Genetic and Epigenetic Analysis of Recurrent Hydatidiform Mole

Familial biparental hydatidiform mole (FBHM) is a maternal‐effect autosomal recessive disorder in which recurrent pregnancy failure with molar degeneration occurs. The phenotype mimics molar pregnancy due to androgenesis, despite the normal genetic makeup of the conceptus. FBHM appears to result from a failure to establish correct maternal epigenetic identity at imprinted loci during oogenesis. Several women affected with FBHM have previously been shown to have biallelic mutations in the NLRP7 gene (NALP7). Here, we present the results of epigenetic and mutational analysis on FBHM patients from 11 families, 10 of them novel. We demonstrate a methylation defect at imprinted loci in tissue from four new FBHM cases. Biallelic NLRP7 mutations, including eight previously undescribed mutations, were found in all but one family. These results indicate for the first time that maternal imprints at some loci may be correctly specified in FBHM conceptions, since differential methylation of SGCE/PEG10 was preserved in all four cases. © 2009 Wiley‐Liss, Inc.     

Donor transmission of malignant melanoma to a liver graft recipient: case report and literature review

Abstract:  Post-transplant malignancy of donor origin is a rare complication of organ transplantation, most likely transmitted as micrometastases within the parenchyma of the donor organ or from circulating tumor cells contained within the organ. Patient survival is dependent upon early diagnoses, and differentiation of the malignancy as of donor or recipient derivation is important in developing a treatment modality. The utilization of fluorescent in situ hybridization chromosome analysis and DNA sequence analysis of the tumor cells can assist in this determination. This case report describes the management of donor transmitted malignant melanoma in a liver graft recipient and a review of the current literature.     

Impact of pregnancy and parturition on the anal sphincters and pelvic floor

Incontinence and defecatory difficulties are commonly reported among women and are often ascribed to traumas sustained during childbirth. Specifically, injuries to the anal sphincters (tears) and conformational changes in the various structures that comprise the pelvic floor (prolapse and perineal descent) have been considered as important contributors to the development of anal incontinence, or difficult defaecation (straining, incomplete evacuation), in later life. An understanding of both the effects of pregnancy and parturition on these structures and the natural history of any traumas sustained are, therefore, of key importance. Unfortunately, the literature on these issues, though vast, is far from complete. While it is evident that pregnancy, per se, imposes changes, primarily through hormonal influences, on colonic, ano-rectal and pelvic floor physiology, the long-term impact of such effects is far from clear. Risk factors for the occurrence of significant, though often occult, anal sphincter injuries during birth have been identified and the role of these tears in the etiology of post-partum incontinence has been well delineated. In contrast, the contribution of such intra-partum events to the later onset of incontinence is far from clear and may well have been over-estimated.     

Brief Report: Brain Activation to Social Words in a Sedated Child with Autism

A functional magnetic resonance imaging (fMRI) study was performed on a 4-year-old girl with autism. While sedated, she listened to three utterances (numbers, hello, her own first name) played through headphones. Based on analyses of the fMRI data, the amount of total brain activation varied with the content of the utterance. The greatest volume of overall activation was in response to numbers, followed by the word ‘hello’, with the least activation to her name. Frontal cortex activation was greatest in response to her name, with less activation for numbers, and the least for the word ‘hello.’ These findings indicate that fMRI can identify and quantify the brain regions that are activated in response to words in children with autism under sedation.     

Memory bias in health anxiety is related to the emotional valence of health-related words

OBJECTIVES: A model based on the associative strength of object evaluations is tested to explain why those who score higher on health anxiety have a better memory for health-related words. METHOD: Sixty participants observed health and nonhealth words. A recognition memory task followed a free recall task and finally subjects provided evaluations (emotionality, imageability, and frequency) for all the words. Hit rates for health words, d', c, and psychological response times (PRTs) for evaluations were examined using multi-level modelling (MLM) and regression. RESULTS: Health words had a higher hit rate, which was greater for those with higher levels of health anxiety. The higher hit rate for health words is partly mediated by the extent to which health words are evaluated as emotionally unpleasant, and this was stronger for (moderated by) those with higher levels of health anxiety. Consistent with the associative strength model, those with higher levels of health anxiety demonstrated faster PRTs when making emotional evaluations of health words compared to nonhealth words, while those lower in health anxiety were slower to evaluate health words. CONCLUSIONS: Emotional evaluations speed the recognition of health words for high health anxious individuals. These findings are discussed with respect to the wider literature on cognitive processes in health anxiety, automatic processing, implicit attitudes, and emotions in decision making.     

A psychometric evaluation of the CDRS and MADRS in assessing depressive symptoms in children

OBJECTIVE: This study compared the psychometric properties of the Children's Depression Rating Scale-Revised (CDRS-R) and the Montgomery-Asberg Depression Rating Scale (MADRS) in children with major depressive disorder. METHOD: Children (N = 96; ages 8 to 11 years inclusive) with nonpsychotic major depressive disorder were enrolled. Participants were part of a multisite, outpatient, randomized, placebo-controlled, 9-week trial of fluoxetine (10 mg/day for the first week and 20 mg/day thereafter). The CDRS-R and MADRS were completed based on clinician interviews with both parents and children. Classic test theory and item response theory analyses were conducted. RESULTS: The MADRS and CDRS-R total scores were correlated at baseline (r = 0.51) and at study exit (r = 0.85). Cronbach's alpha was .86 (CDRS-R) and .82 (MADRS) at exit. The effect sizes for change from baseline to exit between the fluoxetine and placebo groups were 0.78 (CDRS-R) and 0.61 (MADRS). There was agreement between the CDRS-R and MADRS in the declaration of treatment response (50% improvement from baseline to exit) in 84.2% of children. Test information function favored the CDRS-R. CONCLUSIONS: The CDRS-R showed greater effect size for differentiating drug and placebo and better test information than the MADRS in this study of depressed children.     

