Complications of pregnancy and child development after cessation of treatment with 6-mercaptopurine for inflammatory bowel disease

PURPOSE: 6-Mercaptopurine (6-MP) has proven efficacy in the therapy of inflammatory bowel disease. Its teratogenicity is demonstrated in animal studies when used at very high doses, whereas human data suggest that 6-MP at maintenance doses is safe. We report the outcome of 72 pregnancies in patients with inflammatory bowel disease who were previously treated with 6-MP with three different doses of 50, 75, and 100 mg/d, for a median duration of 18 months, along with long-term follow-up of the children. METHODS: We have compared the outcome of pregnancies and development of the offspring in the following two groups: group 1, patients with inflammatory bowel disease who conceived 6 months to 22 years after stopping 6-MP (median 72 months); and group 2, patients with inflammatory bowel disease who never received 6-MP prior to conception. All pregnancies were evaluated in terms of outcome: live full-term birth, premature delivery, stillbirth, spontaneous abortion, ectopic pregnancy, and therapeutic dilatation and curettage. Data on children were obtained regarding birth weight, congenital anomalies, and development. RESULTS: Group 1 included 72 pregnancies carried by 29 women. There were 51 live births (4 premature), 16 spontaneous abortions, 1 stillbirth, 2 therapeutic abortions due to abnormal amniocentesis, and 2 ectopic pregnancies. The total incidence of fetal loss was 29.2%. In group 2, 75 women had 140 pregnancies resulting in 120 live births (8 premature), 18 spontaneous abortions, and 2 stillbirths. There were no cases of ectopic pregnancies or abnormal amniocentesis. The total incidence of fetal loss was 14.3%. There was no increase in the incidence of developmental defects when the mothers had been treated with 6-MP prior to pregnancy. CONCLUSIONS: The incidence of fetal loss is higher in women with inflammatory bowel disease who had been previously treated with 6-MP compared with those who had not. Whether this was related to the older age at conception in 6-MP group, longer duration of disease, initially more severe disease, or use of 6-MP we cannot tell.     

Clinical usefulness of electrophysiologic testing in patients with ventricular tachycardia and chronic chagasic cardiomyopathy treated with amiodarone or sotalol

INTRODUCTION: This study assessed the role of electrophysiologic testing to identify therapeutic strategies for the treatment of patients with sustained ventricular tachycardia (VT) and chronic chagasic cardiomyopathy treated with amiodarone or sotalol. METHODS AND RESULTS: One hundred fifteen patients [69 men (60%); mean age 52 +/- 10 years] with chagasic cardiomyopathy presenting with symptomatic VT were studied after loading with Class III antiarrhythmic drugs; 78 had a history of sustained VT, and 37 with symptomatic nonsustained VT had sustained VT induced at baseline electrophysiologic study. All but 12 patients also underwent baseline electrophysiologic study. Mean left ventricular ejection fraction was 0.49 +/- 0.14. Based on results of electrophysiologic study after loading with Class III drugs, patients were divided into three groups: group 1 (n = 23) had no sustained VT induced; group 2 (n = 45) had only tolerated sustained VT induced; and group 3 (n = 47) had hemodynamically unstable sustained VT induced. After a mean follow-up of 52 +/- 32 months, total mortality rate was 39.1%; it was significantly higher in group 3 than in groups 2 and 1 [69%, 22.2%, and 26%, respectively, P < 0.0001, hazard ratio (HR) 10.4, 95% confidence interval (CI) 3.8, 21.8]. There was no significant difference in total mortality rate between groups 1 and 2 (P = 0.40, HR 1.5, 95% CI 0.75, 4.58). Cardiac mortality and sudden cardiac death rates also were higher in group 3 patients. CONCLUSION: In patients with chagasic cardiomyopathy and sustained VT, electrophysiologic testing can predict long-term efficacy of Class III antiarrhythmic drugs. This may help in the selection of patients for implantable cardioverter defibrillator therapy.     

