Endovascular Treatment for Infra-inguinal Autologous Saphenous Vein Graft Occlusion Using Self Expanding Nitinol Stents.

INTRODUCTION: For patients with infra-inguinal autologous vein bypass graft occlusion, conventional open surgical repair or endovascular treatment (EVT) for native vessel occlusion have generally been performed. REPORT: A 73 year old female with non-healing ulcer and gangrene of the left lower leg was diagnosed as having infra-inguinal autologous saphenous vein graft occlusion. In this case, surgical repair such as patch angioplasty, interposition graft, or replacement graft did not seem promising because of repeated previous infection in the polytetrafluoroethylene (PTFE) vascular prosthesis and absence of available autologous vein due to past surgery. Moreover, there was no chance of crossing the native vessel, since the proximal superficial femoral artery (SFA) had already been resected. Thus, EVT was performed for the occluded autologous vein graft, implanting multiple self expanding bare nitinol stents throughout the vein graft achieving complete revascularization, good medium term patency, and dramatically improved wound healing. CONCLUSION: Endovascular recanalization using multiple bare stents could be an alternative treatment for infra-inguinal autologous vein graft occlusion.

Using breast radiographers' reports as a second opinion for radiologists' readings of microcalcifications in digital mammography.

OBJECTIVE: The aim of this study was to investigate a practical method for incorporating radiographers' reports with radiologists' readings of digital mammograms. METHODS: This simulation study was conducted using data from a free-response receiver operating characteristic observer study obtained with 75 cases (25 malignant, 25 benign and 25 normal cases) of digital mammograms. Each of the rating scores obtained by six breast radiographers was utilized as a second opinion for four radiologists' readings with the radiographers' reports. A logical "OR" operation with various criteria settings was simulated for deciding an appropriate method to select a radiographer's report in all combinations of radiologists and radiographers. The average figure of merit (FOM) of the radiologists' performances was statistically analysed using a jackknife procedure (JAFROC) to verify the clinical utility of using radiographers' reports. RESULTS: Potential improvement of the average FOM of the radiologists' performances for identifying malignant microcalcifications could be expected when using radiographers' reports as a second opinion. When the threshold value of 2.6 in Breast Imaging-Reporting and Data System (BI-RADS®) assessment was applied to adopt/reject a radiographer's report, FOMs of radiologists' performances were further improved. CONCLUSION: When using breast radiographers' reports as a second opinion, radiologists' performances potentially improved when reading digital mammograms. It could be anticipated that radiologists' performances were improved further by setting a threshold value on the BI-RADS assessment provided by the radiographers. ADVANCES IN KNOWLEDGE: For the effective use of a radiographer's report as a second opinion, radiographers' rating scores and its criteria setting for adoption/rejection would be necessary.

Is response rate increment obtained by molecular targeted agents related to survival benefit in the phase III trials of advanced cancer?

BACKGROUND: It remains unclear whether response rate (RR) is related to survival benefit in phase III trials of advanced cancer treated with molecular targeted agents (MTA) in combination with standard therapies. MATERIALS AND METHODS: We carried out a systematic search of PubMed for randomized phase III trials of four solid tumors examining the efficacy of MTA when added to a standard therapy. We examined whether there were any associations between RR increment obtained by the addition of targeted agents (DeltaRR) and survival benefit in phase III trials. RESULTS: We identified 26 phase III trials of MTA with a total of 21 156 patients and 29 experimental arms of MTA. Studies which showed significant survival benefit had higher DeltaRR compared with those which did not show significant benefit. In the receiver operating characteristic curve analysis, using a 7% gain as threshold value for DeltaRR allowed assessment of survival benefit with high sensitivity and specificity. There were also significant relationships between DeltaRR and hazard ratios for overall survival and progression-free survival in the linear regression analysis. CONCLUSION: RR increment obtained by the addition of MTA to a standard therapy may be useful to predict survival benefit in clinical phase III trials of advanced cancer.

Effect of preservation solution on graft viability in single-lung transplantation from heart-beating donors in pigs.

