Late gadolinium enhanced cardiovascular magnetic resonance of lamin A/C gene mutation related dilated cardiomyopathy

Background

The purpose of this study was to identify early features of lamin A/C gene mutation related dilated cardiomyopathy (DCM) with cardiovascular magnetic resonance (CMR). We characterise myocardial and functional findings in carriers of lamin A/C mutation to facilitate the recognition of these patients using this method. We also investigated the connection between myocardial fibrosis and conduction abnormalities.

Methods

Seventeen lamin A/C mutation carriers underwent CMR. Late gadolinium enhancement (LGE) and cine images were performed to evaluate myocardial fibrosis, regional wall motion, longitudinal myocardial function, global function and volumetry of both ventricles. The location, pattern and extent of enhancement in the left ventricle (LV) myocardium were visually estimated.

Results

Patients had LV myocardial fibrosis in 88% of cases. Segmental wall motion abnormalities correlated strongly with the degree of enhancement. Myocardial enhancement was associated with conduction abnormalities. Sixty-nine percent of our asymptomatic or mildly symptomatic patients showed mild ventricular dilatation, systolic failure or both in global ventricular analysis. Decreased longitudinal systolic LV function was observed in 53% of patients.

Conclusions

Cardiac conduction abnormalities, mildly dilated LV and depressed systolic dysfunction are common in DCM caused by a lamin A/C gene mutation. However, other cardiac diseases may produce similar symptoms. CMR is an accurate tool to determine the typical cardiac involvement in lamin A/C cardiomyopathy and may help to initiate early treatment in this malignant familiar form of DCM.     

Fetal Alcohol Effects: Mechanisms and Treatment

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chair was Edward P. Riley. The presentations were (1) Does alcohol withdrawal contribute to fetal alcohol effects? by Jennifer D. Thomas and Edward P. Riley; (2) Brain damage and neuroplasticity in an animal model of binge alcohol exposure during the third trimester equivalent, by Charles R. Goodlett, Anna Y. Klintsova, and William T. Greenough; (3) Ganglioside GM1 reduces fetal alcohol effects, by Basalingappa L. Hungund; and (4) Fetal alcohol exposure alters the wiring of serotonin system at mid-gestation, by F. Zhou, Y. Sari, Charles Goodlett, T. Powrozek, and Ting-Kai Li.     

Association of mast cells with microvessel density in urothelial carcinomas of the urinary bladder

This study aims to investigate the relation of mast cell (MC) accumulation with tumor grade and stage in urothelial carcinomas of the urinary bladder and to determine its relationship with angiogenesis. A total of 78 urothelial carcinomas obtained by transurethral resection were investigated immunohistochemically by using c-Kit (CD117) and anti-CD34. The correlation between MC counts and microvessels was evaluated and compared with histopathologic parameters including tumor stage and grade. There were significant correlations between MC counts, grade, and stage (P < .05; r = 0.69 and 0.63, respectively). However, MC counts in adjacent nontumoral bladder mucosa significantly were higher than the MC counts in tumoral zone (P < .001). On the other hand, significant correlation was found between the number of MCs in tumoral zone and the microvessel density (P < .05, r = 0.56). The results of our study suggest that c-Kit positive MCs in tumoral zone may contribute to tumor angiogenesis and play a significant role in tumor growth and invasion. Further studies are needed to support these observations.     

Post-neonatal hospitalization and health care costs among IVF children: a 7-year follow-up study

BACKGROUND: The objective of this study was to evaluate whether the post-neonatal hospitalization and resulting health care costs are increased among in vitro fertilization (IVF) children up to 7 years of age. METHODS: We conducted a population-based cohort study with linkage to a national hospital discharge register including 303 IVF children, born from 1990 to 1995, and 567 control children (1:2) randomly chosen from the Finnish Medical Birth Register and matched for sex, year of birth, area of residence, parity, maternal age and socioeconomic status. The cost calculations were stratified for singleton (n = 152 vs. n = 285) and twin (n = 103 vs. n = 103) status. Main outcome measures were hospitalizations and societal health care costs. RESULTS: The full-sample and singleton analyses showed that IVF children were significantly more frequently admitted to hospital (mean 1.76 vs. 1.07, P < 0.0001; 1.61 vs. 1.07, P = 0.0004, respectively) and spent significantly more days in the hospital (mean 4.31 vs. 2.61, P < 0.0001; 3.47 vs. 2.56, P = 0.0014, respectively) than control children. No differences were detected between IVF and control twins. The costs of post-neonatal hospital care per child were 2.6-fold for IVF singletons, but 0.7-fold for IVF twins when compared with controls. Cost estimation showed 2.6-fold costs for total IVF population in comparison to general population based controls. CONCLUSIONS: The incidence of multiple births increases the utilization of post-neonatal health care services and costs among IVF children in comparison to naturally conceived children. Increased hospitalization and costs were also seen among IVF singletons.     