Validity of the multidimensional fatigue symptom inventory-short form in an African-American community-based sample

Objectives. This study examined the psychometric properties of the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) in a community-based sample of African-Americans.

Design. A sample of 340 African-Americans (116 men, 224 women) ranging in age from 18–81 years were recruited from the community (e.g., churches, health fairs, and beauty salons). Participants completed a brief demographic survey, the MFSI-SF and the Positive and Negative Affect Schedule.

Results. The structural validity of the MFSI-SF for a community-based sample of African-Americans was not supported. The five dimensions of fatigue (General, Emotional, Physical, Mental, Vigor) found for Whites in prior research were not found for African-Americans in this study. Instead, fatigue, while multidimensional for African-Americans, was best represented by a unique four-four profile in which general and emotional fatigue are collapsed into a single dimension and physical fatigue, mental fatigue, and vigor are relatively distinct. Hence, in the absence of modifications, the MFSI-SF cannot be considered to be structurally invariant across ethnic groups. A modified four-factor version of the MFSI-SF exhibited excellent internal consistency reliability and evidence supports its convergent validity. Using the modified four-factor version, gender, and age were not meaningfully associated with MFSI-SF scores.

Conclusion. Future research should further examine whether modifications to the MFSI-SF would, as the findings suggest, improve its validity as a measure of multidimensional fatigue in African-Americans.     

Oxidative Stress-Induced Signaling Pathways Implicated in the Pathogenesis of Parkinson’s Disease

Parkinson’s disease is the second most common neurodegenerative movement disorder; however, its etiology remains elusive. Nevertheless, in vivo observations have concluded that oxidative stress is one of the most common causes in the pathogenesis of Parkinson’s disease. It is known that mitochondria play a crucial role in reactive oxygen species-mediated pathways, and several gene products that associate with mitochondrial function are the subject of Parkinson’s disease research. The PTEN-induced kinase 1 (PINK1) protects cells from mitochondrial dysfunction and is linked to the autosomal recessive familial form of the disease. PINK1 is a key player in many signaling pathways engaged in mitophagy, apoptosis, or microglial inflammatory response and is induced by oxidative stress. Several proteins participate in mitochondrial networks, and they are associated with PINK1. The E3 ubiquitin ligase Parkin, the protease presenilin-associated rhomboid-like serine protease, the tyrosine kinase c-Abl, the protein kinase MARK2, the protease HtrA2, and the tumor necrosis factor receptor-associated protein 1 (TRAP1) provide different steps of control in protection against oxidative stress. Furthermore, environmental toxins, such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, have been identified as contributors to parkinsonism by increasing oxidative stress in dopaminergic neurons. The present review discusses the mechanisms and effects of oxidative stress, the emerging concept of the impact of environmental toxins, and a possible neuroprotective role of the antioxidant astaxanthin in various neurodegenerative disorders with particular emphasis in Parkinson’s disease.     

Multimodality Monitoring: Informatics,Integration Data Display and Analysis

The goal of multimodality neuromonitoring is to provide continuous, real-time assessment of brain physiology to prevent, detect, and attenuate secondary brain injury. Clinical informatics deals with biomedical data, information, and knowledge including their acquisition, storage, retrieval, and optimal use for clinical decision-making. An electronic literature search was conducted for English language articles describing the use of informatics in the intensive care unit setting from January 1990 to August 2013. A total of 64 studies were included in this review. Clinical informatics infrastructure should be adopted that enables a wide range of linear and nonlinear analytical methods be applied to patient data. Specific time epochs of clinical interest should be reviewable. Analysis strategies of monitor alarms may help address alarm fatigue. Ergonomic data display that present results from analyses with clinical information in a sensible uncomplicated manner improve clinical decision-making. Collecting and archiving the highest resolution physiologic and phenotypic data in a comprehensive open format data warehouse is a crucial first step toward information management and two-way translational research for multimodality monitoring. The infrastructure required is largely the same as that needed for telemedicine intensive care applications, which under the right circumstances improves care quality while reducing cost.