Iron Bezoar Retained in Colon Despite 3 Days of Whole Bowel Irrigation

Concretion formation is a documented complication of large iron ingestions. The generally accepted treatment is supportive care, whole bowel irrigation, and intravenous deferoxamine for systemic toxicity. Laparotomy and gastrotomy have also been used in patients with a high iron burden and bezoar formation. Though experiments suggest that iron is poorly absorbed in the colon, there are no case reports of iron overdose without systemic toxicity, despite a retained colonic bezoar. We report the case of a 16‐month‐old who presented to an Emergency Department 19 h after an iron ingestion. Initial laboratory studies revealed an anion gap of 14 mEq/L, and a 20 h serum iron concentration of 429 mcg/dL. An abdominal radiograph revealed multiple pills throughout the stomach and small bowel; whole bowel irrigation was initiated. Deferoxamine was administered at 10 mg/kg/h and then stopped when the serum iron level reached 27 mcg/dL, 36 h later. At this time, the abdominal radiograph showed an iron bezoar remaining in the ascending colon despite a clear rectal effluent from whole bowel irrigation. Despite whole bowel irrigation over the next 36 h, the iron bezoar was not removed and actually migrated proximally in the colon. Treatment was stopped on the third day and a normal diet was instituted with prompt passage of the bezoar.     

Genome Wide Identification of Recessive Cancer Genes by Combinatorial Mutation Analysis

We devised a novel procedure to identify human cancer genes acting in a recessive manner. Our strategy was to combine the contributions of the different types of genetic alterations to loss of function: amino-acid substitutions, frame-shifts, gene deletions. We studied over 20,000 genes in 3 Gigabases of coding sequences and 700 array comparative genomic hybridizations. Recessive genes were scored according to nucleotide mismatches under positive selective pressure, frame-shifts and genomic deletions in cancer. Four different tests were combined together yielding a cancer recessive p-value for each studied gene. One hundred and fifty four candidate recessive cancer genes (p-value<1.5×10⁻⁷, FDR=0.39) were identified. Strikingly, the prototypical cancer recessive genes TP53, PTEN and CDKN2A all ranked in the top 0.5% genes. The functions significantly affected by cancer mutations are exactly overlapping those of known cancer genes, with the critical exception for the absence of tyrosine kinases, as expected for a recessive gene-set.     

Personalizing therapy for multidrug resistant TB: the potential of Rapid Whole Genome Sequencing

Multidrug resistant tuberculosis is an increasing problem globally. The current gold standard in drug sensitivity testing is slow and cumbersome. To tackle drug resistance effectively, a more rapid method of testing is required. Current molecular tests are fast, but only offer information on a limited number of genetic loci. Whole genome sequencing presents an attractive alternative that can provide comprehensive, clinically relevant information on all described loci. Although the standard approach to whole genome sequencing of Mycobacterium tuberculosis is slow due to the requirement of culture, this article will describe recent advances that mean it has the potential to provide results within days.     

Non Mycobacterial Virulence Genes in the Genome of the Emerging Pathogen Mycobacterium abscessus

Mycobacterium abscessus is an emerging rapidly growing mycobacterium (RGM) causing a pseudotuberculous lung disease to which patients with cystic fibrosis (CF) are particularly susceptible. We report here its complete genome sequence. The genome of M. abscessus (CIP 104536T) consists of a 5,067,172-bp circular chromosome including 4920 predicted coding sequences (CDS), an 81-kb full-length prophage and 5 IS elements, and a 23-kb mercury resistance plasmid almost identical to pMM23 from Mycobacterium marinum. The chromosome encodes many virulence proteins and virulence protein families absent or present in only small numbers in the model RGM species Mycobacterium smegmatis. Many of these proteins are encoded by genes belonging to a “mycobacterial” gene pool (e.g. PE and PPE proteins, MCE and YrbE proteins, lipoprotein LpqH precursors). However, many others (e.g. phospholipase C, MgtC, MsrA, ABC Fe(3+) transporter) appear to have been horizontally acquired from distantly related environmental bacteria with a high G+C content, mostly actinobacteria (e.g. Rhodococcus sp., Streptomyces sp.) and pseudomonads. We also identified several metabolic regions acquired from actinobacteria and pseudomonads (relating to phenazine biosynthesis, homogentisate catabolism, phenylacetic acid degradation, DNA degradation) not present in the M. smegmatis genome. Many of the “non mycobacterial” factors detected in M. abscessus are also present in two of the pathogens most frequently isolated from CF patients, Pseudomonas aeruginosa and Burkholderia cepacia. This study elucidates the genetic basis of the unique pathogenicity of M. abscessus among RGM, and raises the question of similar mechanisms of pathogenicity shared by unrelated organisms in CF patients.     

