7-甲氧基-4′-羟基-3′-二乙胺甲基异黄酮(MHDF)对大鼠血流动力学和主动脉的作用

本实验观察了MHDF对整体大鼠血流动力学和离体大鼠胸主动脉的作用。结果表明iv MHDF(3～12.8 mg/kg)能降低大鼠左心室±dp/dt_max,V_max,V_pm和LVSP,延长T-dp/dt_max,减慢心率。MHDF还能舒张大鼠胸主动脉,ED₅₀为6.5×10^-6mol/L;非竞争拮抗NA和CaCl₂致主脉收缩,pD₂′为3.11±0.21和3.73±0.07;抑制高K⁺致主动脉收缩,IC₅₀为1.76×10^-5mol/L。提示MHDF对血管的作用与α受体阻断剂不同,而可能与钙拮抗有关。     

Costello syndrome: Clinical phenotype,genotype, and management guidelines

Costello syndrome (CS) is a RASopathy caused by activating germline mutations in HRAS. Due to ubiquitous HRAS gene expression, CS affects multiple organ systems and individuals are predisposed to cancer. Individuals with CS may have distinctive craniofacial features, cardiac anomalies, growth and developmental delays, as well as dermatological, orthopedic, ocular, and neurological issues; however, considerable overlap with other RASopathies exists. Medical evaluation requires an understanding of the multifaceted phenotype. Subspecialists may have limited experience in caring for these individuals because of the rarity of CS. Furthermore, the phenotypic presentation may vary with the underlying genotype. These guidelines were developed by an interdisciplinary team of experts in order to encourage timely health care practices and provide medical management guidelines for the primary and specialty care provider, as well as for the families and affected individuals across their lifespan. These guidelines are based on expert opinion and do not represent evidence‐based guidelines due to the lack of data for this rare condition.     

Megalencephaly syndromes associated with mutations of core components of the PI3K‐AKT–MTOR pathway: PIK3CA,PIK3R2, AKT3, and MTOR

Megalencephaly (MEG) is a developmental abnormality of brain growth characterized by early onset, often progressive, brain overgrowth. Focal forms of megalencephaly associated with cortical dysplasia, such as hemimegalencephaly and focal cortical dysplasia, are common causes of focal intractable epilepsy in children. The increasing use of high throughput sequencing methods, including high depth sequencing to more accurately detect and quantify mosaic mutations, has allowed us to identify the molecular etiologies of many MEG syndromes, including most notably the PI3K‐AKT‐MTOR related MEG disorders. Thorough molecular and clinical characterization of affected individuals further allow us to derive preliminary genotype–phenotype correlations depending on the gene, mutation, level of mosaicism, and tissue distribution. Our review of published data on these disorders so far shows that mildly activating variants (that are typically constitutional or germline) are associated with diffuse megalencephaly with intellectual disability and/or autism spectrum disorder; moderately activating variants (that are typically high‐level mosaic) are associated with megalencephaly with pigmentary abnormalities of the skin; and strongly activating variants (that are usually very low‐level mosaic) are associated with focal brain malformations including hemimegalencephaly and focal cortical dysplasia. Accurate molecular diagnosis of these disorders is undoubtedly crucial to more optimally treat children with these disorders using PI3K‐AKT–MTOR pathway inhibitors.     

Molecular characterisation of four cases of intrachromosomal triplication of chromosome 15q11-q14

