A long-surviving patient with recurrences of hepatic alveolar echinococcosis after traumatic intra-abdominal rupture

Alveolar echinococcosis of the liver (AEL) takes a progressive and malignant course. Intra-abdominal dissemination of the parasite has a miserable outcome. Complete resection of the lesion is indispensable for the curative treatment of AEL. We experienced an extremely rare case of intra-abdominal rupture of AEL. The patient had repeated recurrences of AEL following the traumatic rupture of the lesion. After repeated resections of the lesions and appropriate medication, the patient is still alive more than 25 years since the initial onset of the disease. AEL differs from unilocular echinococcosis in terms of biological behavior. We compare the pathophysiology of the two conditions.     

Regular insulin,rather than rapid‐acting insulin,is a suitable choice for premeal bolus insulin in lean patients with type 2 diabetes mellitus

The aim of the present study was to compare the usefulness of premeal rapid‐acting and regular insulin in type 2 diabetes patients. A total of 56 type 2 diabetic patients were investigated during hospitalization. Premeal rapid‐acting insulin was applied instead of other medications. Premeal insulin was titrated to adjust premeal and bedtime blood glucose levels to 81–120 mg/dL. Premeal rapid‐acting insulin was changed to regular insulin just before a meal at the same dosage if the postmeal blood glucose level was lower than the premeal blood glucose level. A total of 15 patients changed to regular insulin, and 41 patients continued rapid‐acting insulin. The blood glucose level was comparable between these two groups. Body mass index was significantly lower in the patients using regular insulin. According to the multivariate logistic regression analysis, low body mass index was an independent variable accounting for the usefulness of regular insulin. Regular insulin, rather than rapid‐acting insulin, is a suitable choice for premeal insulin in lean type 2 diabetic patients.     

Serum monitoring of methotrexate (MTX) and 7-hydroxymethotrexate concentrations in patients treated with MTX using high-pressure liquid chromatography (HPLC) and comparison of serum MTX levels between HPLC method and fluorescence polarization immunoassay (FPIA)

In order to measure simultaneously the serum levels of methotrexate (MTX) and its major metabolite, 7-hydroxymethotrexate (7-OH-MTX), in samples obtained from patients treated with MTX, we have investigated the reversed-phase high-pressure liquid chromatographic assay using ion-pairing reagents. The mobile phase consisted of 77.5% solution of 0.005M tetrabutylammonium and 22.5% acetonitrile. SEP-PAK C18 Cartridges were used for the precolumn. The detectable range of MTX and 7-OH-MTX were 0.02-0.03 and 1.0 mumol/l respectively. A significant positive correlation was observed (r = 0.983) between FPIA and HPLC methods. Serum MTX levels with FPIA were significantly (p less than 0.05) higher than those of HPLC method. The serum 7-OH-MTX levels at 24 hr and 48 hr were 4.857 +/- 1.383 (n = 10) and 1.835 +/- 0.286 (n = 6) mumol/l respectively with the dosage of 400 mg/m2. The serum 7-OH-MTX levels at 48 hr were 6.254 +/- 3.053 mumol/l (n = 5) with the dosage of 3,000 mg. The serum half lives of MTX and 7-OH-MTX were 8.05 +/- 1.03 (n = 4) and 14.8 +/- 1.35 (n = 6) hours respectively between 24 hr and 48 hr after administration. The T1/2 7-OH-MTX/MTX ratio was 1.8. Percent cross-reactivity of 7-OH-MTX with concentrations ranging from 1-10 mumol/l were 0.6-2.0% by FPIA. However, patients' serum levels of 7-OH-MTX were 15-85 times (n = 21) higher than those of MTX. MTX levels of containing both MTX and 7-OH-MTX (7-OH-MTX/MTX ratio was 50/1) were significantly higher than those of containing MTX alone by FPIA.     

Subepicardial aneurysm following ventriculotomy closure of ventricular septal rupture due to ccute myocardial infarction

We report an unusual case of subepicardial aneurysm (SEA) of the left ventricle. An 82-year-old man had undergone patch closure of a ventricular septal rupture due to anterior acute myocardial infarction. A postoperative left ventriculogram showed the presence of contrast medium outside the left ventricle, and urgent surgery was performed. The lesion was diagnosed as SEA, and was repaired before rupture.     

