Detection of genomic deletions of PKP2 in arrhythmogenic right ventricular cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited myocardial disease that predominantly affects the right ventricle and is associated with ventricular arrhythmias that may lead to sudden cardiac death. Mutations within at least seven separate genes have been identified to cause ARVC, however a genetic culprit remains elusive in approximately 50% of cases. Although negative genetic testing may be secondary to pathogenic mutations within undiscovered genes, an alternative explanation may be the presence of large deletions or duplications involving known genes. These large copy number variants may not be detected with standard clinical genetic testing which is presently limited to direct DNA sequencing. We describe two cases of ARVC possessing large deletions involving plakophilin‐2 (PKP2) identified with microarray analysis and/or multiplex ligation‐dependent probe amplification (MLPA) that would have been classified as genotype negative with standard clinical genetic testing. A deletion of the entire coding region of PKP2 excluding exon 1 was identified in patient 1 and his son. In patient 2, MLPA analysis of PKP2 revealed deletion of the entire gene with subsequent microarray analysis demonstrating a de novo 7.9 Mb deletion of chromosome 12p12.1p11.1. These findings support screening for large copy number variants in clinically suspected ARVC cases without clear disease causing mutations following initial sequencing analysis.     

Neurological symptoms in children with intussusception

Aim:  The classical combination of abdominal pain, vomiting, rectal blood loss and a palpable abdominal mass is only present in a minority of children with intussusception. Neurological signs and symptoms have been described, but are not a well understood phenomenon. We performed a retrospective study to ascertain the frequency and nature of these symptoms and to describe the characteristics of the patients presenting in this atypical way.
Methods:  The records of 58 children presenting with intussusception from 2003 to 2008 were reviewed for abdominal and neurological signs and symptoms, duration of symptoms and effectiveness of treatment.
Results:  In 10 out of 58 patients (17%), one or more neurological symptoms were recorded at presentation, with lethargy being the most frequent, followed by hypotonia and fluctuating consciousness. The patients with neurological abnormalities were significantly younger and presented with a shorter duration of symptoms. Therapy was more invasive, although not statistically significant, in this patient category.
Conclusion:  Intussusception should be considered in the differential diagnosis in young children presenting with lethargy, hypotonia and/or sudden alterations of consciousness even in the absence of the classical symptoms of intussusception.     

Autopsies of sudden infant death syndrome—classification and epidemiology

An enquiry into sudden infant death syndrome (SIDS) in 1987 furnished us with detailed epidemiological data for 281 cases that underwent a thorough post-mortem examination. This analysis uses these data to evaluate the role the autopsy plays in explaining sudden death. The cases were classified into three diagnostic groups: explained causes of death (group 1), unexplained deaths with anomalies (group 2), and no anomaly (group 3). These 281 cases show the three essential features that characterize SIDS: over-representation of males, increased deaths during the second and third months of life, and increased deaths during winter. The autopsy examination revealed that many of these deaths had a medical explanation. Almost half were assigned to group 1. At the time of autopsy, no precise pathology could be diagnosed for 147 deaths; of these, 140 showed histological anomalies. There were only seven sudden deaths for which no abnormal sign was evident at the autopsy. These results are compared with those of similar studies and discussed in connection with three factors: the initial selection of cases, the nature and degree of the investigations, and the possible interpretations of the symptoms uncovered.     

Comment on ‘Predicting recurrence in axillary node negative breast cancer patients’, by Rosner and Lane

on behalf of the Nottingham Breast Unit     

Neural and musculoskeletal contributions to the development of stance balance control in typical children and in children with cerebral palsy

Studies on the development of automatic postural responses in both typically developing children and children with cerebral palsy were performed. With the appearance of "pull-to-stand" behavior, typically developing children first began to show muscle responses to platform movements in mainly the ankle muscles. With increased development, additional agonist muscles were added to the response pattern and a consistent distal to proximal sequence began to emerge. Well-organized responses were seen with the onset of independent stance and walking, along with the reduction of antagonist muscle co-activation. The older children with cerebral palsy who were pre-walkers had immature muscle activation patterns like those seen in the typically developing children at the pull-to- stand stage of development. These included disorganized muscle responses and increased frequency of coactivation of both proximal–distal and agonist–antagonist muscles. In order to determine if musculoskeletal constraints contributed to these response patterns, normal children were asked to stand in a crouched posture similar to that of children with CP. This caused postural muscle response patterns to more closely approximate those of children with spastic diplegia.     