Comparative genome hybridization suggests a role for NRXN1 and APBA2 in schizophrenia

Copy number variations (CNVs) account for a substantial proportion of human genomic variation, and have been shown to cause neurodevelopmental disorders. We sought to determine the relevance of CNVs to the aetiology of schizophrenia (SZ). Whole-genome, high-resolution, tiling path BAC array comparative genomic hybridization (array CGH) was employed to test DNA from 93 individuals with DSM-IV SZ. Common DNA copy number changes that are unlikely to be directly pathogenic in SZ were filtered out by comparison to a reference dataset of 372 control individuals analyzed in our laboratory, and a screen against the Database of Genomic Variants. The remaining aberrations were validated with Affymetrix 250K SNP arrays or 244K Agilent oligo-arrays and tested for inheritance from the parents. A total of 13 aberrations satisfied our criteria. Two of them are very likely to be pathogenic. The first one is a deletion at 2p16.3 that was present in an affected sibling and disrupts NRXN1. The second one is a de novo duplication at 15q13.1 spanning APBA2. The proteins of these two genes interact directly and play a role in synaptic development and function. Both genes have been affected by CNVs in patients with autism and mental retardation, but neither has been previously implicated in SZ.     

Enhancing behavioral science education at the Ohio State University College of Medicine.

The social and behavioral sciences play key roles in patient health outcomes. Given this reality, successful development of social and behavioral science curricula in medical education is critically important to the quality of patients' lives and the effectiveness of health care delivery systems. The Institute of Medicine, in a recent report, recommended that medical schools enhance their curricula in these areas and identified four institutions as "exemplars" of social and behavioral science education. The authors describe an ongoing curriculum development and improvement process that produced one such exemplary program at The Ohio State University College of Medicine.The authors provide a historical perspective on behavioral science education, discuss issues that led to curricular change, and describe the principles and processes used to implement reform. Critical factors underlying positive change are addressed: increase active learning, recruit a core group of small-group facilitators who are primary care physicians, diversify teaching methods, support student-directed educational initiatives, enhance student-teacher relationships, centralize course administration, obtain funding, implement a faculty development program, and apply curriculum quality improvement methods. Outcome data from evaluations completed by both students and small-group physician faculty are presented, and future directions regarding further revision are outlined. The authors believe that the strategies they describe can be applied at other institutions and assist behavioral science educators who may experience the challenges typically encountered in this important field of medical education.     

The human GIMAP5 gene has a common polyadenylation polymorphism increasing risk to systemic lupus erythematosus

Background

Several members of the GIMAP gene family have been suggested as being involved in different aspects of the immune system in different species. Recently, a mutation in the GIMAP5 gene was shown to cause lymphopenia in a rat model of autoimmune insulin‐dependent diabetes. Thus it was hypothesised that genetic variation in GIMAP5 may be involved in susceptibility to other autoimmune disorders where lymphopenia is a key feature, such as systemic lupus erythematosus (SLE).

Material and methods

To investigate this, seven single nucleotide polymorphisms in GIMAP5 were analysed in five independent sets of family‐based SLE collections, containing more than 2000 samples.

Result

A significant increase in SLE risk associated with the most common GIMAP5 haplotype was found (OR 1.26, 95% CI 1.02 to 1.54, p = 0.0033). In families with probands diagnosed with trombocytopenia, the risk was increased (OR 2.11, 95% CI 1.09 to 4.09, p = 0.0153). The risk haplotype bears a polymorphic polyadenylation signal which alters the 3′ part of GIMAP5 mRNA by producing an inefficient polyadenylation signal. This results in higher proportion of non‐terminated mRNA for homozygous individuals (p<0.005), a mechanism shown to be causal in thalassaemias. To further assess the functional effect of the polymorphic polyadenylation signal in the risk haplotype, monocytes were treated with several cytokines affecting apoptosis. All the apoptotic cytokines induced GIMAP5 expression in two monocyte cell lines (1.5–6 times, p<0.0001 for all tests).

Conclusion

Taken together, the data suggest the role of GIMAP5 in the pathogenesis of SLE.