New cellular and molecular approaches for the treatment of cardiac disease

Similar to the kidney in uremia, end-stage cardiac failure is an outcome common to many disparate disease processes including hypertension, various inflammatory pathologies, as well as ischemic loss of tissue. In regard to the heart, cellular and molecular mechanisms responsible for heart failure have been investigated with renewed intensity over the past several years with newer techniques of molecular genetics, genomic analysis, and cell biology. Although this article reviews some recent advances made in our understanding of molecular and cellular events in the heart leading to heart failure and explores possible new targets for therapeutics, the main point is to stress the importance of investigative interactions between organ physiologists and molecular and cellular biologists. These interactions between organ physiologists and molecular geneticists is stressed and supported as a mechanism for rapid advancement for both understanding the underlying pathophysiology of human disease and the development of therapeutic strategies.     

CYLD mutation causes multiple familial trichoepithelioma in three Chinese families

Multiple familial trichoepithelioma (MFT) and familial cylindromatosis are two clinically distinct cancer syndromes. MFT patients developed mostly trichoepithelioma in the face while cylindromatosis patients developed cylindromas predominantly (approximately 90%) on the head and neck. However, multiple familial trichoepithelioma is occasionally associated with familial cylindromatosis while cylindromatosis patients can also develop trichoepithelioma. This has led to the speculation that the 2 types of dermatoses may be caused by dysfunction of a common pathway. Previously, a candidate MTF locus has been mapped to 9p21 while disease gene for familial cylindromatosis, the CYLD gene located on 16q21-13 has been identified. Here, we show that mutations in the CYLD gene are also the genetic basis for three different Chinese families with MFT. Sequence analysis reveal a single nucleotide deletion, c.1462delA (P.Ile488fsX9) in exon 9, a nonsense mutation, c.2128C>T (p. Gln710X) in exon 17, and a missense mutation, c.2822A>T (p. Asp941Val) in exon 21 in each of the three families respectively. This provides direct evidence that the mutations in CYLD can cause two clinically distinct cancer syndromes.     

伴发于直肠腺癌的肛周佩吉特病

目的 探讨伴发直肠腺癌的肛周佩吉特病(Paget’s disease)的临床病理学特征、组织学发生及特点。方法 对3例伴发直肠腺癌的肛周佩吉特病进行临床病理学分析,作过碘酸雪夫(PAS)、阿辛蓝和黏液卡红染色,采用免疫组织化学EnVision法行癌胚抗原(CEA)、CK7、CK8、CK10／13、CK20和巨囊性病液体蛋白15(GCDFP15)标记。结果 3例均发生于中老年男性,因便血和(或)大便习惯改变就诊。肛指检查显示距肛1．8～2．0cm处可触及溃疡型或菜花状肿块,3例中2例肛周皮肤伴有湿疹样改变,1例呈细颗粒状。术后标本显示直肠肿瘤位于齿状线上方或紧邻齿状线,组织学上为中分化腺癌(2例)或低分化腺癌(1例)。肛周皮肤内佩吉特细胞主要有两种形态,一种为经典型(A型),另一种为印戒型(B型),两种类型细胞可存在于同一病例中。直肠腺癌细胞和皮肤佩吉特细胞PAS、AB和黏液卡红染色均为强阳性,PAS和AB染色耐淀粉酶消化,并同时表达癌胚抗原、CK7、CK8和CK20标记,而CK10／13和GCDFP15标记均为阴性。结论免疫表型为CK20^ -GCDFP15^-的肛周皮肤佩吉特细胞由结直肠腺癌细胞扩散到表皮内所致。此型肛周皮肤佩吉特病伴结直肠腺癌的概率可高达60％,较发生于其他部位的乳腺外佩吉特病高,提示一旦发现肛周佩吉特病,需注意是否有结直肠癌原发病灶存在的可能性。     

不同内耳畸形人工耳蜗植入效果分析

OBJECTIVE: To describe clinical experiences with multi-channel cochlear implantation in patients with bilateral inner ear malformations. METHODS: Among 410 patients who received multi-channel cochlear implantations from 1996 to 2004 in Beijing Tongren Hospital, 82 patients were diagnosed with inner ear malformations and implanted. A retrospective analysis was performed about the surgical characteristics and mapping characteristics after implantation. RESULTS: (1) All patients had auditory sensations. (2) Gusher was more common than the normal cochlear implantation. (3) The electrodes were inserted in the "cochleostomy" in full length of 80 Patients, but 2 pairs of electrodes remained outside of "cochleostomy" in 2 patients. (4) No serious complications occurred after implantation. (5) The impedance of the electrodes, the T level and C level were similar with the normal cochlear implantation. The results had no significant difference in compare with normal cochlear group (P > 0. 05). (6) The abilities of speech discrimination and spoken language were improved through rehabilitation. CONCLUSIONS: The cochlear implantation can be performed safely in inner ear malformations. The outcome of hearing rehabilitation for patients with inner ear malformations are similar to those children with normal cochlear structure followed the multi-channel cochlear implantation.     