Bacteria: a new player in gastrointestinal motility disorders--infections, bacterial overgrowth, and probiotics

Irritable bowel syndrome (IBS) may result from a dysfunctional interaction between the indigenous flora and the intestinal mucosa, which in turn leads to immune activation in the colonic mucosa. Some propose that bacterial overgrowth is a common causative factor in the pathogenesis of symptoms in IBS; others point to evidence suggesting that the cause stems from more subtle qualitative changes in the colonic flora. Bacterial overgrowth will probably prove not to be a major factor in what will eventually be defined as IBS. Nevertheless, short-term therapy with either antibiotics or probiotics seems to reduce symptoms among IBS patients. However, in the long term, safety issues will favor the probiotic approach; results of long-term studies with these agents are eagerly awaited.     

Bacterial flora in irritable bowel syndrome: role in pathophysiology, implications for management

Irritable bowel syndrome (IBS) may, in part at least, result from a dysfunctional interaction between the indigenous flora and the intestinal mucosa which, in turn, leads to immune activation in the colonic mucosa. Some propose a role for bacterial overgrowth as a common causative factor in the pathogenesis of symptoms in IBS; other evidence points to more subtle qualitative changes in the colonic flora; both hypotheses remain to be confirmed but the likelihood that bacterial overgrowth will prove to be a major factor in IBS now seems remote. Nevertheless, short-term therapy with either antibiotics or probiotics does seem to reduce symptoms among IBS patients. It seems most likely that the benefits of antibiotic therapy are mediated through subtle and, perhaps, localized, quantitative and/or qualitative changes in the colonic flora. How probiotics exert their effects remain to be defined but an anti-inflammatory effect seems likely. While this approach to the management of IBS is in its infancy, it is evident that manipulation of the flora, whether through the administration of antibiotics or probiotics, deserves further attention in IBS.     

Validity of electronically monitored medication adherence and conventional adherence measures in schizophrenia

OBJECTIVE: This study evaluated the validity of prescriber, patient, and research assistant ratings of adherence to prescribed oral antipsychotic medication among outpatients with schizophrenia or schizoaffective disorder in comparison with electronic monitoring. METHODS: Adult outpatients with schizophrenia (N=35) or schizoaffective disorder (N=26) received adherence assessments via electronically monitored medication vial caps as well as by monthly prescriber, patient, and research assistant report for up to six months. RESULTS: Electronic monitoring detected greater nonadherence rates (57%) than either prescribers (7%) or patients (5%), though the research assistant ratings were 54%. No directional bias was found between electronic monitoring and assignment of adherence by research assistants, although disagreement occurred in 36% of cases. CONCLUSIONS: Both patients and prescribers grossly overestimated medication adherence, which may interfere with or reduce the effectiveness of diligent medication management.     

Cyclooxygenase-2 expression is not associated with clinical outcome in synovial sarcoma

Several studies have identified cyclooxygenase-2 (COX-2) expression in a variety of sarcomas, including rhabdomyosarcoma, osteosarcoma and chondrosarcoma. Although overexpression of COX-2 has been associated with poor prognosis and decreased survival in chondrosarcoma and osteosarcoma, no relationship between COX-2 expression and patient outcome has been demonstrated in rhabdomyosarcoma or adult soft tissue sarcomas. Little is known concerning the expression of COX-2 in synovial sarcoma. Therefore, the aim of this study was to examine the expression of COX-2 in synovial sarcoma and if shown, to identify any association with tumor stage and oncologic outcome. Paraffin-embedded specimens from 27 patients with synovial sarcoma who were treated with surgical resection or biopsy were obtained. Specimens were evaluated for the degree of COX-2 expression after immunohistochemical staining. Specimens were assigned an immunoreactivity score (IS) based on the percent positivity of the specimen. A retrospective chart analysis was performed to determine the clinical stage at presentation, incidence of local recurrence, presence of metastatic disease and overall survival. Statistical analysis was then performed to determine whether there was a significant relationship between IS and stage at presentation or patient outcomes. COX-2 expression was detected in 18 of 27 (66.67%) of the pathological specimens. There was a statistically significant relationship between COX-2 expression and patient clinical stage at presentation; however, we were unable to identify a significant relationship between IS and patient survival. We also found no significant relationship between IS and development of metastases or local recurrence. COX-2 was expressed to some degree in 67% of the tumor specimens. There was a significant relationship between IS and patient stage at presentation, but no significant relationship between COX-2 expression and clinical outcome could be identified. The fact that these tumors do express COX-2, however, suggests the potential for an additional target for more effective therapy.