BACKGROUND: Low-potassium-dextran preservation solution Perfadex (PER) may provide better outcome of transplanted lungs than high-potassium Euro-Collins (EC) solution. However, there are no comparative studies of the recipient inflammatory response to the graft. PURPOSE: The purpose of this study was to compare EC versus PER as preservation solutions with respect to the functional performance and inflammatory response in single-lung transplantation from heart-beating donors in pigs. MATERIALS AND METHODS: The donor left lung flushed with the corresponding cold preservation solution was stored at 3 degrees C for 3 hours. We assessed hemodynamic values and pulmonary function in the recipient over a 2-hour reperfusion period calculated as percent of basal values, and expressed as mean of the reperfusion period. Interleukin-8 (IL-8) concentration in the donor was estimated in bronchoalveolar lavage fluid 2 hours after recipient reperfusion. Biopsies of the donor right lung and the transplanted lung were obtained to measure myeloperoxidase (MPO) activity. IL-8 and MPO values were expressed as percent of the donor value. We evaluated the wet/dry pulmonary weight ratio (W/D), polymorphonuclear neutrophil count (PMN), and a score of histological damage in the transplanted graft. RESULTS: Pulmonary function evaluated by % static: 66.6 +/- 6.8 (EC), 82.3 +/- 10.2 (PER), and dynamic: 74.0 +/- 7.3 (EC), 89.3 +/- 7.7 (PER) compliances, as well as % IL-8: 562.5 +/- 168.6 (EC), 232.3 +/- 148.7 (PER), % MPO: 485.9 +/- 194.9 (EC), 140.8 +/- 21.1 (PER), W/D: 9.9 +/- 3.1 (EC), 6.8 +/- 1.4 (PER), PMN 13.5 +/- 6.8 (EC), 5.5 +/- 3.3 (PER) and the histological damage score: 3.0 +/- 1.5 (EC), 0.7 +/- 0.4 (PER) showed significant differences between the EC and the PER (P < .01). CONCLUSIONS: PER affords good lung preservation with early graft function and modest evidences of inflammation, lung injury, and edema compared with the EC perfused lung.

Essential microenvironment for thymopoiesis is preserved in human adult and aged thymus.

Normal human thymuses at various ages were immunohistologically examined in order to determine whether adult or aged thymus maintained the microenvironment for the T cell development and thymopoiesis was really ongoing. To analyze the thymic microenvironment, two monoclonal antibodies (MoAb) were employed. One is MoAb to IL-1 receptor (IL-1R) recognizing medullary and subcapsular cortical epithelial cells of normal infant human thymus. The other is UH-1 MoAb recognizing thymic epithelial cells within the cortex, which are negative with IL-1R-MoAb. Thymus of subjects over 20 years of age was split into many fragments and dispersed in the fatty tissue. However, the microenvironment of each fragment was composed of both IL-1R positive and UH-1 positive epithelial cells, and the UH-1 positive portion was populated with lymphocytes showing a follicle-like appearance. Lymphocytes in these follicle-like portions were mostly CD4+CD8+ double positive cells and contained many proliferating cells as well as apoptotic cells. Thus these follicle-like portions in adult and aged thymus were considered to be functioning as cortex as in infant thymus. Proliferative activity of thymocytes in the thymic cortex and the follicle-like portions definitely declined with advance of age, while incidence of apoptotic thymocytes increased with aging.

Age-related hypermethylation of the hMLH1 promoter in gastric cancers.

To determine whether methylation of the hMLH1 promoter is related to increasing age and gastric carcinogenesis, we examined hMLH1 methylation and expression in 100 gastric cancers. hMLH1 methylation and aberrant protein expression were observed in 9 and 13 cancers, respectively. Normal and intestinal metaplastic tissues adjacent to cancers with hypermethylation did not exhibit any hMLH1 methylation, indicating that it may be specific to gastric cancers. The frequency of hMLH1 methylation significantly increased with age. These results suggest that hMLH1 methylation plays an important role in gastric carcinogenesis in old people.

