THE IMPACT OF DIABETES MELLITUS ON THE PROGNOSIS OF ALCOHOLICS

In this study, the mortality of clinically treated Japanesealcoholics with diabetes mellitus was analysed. Fifty-one diabeticalcoholics without liver cirrhosis (DM), 23 diabetic and cirrhoticalcoholics (DM LC), 44 cirrhotic alcoholics without diabetes(LC), and 354 alcoholics without either complication (AL) admittedto the National Institute on Alcoholism in 1985 were studied.Thirty-seven diabetics required insulin treatment, and 12 oralhypoglycemic agents. The 4.4-year survival and drinking statusafter discharge were studied in 1990. Stepwise logistic regressionanalysis showed that the estimated odds for death increased8.10, 4.38, 3.70, and 3.27 times for the subjects with the alcoholmisuse after discharge, DM, DM LC, and LC, respectively. The4.4-year survival rate of alcoholics who continued misusingalcohol was much lower in DM (26%, P < 0.0005) and LC (35%,P < 0.0001) than in AL (73%). The survival rate of thosewho stopped misusing alcohol was significantly higher in DM(90%, P < 0.0001), LC (88%, P < 0.0001) and AL (94%, P< 0.0005) than those who continued misusing alcohol. Therewas no significant difference in the survival rate between thealcoholics with DM LC who continued misusing alcohol (50%) andthose who stopped misusing alcohol (73%). In the dead patients,56% of DM died unexpectedly or suddenly, whereas 71% of LC diedof liver failure after hospitalization. These results suggestthat diabetic alcoholics should be intensively educated forabstinence.     

Clinical pharmacological study of a plasma‐derived factor VIIa and factor X mixture (MC710) in haemophilia patients with inhibitors – Phase I trial

Summary. MC710, a combined product of plasma‐derived activated factor VII (FVIIa) and factor X (FX) at a protein weight ratio of 1:10, is a novel bypassing agent for haemostasis in haemophilia patients with inhibitors. In this study, pharmacokinetic (PK), pharmacodynamic (PD) parameters and safety of single doses of MC710 were investigated in 11 male haemophilia patients with inhibitors in a non‐bleeding state. This was a multi‐centre, open‐labelled, non‐randomized, active controlled crossover, dose‐escalation study of five doses (20–120 μg kg⁻¹ of FVIIa) with re‐administration of different MC710 dosages to the same subjects. The active controls were NovoSeven (120 μg kg⁻¹) and/or FEIBA (50 and 75 U kg⁻¹) which were used to compare PD parameters. The area under the curve (AUC) and maximum plasma concentration (C_max) of MC710 active ingredients increased dose‐dependently within the range of 20 and 120 μg kg⁻¹. After administration of MC710, activated partial thromboplastin time (APTT) was dose‐dependently improved and prothrombin time (PT) was shortened to approximately 6 s at 10 min, and APTT improvement and PT shortening effects were maintained until 12 h after administration of MC710 at all doses. No serious or severe adverse event was observed after administration of MC710; furthermore, several diagnostic marker values and those changes did not indicate any signs of disseminated intravascular coagulation (DIC). These results suggest that MC710 would have haemostatic potential equal to or greater than NovoSeven and FEIBA and was be tolerable when given at doses up to 120 μg kg⁻¹.     

Gel Chromatographic Analysis of Cyclosporin and Its Metabolites in Human Blood Compartments

Gel chromatography combined with specific and non-specific cyclosporin radioimmunoassays was adopted for quantitative analysis of cyclosporin and metabolites in free and protein-bound forms in blood compartments of kidney transplant patients. The analytical method was proved to be useful for the purpose, although plasma protein-bound forms of neither cyclosporin nor metabolites could be quantitated in the system. The present study also provided, by gel chromatographic analysis, additional examples to prove that concentrations of cyclosporin metabolites in blood compartments may not be deduced or inferred simply from those of cyclosporin.     