Laryngeal embryonal rhabdomyosarcoma: a case of cervical metastases 13 years after treatment and a 25-year review of existing literature

Rhabdomyosarcoma is the most common soft tissue sarcoma in childhood, the majority of which are of the embryonal rhabdomyosarcoma (ER) variety. Present day treatment protocols involve a combination of aggressive surgery, chemotherapy, and radiation therapy. Embryonal rhabdomyosarcoma of the larynx is rare and unlike ER of other regions exhibits excellent response to multimodality treatment without the need for extensive surgery. We report a case of cervical metastases in a 29-year-old man 13 years after treatment of his laryngeal ER. To our knowledge, this is the first reported case of late neck metastases in ER of the larynx and the second reported case of delayed presentation of recurrent disease. A 25-year review of all published reports of ER of the larynx was conducted that highlights the move toward organ preservation with the multimodality treatment protocols. Embryonal rhabdomyosarcoma of the larynx is highly responsive to combination chemoradiotherapy, allowing for excellent cure rates without the need for extensive surgery. Late relapses warrant long-term follow-up.     

硝普钠对豚鼠耳蜗外毛细胞能动性影响的初步研究

目的研究硝普钠(sodium nitroprusside,SNP)对耳蜗OHC在电压刺激下的能动性的改变情况.方法运用全细胞膜片钳电压钳技术,在正常细胞内外液的条件下,观察不同浓度SNP对电压性刺激引起OHC能动性的影响情况.结果在SNP浓度低于100 μMol/L时,SNP对OHC能动性的影响不明显,但当SNP浓度高于100 μMol/L时,SNP对OHC的能动性有明显的抑制作用,结果有统计学意义(P<0.05).结论 SNP对OHC的能动性有抑制作用,作用呈一定的浓度效应关系.     

Longitudinal behaviour of neural response telemetry (NRT) data and clinical implications

Neural response telemetry (NRT) data from 63 subjects equipped with the Nucleus CI24M Cochlear Implant System generally exhibited little change over up to 4 years. Larger changes, when they occurred, were seen only within the first 15 months postoperatively, and these changes diminished over time. Intraoperative NRT data were generally stable enough to be used for assisting in the initial speech processor fitting sessions. It was not possible to predict changes in the subjective map threshold and comfortable loudness levels (T and C levels, respectively) based on observed changes in the NRT data. The long-term stability of the neural response amplitude and the neural response threshold, however, implies that NRT may be useful as a routine diagnostic tool to detect changes to the neural periphery over time.     

胶质瘤多药耐药细胞株大鼠动物模型的建立及其生物学性质

目的建立神经胶质瘤多药耐药细胞株C6/adr及其原始细胞株C6种植在S-D大鼠脑内的动物模型,对照研究其生物学性质.方法体外培养神经胶质瘤多药耐药细胞株C6/adr及其原始细胞株C6,在磁共振连续动态监测下,进行大鼠脑内接种,于接种当天、第3天以及接种后每周进行磁共振随访检查,并对同期大鼠进行组织活检,观察接种后肿瘤大小变化、荷瘤大鼠的生存期.结果体外培养的神经胶质瘤多药耐药细胞株接种大鼠4周以后出现明显的颅内压增高症状,磁共振阳性结果远早于症状的出现,能更准确地动态显示肿瘤在脑内的生长情况,接种后同期病理结果证实了磁共振影像学表现.C6和C6/adr细胞大鼠动物模型的生长特性相似,两者接种后同期的肿瘤大小、生存期无显著差异(P＞0.05).结论应用磁共振对大鼠动物模型进行动态监测,结合同期的病理切片,能够全面了解活体肿瘤的生长情况,并可确立大鼠脑内肿瘤生长的早、中、晚分期,为体内实验的进一步深入研究提供重要的工具和必要的基础.