CONTEXT—Chromosomal abnormalities that involve the proximal region of chromosome 15q occur relatively frequently in the human population. However, interstitial triplications involving one 15 homologue are very rare with three cases reported to date.
OBJECTIVE—To provide a detailed molecular characterisation of four additional patients with interstitial triplications of chromosome 15q11-q14.
DESIGN—Molecular analyses were performed using DNA markers and probes specific for the 15q11-q14 region.
SETTING—Molecular cytogenetics laboratory at the University of Chicago.
SUBJECTS—Four patients with mild to severe mental retardation and features of Prader-Willi syndrome (PWS) or Angelman syndrome (AS) were referred for molecular cytogenetic analysis following identification of a suspected duplication/triplication of chromosome 15q11-q14 by routine cytogenetic analysis.
MAIN OUTCOME MEASURES—Fluorescence in situ hybridisation (FISH) was performed to determine the type of chromosomal abnormality present, the extent of the abnormal region, and the orientation of the extra chromosomal segments. Molecular polymorphism analysis was performed to determine the parental origin of the abnormality. Methylation and northern blot analyses of the SNRPN gene were performed to determine the effect of extra copies of the SNRPN gene on its methylation pattern and expression.
RESULTS—Fluorescence in situ hybridisation (FISH) using probes within and flanking the Prader-Willi/Angelman syndrome critical region indicated that all patients carried an intrachromosomal triplication of proximal 15q11-q14 in one of the two chromosome 15 homologues (trip(15)). In all patients the orientation of the triplicated segments was normal-inverted-normal, suggesting that a common mechanism of rearrangement may have been involved. Microsatellite analysis showed the parental origin of the trip(15) to be maternal in three cases and paternal in one case. The paternal triplication patient had features similar to PWS, one maternal triplication patient had features similar to AS, and the other two maternal triplication patients had non-specific findings including hypotonia and mental retardation. Methylation analysis at exon 1 of the SNRPN locus showed increased dosage of either the paternal or maternal bands in the paternal or maternal triplication patients, respectively, suggesting that the methylation pattern shows a dose dependent increase that correlates with the parental origin of the triplication. In addition, the expression of SNRPN was analysed by northern blotting and expression levels were consistent with dosage and parental origin of the triplication.
CONCLUSIONS—These four additional cases of trip(15) will provide additional information towards understanding the phenotypic effects of this abnormality and aid in understanding the mechanism of formation of other chromosome 15 rearrangements.


Keywords: chromosome 15 triplication; Prader-Willi syndrome; Angelman syndrome; autism     

Familial Miller-Dieker syndrome associated with pericentric inversion of chromosome 17

Recently it has been shown that most cases of the Miller-Dieker syndrome (MDS) are caused by deletion 17p13.3. All familial cases have been associated with a balanced reciprocal translocation in a carrier parent and unbalanced translocations in their affected offspring. We report a new case of familial MDS in whom the mother carries a pericentric inversion of chromosome 17. She has had two children with MDS, one of whom was shown to carry a recombinant 17 consisting of dup(17q) and del(17p). The high frequency of familial MDS and its consistent association with balanced chromosomal rearrangements in one of the parents makes it important to do high-resolution chromosome analysis on all patients with MDS and possibly all patients with lissencephaly. Finding a familial balanced rearrangement makes prenatal diagnosis of this condition feasible.     

Familial cavernous malformations of the central nervous system and retina

We studied a family in which 4 persons from three generations had multiple cavernous malformations ("angiomas") of the central nervous system (CNS) and/or retina and found accounts in the literature of sixteen other families with this condition. In these families with familial cavernous malformation of the CNS and retina, 92% of pathologically documented vascular malformations were cavernous; 50% of those subjects affected had multiple CNS and/or retinal vascular malformations and 68% (excluding probands) were symptomatic. Cutaneous vascular lesions were an inconsistant manifestation. Autosomal dominant inheritance with high penetrance was confirmed.     

Beckman EL-ISE电解质分析仪准确性及故障的分析判断

0 引言为了克服离子选择电极（ISE）法的微量电位信号极易受环境温度变化及电子噪声的干扰问题,该仪器采用了参考电极,把参考电极与其测定电极装在同一测量室内,保持其相同的物理环境,使干扰源对所有电极的影响相同. 以内参液作为参考电极的测量对象,测得一个参考电极电位值,再测样品的电极电位值,二者相抵就消除了所叠加的干扰信号.     

心脏直视手术围术期自体血回输335例的监护

0　引言　自体输血是采集患者体内血或回收自体失血,再输回同一患者,献血者与受血者为同一个体,既可以节约临床用血,减少患者费用,更重要是可以避免或减少同种输血传播感染性疾病.我科对335例体外循环心内直视手术患者实行自体血回输,收到较好的社会效益和经济效益.1　临床资料　1998-09/1999-02,我科心脏直视手术共445例,围术期采用自体输血335例,其中先心病226例,瓣膜手术59例,复杂心内畸形37例,冠心病、大血管13例,占同期体外循环心内直视手术75%.患者主要适应证:心脏及大血管外科手术,术前一般情况尚好,无肝、肾、呼吸功能障碍;术前检查…