线粒体基因的分子诊断:早期氨基糖苷类抗生素耳毒作用的发现与预防

氨基糖苷类抗生素如庆大霉素、链霉素和托普霉素等都是在临床上非常重要的药物,而这些药物的使用常常会导致部分病人听力不可逆的损伤,在耳聋病人中,有很高比例是由于氨基糖苷类抗生素的耳毒性引起的.在家族性的药物损伤性耳聋中,氨基糖苷类抗生素耳毒性的高度敏感通常为母系遗传,提示线粒体DNA上的突变可能是导致此类症状的分子生物学基础.突变分析发现在线粒体12S rRNA上发现了多个和严重的药物性耳聋相关的基因突变,其中尤以A1555G和C1494T突变在氨基糖苷类抗生素引发的耳聋病例中占有显著的比重.A1555G或C1494T突变在12S rRNA的A区形成一个新的结合碱基对,使12S rRNA的二级结构与细菌的16S rRNA更为相似,促进了氨基糖苷类抗生素与之结合,使得带该类突变的个体在使用氨基糖苷类抗生素后会发生或者加重听力缺失.一系列的研究数据提供了有价值的信息和技术,使得预测哪些人具有氨基糖苷类抗生素耳毒性的高风险成为可能,同时提高了氨基糖苷类抗生素治疗的安全性,对于降低耳聋的发病率具有重大的意义.     

Intrahepatic Biliary Anatomy Derived From Right Graft Adult Live Donor Liver Transplantation

Objective

The successful management of the bile duct in right graft adult live donor liver transplantation requires knowledge of both its central (hilar) and distal (sectorial) anatomy. The purpose of this study was to provide a systematic classification of its branching patterns to enhance clinical decision-making.

Patients and Methods

We analyzed three-dimensional computed tomography (3-D CT) imaging reconstructions of 139 potential live liver donors evaluated at our institution between January 2003 and June 2007.

Results

Fifty-four (n = 54 or 38.8%) donor candidates had a normal (classic) hilar and sectorial right bile duct anatomy (type I). Seventy-eight (n = 78 or 56.1%) cases had either hilar or sectorial branching abnormalities (types II or III). Seven (n = 7 or 5.1%) livers had a mixed type (IV) of a rare and complex central and distal anatomy.

Conclusions

We believe that the classification proposed herein can aid in the better organization and categorization of the variants encountered within the right-sided intrahepatic biliary system.     

母乳喂养婴儿血中25羟胆钙化醇水平与日光照射关系的研究

选择未经维生素D补充的1～8月龄母乳喂养婴儿55名,随机分为两组,实验组鼓励多晒太阳;另一组为自然对照。观察两个月,婴儿膳食仅为母乳、果汁和糖水。户外活动时仅暴露面部和前臂。实验开始时,55名婴儿血中25羟胆钙化醇(25-OH-D))浓度低于参考标准低限11ng/ml者约占20％,X线片可诊断为佝偻病者约占18％。两种诊断指标的符合率为68.6％。乳母血中25-OH-D浓度平均为21.9ng/ml,与其婴儿血中25-OH-D浓度相关系数为0.464,相关非常显著。观察期间,婴儿平均每天户外活动时间实验组为116分钟,对照组为63分钟。实验组实验前后血中25-OH-D浓度为29.7±13.3和38.1±20.0ng/ml,差异显著(P<0.01):对照组为20.6±15.5和19.1±13.4ng/ml前后无差异。两组婴儿血中25-OH-D浓度与各自户外活动计分数呈显著相关(r=0.668和0.631)。后者又与日光紫外线照到体表时间(秒)呈相关(r=0.580)。提示婴儿每周户外活动的计分数在800～1000时,可以维持血中25-OH-D浓度在正常范围。     

Vascular and Biliary Anatomy of the Right Hilar Window: Its Impact on Recipient Morbidity and Mortality for Right Graft Live Donor Liver Transplantation

