Factors Predicting Long-term Responses to Splenctomy in Patients with Idiopathic Thrombocytopenic Purpura

Background Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder for which appropriate diagnostic treatments are uncertain. The response to splenectomy varies from 60% to 90%, and the remaining patients relapse and require further treatment. Therefore, it is important to predict the outcome of splenectomy before and after surgery. The objective of this study was to evaluate the efficacy of splenectomy in patients diagnosed with ITP. Materials and Methods From 1988 to 2004, we splenectomized 32 patients with ITP; 17 underwent laparoscopic splenectomy (LS) and 15 underwent conventional open splenectomy (OS). For analysis, patients were separated retrospectively into two groups: the “responding group,” those who showed good outcomes with splenectomy, and the “non-responding group,” those who did not show good outcomes with splenectomy. Blood samples were examined before and immediately after surgery (day 0) and on postoperative days (POD) 1, 3, 5, and 7. Results The median follow-up was 8.3 years (range: 1–16 years). The overall 5- and 10-year survival rates after splenectomy were 96.9% (one death). The responding group included 24 patients (75%), and the non-responding group included 7 (21.9%). Platelet counts in the responding group increased gradually until POD 7, and although platelet counts in the non-responding group were almost constant until POD 5, they subsequently decreased until POD 7. Average platelet counts in the responding and non-responding groups were 269 and 124 × 10⁹/l on POD 7, respectively (P < 0.05). The pre- to post-surgery ratio of platelet counts were almost the same as the result of the actual data. Platelet counts during the long-term follow-up for the responding and non-responding groups were related to those noted on discharge. Conclusions A high platelet count on POD 7 was associated with a good response to splenectomy, but age at surgery, the time interval between diagnosis and splenectomy, and prior responses to corticosteroid were not. We suggest that long-term outcomes of splenectomy can easily be predicted by platelet counts on POD 7.     

Evaluation and related factors in coronary artery calcification in chronic dialysis patients

Electron beam CT (EBCT) has been used to measure coronary artery calcification score (CACS). We have been studied CACS on chronic dialysis patients and examined the relationship between CACS and laboratory variables, incidence of ischemic heart disease, and survival. High CACS is often observed in patients with high serum phosphate, high calcium phosphate product, and dyslipidemia. Several factors for calcification both stimulating and suppressing have been playing a role in chronic dialysis patients. CACS is a surrogate marker of adequate control of uremia.     

Cellular mechanism for herbal medicine Junchoto to facilitate intestinal Cl<Superscript>−</Superscript>/water secretion that involves cAMP-dependent activation of CFTR

Constipation is a common symptom frequently compromising the quality of daily life. Several mechanistically different drugs have been used to mitigate constipation, including Japanese herbal (Kampo) medicines. However, the mechanisms of their actions are often not well understood. Here we aimed to investigate the molecular mechanisms underlying the effects of Junchoto (JCT), a Kampo medicine empirically prescribed for chronic constipation. Cl^? channel activity was measured by the patch-clamp method in human cystic fibrosis transmembrane conductance regulator (CFTR)-expressing HEK293T cells and human intestinal Caco-2 cells. cAMP was measured by a luciferase-based assay. Cell volume change was measured by a particle-sizing and particle-counting analyzer and video-microscopic measurement. In both CFTR-expressing HEK293T and Caco-2 cells, JCT dose-dependently induced whole-cell currents showing typical biophysical and pharmacological features of CFTR. Robust expression of CFTR was confirmed by RT-PCR and Western blotting in Caco-2 cells. Luciferase-based measurement revealed that JCT increases intracellular cAMP levels. Administration of the adenylate cyclase inhibitor SQ22536 or CFTR inhibitor-172, or treatment with small interfering RNAs (siRNA) targeting CFTR, abolished JCT-induced whole-cell currents, suggesting that elevated intracellular cAMP by JCT causes activation of CFTR in Caco-2 cells. Finally, blockade of CFTR activity by CFTR inhibitor-172 or siRNA-knockdown of CFTR or application of SQ22536 markedly reduced the degree of cell volume decrease induced by JCT. JCT can induce a Cl^? efflux through the CFTR channel to promote water secretion, and this effect is likely mediated by increased cAMP production.     

