Reversibility of dopamine receptor antagonist-induced hyperprolactinemia and associated histological changes in Tg RasH2 wild-type mice

The purpose of this study was to better understand the biological effects of increased prolactin levels induced in mice by dopamine D₂ receptor antagonist molindone treatment. Toxicokinetics, prolactin levels, and reproductive tissue histology were evaluated in Tg rasH2 wild-type mice treated orally with molindone at 0, 5, 15, and 50 mg/kg/day for 6 months, followed by a 2-month posttreatment recovery period. A greater than dose-proportional increase in molindone exposure ([AUC]_0 ‒ 24) was observed on Day 180 for both sexes. Statistically significant (P < 0.01) increases in prolactin levels were observed in most treatment groups compared with controls at 0.5 h postdose on Days 1 and 180. Prolactin levels returned to baseline levels during the recovery period. Microscopic changes attributable to hyperprolactinemia, including corpora lutea enlargement and interstitial cell atrophy in the ovaries, and atrophy of the uterus and vagina were observed on Day 180. These changes were reversed during the recovery period in the 5- and 15-mg/kg/day treatment groups. Mice receiving molindone at 50 mg/kg/day also showed signs of reversal on histologic examination.     

临床路径管理实施过程中的障碍原因与处置对策研究

目的探讨临床路径管理实施过程中的障碍原因及处置对策。方法回顾性分析医院2013年8-12月进入临床路径管理的282例患者(病种为胆囊结石腹腔镜胆囊切除术、慢性鼻-鼻窦炎、2型糖尿病)的完整临床资料,按照是否顺利完成临床路径管理分为两组,观察组140例均顺利完成临床路径,对照组142例未顺利完成临床路径,统计分析临床路径实施障碍原因,总结处置对策。结果观察组患者年龄显著小于对照组,文化程度显著优于对照组,自费者显著高于对照组,2型糖尿病患者病程显著短于对照组,差异均具有统计学意义(均P<0.05);多因素分析显示,年龄大、文化程度低、医保就医及2型糖尿病病程长是临床路径管理实施障碍的原因,差异均具有统计学意义(均P<0.05)。结论针对年龄大、文化程度低、医保就医及2型糖尿病病程长等临床路径实施障碍原因,可加强健康教育、心理干预及康复指导,保证临床路径顺利实施。     

Screening for Gaucher Disease Using Dried Blood Spot Tests: A Japanese Multicenter,Cross-sectional Survey

Objective For patients with Gaucher disease (GD), a rare, inherited lysosomal storage disease, obtaining a definitive diagnosis is currently time-consuming and costly. A simplified screening method to measure the glucocerebrosidase (GBA) activity using dried blood spots (DBS) on filter paper has recently been developed. Using this newly developed screening method, we evaluated real-world GD screening in patients suspected of having GD. Methods This multicenter, cross-sectional, observational study with a diagnostic intervention component evaluated real-world screening in patients suspected of having GD based on their clinical symptoms and a platelet count <120,000/μL. The endpoint was the number of patients with low GBA activity determined using DBS. Results In 994 patients who underwent initial DBS screening, 77 had low GBA activity. The assay was not repeated in 1 patient who was diagnosed as having a high possibility of GD due to clinical symptoms, and a further 21 patients completed the study without undergoing the second assay. Of the remaining 55 patients who had 2 DBS assays performed, 11 had a low GBA activity in both assays. Overall, DBS screening identified 12 (1.2%) patients with a low GBA activity, a proportion consistent with prior screening studies. Conclusion These results suggest that the simplified DBS method was less burdensome to patients, was easily utilized by many physicians, and could be a useful first-tier screening assay for GD prior to initiating burdensome genetic testing.     

Aplastic Anemia in a Patient with Cronkhite-Canada Syndrome

Cronkhite-Canada syndrome (CCS) is a rare polyposis disorder accompanied by alopecia and onychodystrophy. A 63-year-old man with a history of CCS and repeated embolism developed progressive thrombocytopenia and mild anemia. Laboratory testing, a bone marrow examination, and magnetic resonance imaging of the spine resulted in a diagnosis of concurrent aplastic anemia (AA). Paroxysmal nocturnal hemoglobinuria (PNH)-type cells were detected in a peripheral blood specimen. In addition, human leukocyte antigen (HLA) included DRB1*15:01 and DRB1*15:02. Mesalazine was discontinued in consideration of possible drug-induced pancytopenia. Immunosuppressive therapy ameliorated both the gastrointestinal symptoms of CCS and pancytopenia. A common autoimmune abnormality might underlie both CCS and AA.