), all of them within a 30-day period. The AV valve replacement was a high risk factor for a complete AV block (P<0.001). At the end of our study 180 patients (96%) were in NYHA I and 8 in NYHA II. CONCLUSIONS: The morbi-mortality of the isolated partial AV septal defect is primarily perioperative and is linked with the presence of an atypical form of the lesion. This atypical form was the main reason for reoperation for AV valve regurgitation. The AV valve replacement was associated with a high mortality and with the occurrence of complete AV block. Using a standardized technique, the AV septal defect can be repaired with excellent long-term clinical and echographic results.     

Plasma fatty acids and lipid hydroperoxides increase after antibiotic therapy in cystic fibrosis.

The present authors investigated whether cystic fibrosis is linked to a defect in fatty acids and assessed the impact of the main patients' characteristics on the levels of several fatty acids, mostly during respiratory exacerbation and after antibiotic therapy. Fatty acid phospholipid and cholesteryl ester levels were measured in stable-state patients and controls. No differences were found concerning either the fractions of palmitic and oleic acids or the cholesteryl esters of alpha-linolenic and arachidonic acids. However, phospholipids of alpha-linolenic and arachidonic acids, as well as cholesteryl esters and phospholipids of stearic and linoleic acids, were lower in patients than in controls, but fractions of dihomo-gamma-linolenic, docosatetraenoic, docosapentaenoic, palmitoleic and eicosatrienoic acids were higher. Fatty acid levels, oxidative stress markers, nutrients, body mass index and forced expiratory volume in one second (FEV(1)) were measured in patients before and after antibiotic courses for bronchial exacerbation. After adjustments, palmitic, stearic, alpha-linolenic, linoleic, arachidonic, palmitoleic and oleic acids generally decreased during exacerbation but almost all increased after antibiotic courses. Nearly all fractions increased along with FEV(1) and a positive relationship linked fatty acids to lipid hydroperoxides. There was no general drop in fatty acids. Patients' fatty acid profiles depended on the pulmonary function and the inflammation state.