Immunohistological analysis of thymoma by molecules differentially expressed in the thymic cortex and medulla, and its application in the differential diagnosis of thymoma from esophageal and lung cancer.

The purpose of this study was to verify the WHO classification of thymic tumors using immunohistological methods, and to discover whether these methods can be applied to differentiate thymoma from squamous cell carcinoma (SCC) of the esophagus and the lung. Twenty-nine thymoma cases were classified according to WHO and were then immunohistologically examined for the positivity of these molecules. All thymoma cases investigated in this study were positive for IL-1R, and most of them were also positive for bek. In contrast, UH-1 was highly positive in B1 and B2 type thymomas, but negative or weakly positive in A, AB and B3 type thymomas. Twelve esophageal cancers and 21 lung cancers were also examined for the positivity of the same molecules. All esophageal cancers were negative for UH-1. Three of 12 cases were weakly positive for IL-1R, and four of these 12 cases were also weakly positive for bek. Twelve of 21 lung cancer cases were adenocarcinomas, all of them negative for IL-1R, bek and UH-1. Nine of 21 lung cancer cases were SCCs, all of them negative for UH-1. Eight of nine SCC cases were strongly positive for IL-1R, while seven of these were weakly positive for bek. We conclude that the WHO classification of thymic tumors is still valid as demonstrated by immunohistological analysis and that the positivity of UH-1, IL- 1R and bek might be helpful in differentiating thymoma from SCC of the esophagus and the lung.

Important role of energy-dependent mitochondrial pathways in cultured rat cardiac myocyte apoptosis.

Recent studies have suggested that apoptosis and necrosis share common features in their signaling pathway and that apoptosis requires intracellular ATP for its mitochondrial/apoptotic protease-activating factor-1 suicide cascade. The present study was, therefore, designed to examine the role of intracellular energy levels in determining the form of cell death in cardiac myocytes. Neonatal rat cardiac myocytes were first incubated for 1 h in glucose-free medium containing oligomycin to achieve metabolic inhibition. The cells were then incubated for another 4 h in similar medium containing staurosporine and graded concentrations of glucose to manipulate intracellular ATP levels. Under ATP-depleting conditions, the cell death caused by staurosporine was primarily necrotic, as determined by creatine kinase release and nuclear staining with ethidium homodimer-1. However, under ATP-replenishing conditions, staurosporine increased the percentage of apoptotic cells, as determined by nuclear morphology and DNA fragmentation. Caspase-3 activation by staurosporine was also ATP dependent. However, loss of mitochondrial transmembrane potential (DeltaPsi(m)), Bax translocation, and cytochrome c release were observed in both apoptotic and necrotic cells. Moreover, cyclosporin A, an inhibitor of mitochondrial permeability transition, attenuated staurosporine-induced apoptosis and necrosis through the inhibition of DeltaPsi(m) reduction, cytochrome c release, and caspase-3 activation. Our data therefore suggest that staurosporine induces cell demise through a mitochondrial death signaling pathway and that the presence of intracellular ATP favors a shift from necrosis to apoptosis through caspase activation.

Gastric proteinase digestion of caseins in newborn pups of the mouse.

Casein micelles of mouse milk consist of alpha-, beta-, gamma-, and kappa-caseins. By digestion with alkaline phosphatase, they were separated as an independent band by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE). The compositions of alpha-, beta-, gamma-, and kappa-caseins were 24.3, 25.1, 9.4, and 41.2% in colostrum, and 36.8, 15.6, 11.9, and 35.7% in mature milk, respectively. Zero-day-old pups were allowed to access either colostrum or mature milk, and the aggregated milk in the stomach was analyzed by SDS-PAGE. Caseins in colostrum were digested more rapidly and efficiently than those in mature milk. Among the seven peptides present in the aggregated caseins, four peptides were colostrum-specific and derived from alpha- and gamma-caseins. It was expected that colostrum-specific and soluble peptides were generated from alpha- and gamma-caseins through gastric proteinase digestion. Amino acid sequence analysis and the pH of the aggregated milk suggested that caseins in the stomach were digested by a chymotrypsin-like proteinase. Caseins in colostrum were different from those in mature milk, with respects to the casein composition as well as the gastric proteinase sensitivity. It is concluded that the lactating mice on the day of parturition supply particular caseins to their young.

