A successfully repaired case of methicillin-resistant Staphylococcus aureus infective endocarditis in a girl with VSD

We report a successful case of active infective endocarditis due to Methicilin-Resistant Staphylococcus aureus (MRSA). A 2-year-old girl who had a ventricular septal defect (VSD) complained of persistent fever. Echocardiography showeda large vegetation on the tricuspid valve and a small VSD. She underwent vegetectomy, tricuspid valvoplasty and direct closure of VSD. Vancomycin treatment was also effective to abolish infection. She was discharged without any complication.     

Fat-suppressed T2-weighted MR imaging of hepatocellular carcinoma and metastases: comparison of conventional spin-echo, fast spin-echo, and echoplanar pulse sequences.

The purpose of our study was to compare the diagnostic accuracy of fat-suppressed T2-weighted magnetic resonance (MR) images obtained with conventional spin-echo (SE), respiratory-triggered fast SE, and breath-hold multishot SE echoplanar (EP) sequences for the detection of hepatocellular carcinoma and metastases. Images obtained with the three sequences in 17 patients (15 with cirrhosis) with 31 hepatocellular carcinomas and 14 patients with 45 metastases were retrospectively analyzed. Image review was conducted on a segment-by-segment basis; in all, 248 liver segments were reviewed separately and independently for detection of solid, malignant lesions. Diagnostic accuracy was evaluated with receiver-operating-characteristic (ROC) curve analysis. Diagnostic accuracy for hepatocellular carcinoma as determined by ROC curve analysis was better by a statistically significant amount for conventional SE (Az = 0.95) images when compared with respiratory-triggered fast SE (Az = 0.83, P < 0.05) and breath-hold multishot SE EP (Az = 0.80, P < 0.05) images. Conventional SE MR sequences should not be replaced with respiratory-triggered fast SE or breath-hold multishot SE EP sequences for T2-weighted MR imaging of patients with hepatocellular carcinoma in cirrhosis, unless sufficient contrast-enhanced dynamic MR imaging is subsequently performed.     

Characteristics of adrenocortical function,gastrin release and gastric secretion in duodenal ulcer etiology

Measurements of serum cortisol and gastrin along with gastric acid-pepsin secretion in the resting state were carried out in gastric and duodenal ulcer patients. Increased basal corticosteroid concentrations were observed in patients with duodenal ulcer and gastric ulcer. Higher concentrations of the hormone were observed in the former group (P<0.05 for the latter). Fasting gastrin levels were significantly higher in gastric ulcer patients where gastric secretion is low than those in duodenal ulcer patients (P<0.001). These results suggest that the effect of adrenal cortical hormone on lowering the threshold of oxyntic gland cell reactivity against gastrin is an important factor in duodenal ulcer etiology. Extra-antral control mechanism(s) of gastric acid-pepsin secretion should not be overlooked. Presented at the 78th Annual Meeting of the Japan Surgical Society in Fukuoka, Japan in 1978 and the 6th World Congress of Gastroenterology in Madrid, Spain in 1978.     

A safety, pharmacokinetic and pharmacodynamic investigation of deferasirox (Exjade®, ICL670) in patients with transfusion-dependent anemias and iron-overload: a Phase I study in Japan

The pharmacokinetics (PK) and pharmacodynamics (PD) of the once-daily, oral ironchelating agent, deferasirox (Exjade((R)), ICL670), have been evaluated further in a Phase I, openlabel, multicenter, dose-escalation study in Japanese patients with myelodysplastic syndromes, aplastic anemia, and other anemias. Deferasirox was initially administered as a single dose of 5 (n = 6), 10 (n = 7), 20 (n = 6) or 30 (n = 7) mg/(kg day) and then after 7 days seven daily doses were administered. Linear PK (C (max) and AUC) were observed at all doses after a single dose and at steady state, and dose-dependent iron excretion was observed. Pharmacokinetic/pharmacodynamic parameters were similar to those reported in a Caucasian beta-thalassemia cohort. Following the single- and multiple-dose phases, 21 of 26 patients progressed to a 3-year extension phase of the study, where dose reductions and increases [5-30 mg/(kg day)] were allowed following safety and efficacy assessments. In the interim, 1-year data show that deferasirox was well tolerated, with generally infrequent and mild adverse events. Reductions in serum ferritin levels were observed and a negative iron balance achieved at doses of 20-30 mg/(kg day). These data suggest that deferasirox has a stable and predictable PK/PD profile, irrespective of underlying disease or race, and a predictable and manageable safety profile suitable for chronic administration.     

