活化自体淋巴细胞过继性免疫治疗在原发性肝细胞癌中的疗效观察

目的：评价活化自体淋巴细胞过继性免疫治疗（adoptive immunotherapy,AIT）是否有助于改善原发性肝细胞癌的临床疗效。方法：选取2016年8月至2018年12月在中国人民解放军总医院第五医学中心确诊的64例原发性肝细胞癌患者,通过分层随机法分为免疫治疗组（n=29）和对照组（n=35）。免疫治疗组患者取60 ml外周血分离制备单个核细胞并在含OKT-3和IL-2的培养基中活化培养,回输前进行质控检测。免疫治疗组中的Ⅰ~Ⅲ期患者（n=14）于一线治疗后接受自体淋巴细胞输注（3个月内输注6次）,Ⅳ期患者（n=15）仅接受自体淋巴细胞输注;对照组患者接受肝细胞癌相关的其他治疗。疗效评估的主要终点是2 年无复发生存（relapse-free survival,RFS）率,次要终点为无进展生存期（progression-free survival,PFS）和总生存期（overall survival,OS）。结果：入组患者中位随访时间为2.8年（0.2~4.2年）。免疫治疗组29名患者共接受了167次（计划174次,完成率96%）预定淋巴细胞输注（平均每人次回输9.30×109个细胞,其中CD3+HLA-DR细胞约占63%）,治疗期间未观察到3级或4级不良反应发生。与对照组相比,免疫治疗组患者2年RFS率显著升高（62.1% vs 22.9%,OR=0.181,95%CI：0.06~0.54,P=0.002）,中位PFS（28 vs 8个月,P=0.004）和中位OS（38 vs 34个月,P=0.915）均显著延长。在Ⅰ~Ⅲ期患者中,免疫治疗组（n=14）2年RFS率较对照组（n=18）显著升高（92.9% vs 33.3%,OR=0.38,95%CI：0.004~0.368,P=0.005）,中位PFS明显延长（38 vs 14.5个月,P=0.005）,而两组OS间无显著差异;Ⅳ期患者两组间PFS（P=0.077）及OS（P=0.994）均未见显著差异。结论：活化自体淋巴细胞AIT为安全可行的肝细胞癌辅助性治疗方法,可提高Ⅰ~Ⅲ期肝细胞癌一线治疗后RFS率、延长患者RFS时间,而对进展期肝细胞癌患者的PFS和OS无明显影响。     

High Efficacy of Disopyramide in the Management of Ventricular Fibrillation Storms in a Patient with Brugada Syndrome

The patient was a 57‐year‐old man with Brugada syndrome, who had been implanted with a implantable cardioverter defibrillator (ICD). The frequency of ventricular fibrillation (VF) started to increase about 4 years after ICD implantation, occurring, at worst, six times in one night. Immediately after starting oral administration of disopyramide, VF stopped occurring. He then discontinued taking disopyramide, but immediately after the discontinuation VF started occurring again, so he restarted taking disopyramide. Thereafter, VF completely stopped occurring. Findings observed in our case suggest that disopyramide could be added in our arsenal of medications for treating arrhythmic storms in patient with Brugada syndrome. (PACE 2010; 33:e53–e56)     

Phenytoin-induced cerebral thrombosis in rats: cerebral ultrastructure, water content and ischaemic volume in the acute phase

A new rat model for multifocal cerebral thrombosis has recently been reported (Tani et al. , 1994; 1995). Ultrastructural changes in the cerebral neocortex in the acute phase were investigated in order to characterize the early pathological events in this model. A bolus injection of alkaline phenytoin solution (pH 10.8) into one internal carotid artery in the rat caused severe endothelial injury accompanied by thrombosis in the cerebral vasculature within 5 minutes, and severe oedema of the ipsilateral hemisphere within an hour. Cerebral water content was measured by the simple dry–wet method, and cerebral surface area and the surface area and volume of the ischaemic zone were measured using computer-aided image analysis. Good correlations were demonstrated between cerebral water content and cerebral surface area, and between the surface area and volume of the ischaemic zone. We report here that quantitative evaluation of acute cerebral damage induced by phenytoin solution is possible with high reliability using simple image analysis.     

Clinically isolated cerebellar metastasis of renal pelvic urothelial cancer

A 70-year-old man who had undergone radical surgery for renal pelvic transitional cell carcinoma 9 months previously developed solitary cerebellar metastasis. Despite neurosurgical removal, the patient died and post-mortem pathological examination revealed microscopic metastatic lesions within microvessels of the lung. No other lesion, including local residual cancer, was detected.     

Inter‐ and intra‐rater reliability in fibroptic endoscopic evaluation of swallowing

Summary Fibroptic endoscopic evaluation of swallowing (FEES) is a useful way for dentists to evaluate oropharyngeal dysfunction. However, no study has paid attention to inter‐ and intra‐rater reliability of FEES evaluation about oropharyngeal dysfunction. The purpose of this study is to verify whether dentist who trained and experienced for evaluation of dysphagia could diagnose oropharyngeal function with FEES. Nine dentists independently evaluated FEES images of 10 cases four times each. At first, evaluators performed the first evaluation without consulting the evaluative criteria. Subsequently, evaluators independently re‐evaluated at 1‐week intervals for three consecutive weeks, consulting the evaluative criteria. And then, inter‐ and intra‐rater reliability was calculated. Cohen’s Kappa was used to assess reliability. The results found that overall inter‐rater reliability was 0·35 ± 0·04 (first evaluation), 0·45 ± 0·05 (s), 0·44±0·05 (third) and 0·46 ± 0·04 (fourth). Most of inter‐rater reliability related to aspiration was moderate to high, but lower for categories that evaluated timing of swallowing and mastication. In contrast, intra‐rater reliability was moderate to high for overall categories, at 0·53 ± 0·04 (first vs. second evaluation), 0·55 ± 0·04 (first vs. third), 0·53 ± 0·04 (first vs. fourth), 0·55 ± 0·03 (second vs. third), 0·60 ± 0·03 (second vs. fourth) and 0·78 ± 0·03 (third vs. fourth). FEES is reliable for experienced dentists to diagnose oropharyngeal function. Moreover, repeated evaluation with the aids of evaluative criteria is useful to improve the reliability of FEES.     

