Angiotensin blockade inhibits osteopontin expression in non-infarcted myocardium after myocardial infarction

Osteopontin has been reported to have an important role in cardiac fibrosis. However, little is known about the effects of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin type 1 receptor blockers (ARB) on osteopontin expression in infarcted myocardium. The purpose of this study was to elucidate the effects of an ACEI (perindpril) and an ARB (candesartan cilexitil) on cardiac function as assessed by Doppler echocardiography and cardiac osteopontin expression associated with cardiac remodeling in myocardial infarcted rats. ACEI or ARB was administered after myocardial infarction (MI). At 4 weeks after MI, cardiac function, and mRNAs in non-infarcted myocardium were analyzed. ACEI and ARB equally prevented left ventricular dilatation, reduction of ejection fraction, and the increase in E/A wave velocity ratio and the rate of E wave deceleration by MI. ACEI and ARB significantly suppressed increased mRNA expression of atrial natriuretic peptide, brain natriuretic peptide, osteopontin, and collagen I and III in the non-infarcted ventricle at 4 weeks. Immunohistochemically stained osteopontin was increased in interstitial fibrosis of non-infarcted myocardium. Both ACEI and ARB significantly prevented cardiac fibrosis and osteopontin expression. In conclusion, angiotensin blockade inhibits osteopontin expression in non-infarcted myocardium and prevents cardiac remodeling after MI.     

Preparing oral dosage form of ketamine in the hospital for simplicity and patient compliance--preparations using agar

Ketamine has been widely used in the operation as intravenous and intramuscular injections, since ketamine has dissociative anesthetic properties. When it is given in sub-anesthetic dose, ketamine is known to have an analgesic effect. The analgesic effect is observed for patients with neuropathic pain when administrated not only by injection but also orally. In Japan, since ketamine is not commercially available except injection forms, patients have to take it as solution of injections for the oral medication. Since the solution of injections has extremely bitter taste, patients intensely desire the development of preparations without the bitterness. In the present study, we prepared oral gel dosage forms of ketamine using agar. It is simple to prepare this dosage form, and most pharmacists can prepare it easily in many hospitals. This gel dosage form met content uniformity requirements and the shape of that was maintained intact during the dissolution test (for 10 hours). The release rate was reduced by additions of additives such as sugar and a flavor in the gel. The reason for the reduction in release could be the suppression of ketamine diffusion depended on the micro-viscosity of solution in the gel. The ketamine contents and the release profile of the gel preparations were unchanged at the room temperature for 12-week storage. The gel preparations in this study would be useful for the oral medication of ketamine, since it is easy for patients to carry them when they go out and the intensely bitter taste could be improved by the addition of a flavor.     

Improved graft survival in ABO-incompatible living donor kidney transplantation

INTRODUCTION: We reviewed ABO-incompatible living donor kidney transplantations (LDKT) performed in our institute. PATIENTS: Fourteen ABO-incompatible LDKT were carried out in the first era (September 1990-August 1996) and 13 were in the second era (October 2001-July 2004). All patients were treated with sessions of plasmapheresis before transplantation to reduce antibody titers <1:8. In the second era, those with rebound increase of antibody titers >1:64 after repeated plasmapheresis were not subjected to transplantation. Posttransplantation immunosuppression consisted of cyclosporin, predonisone, azathioprine, gusperimus hydrochloride (DSG), and antilymphocyte globulin (ALG) in the first era, and tacrolimus, mycophenolate mofetil, predonisone, and DSG in the second era. Splenectomy was performed during the transplantation. Anticoagulant therapy was introduced in the second era. RESULTS: One-, 2-, and 5-year graft survival in the first era was 57%, 57%, and 50%, respectively, values that were significantly lower than those of ABO-compatible cases in the same period (n = 101), namely, 1-, 3-, and 5-year graft survival rates 93%, 83%, and 76%, respectively. The main reason for graft and patient losses was infectious complications. In the second era, no recipient suffered a severe infectious complication and 1- and 2-year graft survival rates were both 100%. Four patients in the first era and 1 in the second era experienced a graft rejection episode between 10 days and 14 months after transplantation, but they were successfully treated with steroid pulse therapy. CONCLUSION: Although patients with high blood group antibody titers remain problematic, ABO-incompatible LDKT is an increasingly viable option for patients whose only donor is blood group-incompatible.     

