Antimicrobial activities of hydrophobic 2-arylbenzofurans and an isoflavone against vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus

Eight 2-arylbenzofurans and an isoflavone isolated from medicinal plants were tested for their antimicrobial activities against vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA). Among these compounds, six hydrophobic 2-arylbenzofurans (log P = 4.4-8.7) exhibited considerable antibacterial activity against five VRE strains(VanA-, VanB-, and VanC-phenotypes) (MICs = 3.13-6.25 microg/mL). Five compounds also showed antibacterial activity against ten MRSA strains (MIC80 = 3.13 microg/mL).     

Tumor-promoting activity and mutagenicity of 5 termiticide compounds

The tumor-promoting activities of 5 commercial compounds used in termiticides were measured by a cell-transformation assay employing Bhas 42 cells. Their initiating activities were also measured by the microsuspension assay employing S. typhimurium TA98 and TA100 strains. The results of the transformation assay confirmed the tumor-promoting activities of fenitrothion, silafluofen and bifenthrin. Furthermore, the mutagenicity of S-421 and fenitrothion were also confirmed. Consideration of 2-stage carcinogenesis suggests that concurrent use of and long-term exposure to these compounds that have tumor-promoting and initiator activity, and compounds exhibiting either type of activity individually should be avoided as much as possible.     

Analysis of 5'-end sequences of chimpanzee cDNAs

We constructed full-length enriched cDNA libraries from chimpanzee brain, skin, and liver tissues by the oligo-capping method to establish a database of sequences of chimpanzee genes. Randomly selected clones from the libraries were subjected to one-pass sequencing from their 5'-ends. As a result, we collected 6813 chimpanzee cDNA sequences longer than 400 bp. Homology search against human mRNA sequences (RefSeq mRNAs) revealed that our collection included sequences of 1652 putative chimpanzee genes. In order to calculate the sequence identity between human and chimpanzee homologs, we constructed 5'-end consensus sequences of 226 chimpanzee genes by aligning at least three sequences for individual genes. Sequence identity was estimated by comparing these consensus sequences and the corresponding sequences of their human homologs. The average sequence identity of the 5'-end cDNAs was 99.30%. Those of the 5'-UTRs and CDSs were 98.79% and 99.42%, respectively. The results confirmed that human and chimpanzee genes are highly conserved at the nucleotide level. As for amino acids, the average sequence identity was 99.44%. The average synonymous (K(S)) and nonsynonymous (K(A)) divergences were estimated to be 1.33% and 0.28%, respectively.     

Development of measure for disease-specific quality of life in patients with chronic heart failure

OBJECTIVES: To develop a measure for disease-specific health-related quality of life in patients with heart failure and examine its reliability and validity. METHODS: One hundred and four patients with stable chronic heart failure (74 males, 30 females, mean age 64.2 +/- 10.0 years) with left ventricular ejection fractions of less than 40% were enrolled in this study. Each patient responded to the Medical Outcomes Study Short Form 36 (SF-36) and a disease specific questionnaire comprising four categories (dyspnea, sleep, appetite and fatigue), each consisting of five to six questions. A stepwise exploratory factor analysis was applied to the disease-specific measure to consider categorical fitness. In 25 of the 104 patients, the data in the questionnaire were compared with peak oxygen uptake, anaerobic threshold, slope of the regression line relating the ventilatory equivalent to carbon dioxide output (VE/VCO2 slope) and peak work rate. Correlations between the questionnaire and eight components of SF-36 were evaluated. RESULTS: The appetite category proved unreliable and was excluded from consideration, so 12 questions were adopted from the other three categories. Cronbach's a values ranged from 0.68 to 0.89 and the coefficients of test-retest were from 0.84 to 0.94, so both internal consistency and reproducibility of these questions were considered excellent. The scores of three categories well reflected the severity of heart failure based in New York Heart Association functional class. The anaerobic threshold (r = 0.53), peak oxygen uptake (r = 0.66), VE/VCO2 slope (r = -0.48) and peak work rate (r = 0.41) correlated with the total score of the 12 questions. The total scores were closely correlated with the eight components of SF-36. CONCLUSIONS: This study suggests that the disease-specific questionnaire is applicable to evaluation of the health-related quality of life in patients with heart failure.     

Multiple enhancing lesions detected on dynamic helical computed tomography-mammography

OBJECTIVES: To review pathologic diagnoses of multiple enhancing lesions in a unilateral breast detected on dynamic helical computed tomography (CT)-mammography and to correlate imaging findings with pathologic results. METHODS: From May 1998 to July 2001, preoperative contrast-enhanced helical CT scanning of the breast was performed in 200 female patients clinically diagnosed with breast cancer. The patients were scanned in the prone position in a specially designed CT-compatible device, with rapid intravenous bolus injection of 100 mL contrast material. Three-dimensional maximum intensity projection images were reconstructed. The cases with multiple enhancing lesions in a unilateral breast were retrospectively reviewed. The maximum diameter of the largest stain in each breast was measured, the patterns of multiple enhancing lesions were classified, and imaging findings were correlated with surgical and pathologic outcomes. RESULTS: Twenty-five of 200 (12.5%) patients (age range: 39-86 years, mean age: 56 years) showed multiple stains on CT-mammography. Two patients showed multiple stains in bilateral breasts. The maximum diameter of the largest stain in each breast ranged from 5 to 55 mm (average: 22 mm). Among cases with multiple stains, 21 (78%) were shown to be invasive ductal carcinoma with multiple satellite cancer nodules. Four cases were ductal carcinoma in situ with multiple satellite nodules. One case revealed multiple fibroadenomas, and another showed intraductal papilloma. CONCLUSIONS: Multiple enhancing lesions on CT-mammography in patients with breast cancer were relatively common, and most of them represented multiple cancer lesions. Dynamic CT-mammography is potentially useful in evaluating the spread of breast cancer.     