Clinicopathological study of nonalcoholic fatty liver disease in Japan: the risk factors for fibrosis

Background/Aims: We evaluated patients with nonalcoholic fatty liver disease (NAFLD) and compared the clinical and pathological features to identify the risk factors for NAFLD with severe fibrosis. Methods: One hundred and eighty‐two patients with biopsy‐confirmed NAFLD from various medical centres were recruited into this study. Results: The variables that were significantly associated with severe steatosis were male gender (mild:severe=36%:53%, P=0.02), younger age (mild:severe=57%:82%, P>0.001) and absence of type 2 diabetes (mild:severe=43%:71%, P>0.001). There was no significant difference in the degree of inflammation among the clinical groups. The variables that were significantly associated with severe fibrosis were female gender (mild:severe=54%:84%, P=0.002), older age (≥60 years old) (mild:severe=29%:53%, P=0.020), type 2 diabetes (mild:severe=42%:71%, P=0.020) and hypertension (mild:severe=24%:53%, P=0.002). Although there were more obese patients in the group with severe fibrosis, the association was not statistically significant (mild:severe=67%:78%, P=0.229). The prevalence of high serum triglyceride levels was similar between the two groups. The N (Nippon) score (total number of risk factor) could significantly predict severe fibrosis in NAFLD patients (1.48 ± 1.14 vs. 2.66 ± 0.94, P<0.001). Conclusions: The N score can be used to predict severe fibrosis in cases of NAFLD.     

Alpha1-adrenoceptor-mediated breakdown of phosphatidylinositol 4,5-bisphosphate inhibits pinacidil-activated ATP-sensitive K+ currents in rat ventricular myocytes

Phosphatidylinositol 4,5-bisphosphate (PIP2) stimulates ATP-sensitive K+ (K(ATP)) channel activity. Because phospholipase C (PLC) hydrolyzes membrane-bound PIP2, which in turn may potentially decrease K(ATP) channel activity, we investigated the effects of the alpha1-adrenoceptor-G(q)-PLC signal transduction axis on pinacidil-activated K(ATP) channel activity in adult rat and neonatal mouse ventricular myocytes. The alpha1-adrenoceptor agonist methoxamine (MTX) reversibly inhibited the pinacidil-activated K(ATP) current in a concentration-dependent manner (IC50 20.9+/-6.6 micromol/L). This inhibition did not occur when the specific alpha1-adrenoceptor antagonist, prazosin, was present. An involvement of G proteins is suggested by the ability of GDPbetaS to prevent this response. Blockade of PLC by U-73122 (2 micromol/L) or neomycin (2 mmol/L) attenuated the MTX-induced inhibition of K(ATP) channel activity. In contrast, the MTX response was unaffected by protein kinase C inhibition or stimulation by H-7 (100 micro mol/L) or phorbol 12,13-didecanoate. The MTX-induced inhibition became irreversible in the presence of wortmannin (20 micro mol/L), an inhibitor of phosphatidylinositol-4 kinase, which is expected to prevent membrane PIP2 replenishment. In excised inside-out patch membranes, pinacidil induced a significantly rightward shift of ATP sensitivity of the channel. This phenomenon was reversed by pretreatment of myocytes with MTX. Direct visualization of PIP2 subcellular distribution using a PLCdelta pleckstrin homology domain-green fluorescent protein fusion constructs revealed reversible translocation of green fluorescent protein fluorescence from the membrane to the cytosol after alpha1-adrenoceptor stimulation. Our data demonstrate that alpha1-adrenoceptor stimulation reduces the membrane PIP2 level, which in turn inhibits pinacidil-activated K(ATP) channels.