Implantation of biventricular assist devices for chronic heart transplant rejection

Mechanical circulatory support has been used to treat graft failure caused by rejection after heart transplantation, but the prognosis remains bleak. Organ failure induced by the addition of or an increase in immunosuppressive medication is known to be a cause of the poor outcomes. Thus we tried a new therapeutic technique that allows complete withdrawal of immunosuppressive medication, as the donor heart is removed and circulatory support is maintained with a biventricular assist device.     

Tumour specific promoter region methylation of the human homologue of the Drosophila Roundabout gene DUTT1 (ROBO1) in human cancers

The human homologue of the Drosophila Roundabout gene DUTT1 (Deleted in U Twenty Twenty) or ROBO1 (Locus Link ID 6091), a member of the NCAM family of receptors, was recently cloned from the lung cancer tumour suppressor gene region 2 (LCTSGR2 or U2020 region) at 3p12. DUTT1 maps within a region of overlapping homozygous deletions characterized in both small cell lung cancer lines (SCLC) and in a breast cancer line. In this report we (a) defined the genomic organization of the DUTT1 gene, (b) performed mutation and expression analysis of DUTT1 in lung, breast and kidney cancers, (c) identified tumour specific promoter region methylation of DUTT1 in human cancers. The gene was found to contain 29 exons and spans at least 240 kb of genomic sequence. The 5' region contains a CpG island, and the poly(A)(+) tail has an atypical 5'-GATAAA-3' signal. We analysed DUTT1 for mutations in lung, breast and kidney cancers, no inactivating mutations were detected by PCR-SSCP. However, seven germline missense changes were found and characterized. DUTT1 expression was not detectable in one out of 18 breast tumour lines analysed by RT-PCR. Bisulfite sequencing of the promoter region of DUTT1 gene in the HTB-19 breast tumour cell line (not expressing DUTT1) showed complete hypermethylation of CpG sites within the promoter region of the DUTT1 gene (-244 to +27 relative to the translation start site). The expression of DUTT1 gene was reactivated in HTB-19 after treatment with the demethylating agent 5-aza-2'-deoxycytidine. The same region was also found to be hypermethylated in six out of 32 (19%) primary invasive breast carcinomas and eight out of 44 (18%) primary clear cell renal cell carcinomas (CC-RCC) and in one out of 26 (4%) primary NSCLC tumours. Furthermore 80% of breast and 75% of CC-RCC tumours showing DUTT1 methylation had allelic losses for 3p12 markers hence obeying Knudson's two hit hypothesis. Our findings suggest that DUTT1 warrants further analysis as a candidate for the tumour suppressor gene (TSG) at 3p12, a region defined by hemi and homozygous deletions and functional analysis.     

血府逐瘀汤对乳鼠心肌细胞缺血再灌注损伤的影响

目的为探讨血府逐瘀汤对乳鼠心肌细胞缺血再灌注损伤的影响。方法应用培养的乳鼠心肌细胞造成缺血再灌注损伤的动物模型,观察心肌细胞中超氧化物岐化酶(SOD)的水平,推断细胞内活性氧的生成量;观察培养液中乳酸脱氢酶(LDH)活性改变以判断细胞损伤情况;并进行DNA琼脂糖凝胶电泳及末端脱氧核苷酸介导的脱氧尿苷三磷酸缺口末端标记法(TUNEL),以判断细胞死亡类型及程度。结果血府逐瘀汤可显著升高缺血再灌注时SOD的水平,显著降低LDH的水平。DNA电泳图谱表明:血府逐瘀汤可使DNA的拖尾基本消失;TUNEL显示血府逐瘀汤可显著减少缺血再灌注所致的心肌细胞死亡。结论血府逐瘀汤有保护缺血再灌注时心肌细胞免于死亡之功效。     

Standards for total body fat and fat-free mass in infants

Data on body composition in conjunction with reference centiles are helpful in identifying the severity of growth and nutritional disorders in infancy and for evaluating the adequacy of treatment given during this important period of rapid growth. Total body fat (TBF) and fat-free mass (FFM) were estimated from total body electrical conductivity (TBEC) measurements in 423 healthy term Caucasian infants, aged 14-379 days. Cross sectional age, weight, and length related centile standards are presented for TBF and FFM. Centiles were calculated using Altman's method, based on polynomial regression and modelling of the residual variation. The TBF percentage steeply increased during the first half year of life, and slowly declined beyond this age. Various simple TBEC derived anthropometric prediction equations for TBF and FFM are available to be used in conjunction with these standards. Regression equations for the P50 and the residual SD, depending on age, weight, or length, are provided for constructing centile charts and calculating standard deviation scores.     

Roxatidine versus ranitidine in the treatment of duodenal ulcers: A randomized double-blind controlled multicentre study in Singapore

Roxatidine acetate, a new H₂ receptor antagonist, was compared with ranitidine in the treatment of duodenal ulcers in a double-blind multicentre study. Eighty-four patients with endoscopically proven duodenal ulcer were randomized to receive 150 mg roxatidine acetate or 300 mg ranitidine at bedtime. Repeat endoscopy was performed after 4 weeks (25–33 days) and if the ulcer had not healed, another endoscopy was performed after a further 4 weeks of treatment. Using per protocol analysis 73.6% of ulcers treated with roxatidine healed at 4 weeks compared to 72.2% of ulcers treated with ranitidine (P=NS). The healing rates at 8 weeks were 92% with roxatidine and 83.3% with ranitidine (P=NS). Using equivalence tests, the healing rate of roxatidine was found to be equivalent to that of ranitidine within a 20% region. Roxatidine users took significantly less antacids than ranitidine users (P < 0.05). There were no significant adverse effects due to roxatidine or ranitidine. Roxatidine is a safe effective drug in the treatment of duodenal ulcers with a healing rate comparable to that of ranitidine.