骨质疏松性椎体骨折模型的建立

目的:建立大鼠的骨质疏松性椎体骨折模型,探讨骨折愈合程度与X射线、骨结构和力学性能的相互关系,以期能为临床治疗提供科学的指导和理论依据。方法:实验于2005-07/2006-07在解放军兰州军区总医院骨研所完成。实验动物:选择雌性SPF级8个月龄SD大鼠54只。实验分组:采用随机数字法将大鼠分为2组:骨质疏松组和对照组,每组27只。实验干预:骨质疏松组经双背侧手术切除卵巢,对照组行伪手术。术后3个月,所有动物麻醉下,采用L5椎体手术开窗刮除术区内松质骨方法建立人工椎体骨折模型。实验评估:于术后1,2,4,6,8,12周观察两组大鼠腰椎影像学、骨组织切片组织学与受累椎体力学性能。结果:54只SD大鼠全部进入结果分析。①影像学观察:术后两组X射线片示L5椎体有一骨折缺损透光区。对照组在术后6周时原透光区与周围骨质无明显差别,而骨质疏松组原透光区仍清晰可见,于8周时无明显差别。②组织学观察:两组软骨细胞在骨愈合1周时出现,形成软骨岛,但骨质疏松组软骨细胞每高倍视野数量明显少于对照组,另外,软骨细胞改建成成熟骨细胞,骨小梁形成数量,胶原纤维排列与对照组比较有显著性差异。③力学性能:在骨质愈合6～12周,L5椎体的最大载荷、弹性模量、最大应力明显低于同期对照组,差异有显著性意义(P<0.05)。结论:骨质疏松性椎体骨折SD大鼠模型,符合动物模型标准,可用于研究新骨形成与正常骨质结构关系,观察骨质疏松性椎体骨折愈合机制,并证明骨质疏松性松质骨骨折修复过程中,骨折愈合质量降低。     

Dental caries and erosion status of 12-year-old Hong Kong children

Background

We examined the association of alcohol use disorders (AUD) with adherence to and health-related quality of life (HRQOL) outcomes of antiretroviral treatment (ART) for HIV/AIDS patients.

Methods

A cross-sectional multi-site survey was conducted in 468 drug users and 648 non-drug users (age: 35.4 ± 7.0 years; 63.8% male) in 3 epicentres of Vietnam. AUD, ART adherence, and HRQOL were measured using the Alcohol Use Disorders Identification Test - Consumption (AUDIT-C), the self-reported Visual Analogue Scale (VAS), and the World Health Organization Quality of Life instrument (WHOQOL-HIV BREF).

Results

35.0% of drug users were hazardous drinkers, compared to 25.9% of non-drug users. 22.3% of drug users engaged in binge drinking, and 25.9% reported suboptimal ART adherence. Adjusting for propensity scores of AUD, patients who had either at-risk or binge drinking behaviour were about twice as likely to be treatment non-adherent as those who did not have AUD. Hazardous drinkers reported small to medium decrements in the Performance, Physical, Social, Spirituality, and Environment quality of life domains. Binge drinkers had a slightly higher score in Social dimension.

Conclusion

AUD is prevalent and negatively affecting adherence to and HRQOL outcomes of ART services in injection-driven HIV epidemics. Screening and intervention are recommended for AUD, especially during the stable periods of ART. Other social and psychological interventions might also enhance patients’ responses to and outcomes of ART in Vietnam.