Left Ventricular Lead Fracture 6 Years after Implantation with a Retained Guidewire

We reported a case that left ventricular (LV) lead with retained guidewire was used 6 years ago, but the LV lead was broken during 6 years of follow‐up. Although the retained guidewire technique has already been abandoned, the long‐term safety of retained guidewire lead appears to be an even greater concern.     

Astrocyte-Specific Genes Are Generally Demethylated in Neural Precursor Cells Prior to Astrocytic Differentiation

Epigenetic changes are thought to lead to alterations in the property of cells, such as differentiation potential. Neural precursor cells (NPCs) differentiate only into neurons in the midgestational brain, yet they become able to generate astrocytes in the late stage of development. This differentiation-potential switch could be explained by epigenetic changes, since the promoters of astrocyte-specific marker genes, glial fibrillary acidic protein (Gfap) and S100β, have been shown to become demethylated in late-stage NPCs prior to the onset of astrocyte differentiation; however, whether demethylation occurs generally in other astrocyctic genes remains unknown. Here we analyzed DNA methylation changes in mouse NPCs between the mid-(E11.5) and late (E14.5) stage of development by a genome-wide DNA methylation profiling method using microarrays and found that many astrocytic genes are demethylated in late-stage NPCs, enabling the cell to become competent to express these genes. Although these genes are already demethylated in late-stage NPCs, they are not expressed until cells differentiate into astrocytes. Thus, late-stage NPCs have epigenetic potential which can be realized in their expression after astrocyte differentiation.     

Startling Mosaicism of the Y-Chromosome and Tandem Duplication of the SRY and DAZ Genes in Patients with Turner Syndrome

Presence of the human Y-chromosome in females with Turner Syndrome (TS) enhances the risk of development of gonadoblastoma besides causing several other phenotypic abnormalities. In the present study, we have analyzed the Y chromosome in 15 clinically diagnosed Turner Syndrome (TS) patients and detected high level of mosaicisms ranging from 45,XO:46,XY=100:0% in 4; 45,XO:46,XY:46XX=4:94:2 in 8; and 45,XO:46,XY:46XX=50:30:20 cells in 3 TS patients, unlike previous reports showing 5–8% cells with Y- material. Also, no ring, marker or di-centric Y was observed in any of the cases. Of the two TS patients having intact Y chromosome in >85% cells, one was exceptionally tall. Both the patients were positive for SRY, DAZ, CDY1, DBY, UTY and AZFa, b and c specific STSs. Real Time PCR and FISH demonstrated tandem duplication/multiplication of the SRY and DAZ genes. At sequence level, the SRY was normal in 8 TS patients while the remaining 7 showed either absence of this gene or known and novel mutations within and outside of the HMG box. SNV/SFV analysis showed normal four copies of the DAZ genes in these 8 patients. All the TS patients showed aplastic uterus with no ovaries and no symptom of gonadoblastoma. Present study demonstrates new types of polymorphisms indicating that no two TS patients have identical genotype-phenotype. Thus, a comprehensive analysis of more number of samples is warranted to uncover consensus on the loci affected, to be able to use them as potential diagnostic markers.     

