Competing risks of death and Hardy-Weinberg equilibrium in case-control studies of gene-disease association

OBJECTIVE: To study the impact of competing risks on Hardy-Weinberg equilibrium and their consequences in case-control studies of gene-late onset disease association. METHODS: Based on a population born in Hardy-Weinberg equilibrium for a particular gene, the genetic composition when the gene is associated with a lethal early-onset disease and its consequences on a late-onset disease can be deduced. Odds ratios estimates are unbiased in case-control studies when controls are sampled by density, even if the controls are in Hardy-Weinberg disequilibrium. RESULTS: An example in which a mutant gene is associated with early mortality is presented, producing a departure from Hardy-Weinberg equilibrium; as a result, controls in later ages are in disequilibrium, producing an odds ratio equal to 1.61. CONCLUSION: Although the main causes of Hardy-Weinberg disequilibrium in controls are selection bias or genotyping error, a competing risk of death associated with the mutant gene would also result in Hardy-Weinberg disequilibrium among controls.     

The fibroblastic nature of dermatofibrosarcoma protuberans

Summary Dermatofibrosarcoma protuberans has been considered to be of fibrohistiocytic or fibroblastic origin. The purpose of this paper is to identify the original cell strain from which this neoplasm derives, using tissue culture and electron microscopic methods. Thirteen cases of DFSP characterised by clinical, topographical, histological and behavioral criteria were explanted. The emigrating cells were bipolar with two opposed processed and showed a radial arrangement in respect to the expiants. After the second week the distal processes tended to curve back towards the cell body forming flame-like structures. This cell morphology and cellular orientation persisted during the whole life of the culture. Electron microscopy was performed in three cases; the newly grown cells maintained an electron microscopic picture similar to that found in the original tumors.This pattern of behaviour is characteristic of fibroblastic tumors and has been found in explants of normal fibroblasts, of fibromatosis and of fibrosarcomas used as controls. On this basis, we believe that DFSP is a fibrosarcoma of the skin of low grade malignancy.     

Relapsing polychondritis studied by computed tomography

Computed tomographic findings in a patient with relapsing polychondritis are described. Collapse of the cartilage of the nose and calcification in cartilages of the ears were clearly demonstrated. CT scanning was also helpful in evaluating the tracheobronchial tree for airway compromise, which could prove fatal in this condition.     

Mortality of multiple sclerosis in Spain: demonstration of a north-South gradient

OBJECTIVE: To analyse the geographical distribution of multiple sclerosis in Spain from 1975 to 1998. METHODS: Age-adjusted mortality rates by province were obtained by the indirect method using the whole Spanish population as the reference. Then, standardised mortality ratios (SMRs) and their 95% confidence intervals were estimated. RESULTS: For both men and women, provinces with SMRs higher than the mean tended to be in the northern third of Spain, whilst those with SMRs lower than the mean were mostly located in the southern half. A linear regression analysis showed a significant positive association between mortality and latitude. CONCLUSION: A north-south gradient in age-adjusted multiple sclerosis mortality exists in Spain.     

Prefrontal cognitive functions in stabilized first-episode patients with schizophrenia spectrum disorders: a dissociation between dorsolateral and orbitofrontal functioning

Specific prefrontal cognitive impairments have been reported in first-episode and chronic schizophrenia. We sought to investigate potential impairments in specific prefrontal cortical cognitive functions among stabilized patients with a first-episode of schizophrenia. A sample of 80 individuals with a first-episode of schizophrenia spectrum disorders and 22 healthy volunteers underwent a neurocognitive battery assessing orbitofrontal (OFC) [The Iowa Gambling Task (GT)], and dorsolateral prefrontal (DLPFC) functions (WAIS III Backward digits, verbal fluency test (FAS), and Trail Making Test). Cognitive data were obtained following stabilization of acute psychotic symptoms. Clinical symptoms after six weeks of treatment were assessed by using the SAPS and SANS scales. While there were no significant group differences in overall scores and in the profile of progress of performance along periods on the GT, patient group showed a significant impairment when performing DLPFC tasks. Only FAS score was correlated to the severity of negative symptomatology. The OFC functions are unimpaired at the early phases of psychosis and in contrast there is a significant deficit in DLPFC functions in first-episode of schizophrenia.     

Performance of asialotransferrin in detecting alcohol abuse

BACKGROUND: The spectrum of alcohol use disorders covers hazardous use, alcohol abuse, and alcohol dependence. The present study evaluated the performance of asialotransferrin, a newly proposed biomarker for alcohol use disorders, in detecting alcohol abuse and alcohol dependence. METHOD: A 4-month trial was conducted in three groups of participants: alcohol abusers and alcohol-dependent patients, as defined in DSM-IV, and a control group. Asialotransferrin was assayed by capillary zone electrophoresis. RESULTS: Asialotransferrin demonstrated a sensitivity of 0.34 and a specificity of 1.00 for alcohol abuse. The sensitivity of asialotransferrin increased to 0.57 in alcohol-dependent patients. CONCLUSION: Despite the high specificity of asialotransferrin in alcohol use disorders, its sensitivity is too low to make it a useful marker of alcohol abuse.