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.     

Pharmacokinetics--a relevant factor for the choice of a drug?

Pharmacokinetics may be utilized as a tool in the drug development process, either with respect to therapeutics or in allowing a drug's disposition characteristics to be defined. If two drugs of the same class have a similar dose-efficacy profile, then the favourable/unfavourable balance of the pharmacokinetic characteristics of the drugs may determine the drug of choice. Pantoprazole, a proton pump inhibitor, appears to meet the above criteria and has been found to exhibit reliable, predictable pharmacokinetic characteristics as opposed to other members of the class. The pharmacokinetics of pantoprazole over a range of intravenous and oral doses are described in healthy volunteers and are compared with values obtained for omeprazole. Studies in patients with severe cirrhosis, renal failure, and in the elderly are also described as well as potential interactions due to food and five other drugs.     

A computerized documentation system for cancer pain management units.

A cancer pain management unit can benefit markedly from a well-planned documentation system for administrative and scientific purposes. This article presents the principles of such a computerized system based on relational data base programs. The described system has been used by the authors for the last seven years. The successful documentation of more than 1400 patients over treatment periods of up to 2 years has provided detailed administrative and scientific information.     

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.     

Cytogenetic studies on human myeloma cell lines

Cell lines (U-266, U-1957, U-1996 and U-2030) established from 4 patients with multiple myeloma (MM) were analyzed cytogenetically. The cell lines represent different stages in B-cell differentiation as evidenced by ultrastructural and functional characteristics. The karyotypic pattern in 3 newly established myeloma lines was studied after a few months in culture and compared to the old myeloma cell line U-266, which was examined after 6, 7 and 8 years of continuous cultivation. Frequency of progressive numerical and structural aberrations during long-term cultivation and their correlation with alterations in growth properties were addressed. We describe the presence of a high frequency of both numerical and structural chromosomal abnormalities in the cells of all 4 myeloma lines studied. Chromosomes often associated with structural abnormalities were 1, 3, 6, 12 and 14. A 14q + marker chromosome was detected in 2 of the 4 cell lines. The breakpoints on the chromosomes participating in structural aberrations in myeloma exhibit some correlation to chromosome sites at or close to locations of mapped oncogenes. No translocations of c-myc were found. These data were further supported by Southern blot analysis (unpublished data). The extent of numerical, but not structural, aberrations correlates with the differentiation stage of the myeloma lines in that the 2 mature lines U-266 and U-1957 were both near-diploid. Multiple progressive chromosomal changes have emerged in U-266 during a period of 8 years with development of independence of feeder cells and increased growth rate. However, capacity for production of complete Ig molecules has remained stable.     

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.