Effect of subjective reasoning and neurocognition on medication adherence for persons with schizophrenia

OBJECTIVE: This study investigated the relationship between patients' reasoning about medication adherence and neurocognitive and clinical indices for a treatment-compliant sample of Japanese patients with schizophrenia. METHODS: Subjective reasoning about medication adherence was assessed by the Rating of Medication Influences (ROMI) scale. General intelligence, executive function, and verbal memory were assessed by the Wechsler Adult Intelligence Scale-Revised, Wisconsin Card Sorting Test, and Rey Auditory Verbal Learning Test, respectively. RESULTS: Higher prevention scores were associated with lower executive functioning and older age. Influence of others was associated with years of education, medication dosage, and IQ, and medication affinity was associated with education. CONCLUSIONS: These results suggest that executive functioning, education, and general IQ may all be important factors in individual motivation for medication adherence.     

Pre-analytical problems on assay conditions for blood midkine

We have established the assay conditions of midkine (MK) measurement, the reference intervals and evaluation for clinical significance of blood MK measurement. MK is a kind of cytokines and basic protein which is a heparin-binding growth factor of various cells. The increase of MK expression suggests a prognostic value in early stage on cancers or inflammation. But significant problems in the MK measurement are alterations resulting from standing time and temperature instability after blood collection. Assay of MK was performed with solid phase human MK immunoassay recently developed sensitive enzyme linked immunosorbent method. The assay condition of MK was required to be separated immediately after blood sampling within 24 hrs at 4 degrees C or within 2 hrs at room temperature-standing. Plasma sample obtained with EDTA-2Na or citric acid-Na, and serum obtained from plain tube container showed good results. Linearity was obtained up to 1500 pg/ml and repeatability and reproducibility were within 10% as CV%. The recovery of MK was 101.1+/-3.8% with 10 specimens ranged 97-105%. Addition of interfering substances showed no effect on assay results when hemoglobin, EDTA-Na, citrate and turbidity check, but conjugated bilirubin (over 0.68 mmol/l) and gave negative errors within 10% in the assay results and heparin gave negative errors. The reference interval was 550 +/- 160 pg/ml in healthy individuals serum.     

Mucin-producing tumors of the pancreas: clinicopathological features, surgical treatment, and outcome

Mucin-producing tumors (MPTs) of the pancreas are increasingly being recognized. To evaluate the appropriate surgical treatment and predict the prognosis of MPTs, we performed a retrospective clinicopathological study in 51 patients, 27 with benign tumors and 24 with borderline/malignant tumors. Three of the malignant tumors showed stromal invasion and lymph node metastasis on histological examination. Of the 24 patients with borderline/malignant tumors, 2 died of MPTs and 4 died of other diseases. At the last follow-up, 35 patients were alive and well. The 5-year postoperative survival rate was 90% for patients with benign tumors, and 78% of these with borderline/malignant tumors. Five of the patients with borderline/malignant tumors had multicentric tumors. Three of these patients underwent resection of the rest of the pancreas, 5, 6, and 8 years, respectively, after the first operation. Extended radical resection is required for malignant MPT with invasion of the pancreatic stroma. We prefer to perform pancreatogastrostomy or Imanaga's procedure to allow examination of the body and tail of the pancreas by endoscopic retrograde pancreatography after resection of the pancreatic head. Careful follow-up for a long period may be the most prudent approach for detecting multiple MPTs in the residual pancreas after surgical treatment. Received for publication on June 30, 1998; accepted on March 3, 1999     

Post-priming actions of ATP on Ca2+-dependent exocytosis in pancreatic beta cells

