Capability and Limitations of Recent Diagnostic Criteria for Autoimmune Pancreatitis

Because a diagnostic serological marker is unavailable, autoimmune pancreatitis (AIP) is diagnosed based on unique features. The diagnostic capabilities and potential limitations of four sets of diagnostic criteria for AIP (Japanese diagnostic criteria 2006 and 2011, Asian diagnostic criteria, and international consensus diagnostic criteria (ICDC)) were compared among 85 patients who were diagnosed AIP according to at least one of the four sets. AIP was diagnosed in 87%, 95%, 95%, and 95% of the patients according to the Japanese 2006, Asian, ICDC, and Japanese 2011 criteria, respectively. The ICDC can diagnose types 1 and 2 AIP independently and show high sensitivity for diagnosis of AIP. However, as the ICDC are rather complex, diagnostic criteria for AIP should perhaps be revised and tailored to each country based on the ICDC

Cost-effectiveness of the Introduction of Low-dose CT Screening in Japanese Smokers Aged 55 to 74 Years Old

The validity of low-dose CT screening for lung cancer in heavy smokers was supported by the results of National Lung Screening Trials (NLST) conducted in the U.S.A. The present study investigated the appropriateness of the introduction of low-dose CT screening for lung cancer in Japanese smokers aged between 55 and 74 years old, in terms of cost-effectiveness and age. To examine changes in the shift from conventional chest radiography (CR) to low-dose CT (LDCT) screening for lung cancer, we estimated the incremental cost-effectiveness ratio (ICER) using Iinuma’s mathematical model, and also conducted sensitivity analysis to determine the requirements for the introduction of a population-based screening. As the result, the incremental cost for one life-year saved was one million yen or lower when the costs of the screening were 8,000 and 6,000 yen and the recall rate was 10% for male and female smokers aged 55 to 59 years old, respectively. The recall rate was smaller when the interval between cancer screenings was two years, and the subjects were males. The higher the age of the subject, the smaller the incremental cost. In conclusion, at present, the mean cost of the LDCT test is approximately 10,000 yen in Japan. With a reduction in this cost by a few thousand yen, all Japanese smokers aged 55 to 74 years will be able to undergo LDCT screening for lung cancer annually

Integrated heart/cancer on a chip to reproduce the side effects of anti-cancer drugs in vitro

抗がん剤の副作用を生体外で再現するデバイス「ボディ・オン・チップ」の開発に成功. 京都大学プレスリリース. 2017-07-31.Pre-clinical animal tests are used to assess drug efficacy and safety, but are limited by factors such as their suitability as a model for humans, robustness, cost, and ethical issues. While an organ-on-a-chip using human cells is promising for recapitulating human physiological conditions, it is highly desirable in investigations of the side effects of drugs to integrate more than one type of tissue using a designed circulatory system. We have developed a microfluidic device—an Integrated Heart/Cancer on a Chip (iHCC)—using human healthy heart cells (hCMs) and liver cancer cells (HepG2) to recapitulate the side effects of an anti-cancer drug, doxorubicin (DXR), to achieve individual cultures of cells from different tissues on a single device with three sets of artificial blood circulation loops, microfabrication technology for micro valves and a pump provides accurate fluid operation. Using improved soft lithography adopting numerical optimization simulation, the microfluidic device was fabricated with on-chip integration of pneumatic valves and a peristaltic micropump establishing precision fluid flow. The iHCC developed allows modelling of the side effects of DXR on heart cells caused by the production of toxic metabolites (doxorubicinol; DXRol) by HepG2 cells and the delivery of DXRol to heart cells via the circulation loop. Our findings open the door towards the development of a “Body-on-a-Chip.

Evaluation of selective competitive binding of basic drugs to α1-acid glycoprotein variants

金沢大学医薬保健研究域薬学系We examined the binding of various basic drugs to the F1S and A genetic variants of α1-acid glycoprotein (AGP), which were isolated from native human commercial AGP (total AGP) by chromatography on an immobilized copper(II) affinity adsorbent. The values of the dissociation constant (Kd) of some basic drugs with the F1S variant in equilibrium dialysis differed characteristically from those with the A variant. The selective binding to these variants was evaluated by measuring the displacement ratio of dicumarol bound to the F1S variant or that of acridine orange bound to the A variant, using circular dichroism spectroscopy. There was reasonably good agreement between the Kd values and displacement ratios. There was a characteristic difference between the values of inhibition constant (Ki) of basic drugs towards dipyridamole binding to F1S and towards disopyramide binding to A in total AGP. We found that the Ki values for dipyridamole binding were well correlated with the Kd values for the F1S variant, whereas those for disopyramide binding were well correlated with the Kd values for the A variant. In conclusion, the higher the affinity of basic drugs for AGP, the more they inhibit the binding of other basic drugs, and further, the inhibitory potency depends on the selectivity of binding to the AGP variants. © 2010 Pharmaceutical Society of Japan

Comparison of Psychological Quality of Life Between Long-term Survivors of Childhood Cancer and Their Families

[Purpose:] Although treatment outcomes for childhood cancer have improved in recent years, some patients continue to experience physical symptoms and psychological stress several years after the end of treatment. This study aimed to examine the correlation between the quality-of-life (QOL) scores of childhood cancer survivors (CCSs) aged 18–39 and (1) their families and (2) the time since the end of treatment. [Methods:] Measuring the QOL of CCSs attending the long-term follow-up (LTFU) and those of their families. The Short-Form Health Survey (SF-36) was used for CCSs and the Caregiver Quality of Life Index-Cancer (CQOLC) for their families. Spearman's rank correlation analyses were used to examine the relationship between the CCSs' and their families' QOL and the time since the end of treatment. [Results:] Twenty-nine CCSs (mean age, 24.2 years; mean the time since the end of treatment, 13.9 years), each paired with one family member, were included. Time since the end of treatment was positively correlated with the CCSs' QOL on the physical component score (ρ = 0.42, p = 0.03) and negatively correlated with mental health (MH) (ρ = −0.50, p = 0.01), a subscale of the mental component score (MCS). Furthermore, the CCSs' QOL on the MCS was positively correlated with their families' QOL scores (ρ = 0.58, p < 0.01). [Conclusion:] Psychological stress may persist in CCSs long after treatment, even when physical symptoms improve. Therefore, it is necessary to establish a comprehensive support system for the LTFU of CCSs, including MH care and QOL monitoring for patients and their families