Inflammatory bowel disease and the X chromosome

A review of documented cases demonstrates a significant association of Turner's syndrome with Crohn's disease and ulcerative colitis; this association relates particularly to genetic constitutions comprising an abnormal rather than an absent X chromosome. The karyotype 46XiXq, in pure or mosaic form, appears to be a significant susceptibility factor for inflammatory bowel disease. This karyotype often gives rise to relatively weak phenotypic characteristics of Turner's syndrome, which may be overlooked in short females with inflammatory bowel disease. The association of inflammatory bowel disease with Turner's syndrome may reflect the presence on the X chromosome of genes involved in disease pathogenesis. Linkage analysis studies, involving microsatellite markers on the X chromosome, are being performed.      

Donor sepsis is not a contraindication to cadaveric organ donation

Systemic donor infection is regarded as being an absolute contraindication to cadaveric organ donation for transplantation. This is largely due to fear of transmitting pathogenic organisms to the immunosuppressed recipient. However, due to the current shortage of organs available for transplantation, clinicians are faced with the option of using organs from 'non-ideal' donors, such as those patients with documented evidence of infection. We report the successful outcome of six orthotopic liver transplants, 11 renal transplants, one combined heart lung transplant and one simultaneous kidney and pancreas transplant with organs from eight donors in whom bacterial meningitis (n = 7) and acute bacterial epiglottitis (n = 1) were the antecedent causes of death.      

Angiomyolipomas of the liver in tuberous sclerosis

Although the association of tuberous sclerosis and renal angiomyolipomas is well established, the occurrence of hepatic hamartomatous lesions in this disease is less well documented. We describe two cases of tuberous sclerosis with associated multiple intrahepatic angiomyolipomas, and we review the literature on this subject. Radiologically, angiomyolipomas can range from entirely lipomatous to completely solid, features which are present in our cases. A characteristic finding of the hepatic involvement in this disease appears to be the multiplicity of the lesions. We suggest that in the setting of tuberous sclerosis it is reasonable to assume that intrahepatic lesions represent angiomyolipomas. However, in nontuberous sclerosis patients with similar findings malignancy cannot be excluded.An invited commentary on this article follows on pp. 552–553.     

A Randomized,Double-Blind,Placebo-Controlled,Trial of Lamotrigine Therapy in Bipolar Disorder,Depressed or Mixed Phase and Cocaine Dependence

Bipolar disorder is associated with very high rates of substance dependence. Cocaine use is particularly common. However, limited data are available on the treatment of this population. A 10-week, randomized, double-blind, placebo-controlled trial of lamotrigine was conducted in 120 outpatients with bipolar disorder, depressed or mixed mood state, and cocaine dependence. Other substance use was not exclusionary. Cocaine use was quantified weekly by urine drug screens and participant report using the timeline follow-back method. Mood was assessed with the Hamilton rating scale for depression, quick inventory of depressive symptomatology self-report, and young mania rating scale. Cocaine craving was assessed with the cocaine-craving questionnaire. Data were analyzed using a random regression analysis that used all available data from participants with at least one postbaseline assessment (n=112). Lamotrigine and placebo groups were similar demographically (age 45.1±7.3 vs 43.5±10.0 years, 41.8% vs 38.6% women). Urine drug screens (primary outcome measure) and mood symptoms were not significantly different between groups. However, dollars spent on cocaine showed a significant initial (baseline to week 1, p=0.01) and by-week (weeks 1–10, p=0.05) decrease in dollars spent on cocaine, favoring lamotrigine. Few positive trials of medications for cocaine use, other than stimulant replacement, have been reported, and none have been reported for bipolar disorder. Reduction in amount of cocaine use by self-report with lamotrigine suggests that a standard treatment for bipolar disorder may reduce cocaine use. A study limitation was weekly assessment of urine drug screens that decreased the ability to detect between-group differences.     

Predictors of attrition with buprenorphine/naloxone treatment in opioid dependent youth

Background

In opioid dependent youth there is substantial attrition from medication-assisted treatment. If youth at risk for attrition can be identified at treatment entry or early in treatment, they can be targeted for interventions to help retain them in treatment.

Methods

Opioid dependent adolescents and young adults (n = 152), aged 15–21, were randomized to 12 weeks (BUP, n = 74) or 2 weeks of detoxification (DETOX, n = 78) with buprenorphine/naloxone (Bup/Nal), both in combination with 12 weeks of psychosocial treatment. Baseline and early treatment related predictors of treatment attrition were identified in each group using bivariate and multivariate logistic regression.

Results

In the DETOX group 36% left between weeks 2 and 4, at the end of the dose taper, while in the BUP group only 8% left by week 4. In the BUP group, early adherence to Bup/Nal, early opioid negative urines, use of any medications in the month prior to treatment entry, and lifetime non-heroin opioid use were associated with retention while prior 30-day hallucinogen use was associated with attrition. In the DETOX group, only use of sleep medications was associated with retention although not an independent predictor. A broad range of other pre-treatment characteristics was unrelated to attrition.

Conclusions

Prompt attention to those with early non-adherence to medication or an early opioid positive urine, markers available in the first 2 weeks of treatment, may improve treatment retention. Extended Bup/Nal treatment appeared effective in improving treatment retention for youth with opioid dependence across a wide range of demographics, and pre-treatment clinical characteristics.