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.     

Rapid Detection of Candida albicans in Clinical Samples by DNA Amplification of Common Regions from C. albicans-Secreted Aspartic Proteinase Genes

Laboratory diagnosis based on genomic amplification methods such as PCR may provide an alternative and more sensitive method than conventional culture for the early detection of deep-seated candidiasis, an increasing cause of morbidity and mortality among immunocompromised patients. A novel method of DNA extraction from clinical samples based on treatment with proteinase K and isolation of DNA on a silica membrane was developed. The targets used for DNA amplification were the Candida albicans-secreted aspartic proteinase (SAP) genes, a multiple-gene family of at least seven members in C. albicans. A single pair of primers was designed in order to detect six of these SAP genes and, subsequently, to increase the sensitivity of the test. Detection of the PCR product by enzyme-linked immunosorbent assay was found to be as sensitive as Southern blotting with an SAP-labeled probe. The sensitivity of the assay was 1 cell/ml from serially diluted Candida cultures and 1 to 4 cells/ml from seeded blood specimens. The sensitivity and specificity of the present assay were tested in a retrospective study performed blindly with 156 clinical samples and were 100 and 98%, respectively, compared with the results of culture. For the subset of blood culture samples (n = 124), the sensitivity and the specificity were 100%. The two false-positive PCR samples came from patients treated with azole antifungal agents, indicating that PCR was probably able to detect damaged organisms that could not be recovered by culture.     

Cobas-Bact system for identification of members of the family Enterobacteriaceae in 4 h 20 min

The Cobas-Bact (Roche Diagnostics, Basel, Switzerland) new rotor for the identification (ID) in 4 h 20 min of 33 members of the family Enterobacteriaceae to genus and species level was evaluated by testing 444 strains of which 398 belonged to common species and 46 belonged to rare species of Enterobacteriaceae. Each strain was identified by the API 20E system (Analytab Products, Plainview, N.Y.), and additional discriminating tests were set up if necessary. Only first-choice ID were considered in this study and were classified either as high-confidence ID (normalized likelihood, greater than or equal to 80%) or as low-confidence ID (normalized likelihood, less than 80%) requiring additional tests for confirmation. The data were analyzed by two versions of Cobas-Bact software. With the first version of the software (SW8446), the overall accuracy of Cobas-Bact was 95.5% (424 correct ID of 444). When restricted to high-confidence ID it rose to 99.4% (350 of 352) for the common species and 96.9% (31 of 32) for the rare species. Only three strains of the high-confidence group were misidentified. Sixty ID were considered unacceptable because of their low confidence. Using the first software version (SW8446) they represented 12% (46 of 398) of the common species (17 typical strains, 10 Shigella species, 10 inactive Escherichia coli strains, and 9 rare biotypes) and 30% (14 of 46) of the rare species. The same data analyzed by the new version (SW8524) of the Cobas-Bact software resulted in an overall accuracy of 93.9% (417 correct ID). The number of high-confidence ID rose to 401, of which 392 (97.7%) were accurate. The decrease in low-confidence ID (43 versus 60) was mainly due to the Shigella species. In conclusion the accuracy of Cobas-Bact identification system was very good when restricted to high-confidence ID. The Cobas-Bact performance for rare species ID was poorer, but the small number of strains tested does not allow definitive conclusions.