Use of human liver S9 in the Ames test: assay of three procarcinogens using human S9 derived from multiple donors

The purpose of the present study was to examine the inter-individual variation in the mutagenicity of chemicals using a variety of human S9 fractions. For this purpose, three procarcinogens, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), benzo[a]pyrene (BP), and dimethylnitrosamine (DMN), were selected for the Ames test and their mutagenicity was examined using human liver S9 fractions prepared from 18 different donors and one pooled liver S9 fraction prepared from 15 different donors. In addition, rat S9 fraction prepared from male rats pretreated with phenobarbital and 5,6-benzoflavone (PB/BF) was used as reference in order to examine the mutagenic differences between human and rat (PB/BF) S9 fractions. The data demonstrate a large inter-individual diversity in the mutagenic response to procarcinogens. The mutagenicity of IQ and BP in the presence of a human liver S9 fraction (lot HLS-014) was equal to that observed in the presence of rat (PB/BF) S9 fraction. The mutagenicity of IQ and BP in the presence of a pooled human liver S9 fraction was lower (90 and 95%, respectively) than that observed in the presence of rat (PB/BF) S9. On the contrary, the mutagenicity of DMN in the presence of either a selected human liver S9 fraction (lot HLS-014) or pooled fraction was 8-fold higher than that found in the presence of rat (PB/BF) S9 fraction. Human liver S9 fraction (lot HLS-014) had one of the highest cytochrome P450 enzyme activities among the 18 different donors and higher than the pooled human liver S9 fraction. These results suggest that the use of both selected human liver S9 fractions with high metabolic activity (e.g., lot HLS-014 as used in this study) and a pooled S9 fraction with moderate metabolic activity could be used as a means to evaluate the inter-individual variability in mutagenic response to chemicals and to confirm positive responses from studies completed with rodent S9.     

Increased plasma concentrations of the mature form of adrenomedullin during cardiac surgery and hepatosplanchnic hypoperfusion

Adrenomedullin is a potent vasodilatory peptide. Plasma adrenomedullin (AM) concentrations increase during and after cardiopulmonary bypass (CPB). However, the cause of this increase and its site of production have not been identified. We investigated the role of the hepatosplanchnic and cerebral circulations in the increase of plasma AM and investigated whether tissue hypoxygenation is a cause of the AM increase seen during CPB. We measured plasma total AM (AM-T) and the biologically active form of AM, mature AM (AM-m), in seven patients undergoing CPB. Both plasma AM-T and AM-m concentrations increased significantly 60 min after weaning from CPB. At this time point, arterial AM-T and AM-m concentrations were 18-fold and 10-fold larger, respectively, than baseline values measured after the induction of anesthesia. The plasma AM-m concentration and the ratio of AM-m/AM-T in blood from the hepatic vein were significantly larger than those from the radial artery or jugular bulb. The AM-m/AM-T ratio decreased during CPB, suggesting that production of the intermediate form of AM, AM-glycine, is more than that of AM-m. The oxygen tension of the hepatic venous blood (PhvO2) was significantly less during CPB. Plasma AM-m concentrations sampled from the hepatic vein showed a significant negative correlation with PhvO2 at 10 min (r = 0.824; P < 0.02) and 60 min (r = 0.828; P < 0.02) after the onset of CPB. These data suggest that the hepatosplanchnic circulation is an important source of AM-m during CPB. Furthermore, hypoxygenation of the hepatosplanchnic region may be an important cause of this AM-m increase.     

Modified Daggett's technique for early repair of postinfarct posterior ventricular septal rupture

A surgical modification for safe early repair of posterior septal rupture is described. This technique is based on the method described by Daggett, but adds one internal patch, plus the application of fibrin glue between the internal and external patch for minimizing bleeding. This modification is a simple and reliable one for repairing posterior ventricular septal rupture.     

Successful treatment of Novacor pump pocket infection by omental transposition

Device-related infection remains a major factor restricting the long-term use of left ventricular assist systems. Severe pocket infection is especially difficult to manage and removal of the device has been the only curative treatment in most cases. We report a case of a Novacor device pocket infection treated successfully with continuous local irrigation and transposition of omental flap. This procedure provides another option for the management of pocket infection, which is mandatory for destination therapy the permanent usage of LVAS for the purpose of circulatory supports in patients with end-stage heart failure, who are not indicated for heart transplantation.     

Optimal scan time for evaluating pancreatic disease with positron emission tomography using F-18-fluorodeoxyglucose

OBJECTIVE: Image interpretation in positron emission tomography (PET) using F-18-fluoro-2-deoxy-D-glucose (FDG) is usually performed for images obtained at 1 h postinjection (PI) of FDG, but it remains unknown whether this is the optimal time for imaging patients with pancreatic disease. The aim of this study was to assess the optimal scan time for FDG-PET for patients suspected of having pancreatic cancer. PATIENTS AND METHODS: Forty-four patients with suspected pancreatic cancer underwent FDG-PET scans at both 1 h and 2 h PI. Tracer uptake in the pancreatic lesions and possible liver metastasis was interpreted qualitatively, using a 5-point grading system (0 = normal, 1 = probably normal, 2 = equivocal, 3 = probably abnormal, and 4 = definitely abnormal) by 4 nuclear medicine physicians independently, who were blind to all clinical information. Detection performance with each image was compared using receiver operating characteristic (ROC) analysis. An average score of the 4 readers for each patient was also defined as consensus average index (CAI) and compared between the two images. RESULTS: ROC results indicated no significant differences in detection performance (Averaged areas under ROC curves of 1 h vs. 2 h were 0.92 vs. 0.90 for primary tumor, and 0.81 vs. 0.85 for liver metastases). There were no significant differences in CAIs between 1 h and 2 h PI images in interpreting primary tumor and positive liver metastases, but a significant difference was observed for cases without liver metastases (p < 0.05). CONCLUSIONS: The certainty of excluding liver metastases was increased when the 2h image was used, although ROC analysis did not establish a difference between 1 h and 2 h imaging for differentiating malignant and benign lesions in primary pancreatic cancer or its liver metastases.     

