Relationship between preoperative radial artery and postoperative arteriovenous fistula blood flow in hemodialysis patients

Background: It is recommended that arteriovenous fistula (AVF) blood flow should be more than 425 ml/min before cannulation. However, the relationship between preoperative radial artery flow (RAF) and postoperative AVF blood flow has still not been examined. Methods: Sixty-one patients with end-stage kidney disease (ESKD) were examined. They had an AVF prepared at Juntendo University Hospital from July 2006 through August 2007. Preoperative RAF and postoperative AVF blood flows were measured by ultrasonography. Results: AVF blood flow gradually increased after the operation. AVF blood flow was significantly correlated with preoperative RAF. When preoperative RAF exceeded 21.4 ml/min, AVF blood flow rose to more than 425 ml/min. The postoperative AVF blood flow in the group with RAF of more than 20 ml/min was significantly higher than that in those with less than 20 ml/min. Preoperative RAF of less than 20 ml/min had a significantly high risk of primary AVF failure within 8 months compared with that of more than 20 ml/min. Conclusions: It appears that measurement of RAF by ultrasonography is useful for estimating AVF blood flow postoperatively and can predict the risk of complications in ESKD patients.     

Development and evaluation of FSSG: frequency scale for the symptoms of GERD

Background The aim of this study was to produce a simplified questionnaire for evaluation of the symptoms of gastroesophageal reflux disease (GERD).Methods A total of 124 patients with an endoscopic diagnosis of GERD completed a 50-part questionnaire, requiring only yes or no answers, that covered various symptoms related to the upper gastrointestinal tract, as well as psychosomatic symptoms. The 12 questions to which patients most often answered yes were selected, and were assigned scores (never = 0; occasionally = 1; sometimes = 2; often = 3; and always = 4) to produce a frequency scale for symptoms of GERD (FSSG). Sensitivity, specificity, and accuracy of the FSSG questionnaire were evaluated in another group of patients with GERD and non-GERD. The usefulness of this questionnaire was evaluated in 26 other GERD patients who were treated with proton pump inhibitors for 8 weeks.Results When the cutoff score was set at 8 points, the FSSG showed a sensitivity of 62%, a specificity of 59%, and an accuracy of 60%, whereas a cutoff score of 10 points altered these values to 55%, 69%, and 63%. The score obtained using the questionnaire correlated well with the extent of endoscopic improvement in patients with mild or severe GERD.Conclusions This new questionnaire is useful for the objective evaluation of symptoms in GERD patients.     

Class IA phosphatidylinositol 3‐kinase regulates osteoclastic bone resorption through protein kinase B–mediated vesicle transport

Class IA phosphatidylinositol 3‐kinases (PI3Ks) are activated by growth factor receptors and regulate a wide range of cellular processes. In osteoclasts, they are activated downstream of α_vβ₃ integrin and colony‐stimulating factor‐1 receptor (c‐Fms), which are involved in the regulation of bone‐resorbing activity. The physiological relevance of the in vitro studies using PI3K inhibitors has been of limited value, because they inhibit all classes of PI3K. Here, we show that the osteoclast‐specific deletion of the p85 genes encoding the regulatory subunit of the class IA PI3K results in an osteopetrotic phenotype caused by a defect in the bone‐resorbing activity of osteoclasts. Class IA PI3K is required for the ruffled border formation and vesicular transport, but not for the formation of the sealing zone. p85α/β doubly deficient osteoclasts had a defect in macrophage colony‐stimulating factor (M‐CSF)–induced protein kinase B (Akt) activation and the introduction of constitutively active Akt recovered the bone‐resorbing activity. Thus, the class IA PI3K‐Akt pathway regulates the cellular machinery crucial for osteoclastic bone resorption, and may provide a molecular basis for therapeutic strategies against bone diseases. © 2013 American Society for Bone and Mineral Research.     

Phase II study of paclitaxel (BMS-181339) intravenously infused over 3 hours for advanced or metastatic breast cancer in Japan

A Phase II study of paclitaxel in patients with primary advanced or metastatic breast cancer was conducted by a cooperative study group consisting of 16 institutions in Japan. Paclitaxel at a dose of 210 mg/m2 was intravenously infused over 3 hours, along with premedication to prevent hypersensitivity reactions. The course was repeated at 21-day intervals. Of 62 eligible patients, 60 were evaluable for toxicity and 59 were evaluable for efficacy. Forty-five patients were previously treated with anthracyclines. Twenty-one of 59 patients (35.6%) had a major objective response including 2 CRs and 19 PRs (95% confidence interval, 23.6–49.1%). A response rate of 35.5% (CR1, PR10) was observed in 31 patients refractory to the anthracyclines containing prior metastatic chemotherapy. Median (range) time was 41 (6–100) days to onset of and median duration of response was 125 (36–305) days. Toxicities included leukopenia (grade 3, 4: 67%), anemia (grade 1–3: 80%), thrombocytopenia (grade 1: 8%), alopecia (grade 3: 43%), peripheral neuropathy (grade 1–3: 93%), arthralgia (59%), myalgia (46%), nausea and vomiting (40%), fever (33%), allergic reaction (grade 3: 2%) and hypotension (grade 3: 5%). All toxicities were tolerable and manageable. Paclitaxel intravenously infused over 3 hours demonstrated a significant antitumor activity for metastatic breast cancer. Furthermore, paclitaxel exhibited non-cross resistance to anthracycline. Paclitaxel administered as a convenient 3-hour infusion is effective for patients with metastatic breast cancer and has an acceptable toxicity profile.     

Positron emission tomography with 4-[18F]fluoro-L-m-tyrosine in MPTP-induced hemiparkinsonian monkeys

PET imaging studies with 4-[¹⁸F]fluoro-L-m-tyrosine (FMT) in normal macaca monkeys showed selective accumulations of radioactivity in the striatum with time. In monkeys rendered hemiparkinsonian by intracarotid infusion of l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP), FMT uptake was eliminated in the lesioned striatum. FMT-PET studies were able to detect dopaminergic terminals in both normal and hemiparkinsonian monkeys, and clearly showed a reduction in aromatic L-amino acid decarboxylase (AAAD) activities in the MPTP-lesioned striatum. These results show that FMT is promising as a PET tracer for the evaluation of central dopaminergic systems in parkinsonism.