Autozygome maps dispensable DNA and reveals potential selective bias against nullizygosity

PurposeCopy number variants are an important source of human genome diversity. The widespread distribution of hemizygous copy number variants in the DNA of healthy humans suggests that haploinsufficiency is largely tolerated. However, little is known about the extent to which corresponding nullizygosity (two-copy deletion) is similarly tolerated.MethodsWe analyzed a cohort of first cousin unions to enrich for shared parental hemizygous events and tested their Mendelian inheritance in offspring.ResultsAnalysis of autozygous DNA blocks (autozygome) in the offspring not only proved an efficient method of mapping “dispensable” DNA but also revealed potential selective bias against the occurrence of nullizygous changes. This bias was not restricted to genic copy number variants and was not accounted for by a high rate of miscarriages.ConclusionsThe autozygome is an efficient way to map dispensable segments of DNA and may reveal selective bias against nullizygosity in healthy individuals.Genet Med 2012:14(5):515–519     

Electromyographic investigation of unstable patella before and after its realignment operation

Background:

Patellar dislocations are either due to superolateral contracture of the soft tissue or imbalance of the power between the vastus medialis (VM) and the vastus lateralis (VL). The imbalance of muscle power as an etiology of patellar dislocation has not been studied. Hence, we studied the recurrent, habitual and permanent dislocations of the patella with an electromyogram (EMG) of the vastus medialis, vastus lateralis, and pes anserinus, before and after realignment operations, to document the muscle imbalance and effectiveness of the realignment operation.

Materials and Methods:

An electromyographic investigation was carried out on the vastus medialis and vastus lateralis in nine recurrent, 20 habitual, and 13 permanent dislocations of the patella, before and after their realignment operations. Pes anserinus transposition, which acted as a medial stabilizer of the patella, was also investigated with an EMG study, to understand its role on patellar stability at 0°, 30°, 60°, 90°, 120°, 150°, and full flexion of the knee. The age of the patients varied from nine to 30 (mean 15) years. There were 24 males and 18 females. Twenty-six patellar dislocations were on the right and 16 were on the left side.

Results:

Electromyographic pictures reveal subnormal activity of the vastus medialis in all types of dislocations and similar activities of the vastus lateralis in permanent and habitual dislocations recorded pre operatively, which recovered to almost normal values postoperatively, at the mean one-year follow-up. Pes anserinus, which was used for medial stabilization of the patella after its realignment, maintained normal EMG activity before and after the operation.

Conclusion:

This study is significant for understanding the imbalance of muscle activities in patients with an unstable patella, which can be rectified without recurrence after pes anserinus transposition.     

Transvaginal ultrasonography associated with colour Doppler energy in the diagnosis of hydrosalpinx

The aims of this prospective study were to investigate the accuracy of B-mode transvaginal ultrasonography alone, using the typical finding of the presence of an elongated shaped mass with incomplete septa, in the screening of hydrosalpinx in women undergoing surgery for gynaecological diseases, and to determine the predictive value of this method combined with colour Doppler energy (CDE) imaging evaluation and CA125 concentrations in differentiating hydrosalpinx from other adnexal masses. In the first part of the study, 378 consecutive pre-menopausal non-pregnant women were submitted to transvaginal ultrasonography alone before surgery. In the second part of the study, 256 adnexal masses underwent transvaginal ultrasonography combined with CDE imaging evaluation associated with spectral Doppler analysis and plasma concentrations of CA125. Sensitivity and specificity for the ultrasonographic screening were 84.6 and 99.7% respectively, calculated for each adnexum (n = 756) and 93.3 and 99.6% respectively, calculated for each mass, for differentiating hydrosalpinx from other adnexal masses. The CDE imaging and the evaluation of CA125 plasma concentrations do not seem to increase the accuracy of B-mode transvaginal ultrasonography. Inter- and intra-observer agreement, expressed in terms of k-values, was high (0.87 and 0.93 respectively). In conclusion, transvaginal ultrasonography alone is a useful method of detection of hydrosalpinx.     