Estimation of usefulness of N-butyl-2-cyanoacrylate-lipiodol mixture in transcatheter arterial embolization for urgent control of life-threatening massive bleeding from gastric or duodenal ulcer

We estimated the usefulness of a mixture of N-butyl-2-cyanoacrylate (NBCA) with lipiodol for transcatheter arterial embolization (TAE) used to control massive bleeding from gastric or duodenal ulcer. Thirty patients who had gastric or duodenal ulcers and massive bleeding that was uncontrollable by endoscopic procedures were included in this study. All patients were subjected to TAE (without NBCA in 23 and with NBCA in seven patients). Coils and/or gelfoam were also used. The achievement of haemostasis, occurrence of rebleeding and the time taken for TAE were compared between patients who received TAE without and with NBCA. Eighteen of 23 patients (78.3%) who received TAE without NBCA and six of seven patients (85.7%) who underwent TAE with NBCA achieved complete haemostasis without rebleeding. The time for TAE was significantly shorter in patients who received NBCA compared with those who did not (P= 0.0095). TAE using NBCA or a combination of NBCA and coils achieved a rapid, complete embolization regardless of vascular distribution or arterial diameter. Thus NBCA is considered to be useful as a secondary embolization material in TAE that is urgently conducted to control massive bleeding from gastric or duodenal ulcers.     

Results for 79 patients with neuroblastoma detected through mass screening at 6 months of age in a single institute

BACKGROUND: In Japan, mass screening for neuroblastoma has been performed at 6 months of age to improve the prognosis of this condition for more than 20 years. In recent years, most neuroblastomas detected by mass screening were considered to have favorable biological features and sometimes tend to regress spontaneously. METHODS: The authors established non-treated observation criteria in 1997 and criteria for observation of residual tumor after first-line chemotherapy in 1999, and have made an effort to reduce the intensity of medical treatment for neuroblastoma. The authors examined outcomes of 79 patients who were found in the Shizuoka neuroblastoma mass screening at 6 months of age and who received medical treatment or underwent observation in Shizuoka Children's Hospital, Shizuoka, Japan, between December 1981 and December 2004. RESULTS: A total of 77 patients survived but the remaining two patients died from complications of medical treatment. None of the patients died due to progression of neuroblastoma. In the cases, non-treated observation was performed in 17. Of those, 12 patients are now under non-treated observation. Of their tumors, two have disappeared, nine have become smaller and another one has not change in size. Observation of residual tumor after first-line chemotherapy was performed in 15 cases, and three disappeared and the other 12 cases became smaller. Medical treatment-related complications were observed in 20 of 67 patients who received medical treatment, and 18 of the 20 patients were seen before establishing non-treated observation criteria. CONCLUSION: Non-treated observation and observation of residual tumor after first-line chemotherapy were useful to reduce medical treatment-related complications.     

Interspecies-specific Ovarian Autoantigens Involved in Neonatal Thymectomy-induced Murine Autoimmune Oophoritis

PROBLEM: Thymectomy of mice on day 3 after birth (3d-Tx) gives rise to the appearance of a particular type of ovarian lesion known as experimental autoimmune oophoritis (AIO). METHOD: In the present study, the spleen cells from BALB/c mice having undergone 3 day-Tx AIO were fused with X63-Ag8-6.5.3 myeloma cells, and a number of hybridoma clones producing autoantibodies against ovarian tissue were established. RESULTS: On the basis of immunohistochemical and protein-chemical analysis, two independent clones, designated as T2.2 and S1.6, were found to react with interstitial tissues surrounding the follicles. These monoclonal antibodies showed broad cross-species reactivity, in that they recognized similar antigenic macromolecules in the rat, pig, human, and mouse. The antigenic determinants were strongly resistant to heat and acid, especially to the treatment of periodic acid, indicating that the antigenic determinants had no relation with carbohydrate components. CONCLUSIONS: By antibody affinity chromotography, two kinds of autoantigens were identified. SDS-PAGE, under reduced or nonreduced conditions, revealed an 80/85 kDa protein for T2.2, and an 82 kDa for S1.6, respectively.     

Dendritic and histochemical development and ageing in patients with Down's syndrome

ABSTRACT. Mental retardation and dementia characteristic of Down's syndrome (DS) have a complex pathogenesis. Golgi and immunohistochemical studies were done on DS patients and controls from foetuses and elderly adults. Golgi studies on the cerebral cortex revealed that the postsynaptic spines on the basal dendrites increase from neonate to 15 years of age and gradually decrease after 20 years in controls, but poorly increase in children and rapidly decrease in adults with DS. This deficient synaptogenesis and dendritic atrophy may be related to mental retardation. On the other hand, immunohistochem-istry on proteins, whose genes are located on chromosome 21, revealed that c-temiinal protein of beta-amyloid appears in neurons of DS, S-100-positive glia increases in the hippocampus of neonates and adults, and membrane protein OK-2 is expressed earlier and is more widespread in the DS brains. The overexpression and early appearance of gene products in DS brains may be related to the pathogenesis of or predisposition to mental disorders or to dendritic hypogenesis.