Cytological findings of ROS1‐rearranged lung adenocarcinoma

ROS1‐rearranged lung adenocarcinoma has been recently identified. We report a case of ROS1‐rearranged lung adenocarcinoma with special emphasis on cytological findings. Here, we report a case of young woman with ROS1‐rearranged lung adenocarcinoma diagnosed by cytology and discuss the clinical, cytological, and molecular findings. Cytologically, the tumor consisted of small tight clusters of cells with high nuclear/cytoplasmic ratio. Nuclei were enlarged and small nucleoli were occasionally observed. Signet‐ring cells were focally identified. Neoplastic cells were positive for ROS1 immunocytochemistry. Subsequently, the translocation of ROS1 gene was confirmed in a histological specimen. In conclusion, the specific histology of adenocarcinoma on cytological materials should promote testing for ROS1 immunohistochemistry. Immunocytochemical detection of ROS1 protein helps identify patients suitable for molecular targeted therapy.     

Perfectionism underlying psychological background correlated with the symptoms of functional dyspepsia

BACKGROUNDS: Early satiety, bloating, and postprandial distress are common symptoms in patients with functional dyspepsia (FD) and anorexia nervosa (AN). Perfectionism is known to be associated with AN, accompanied by abnormal eating behavior. We analyzed perfectionism in FD as compared with that in AN, and investigated the correlation of perfectionism with abdominal symptoms. METHODS: The study group comprised 168 patients with FD according to the Rome II criteria (65% females, mean age 47.7 years) and 101 with AN according to the DSM-IV criteria (100% females, mean age 23 years). As control, 130 healthy subjects (81% females, mean age 26.2 years) were studied. Frost's Multidimensional Perfectionism Scale (FMPS) was used to evaluate perfectionism. Abdominal symptoms were evaluated on the Gastrointestinal Symptoms Rating Scale (GSRS). RESULTS: All subscale scores except for organization were significantly higher in patients with AN than in controls. The parental criticism (PC) score in patients with FD was also significantly higher than that in controls, but lower than that in patients with AN. PC was significantly correlated with the total GSRS, particularly indigestion scores of FD patients (P = 0.0476 and P = 0.0294). CONCLUSIONS: Perfectionism such as PC underlying the psychological background of FD patients may be correlated with their abdominal symptoms.     

Heterogeneity and potentiation of AMPA type of glutamate receptors in rat cultured microglia

alpha-amino-hydroxy-5-methyl-isoxazole-4-propionate (AMPA) receptor in rat cultured microglia were analyzed precisely using flop- and flip-preferring allosteric modulators of AMPA receptors, 4-[2-(phenylsulfonylamino)ethylthio]-2,6-difluoro-phenoxyacetamide (PEPA) and cyclothiazide (CTZ), respectively. Glutamate (Glu)- or kainite (KA)-induced currents were completely inhibited by a specific blocker of AMPA receptor, LY300164, indicating that functional Glu-receptors in cultured microglia are mostly AMPA receptor but not KA receptor in many cells. Glu- and KA-induced currents were potentiated by PEPA and CTZ in a concentration-dependent manner. The ratio of the potentiation by PEPA to the potentiation by cyclothiazide varied with cells between 0.1 and 0.9, suggesting cell-to-cell heterogeneity of AMPA receptor subunits expressed in microglia. Quantitative RT-PCR revealed that GluR1-3 mainly occurred in the flip forms, which agreed with the stronger potentiation of receptor currents by CTZ vs. PEPA. Finally, the potentiation of microglial AMPA receptors by PEPA and CTZ inhibited the Glu-induced release of tumor necrosis factor-alpha (TNF-alpha) unpredictably. The increase in TNF-alpha release by Glu or KA required extracellular Na+ and Ca2+ ions but not mitogen-activated protein kinase (MAPK), suggesting the effects of PEPA and CTZ were not due to the inhibition of MAPK. These results suggest that potentiation of microglial AMPA receptors serves as a negative feedback mechanism for the regulation of TNF-alpha release and may contribute to the ameliorating effects of allosteric modulators of AMPA receptors.