Effects of Potential Agonist-Replacement Therapies for Stimulant Dependence on Inhibitory Control in Cocaine Abusers

Two experiments were conducted to determine whether methylphenidate or modafinil, two potential pharmacotherapies for stimulant dependence, would impair inhibitory behavior in cocaine users. Eleven cocaine abusers were administered methylphenidate (0, 15, 30, and 45 mg) or modafinil (0, 150, 300, and 450 mg) across four experimental sessions. A cued go–no-go task was used to measure response execution and inhibition. Subjective and cardiovascular measures were collected. Neither methylphenidate nor modafinil impaired inhibitory control, but produced prototypical subject-rated and cardiovascular effects. The results of these studies may have implications for the use of these drugs as agonist-replacement therapies for stimulant dependence.     

Identification of major loci controlling clinical manifestations of ankylosing spondylitis

OBJECTIVE: To identify genomic regions linked with determinants of age at symptom onset, disease activity, and functional impairment in ankylosing spondylitis (AS). METHODS: A whole genome linkage scan was performed in 188 affected sibling pair families with 454 affected individuals. Traits assessed were age at symptom onset, disease activity assessed by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and functional impairment assessed by the Bath Ankylosing Spondylitis Functional Index (BASFI). Parametric and nonparametric quantitative linkage analysis was performed using parameters defined in a previous segregation study. RESULTS: Heritabilities of the traits studied in this data set were as follows: BASDAI 0.49 (P = 0.0001, 95% confidence interval [95% CI] 0.23-0.75), BASFI 0.76 (P = 10(-7), 95% CI 0.49-1.0), and age at symptom onset 0.33 (P = 0.005, 95% CI 0.04-0.62). No linkage was observed between the major histocompatibility complex (MHC) and any of the traits studied (logarithm of odds [LOD] score <1.0). "Significant" linkage (LOD score 4.0) was observed between a region on chromosome 18p and the BASDAI. Age at symptom onset showed "suggestive" linkage to chromosome 11p (LOD score 3.3). Maximum linkage with the BASFI was seen at chromosome 2q (LOD score 2.9). CONCLUSION: In contrast to the genetic determinants of susceptibility to AS, clinical manifestations of the disease measured by the BASDAI, BASFI, and age at symptom onset are largely determined by a small number of genes not encoded within the MHC.     

Reducing hospitalizations and arrests for substance abusers

This four-year outcome study examines the results of the VA Contracted Residential Substance Abuse Treatment for veterans with substance abuse problems. Race, marital status, housing status, and exposure to combat in the military characterized the male veteran subjects. Hospitalization rates and arrest rates were tracked for two years prior to and two years post-residential treatment. The authors also examined treatment outcomes for those who completed outpatient substance abuse treatment after an episode of residential care. This study shows a 30% reduction of hospitalizations and arrests following residential treatment. Those veterans who completed both residential and outpatient treatment had the best outcomes in terms of number of hospitalizations and arrests in a two-year follow-up.     

Management of pseudoaneurysm of the ascending aorta performed under circulatory arrest by port-access

Pseudoaneurysms of the ascending aorta following previous thoracic surgery pose a difficult surgical management problem. In this report, we present a case of a patient with aortic insufficiency and a pseudoaneurysm of the ascending aorta at the site of a previous anastomosis. The particularity of this case is in the atypical use of Port-Access technology (Heartport, Redwood City, CA) to overcome surgical concerns [1].     

Testing drug response in the presence of genetic information: sampling issues for clinical trials

Progress towards construction of a dense map of di-allelic markers across the human genome has generated considerable enthusiasm for pharmacogenomic applications. To date, however, nearly all of the effort on single nucleotide polymorphism (SNP) projects has been focused on marker identification and screening, not on how the SNP genotype data actually can be used in clinical trials to advance medical practice. Here, we explore how different properties of SNPs impact the size, scope and design of clinical trials using a simple trial design. We evaluate the clinical trial sampling requirements under different allele frequencies, gene action, gene effect size and number of markers in a genome screen. Power and sample size calculations suggest that allele frequency and type of gene action can have a dramatic impact on trial sample sizes, in that under some conditions the required sample sizes are too large to be applicable in a costly clinical trial setting. In other situations, however, pharmacogenomic clinical trials can yield significant sampling/cost savings over traditional trials. These properties are discussed with regard to the general usage of genetic information in clinical trial settings.     

Prognostic factors of inoperable localized lung cancer treated by high dose radiotherapy

A retrospective study was made of the results of high dose radiotherapy (≥50 Gy) given to 171 patients with inoperable, intrathoracic non small cell lung cancer from January 1971–April 1973. Local control was dependent on the total tumor dose: after one year local control was 63% for patients treated with >65 Gy, the two year local control was 35%. If treated with <65 Gy the one year local control was ≤40%. Tumor doses correlated with the size of the booster field. If the size of the booster field was <100 cm², the one year local control was 72%; the two year local control was 44%. Local control was also influenced by the performance status, by the localization of the primary tumor in the left upper lobe and in the periphery of the lung. Local control for tumors in the left upper lobe and in the periphery of the lung was about 70% after one year, and about 40% after two years. The one and two years survival results were correlated with the factors influencing local control. The dose factor, the localization factors and the performance influenced local control independently. Tumors localized in the left upper lobe did metastasize less than tumors in the lower lobe, or in a combination of the two. This was not true for the right upper lobe. No correlation between the TNM system, pathology and the prognosis were found.