The role of cytosolic ATP in exocytosis was investigated by using amperometric measurement of insulin exocytosis in pancreatic beta cells, which were stimulated with photolysis of caged Ca²⁺ compounds. Insulin exocytosis occurred with two rates. We found that ATP hastened and augmented the exocytosis via selective enhancement of the exocytosis with the faster rate. A nonhydrolysable analog of ATP, adenosine 5′-O-(3-thiotriphosphate), which blocks ATPase, was even more effective than ATP, indicating that the phosphorylation event occurred downstream of ATP-dependent vesicle transportation and priming. The action of ATP was eliminated by a competitive antagonist of cAMP, and by an inhibitor of adenylate cyclase. These data characterize an ATP sensing mechanism for the Ca²⁺-dependent exocytosis involving adenylate-cyclase, cAMP-dependent protein kinase, and, possibly, the fusion machinery itself. Thus, the fast exocytotic machinery requires both phosphorylation and Ca²⁺ for the final triggering and likely constitutes a distal ATP sensor for insulin exocytosis that acts in concert with ATP-sensitive K⁺ channels.     

Psychophysiological correlates of social skills deficits in persons with schizophrenia

Social skill deficits in schizophrenia profoundly affect patients’ life-long outcome, although the profile of the underlying cognitive dysfunction still remains a matter of debate. In the present study, we investigated the relationship between social skills and event-related potentials (ERPs) in an auditory selective attention task, in addition to the neurocognitive indices obtained from the degraded-stimulus continuous performance test (CPT) and clinical indices, such as Brief Psychiatric Rating Scale (BRPS) and global assessment of function (GAF) scores. Social skills were assessed using a Japanese version of the structured role play test. Fourteen persons with schizophrenia participated in the study. Non-verbal skills showed a positive correlation with GAF, the performance level, N1 and N2b amplitude in the ERP task, and hit rate in the CPT, and a negative correlation with reaction time in the CPT. Verbal communication skills showed a positive correlation with GAF, the performance level and N2b amplitude in the ERP task, and hit rate in the CPT, and a negative correlation with reaction time in the CPT. Processing skills showed a positive correlation with the performance level and N1 amplitude in the ERP task and a negative correlation with reaction time in the CPT. These findings suggested that the social skill deficits of persons with schizophrenia were related to the vigilance level and controlled stimulus detection processing.     

Ito S,Nakanishi H,Ikehara Y,Kato T,Kasai Y,Ito K,Akiyama S,Nakao A,Tatematsu M. Real‐time observation of micrometastasis formation in the living mouse liver using a GFP gene‐tagged rat tongue carcinoma cell line. International Journal of Cancer 2001; 93(2) 212–217.

The original article to which this Erratum refers was published in International Journal of Cancer; 2001; 93(2) 212–217.     

移植的齿状回颗粒细胞在培养的大鼠海马组织上移行特征

为探讨齿状回颗粒细胞在培养的海马组织表面上的移行过程以及苔状纤维的投射特征,本实验从生后3d的绿色荧光蛋白(GFP)基因导入的SD大鼠海马组织切片中分离出齿状回颗粒细胞层,移植到培养的SD大鼠海马组织切片表面上,共同培养3～4d后,激光共聚焦显微镜观察。结果显示,97.6%的细胞移行到齿状回和CA3区,仅有2.4%细胞移行到CA2和CA1区。移行到齿状回颗粒细胞层的颗粒细胞投射苔状纤维到齿状回门区和CA3区的透明层,却不到CA2和CA1区。上述结果提示,在海马组织培养中移植的齿状回颗粒细胞的移行以及苔状纤维的投射方向明显受宿主的影响。     

Adenovirus-Mediated Transduction of Escherichia coli Uracil Phosphoribosyltransferase Gene Increases the Sensitivity of Esophageal Cancer Cells to 5-Fluorouracil