Poor responsiveness of heart rate to treadmill exercise in vasospastic angina

Heart rate response to submaximal graded treadmill exercise was measured in 45 patients with vasospastic angina, 31 with effort angina, and 40 normal controls. There was no difference of resting heart rate among the three groups. Vasospastic angina showed significantly poor responsiveness of heart rate to exercise at every stage: stage 1, 2.5 km/h (10%), stage 3, 4.5 km/h (10%), stage 5, 5.5 km/h (14%), stage 7, 5.5 km/h (22%), when compared with those in normal controls. The effort angina group also showed lower heart rates at stages 3 and 5 than those in control subjects, although their heart rate at stage 1 was not different from that in normals. When abnormal response suggesting vasospastic angina was defined as heart rate at each stage lower than values of mean heart rate +/- 1 SD in normal controls, positive test results were obtained in 15 of 45 patients (33%). The use of heart rate criteria in addition to ischemic criteria raises sensitivity from 27 to 51% (p less than 0.02).     

YM-201627: an orally active antitumor agent with selective inhibition of vascular endothelial cell proliferation

We developed an oral administration-compatible, small molecular weight antitumor agent, YM-201627 by screening for the inhibition of the proliferation of VEGF-stimulated HUVECs. YM-201627 selectively inhibited the proliferation of various endothelial cell lines induced by VEGF, bFGF, and FBS (at IC50s of 0.0039-0.12 microM), that would not be expected to have any direct antiproliferative effect on other cell types. YM-201627 inhibited angiogenesis in vitro at a concentration of 0.01 microM. In the in vivo studies, it inhibited microvessel formation induced by human melanoma A375 cells suspended in Matrigel (86% with twice-daily doses of 30 mg/kg). Moreover, once-daily oral dosing of YM-201627 to mice bearing A375 xenografts elicited significant antitumor activity (73% with daily doses of 10 mg/kg). These results suggest that YM-201627 is a selective growth inhibitor of endothelial cells, which may be useful for treatment of solid tumors.     

YM-231146, a novel orally bioavailable inhibitor of vascular endothelial growth factor receptor-2, is effective against paclitaxel resistant tumors

Chemotherapy using anticancer drugs induces serious the problem of multidrug resistance (MDR) in the cancer cells. In contrast, endothelial cells so rarely acquire MDR that antiangiogenesis therapy has recently been considered as an effective means for cancer chemotherapy. We screened compounds in the chemical library to find a novel and orally active antitumor agent with vascular endothelial growth factor receptor-2 tyrosine kinase (VEGF-R2 TK) inhibition. The result was YM-231146 (IC50=0.080 microM). YM-231146 inhibited VEGF-stimulated proliferation, VEGF-R2 autophosphorylation, and vessel sprout formation of human vascular endothelial cells at concentrations between 0.15-0.30 microM. However, YM-231146 did not inhibit cancer cell proliferation at these concentrations (IC50>5 microM). In the in vivo studies, once-daily oral dosing of YM-231146 to human cancer xenografts elicited antitumor activity at doses of 3-100 mg/kg. Moreover, YM-231146 completely inhibited tumor growth of paclitaxel-resistant cancer cells without decreasing body weight at a dose of 100 mg/kg. These results suggest that YM-231146 is a novel orally bioavailable inhibitor of VEGF-R2 that would be useful for the treatment of multidrug resistant tumors.     

Disinfection of water of remove Legionella species: evaluation of an antimicrobial ceramic

To evaluate the efficacy of an antimicrobial ceramic for killing Legionella strains in vitro, bacteria were exposed to the ceramic soaked in PBS at 25 degrees C or 42 degrees C. The number of L. pneumophila began to decrease significantly after 4 h of exposure at 25 degrees C and reached < 10 log cfu/ml after 12 h. A similar significant decrease was also observed after exposure at 42 degrees C. Furthermore, it was found that the antimicrobial ceramic showed bactericidal activity against six strains of Legionella isolated from various water sources, including L. pneumophila (serotype 1-4), L. micdadei, and L. dumoffii, after 24 h of exposure. The antimicrobial activity against L. pneumophila of the supernatant obtained by soaking the ceramic in PBS for 24 h was also assessed. Bactericidal activity of this supernatant was also noted. Analysis of the supernatant by ICP-MS resulted in the detection of eight metals (Mg, Al, Ca, Mn, Zn, Sr, Ag, and Ba) at a maximum concentration of 2.5 mg/l. When reconstituted PBS was made with all eight metals at the same concentrations as in the supernatant, the reconstituted PBS containing Ag alone and all metals showed significantly bactericidal activity against L. pneumophila, but PBS with only one metal component except Ag or a combination of Ag with Zn and/or Ca did not. These findings suggest that the antimicrobial ceramic possesses strong bactericidal activity against Legionella species and that eight metals released from the ceramic have a synergistic bactericidal effect against Legionella. When the antimicrobial ceramic was placed in hot spring water or cooling tower water instead of PBS, the number of L. pneumophila in the water decreased to < 10 log cfu/ml after 24 h of exposure and the bactericidal activity persisted for 5 weeks. These results indicate that the antimicrobial ceramic can be used to eradicate Legionella species contaminating various water sources.