Detection of malignant hepatic tumors: comparison of gadolinium-and ferumoxide-enhanced MR imaging.

OBJECTIVE: The purpose of our study was to compare how well gadolinium-enhanced and ferumoxide-enhanced MR imaging reveal malignant hepatic tumors. SUBJECTS AND METHODS: Both gadolinium-enhanced and ferumoxide-enhanced MR imaging were separately performed in 53 patients with a total of 87 malignant hepatic tumors (57 hepatocellular carcinomas, 28 metastases, two cholangiocarcinomas). Thirty-one of the 53 patients had hepatic cirrhosis. Images were reviewed by three independent off-site observers. Observer performance was evaluated by means of sensitivity, specificity, and receiver operating characteristic curve analyses. RESULTS: Gadolinium-enhanced MR imaging outperformed ferumoxide-enhanced MR imaging in sensitivity (81% versus 62%, p < 0.01) for malignant-tumor detection. Specificity was comparable (94%) between the two types of MR imaging. Area under receiver operating characteristic curve (A(z)) value was significantly higher with gadolinium-enhanced MR imaging than with ferumoxide-enhanced MR imaging in patients overall (A(z) = 0.896 versus 0.805, p < 0.001), in patients with cirrhosis (A(z) = 0.907 versus 0.807, p < 0.001), and in patients without cirrhosis (A(z) = 0.899 versus 0.834, p < 0.01). The superiority was enhanced in the subset of patients with cirrhosis. CONCLUSION: Gadolinium-enhanced MR imaging outperforms ferumoxide-enhanced MR imaging in revealing malignant hepatic tumors. Gadolinium-enhanced MR imaging is recommended, particularly for patients with cirrhosis.

Acute myocardial infarction due to a regressed giant coronary aneurysm as possible sequela of Kawasaki disease.

We report on a young patient admitted with an acute myocardial infarction due to a regressed coronary aneurysm who was treated with balloon angioplasty. The wall morphology of the coronary aneurysm using intravascular ultrasound imaging closely resembled that occurring after Kawasaki disease (KD), although our patient had no obvious past history of KD, suggesting so-called atypical KD.

Cytokine-induced nitric oxide production inhibits mitochondrial energy production and impairs contractile function in rat cardiac myocytes.

OBJECTIVES: The present study examined whether nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) can directly inhibit aerobic energy metabolism and impair cell function in interleukin (IL)-1beta,-stimulated cardiac myocytes. BACKGROUND: Recent reports have indicated that excessive production of NO induced by cytokines can disrupt cellular energy balance through the inhibition of mitochondrial respiration in a variety of cells. However, it is still largely uncertain whether the NO-induced energy depletion affects myocardial contractility. METHODS: Primary cultures of rat neonatal cardiac myocytes were prepared, and NO2-/NO3- (NOx) in the culture media was measured using Griess reagent. RESULTS: Treatment with IL-1beta (10 ng/ml) increased myocyte production of NOx in a time-dependent manner. The myocytes showed a concomitant significant increase in glucose consumption, a marked increase in lactate production, and a significant decrease in cellular ATP (adenosine 5'-triphosphate). These metabolic changes were blocked by co-incubation with N(G)-monomethyl-L-arginine (L-NMMA), an inhibitor of NO synthesis. Sodium nitroprusside (SNP), a NO donor, induced similar metabolic changes in a dose-dependent manner, but 8-bromo-cyclic guanosine 3',5'-monophosphate (8-bromo-cGMP), a cGMP donor, had no effect on these parameters. The activities of the mitochondrial iron-sulfur enzymes, NADH-CoQreductase and succinate-CoQreductase, but not oligomycin-sensitive ATPase, were significantly inhibited in the IL-1beta, or SNP-treated myocytes. Both IL-1beta and SNP significantly elevated maximum diastolic potential, reduced peak calcium current (I(Ca)), and lowered contractility in the myocytes. KT5823, an inhibitor of cGMP-dependent protein kinase, did not block the electrophysiological and contractility effects. CONCLUSIONS: These data suggest that IL-1beta-induced NO production in cardiac myocytes lowers energy production and myocardial contractility through a direct attack on the mitochondria, rather than through cGMP-mediated pathways.