Perioperative cerebral ischemia and the possibility of neuroprotection by inhalational anesthetics

Deteriorated neurological outcome is not rare after major surgeries. With aging of the surgical population in Japan, an increasing frequency of perioperative cerebral ischemia is expected. To avoid neurological deterioration after surgery and general anesthesia, especially in high-risk patients, it is important to provide appropriate CNS-oriented anesthesia management. Controlling factors such as cerebral perfusion pressure, arterial blood gases, blood glucose concentration and body temperature may influence brain metabolism and neurological outcome. Inhalational anesthetics may also play an important role in perioperative neurological management, because numerous studies have demonstrated some degree of neuroprotective effect with halothane, sevoflurane, desflurane and isoflurane. Among these inhalational anesthetics, isoflurane has been most extensively studied regarding neuroprotection against cerebral ischemic insult. Although no clinical outcome trials have been performed, both in vivo and in vitro studies have consistently shown that the isoflurane provides neuroprotection. However, it is also suggested that factors such as sympathetic reactivity, brain temperature, anesthetic dosage, timing of anesthetic administration, and co-administration of nitrous oxide might affect the neuroprotective effect of isoflurane.     

Postoperative recurrence of venous thromboembolism in patients with episodes of preoperative thromboembolism

BACKGROUND: Venous thromboembolism (VTE) has become a major health problem in Japan. METHODS: We examined, postoperative recurrence of VTE in patients with preoperative venous thromboembolic events and evaluated factors that are relevant to the occurrence of postoperative VTE. RESULTS: Forty-four cases out of 38500 had been diagnosed preoperatively as having VTE in the period of 1995-2001 at Kitasato University Hospital. Postoperative VTE was detected in four patients (9%) out of these 44 cases. Patients who had thrombophilia (antiphosholipid syndrome) or recent episode of VTE within 1 month were higher in the incidence of postoperative recurrence of VTE than the others. Temporary infra-vena cava filters were placed to prevent pulmonary thromboembolism in twelve patients. In 8 of the patients, thrombi were detected in or at the filter before explantation. Three patients (7%) had undergone thrombolysis therapy. Postoperative VTE was not found in patients who had already received anticoagulant therapy (warfarin) for 3 or more months. CONCLUSIONS: It is concluded that newly developed VTE occurred perioperatively in 9% of patients with preoperative VTE, and that thrombophilia and a recent episode of VTE were considered as risk factors of perioperative VTE. Temporary infra-vena cava filters are a valuable device for prevention of postoperative pulmonary thromboembolism.     

A case responding to weekly paclitaxel (TXL) therapy as third line chemotherapy for scirrhous type gastric cancer

A 67-year-old female was admitted to our hospital in May, 2001 for examination. She was diagnosed with advanced gastric cancer that was inoperable due to peritoneal dissemination. Seventeen courses of sequential MTX and 5-FU therapy, and 2 courses of TS-1 plus CDDP were carried out. A partial response (PR) and prolonged NC were obtained after these chemotherapies. However, pleural effusion and ascites appeared again, and we diagnosed progressive disease. As a third line chemotherapy for this patient, paclitaxel (TXL) was administered. Treatment consisted of two 3-week courses of paclitaxel 70 mg per m2 on day 1 of each week, with a 1-week break between the courses. Two weeks after the start of this therapy, pleural effusion and ascites had completely disappeared. Paclitaxel is considered to be promising for advanced gastric cancers, as second or third line chemotherapy with paclitaxel for patients with inoperable gastric cancer seems to be effective in improving QOL.     

A case of advanced gastric cancer which became operable after chemotherapy with combination of TS-1/CDDP and in which complete disappearance of liver metastasis was histopathologically confirmed

We encountered a patient in whom TS-1/cisplatin (CDDP) combination chemotherapy was effective. The cancer became operable, and complete disappearance of liver metastasis was histopathologically confirmed. The patient was a 65-year-old man who presented with complaints of epigastric discomfort and anorexia. Based on upper GI endoscopy and abdominal CT, type 1 gastric cancer associated with liver and abdominal lymph node metastases was diagnosed. The cancer was judged to be inoperable, and chemotherapy with a combination of TS-1 and CDDP was initiated. One course of treatment consisted of administration of 120 mg/day of TS-1 for 21 days followed by 14 days of withdrawal, and administration of 100 mg/body/day of CDDP on day 8 (80 mg/body/day in the second course). After two courses of treatment, the primary lesion and the liver and lymph node metastatic lesions decreased in size (reduction ratios were 42.3%, 90.5% and 85.2%, respectively). The tumor marker values became normal. Subsequently, the cancer was judged to have become operable. After consultation with the patient, total gastrectomy, splenectomy, partial hepatectomy, and D3 dissection were performed, and curability B was achieved. The only adverse event of Grade 2 or more severity observed during drug administration was anorexia. Liver metastasis was judged from pathological findings to have disappeared. The postoperative course was uneventful and the patient was discharged from the hospital. To date, there have been no signs of recurrence. TS-1/CDDP therapy is believed to provide effective treatment against liver metastasis and lymph node metastasis of gastric cancer.