A tissue-selective nonsteroidal progesterone receptor modulator: 7,9-difluoro-5-(3-methylcyclohex-2-enyl)-2,2,4-trimethyl-1,2-dihydrochromeno[3,4-f]quinoline

The progesterone receptor plays an important role in the female reproductive system. Here we describe the discovery of a new selective progesterone receptor modulator (SPRM). In rats, the lead compound, 7,9-difluoro-5-(3-methylcyclohex-2-enyl)-2,2,4-trimethyl-1,2-dihydrochromeno[3,4- f]quinoline ( 5c), inhibited ovulation and showed full efficacy in uterine and vaginal tissue but was a mixed partial agonist/antagonist in breast tissue. The compound also suppressed ovulation in monkeys, but in contrast to currently approved steroidal PR agonists, it did not suppress estradiol levels.     

The many faces of peroxisomal disorders: Lessons from a large Arab cohort

Defects in the peroxisomes biogenesis and/or function result in peroxisomal disorders. In this study, we describe the largest Arab cohort to date (72 families) of clinically, biochemically and molecularly characterized patients with peroxisomal disorders. At the molecular level, we identified 43 disease-causing variants, half of which are novel. The founder nature of many of the variants allowed us to calculate the minimum disease burden for these disorders in our population ~1:30 000, which is much higher than previous estimates in other populations. Clinically, we found an interesting trend toward genotype/phenotype correlation in terms of long-term survival. Nearly half (40/75) of our peroxisomal disorders patients had documented survival beyond 1 year of age. Most unusual among the long-term survivors was a multiplex family in which the affected members presented as adults with non-specific intellectual disability and epilepsy. Other unusual presentations included the very recently described peroxisomal fatty acyl-CoA reductase 1 disorder as well as CRD, spastic paraparesis, white matter (CRSPW) syndrome. We conclude that peroxisomal disorders are highly heterogeneous in their clinical presentation. Our data also confirm the demonstration that milder forms of Zellweger spectrum disorders cannot be ruled out by the “gold standard” very long chain fatty acids assay, which highlights the value of a genomics-first approach in these cases.     

Allocation of health care resources in the neonatal and perinatal area �CCPS Symposium 1996

There have been publically expressed concerns about the costs and allocation of neonatal and perinatal health care resources in Canada and elsewhere for the past 15 years. This paper reports information from a symposium held during the 1996 Canadian Paediatric Society (CPS) annual meeting sponsored by the CPS Section on Perinatal Medicine. Experts in perinatal epidemiology, health care economics, public policy and finance, and consumer perspectives on the outcomes of neonatal and perinatal intensive care explored the following questions: How should the need for health care resources in the neonatal and perinatal area be objectively determined? When there are competing needs between the maternal-newborn area and other areas, how should these be rationalized? What evidence should be used (or should be available) to support the present use of resources? What evidence should be available (or is needed) to change or introduce new uses of resources? The conclusions indicated that there are no generally accepted methods to determine the allocation of health care resources but that considerations need to include population characteristics, desired outcomes, achievable results, values, ethics, legalities, cost-benefit analyses and political objectives. Information from families and adolescents who required the use of high technology and/or high cost programs will contribute individual, family and societal values that complement cost-efficacy analyses.     

B7-1和IL-12基因转染对肝癌细胞免疫原性的影响

目的 观察Ｂ７－１和ＩＬ－１２基因表达对人肝癌细胞免疫原性原影响。方法 分别将Ｂ７－１和ＩＬ－１２基因以逆转录病毒介导转染ＨｅｐＧ２细胞。阳性克隆细胞与健康人外周血淋巴细胞（ＰＢＬ）混合培养后,用流式细胞仪检测ＰＢＬ表面Ⅰ类人白细胞抗原（ＨＬＡ－Ⅰ）分子表达,以ＭＴＴ法检测ＰＢＬ的特异性杀伤活性Ｋ５６２细胞的活性。结果 混合ＨｅｐＧ２／Ｂ７－１ＨｅｐＧ２／ＩＬ－１２细胞组ＰＢＬ表面的ＨＬＡ－Ⅰ分子     

Coronary embolus complicating peripartum cardiomyopathy

Peripartum cardiomyopathy is a rare disorder in which heart failure occurs during the last month of pregnancy or within 5 months of delivery, in the absence of any other etiology or prior heart disease. We present the case of a 42-year-old woman with peripartum cardiomyopathy. She was admitted with an acute myocardial infarction. Multiple mobile ventricular thrombi were seen in the echocardiogram. Coronary angiogram showed consequential coronary embolus occluding the left anterior descending artery. A successful embolectomy was performed followed by coronary stenting. There have been only two reports in the medical literature of coronary embolic events in the setting of peripartum cardiomyopathy; however, to our knowledge, we believe our case is the first to describe coronary intervention as treatment for the event.