Esophageal cancer is associated with the poorest prognosis among the digestive tract cancers, and chemotherapy is the treatment of choice for many patients. In this study, we experimentally introduced an Escherichia coli-derived uracil phosphoribosyltransferase (UPRT) gene to cultured esophageal cancer cell lines to potentiate the antitumor effects of a representative anticancer drug, 5-fluorouacil (5-FU). UPRT is a pyrimidine salvage enzyme that catalyzes the synthesis of uridine monophosphate from uracil and PRPP. The UPRT gene was transduced into five cultured esophageal cancer cell lines, TE1, TE2, TE3, NUEC1, and T.T, using an adenovirus vector. It was confirmed that the sensitivities of all cultured cell lines to 5-FU were increased in vitro. Subsequently, the T.T line was subcutaneously inoculated into nude mice to induce tumors, after which 5-FU was administered intraperitoneally. When a UPRT gene-recombinant adenovirus vector was directly injected into the tumors, tumor proliferation was markedly inhibited compared with that in the group treated with 5-FU alone, suggesting potentiation of 5-FU sensitivity by UPRT gene transduction in vivo. Therefore, we potentiated the effects of commercially available anticancer drugs by gene transduction. Our method may prove useful as a new form of cancer gene therapy in the future. Received: June 23, 2000 / Accepted: March 6, 2001     

Pharmacodynamic analysis of eribulin safety in breast cancer patients using real‐world postmarketing surveillance data

Postmarketing surveillance is useful to collect safety data in real‐world clinical settings. In this study, we applied postmarketing real‐world data on a mechanistic model analysis for neutropenic profiles of eribulin in patients with recurrent or metastatic breast cancer. Demographic and safety data were collected using an active surveillance method from eribulin‐treated recurrent or metastatic breast cancer patients. Changes in neutrophil counts over time were analyzed using a mechanistic pharmacodynamic model. Pathophysiological factors that might affect the severity of neutropenia were investigated, and neutropenic patterns were simulated for different treatment schedules. Clinical and laboratory data were collected from 401 patients (5199 neutrophil count measurements) who had not received granulocyte colony‐stimulating factor and were eligible for pharmacodynamic analysis. The estimated mean parameters were as follows: mean transit time = 104.5 h, neutrophil proliferation rate constant = 0.0377 h^?1, neutrophil elimination rate constant = 0.0295 h^?1, and linear coefficient of drug effect = 0.0413 mL/ng. Low serum albumin levels and low baseline neutrophil counts were associated with severe neutropenia. The probability of grade ≥3 neutropenia was predicted to be 69%, 27%, and 27% for patients on standard, biweekly, and triweekly treatment scenarios, respectively, based on virtual simulations using the developed pharmacodynamic model. In conclusion, this is the first application of postmarketing surveillance data to a model‐based safety analysis. This analysis of safety data reflecting authentic clinical settings will provide useful information on the safe use and potential risk factors of eribulin.     

伊朗 Graves 眼病的临床特点

目的:研究分析伊朗 Graves 眼病患者的临床特点.方法:回顾分析 2003/2005 年确诊为 Graves 眼病的103例患者临床资料.结果:在103例 Graves 眼病患者中,48例(46.6%)为男性,55例(53.3%)为女性(男女比例为1.1).年龄18-73(平均45)岁,95例(92.2%)表现为甲状腺机能亢进,3例(2.9%)表现为原发性甲状腺机能减退,5例(4.8%)甲状腺机能正常.出现眼部症状的时间为2～95 (平均3.2)mo,而表现出甲状腺功能障碍的时间为6～180(平均39.4)mo.12例患者单眼发病,90例(87%)患者有眼睑退缩,80例(77.6%)患者表现出眼球突出,其中30例(29%)伴有局限性眼外肌运动障碍;CT扫描显示70例患者中有52例(74%)有眼外肌肥大.6例患者(5.8%)有视神经功能障碍,22例患者(21%)表现出Graves眼病相关的青光眼.其中7例(6.7%)为正常眼压青光眼.结论:本组病例中眼睑退缩是Graves眼病最常见的临床表现.未来需要更大范围的病例研究,以评价分析Graves眼病在伊朗人群中的发病率以及不同人种之间临床表现差异.