Background  Intrahepatic anatomic variations have been associated with both morbidity and mortality associated with live donor liver transplantation. The aim of our study was to evaluate central hilar and peripheral segmental vascular/biliary anatomy in right graft living donor liver transplantation. Methods  From January 2003 to August 2007, three-dimensional (3D) computed tomography (CT) reconstructions and virtual 3D hepatectomies were performed in 71 consecutive right graft live liver donors. A combined two-level classification system addressing the four possible combinations of normal (N) and abnormal (A) central hilar and peripheral features based on both the existing classification and our own classification for portal (portal vein, PV), arterial (hepatic artery, HA) and biliary (bile duct, BD) systems was defined as follows: type I, N/N; type II, N/A; type III, A/N; and type IV, A/A. Results  A simultaneous normal central hilar and peripheral segmental (N/N) anatomy for each system (PV, HA, BD) was found in <50% of grafts. The highest incidence of complex vascular and biliary reconstructions was observed with grafts having abnormal central (type III) or combined abnormal central/peripheral (type IV) anatomy. Central hilar arterial and biliary anomalies were predictors of morbidity by both univariable and multivariable analyses. Conclusions  Our two-level classification and 3D imaging techniques allowed a cautious surgical approach in high-risk cases. Central hilar anatomic variants of the arterial and biliary systems were associated with increased morbidity. Further randomized trials will help determine the precise extent of our observations.     

Early micro‐ and macrostructure of sensorimotor tracts and development of cerebral palsy in high risk infants

Infants born very preterm (VPT) are at high risk of motor impairments such as cerebral palsy (CP), and diagnosis can take 2 years. Identifying in vivo determinants of CP could facilitate presymptomatic detection and targeted intervention. Our objectives were to derive micro‐ and macrostructural measures of sensorimotor white matter tract integrity from diffusion MRI at term‐equivalent age, and determine their association with early diagnosis of CP. We enrolled 263 VPT infants (≤32 weeks gestational age) as part of a large prospective cohort study. Diffusion and structural MRI were acquired at term. Following consensus guidelines, we defined early diagnosis of CP based on abnormal structural MRI at term and abnormal neuromotor exam at 3–4 months corrected age. Using Constrained Spherical Deconvolution, we derived a white matter fiber orientation distribution (fOD) for subjects, performed probabilistic whole‐brain tractography, and segmented nine sensorimotor tracts of interest. We used the recently developed fixel‐based (FB) analysis to compute fiber density (FD), fiber‐bundle cross‐section (FC), and combined fiber density and cross‐section (FDC) for each tract. Of 223 VPT infants with high‐quality diffusion MRI data, 14 (6.3%) received an early diagnosis of CP. The cohort''s mean (SD) gestational age was 29.4 (2.4) weeks and postmenstrual age at MRI scan was 42.8 (1.3) weeks. FD, FC, and FDC for each sensorimotor tract were significantly associated with early CP diagnosis, with and without adjustment for confounders. Measures of sensorimotor tract integrity enhance our understanding of white matter changes that antecede and potentially contribute to the development of CP in VPT infants.     

Dandy-Walker anomaly in Meckel-Gruber syndrome

We report a fetus affected by Meckel-Gruber syndrome whose phenotype was characterized by macrocephaly, frontal bossing, a saddle nose, marked micrognathia, a distended abdomen, omphalocele, post-axial polydactyly and talipes equinovarus. The main neuropathological finding at autopsy was in a very large cyst located in an abnormally wide posterior cranial fossa consistent with a Dandy-Walker anomaly. Intestinal malrotation, enlarged cystic dysplastic kidneys and hepatic portal fibrosis coexisted. The occurrence of a Dandy-Walker malformation in Meckel-Gruber syndrome confirms a disturbance in rhombencephalon development. Although uncommon, it should be included among the central nervous anomalies representative of the syndrome.     

美洲钝眼蜱幼虫叮咬导致多发性瘙痒性丘疹

背景:蜱是世界上第二大人类传染病的携带者。除了携带病菌,蜱及其幼虫还可引起原发性皮肤表现。蜱幼虫引起的皮损不易被识别,仅有3例文献报道。出现多发性皮损及部分6足蜱幼虫皮肤隧道对临床医师的诊断是一个挑战。观察:作者描述一51岁健康女性,在去过南肯塔基州一处森林5d后出     

Klippel-Feil syndrome, thenar hypoplasia, carpal anomalies and situs inversus viscerum

A 27-year-old female is described with Klippel-Feil syndrome, thenar hypoplasia, carpal anomalies and situs inversus viscerum. Other anomalies occurring with Klippel-Feil syndrome are discussed.