Determination of time of biologic fixation after anterior cruciate ligament reconstruction with hamstring tendons

BACKGROUND: It has been unclear when a hamstring tendon graft becomes biologically fixed in the bone tunnel after anterior cruciate ligament reconstruction. HYPOTHESIS: Postoperative biomechanical testing and magnetic resonance images can indicate biologic fixation of the graft in the femoral bone tunnel. STUDY DESIGN: Prospective cohort study. METHODS: Sixty-four patients were evaluated by serial biomechanical testing, magnetic resonance imaging, and second-look arthroscopy 2 years after surgery. Biologic fixation of the graft was confirmed radiographically by injecting a contrast medium into the femoral bone tunnel. RESULTS: Forty-two stable knees with graft fixation maintained a high stiffness (120% of normal) and showed low signal intensity in an early postoperative magnetic resonance image (12 +/- 8 months). Fourteen stable knees without graft fixation had gradually increased anterior displacement with nearly normal stiffness and high signal intensity. Five unstable knees with graft fixation retained low stiffness (70%) and showed late low signal intensity at 20 +/- 9 months. Three unstable knees without biologic fixation had rapidly increased anterior displacement, with half the stiffness of a normal knee. CONCLUSION: Postoperative low stiffness and high signal intensity might indicate late biologic graft fixation, predicting a possibility of postoperative anterior knee instability.     

The significance of prostate-specific antigen alpha-1-antichymotrypsin complex and its indices for the detection of prostate cancer

We examined the usefulness of prostate specific antigen alph-1-antichymotrypsin complex (PSA-ACT) and its indices for the detection of prostate cancer in patients with a prostate specific antigen (PSA) level between 2.1 and 10.0 ng/ml. Between July 1999 and October 2001, 151 patients with a PSA level between 2.1 and 10.0 ng/ml underwent a systematic biopsy under transrectal ultrasound (TRUS) guidance. The clinical values of total PSA, PSA-ACT, PSA density (PSAD), PSA-ACT density (PSA-ACTD), PSA transition zone density (PSATZD) and PSA-ACT transition zone density (PSA-ACTTZD) for the detection of prostate cancer were compared by using receiver operating characteristic (ROC) curve analysis. Of the 151 patients, 36 (23.8%) were histologically confirmed as having prostate cancer. The differences between patients with prostate cancer and benign prostatic disease were significant with respect to the PSA and PSA-ACT related parameters examined in this study. According to ROC curve analysis, the area under the curve (AUC) of PSA-ACTTZD was the greatest of all the parameters. The differences was significant between the AUC of PSA-ACTTZD and total PSA (p < 0.05). The cutoff value of PSA-ACTTZD with 0.20 ng/ml2 showed the highest sum of sensivitity (90%) and specificity (55%). Also, in 86 patients with a PSA level between 2.1 and 6.0 ng/ml, the AUC of PSA-ACTTZD was the greatest of all the parameters. Measuring the level of PSA-ACT and its indices may provide a better differentiation of prostate cancer and benign prostatic disease than total PSA alone in patients with intermediate PSA levels. PSA-ACTTZD is the most useful indicator among PSA-ACT and its volume indices.     

Anesthetic management of a patient with suspected pseudothrombocytopenia

A 74-year-old male was operated for sigmoid colon cancer. Because of an agglutination of the patient's platelet, it was difficult to measure his platelet count under ethylene diamine tetra acetate (EDTA), heparin or citrate as anticoagulants with an automated cell counter. Even though there was a strong possibility of pseudothrombocytopenia, anesthetic management for the patient was safely conducted. His condition was stable throughout the perioperative course and no bleeding tendency was observed. Nitrous oxide, oxygen, sevoflurane, propofol and pancuronium were useful in this case.     

Accelerated dynamic MR imaging with a parallel imaging technique for hypervascular hepatocellular carcinomas: usefulness of a test bolus in examination and subtraction imaging

PURPOSE: To assess the impact of the accelerated dynamic MR imaging (ADMRI) approach using parallel imaging for detecting hypervascular hepatocellular carcinomas (HCCs) and to evaluate the usefulness of a test bolus in examination and subtraction imaging in this setting. MATERIALS AND METHODS: Thirty patients with 135 HCCs underwent ADMRI using a two-dimensional gradient-recalled echo sequence with parallel imaging. Seventeen patients were evaluated without a test bolus and 13 patients with a test bolus. The detectability of HCCs was calculated between the groups with and without a test bolus. ADMRI was evaluated regarding the signal-to-noise ratio (SNR) of the lesion and the liver, the contrast-to-noise ratio (CNR) of the lesion vs. the liver, and the feasibility of subtraction images. RESULTS: ADMRI with and without a test bolus had almost equal sensitivity (92.5% and 92.6%). No significant difference was seen in the SNR of lesions and the CNR of lesions vs. livers between both groups. With a test bolus, ADMRI could depict the peak enhancement of nodules on the 2nd or 3rd dynamic phases and optimized the timing of peak lesion enhancement. Subtraction images could be obtained regarding minimal slice misregistration. CONCLUSION: ADMRI had high detectability of HCCs with and without a test bolus.