Development of a digital image database for chest radiographs with and without a lung nodule: receiver operating characteristic analysis of radiologists' detection of pulmonary nodules.

OBJECTIVE: We developed a digital image database (www.macnet.or.jp/jsrt2/cdrom_nodules.html ) of 247 chest radiographs with and without a lung nodule. The aim of this study was to investigate the characteristics of image databases for potential use in various digital image research projects. Radiologists' detection of solitary pulmonary nodules included in the database was evaluated using a receiver operating characteristic (ROC) analysis. MATERIALS AND METHODS: One hundred and fifty-four conventional chest radiographs with a lung nodule and 93 radiographs without a nodule were selected from 14 medical centers and were digitized by a laser digitizer with a 2048 x 2048 matrix size (0.175-mm pixels) and a 12-bit gray scale. Lung nodule images were classified into five groups according to the degrees of subtlety shown. The observations of 20 participating radiologists were subjected to ROC analysis for detecting solitary pulmonary nodules. Experimental results (areas under the curve, Az) obtained from observer studies were used for characterization of five groups of lung nodules with different degrees of subtlety. RESULTS: ROC analysis showed that the database included a wide range of various nodules yielding Az values from 0.574 to 0.991 for the five categories of cases for different degrees of subtlety. CONCLUSION: This database can be useful for many purposes, including research, education, quality assurance, and other demonstrations.

Pindolol potentiates the effect of fluoxetine on hippocampal seizures in rats.

Recent studies have shown that behavioral and neurochemical changes induced by selective serotonin (5-HT) reuptake inhibitors such as fluoxetine are potentiated by coadministration of a 5-HT1A receptor antagonist. The present study assessed the effects of concomitant administration of fluoxetine and a 5-HT1A receptor antagonist, pindolol, on focal hippocampal (HIP) seizures elicited by electrical stimulation in rats. A 10 mg/kg dose of fluoxetine, which was ineffective by itself, produced a significant increase in the afterdischarge threshold of HIP seizures when combined with pindolol at 10 mg/kg. The inhibitory effect of this combination was eliminated by pretreatment with parachlorophenylalanine, a depletor of brain 5-HT. These findings suggest that treatments designed to increase 5-HT neurotransmission inhibit the generation of HIP seizures. A combination of fluoxetine with a 5-HT1A receptor antagonist could thus be therapeutically useful for the treatment of depressive symptoms in patients with epilepsy.

[MR cholangiopancreatography using respiratory triggered half-Fourier RARE technique].

We evaluate the usefulness of MRCP using respiratory triggered HASTE technique in 68 patients. Eleven subsequent slices were obtained for MRCP. To determine the optimal trigger rate, MRCP with various trigger rates were compared in 25 patients. Respiratory triggered MRCP and breath hold MRCP were compared in 68 patients. Respiratory triggered MRCP was also performed in 3 infants. The optimal trigger rate was 10%. In 17 patients who could not stop their breath for 10 seconds, respiratory triggered MRCP were better than breath hold MRCP in 14 (82%) for the source images and in 17 (100%) for the MIP images. Respiratory triggered MRCP could depict cystic duct and main pancreatic duct even in 14 month infant. MRCP with high spatial resolution could be obtained with respiratory triggered HASTE technique in critically ill, or non-cooperative patients.

[Myelodysplastic syndrome (RAEB in T) developed in a renal allograft recipient].

