Molecular prenatal diagnosis in 2 pregnancies at risk for spondyloepiphyseal dysplasia congenita

BACKGROUND: Spondyloepiphyseal dysplasia congenita (SEDC) is an autosomal dominant skeletal dysplasia characterized by short stature, abnormal epiphyses, and flattened vertebral bodies. Secondary prevention of SEDC can be achieved by prenatal diagnosis. Reports of antenatally-diagnosed SEDC fetuses have been very rare and molecular prenatal diagnosis even rarer. We previously reported a familial G504S mutation in the type II collagen (COL2A1) gene resulting in SEDC. In this study, molecular prenatal diagnosis was performed to 2 couples in this family with pregnancies at risk for SEDC. METHODS: Amniotic fluid was sampled by amniocentesis under ultrasound guidance at 19+3 and 18+6 weeks' gestation, respectively. Karyotype and molecular genetic analysis were performed on cultured amniotic fluid cells. Maternal cell contamination was excluded by short tandem repeat (STR) analysis. Direct DNA sequencing and DHPLC were conducted to detect the potential mutation in exon 23 of COL2A1 gene. Both women underwent serial sonograms because they insisted that the molecular diagnosis should be confirmed by another method, although they had been informed that mutation analysis is predictive of the disease. RESULTS: Karyotype of both fetuses was normal and molecular genetic analysis revealed that fetus 1 carried a G504S mutation in exon 23, while fetus 2 was normal. In case 1, femur length of the fetus was markedly below the 5th centile at 23 weeks' gestation, which confirms the accuracy of molecular diagnosis. A medical termination was carried out at 27+5 weeks' gestation and a male fetus with a relatively large head and short limbs was delivered. The fetal radiograph demonstrated a number of features, including generalised platyspondyly, absent ossification of the vertebral bodies in the cervical region and significant shortening of the long bones. The diagnosis of SEDC was thus confirmed clinically. Ultrasound monitoring of fetus 2 showed that its femur length was normal for gestational age at repeated scans, which was consistent with the molecular diagnosis. CONCLUSIONS: Molecular analysis allows early and accurate prenatal diagnosis for SEDC once mutation is known in a family. However, considering the poor genotype/phenotype correlation in many cases of SEDC, the combination of ultrasound as well as molecular genetic approach might be needed.     

Elevated lipid peroxidation biomarkers and low antioxidant status in atherosclerotic patients with increased carotid or iliofemoral intima media thickness.

OBJECTIVES: Lipid peroxidation plays an important role in the development of atherosclerosis, a chronic, age-related disease process of the arterial wall with onset decades prior to its clinical manifestations. The aim of the study was to assess the association between the intima media thickness (IMT) of the major arteries as a clinical marker of atherosclerosis and markers of lipid peroxidation along with the antioxidant status in humans. DESIGN: Case-control study. SETTING: A university-affiliated outpatient clinic. SUBJECTS: Thirty patients (22 males, 8 females; 70.4 +/- 7.3 years) with atherosclerosis of the carotid or iliofemoral arteries and 62 healthy controls (30 males, 32 females; 68.3 +/- 4.3 years). METHODS: Plasma levels of 8,12-isoprostane F2alpha-VI (8,12-IPF2alpha-VI) were measured by gas chromatography/mass spectrometry, whereas levels of malondialdehyde (MDA), vitamins A (retinol) and E (alpha- and gamma-tocopherol), and carotenoids were determined by high-performance liquid chromatography. The IMT was measured by B-mode ultrasonography. RESULTS: Patients showed, independent of fruit and vegetable intake, significantly lower plasma levels of retinol, alpha-tocopherol, and all carotenoids excluding beta-cryptoxanthin compared with controls. On the contrary, plasma 8,12-IPF2alpha-VI levels were almost doubled (p < .001) and MDA levels increased by one-third (p < .01) in atherosclerotic patients compared with controls. CONCLUSIONS: The analyses of isoprostanes and antioxidant nutrients in plasma as markers of oxidative stress and the parallel evaluation of IMT as a structural marker of atherosclerosis are suitable tools for investigating the role of antioxidants and oxidative stress in atherosclerosis.     

The Changing Paradigms for Breast Cancer Surgery: Performing Fewer and Less-Invasive Operations

Historically, through the conduct of prospective clinical trials, breast cancer surgeons have performed less radical breast and axillary surgeries with no survival decrement to our patients. Currently, other opportunities exist for the treating breast surgeon to do less. Possibilities include active surveillance for ductal carcinoma in situ, ablative therapy for small primary breast cancers, selective omission of a sentinel node biopsy, and selective elimination of breast surgery after neoadjuvant systemic therapy. Breast surgeons must be leaders in the development and testing of effective therapy with the least intervention possible.     

腹腔镜联合胆道镜经胆囊管治疗胆总管结石的疗效观察

【摘要】〓目的〓评价腹腔镜联合胆道镜经胆囊管治疗胆总管结石的疗效。方法〓回顾性分析2012年1月至2014年9月在广东医学院附属福田医院治疗的195例胆总管结石患者,按照术式分为腹腔镜联合术中胆道镜经胆囊管胆道探查取石术(LTCBDE)组(43例)、腹腔镜胆道探查“T”管引流(LCBDE)组(65例)和剖腹胆囊切除、胆总管探查取石、“T”管引流术(OCBD)组(87例)。比较三组患者手术时间、术中出血量、术后肛门排气时间、视觉模拟评分法(VAS)评分、并发症发生率,以及三组治疗前后CRP、PA、TBIL和ALT水平的变化。结果〓3组患者均成功进行手术,LTCBDE组除手术时间比OCBD组长外,术中出血量、术后VAS评分、肛门排气时间、术后住院时间和并发症明显少于LCBDE和OCBD组(P<0.001)。LTCBDE组的并发症发生率为4.7%,明显低于LCBDE组的15.4%和OCBD组的23.0%,差异有统计学意义(P<0.05)。治疗后,三组的CRP、TBIL和ALT水平比治疗前明显降低(P<0.001),而PA水平比治疗前明显升高(P<0.001)。LTCBDE组的降低和升高水平比其余两组更为明显(P<0.001)。结论〓LTCBDE具有创伤小、并发症少、费用低、术后生活质量高等优点,是一种有效、安全及经济的术式。