再次腹腔镜手术处理胆管残石和胆管再生结石

目前,对腹腔镜胆囊切除术（ＬＣ）后胆管残石及腹腔镜胆道探查术（ＬＣＤＥ）后胆管再生结石的处理,多采用经内镜乳头切开（ＥＳ）或者开腹胆道探查（ＯＣＤＥ）。我院从１９９７年６月到１９９９年２月,对５例ＬＣ术后胆管残石和２例ＬＣＤＥ术后胆管再生石,选用再次ＬＣＤＥ处理。两次手术间隔１天到５年。术中一次取净结石。２例术后安置Ｔ管,５例胆管一期缝合。Ｔ管于术后６周拔除,并经Ｔ管窦道行胆道镜检查。胆管一期缝合者,术后３月行静脉胆道造影（ＩＶＣ）,均未发现残石和狭窄。结论：腹腔镜手术的微创优越性,使再次腹腔镜手术处理胆管残石和再生石成为可能。     

临床患者血培养分离出卡明斯假谷氨酸杆菌的全基因组测序及基因功能分析

目的 应用全基因组测序及生物信息学分析方法对一株分离自腹膜间皮瘤患者血液标本中的卡明斯假谷氨酸杆菌菌株进行基因测序和功能分析。方法 于2018 年8 月2 日~8 月15 日,两次从临床患者血液中分离出的微生物经基质辅助激光解析电离- 飞行时间质谱( matrix-assisted laser desorption ionization time-of-flight mass spectrometry,MALDITOF)鉴定为卡明斯假谷氨酸杆菌。应用基因组测序软件构建、自组装的基因功能表注释器及anti SMASH 等软件预测其次级代谢反应和产物蛋白生物合成调控相关的基因及基因簇。通过查询COG,KEGG,GO,NR,CAzy 和Swiss-Prot 数据库对预测的基因进行功能注释。结果 卡明斯假谷氨酸杆菌基因组经过重组装、分析筛选及基因序列整合筛选和优化,得到了约300 个Scaffolds,总长度约2 456 693bp,GC 含量平均约为58.39%。分析发现其中约有2 097 个编码基因,1 431 个功能注释蛋白。其中427 个蛋白功能未知,KEGG 预测到的编码蛋白主要集中在碳水化合物代谢、氨基酸代谢、能量代谢、维生素代谢、脂类代谢和遗传信息传递和表达等通路。CAZy 注释发现27 个碳水化合物代谢相关酶,通过基因序列比对识别出21 个与β- 内酯合成有关的次级代谢基因,序列分析发现89 个抗药性基因。结论 首次成功全面深入分析了卡明斯假谷氨酸杆菌的基因组序列,为今后研究该菌株的代谢特点、致病性及抗药性奠定了基础。     

胎儿房室间隔缺损的超声诊断及全基因组检测

目的 分析胎儿房室间隔缺损（AVSD）的超声特点，并研究应用二代测序技术检测AVSD基因的发生特点。方法 2013年9月-2017年6月北京安贞医院胎儿心脏病母胎医学会诊中心就诊及转诊的胎儿21179例，其中房室间隔缺损AVSD胎儿150例，终止妊娠后取得胎儿标本47例，对其超声心动图特征进行总结，并对47例标本取脐带组织与胎儿父母外周血一起进行基因测序。结果：47例AVSD胎儿，部分型AVSD7例（14.89%），过渡型AVSD2例（4.26%），完全型38例（80.85%）。27例（57.44%）合并心内畸形；19例（40.43%）合并心外畸形；14例（51.85%）合并心内及心外畸形。47例胎儿脐带组织进行全基因组及全外显子测序，4例组织降解，余43例中基因结果阳性22例（51.16%）。27例合并心内畸形中11例基因检测结果阳性（40.74%）；19例合并心外畸形中14例基因检测结果阳性（73.68%）；14例合并心内及心外畸形中11例基因检测结果阳性（78.57%）。 结论：胎儿心内膜垫缺损易合并心内／外畸形，尤其是完全型AVSD；AVSD基因检测异常比例高，可发生在染色体非整倍体、拷贝数变异、单基因突变水平；产前诊断AVSD后应强烈建议遗传学检测，尤其是推荐二代测序技术，有助于发现不同水平的基因异常。