A 46-year-old man who had been treated with azathioprine (150 mg/day) and prednisolone (7.5-10 mg/day) for 16 years after allogeneic renal transplantation was admitted to our hospital in July 1996 for evaluation of pancytopenia. Three years earlier he had been given a diagnosis of renal pelvic and ureteral cancer, and underwent left nephrectomy with total uretectomy. His bone marrow was normocellular with excess of blasts (27.6%), and displayed trilineage myelodysplasia. A chromosomal analysis of the bone marrow revealed 43-45, XY with del (1) (p13), -5, del (7) (q22), -17, -18, and -19. The patient was given a diagnosis of refractory anemia with excess of blasts in transformation (RAEB in T), and treated with idarubicin and cytosine arabinoside. Two months later, overt acute leukemia developed and reinduction chemotherpay was started, but the patient died of cerebral hemorrhage in October. This case suggests that immunosuppressive agents such as azathioprine might play an important role in the pathogenesis of MDS (RAEB in T) and renal pelvic and ureteral cancer after renal transplantation.

Effects of the 5-HT3 receptor agonist 1-(m-chlorophenyl)-biguanide in the rat kindling model of epilepsy.

This study assessed the action of the serotonin3 (5-HT3) receptor agonist, 1-(m-chlorophenyl)-biguanide (m-CPBG), against both kindled seizures and kindling development from the rat amygdala (AM). The intracerebroventricular (i.c.v.) administration of 40 microg m-CPBG significantly increased the duration of afterdischarge and bilateral forelimb clonus of generalized kindled seizures. In addition, daily i.c.v. treatment with m-CPBG at the same dose prior to each electrical stimulation to the AM significantly facilitated behavioral and electrographic seizure development and reduced the number of stimulations needed to elicit generalized seizures. The present results indicate that m-CPBG increases the duration of fully kindled seizures and facilitates the developmental seizure process, suggesting an excitatory role of 5-HT3 receptors in the kindling model of epilepsy.

Role of serotonin receptor subtypes in the development of amygdaloid kindling in rats.

The present study was conducted to identify serotonin (5-HT) receptor subtypes involved in the development of amygdala (AM) kindling. We used 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a 5-HT1A agonist, and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a 5-HT2 agonist, both of which were injected subcutaneously 15 min prior to each daily electrical stimulation to the rat AM. Treatment with 8-OH-DPAT (1 mg/kg) slightly suppressed behavioral and electrographic seizure development during the course of kindling. In contrast, DOI (1 mg/kg) strongly facilitated kindling development and reduced the number of stimulations needed to produce generalized seizures. These facilitatory effects of DOI were completely blocked by pretreatment with a 5-HT2 antagonist ketanserin. The present results suggest that the activation of 5-HT1A receptors can retard the development of AM kindling, whereas 5-HT2 receptors play a facilitatory role in this developmental seizure process.

Digital chest radiography: effect of temporal subtraction images on detection accuracy.

PURPOSE: To improve early detection of disease in chest radiographs, the authors developed a digital processing technique that geometrically warps and subtracts a previous radiograph from a current radiograph to produce a temporal subtraction image. An observer test was performed to evaluate the effects of the temporal subtraction image technique on detection of interval change. MATERIALS AND METHODS: Fifty pairs of chest radiographs, including a baseline examination and a subsequent radiograph, were selected (25 cases in which potentially important new abnormalities had developed, and 25 in which there was no interval change). The baseline examination was chosen from multiple prior radiographs to minimize initial misregistration. By means of receiver operating characteristic (ROC) analysis, the ability of 11 observers to detect pathologic change when viewing the paired digitized baseline and subsequent radiographs was compared with their ability when viewing the same paired radiographs together with temporal subtraction images. Positive cases demonstrated focal new abnormalities that were greater than 1 cm in diameter. RESULTS: The mean area (Az) under the ROC curves increased from 0.89 without to 0.98 with the temporal subtraction images. When the paired digitized previous and current chest radiographs were viewed in conjunction with the temporal subtraction images, a significant improvement in detection of new abnormalities was achieved (P = .00004), whereas the mean interpretation time was reduced by 19.3% (from 52 to 42 seconds, including the time to record the score and to move to the next case) (P = .0019). CONCLUSION: The temporal subtraction technique can significantly improve sensitivity and specificity for detection of interval change in chest radiographs.