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。     

Developmental Abnormalities of Dendrites of the Cerebral Cortical Neurons in Mental Retardation*

Abstract This paper of Golgi studies describes abnormal dendritic structure and development assessed by camera lucida representation, quantitation of dendritic spines, and dendritic branch measurement in metabolic and chromosomal diseases with mental retardation, reviewing the literatures of Golgi study. Neuronal lipid storage diseases with progressive mental and motor deterioration show characteristic meganeurites between the soma and origin of the axon, and all dendrites have fewer number of branches, shorter total basal dendritic length and marked reduction of spines. Phenylketonuria and Lesch-Nyhan syndrome also present decreased number of spines. On the other hand, children and adults with Down's syndrome show poor dendritic spine density and dendritic branchings as well as structural irregularity of spines. This poor' development of dendrites suggesting postnatal poor synaptogenesis may be related to mental retardation in children. These postnatal dendritic abnormalities may be based on genetic factors such as diminished number of cortical granular cells and extrinsic factors which include poor perception of external stimuli as noted in sensory deprivation. Thus, dendritic spine abnormalities may be correlated with mental retardation. However, we need better staining method and more sytemic study.     

Clinical Evaluation of Brushing Cytology and Biopsy of the Pancreatic Duct in Patients with Mucin Producing Tumor of the Pancreas

Abstract: A cytological study of pure pancreatic juice obtained endoscopically after brushing the lesion of the pancreatic duct urns performed in 10 patients with mucin producing tumors of the pancreas. In 6 of these 10 patients, biopsies from the lesion in the pancreatic duct were also carried out endoscopically. The brushing cytology in all 6 patients with mucin producing carcinoma of the pancreas, except for the sidebranch type, showed cellular atypism and the cytological diagnoses were Class IV or Class V. The results of the brushing cytology in the patients assumed clinically benign were Class I ? Class III. Biopsy results in 4 patients with mucin producing carcinoma of the pancreas indicated that one of them had adenocarcinoma, and the other 3 had atypical hyperplasia which suggests the existence of malignancy. In the patient with adenoma, diagnosis of the biopsy specimen revealed hyperplasia only. It was concluded that cytology and biopsy of lesions in the pancreatic duct are a valuable way of assessing mucin producing tumors of the pancreas before surgery.     

Abnormalities of Immunologic Response of Lymphocytes in Patients With Cancer of the Digestive Organs

The lymphocyte functions of 174 patients with cancer of thedigestive organs were studied, with particular reference tothe percentage of T cells bearing receptors for the Fc portionof IgG (T_G cells), phytohemagglutinin (PHA) response of thelymphocytes and the helper activity of T cells. The percentageof T_G cells was 12.18±6.91% (mean±SD) before treatment,exceeding the upper limit of the normal value (8%) in 49.4%of the patients. However, it decreased significantly to 7.98±6.3%after surgical removal of the tumors (r=0.746, P<0.001).The possible correlations of this parameter with two otherswere investigated in order to find a more reasonable parameterfor tumor immunology. An increased percentage of T_G cells anda decreased PHA response of the lymphocytes were found in 5.8%of the cases of stage I, 42.8% of the cases of stage II, 33.3%of the cases of stage III and 48.9% of the cases of stage IVcancer. An increased percentage of T_G cells and a decreasedhelper activity of T cells were found in 20% of the cases ofstage I, 20% of the cases of stage II, 25% of the cases of stageIII and 33.3% of the cases of stage IV. When only gastric cancerpatients were considered, a decreased PHA response of the lymphocytesand an increased percentage of T_G cells were found in 12.5%of the patients with early stages. while this profile was observedin 25.5% of the patients with advanced stages of the disease.An increased percentage of T_G cells and a decreased helper activityof T cells were found in 18.7% of the patients with early stagesand 37.9% of the patients with advanced stages. These findingssuggest that if the three immunological parameters were usedin the above combinations, they might more accurately reflectchanges in immunity with the progress of cancer.     

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.     

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.