Intestinal bleeding during the treatment of chronic myeloid leukemia with imatinib mesylate

A 35-year-old woman attended our hospital with chronic myeloid leukemia and was prescribed imatinib mesylate. She was admitted with lower abdominal pain, stomatitis, and hyposthenia after an increase in her dose of imatinib mesylate. When the treatment was changed to interferon-alpha and Ara-C, the lower abdominal pain, stomatitis, and hyposthenia improved, but bone marrow aspiration showed 36.4% blasts. After the treatment was changed back to an increased dose of imatinib mesylate (800 mg), the stomatitis deteriorated and intestinal bleeding reoccurred. Endoscopy demonstrated the presence of multiple ulcers in the ascending colon and 99mTc RBC scintigraphy demonstrated lesions of the large and small intestine. The patient declined any treatment except for transfusion and died suddenly after ten days. The present case suggests that we should carefully consider the possibility of intestinal bleeding when prescribing imatinib mesylate.     

Cobalt chloride induces neurite outgrowth in rat pheochromocytoma PC-12 cells through regulation of endothelin-2/vasoactive intestinal contractor

We investigated whether endothelin-2/vasoactive intestinal contractor (ET-2/VIC) gene expression, upregulated by hypoxia in cancer cells, was associated with differentiation in neuronal cells. RT-PCR analysis, morphological observations, and immunostaining revealed that CoCl2, a hypoxic mimetic agent, at 200 microM increased expression of the ET-2/VIC gene, decreased expression of the ET-1 gene, and induced neurite outgrowth in PC-12 rat pheochromocytoma cells. These effects induced by 200 microM CoCl2 were completely inhibited by the antioxidant N-acetyl cysteine at 20 mM. In addition, CoCl2 increased the level of intracellular reactive oxygen species (ROS) at an early stage. Furthermore, interleukin (IL)-6 gene expression was upregulated upon the differentiation induced by CoCl2. These results suggest that expression of ET-2/VIC and ET-1 mediated by ROS may be associated with neuronal differentiation through the regulation of IL-6. When the cells were treated with 500 microM CoCl2 for 24 hr, however, ET-2/VIC gene expression disappeared, IL-6 gene expression was downregulated, and necrosis was subsequently induced in the PC-12 cells.     

T staging of gastric cancer: role of multi-detector row CT

PURPOSE: To evaluate retrospectively the accuracy of multi-detector row computed tomography (CT) in the assessment of serosal invasion in patients with gastric cancer. MATERIALS AND METHODS: The Ethics Committee does not require approval or informed consent for retrospective studies. Forty-one consecutive patients (24 men, 17 women; mean age, 68 years) with gastric cancer were included in this study. All patients were given 600 mL of tap water to drink and were positioned prone or supine on the scanning table. The detector row configuration included four detector rows, a section thickness of 1.25 mm, a pitch of 6, and a reconstruction interval of 0.63 mm. Transverse and multiplanar reconstruction images were simultaneously evaluated by two independent observers to assess the depth of tumor invasion in the gastric wall (ie, T stage). T staging at multi-detector row CT was compared with T staging at histologic evaluation (reference standard), which was performed by means of surgical or histologic examination of the resected specimen. We also calculated the sensitivity, specificity, and accuracy of multi-detector row CT for each observer in the assessment of serosal invasion. RESULTS: Analysis of interobserver agreement showed substantial or almost perfect agreement (nonweighted kappa value of 0.78 and weighted kappa value of 0.85). Correct assessment of gastric wall invasion was 80% and 85% for observers 1 and 2, respectively. The sensitivity, specificity, and accuracy of multi-detector row CT in the assessment of serosal invasion were 90%, 95%, and 93%, respectively, for observer 1 and 80%, 97%, and 93%, respectively, for observer 2. Overstaging occurred in six patients, and understaging occurred in five patients. All understaged tumors were scirrhous subtype gastric cancer. CONCLUSION: Multi-detector row CT scanning of patients with gastric cancer gave 93% accuracy in the assessment of serosal invasion in patients with gastric cancer.     

Prospective respiratory-triggered multidetector row CT (MDCT) for abdominal examinations: initial experience with a prototype

PURPOSE: To develop a prototype for prospective respiratory-triggered multidetector row computed tomography (MDCT) for abdominal examinations and to assess its feasibility. MATERIALS AND METHODS: The prototype consisted of the following components: an MDCT unit, personal computer (PC), and a respiratory motion detector in the form of a wearable belt with sensors to measure differences in pressure caused by breathing excursions. The registered signals were processed by the PC. The abdominal MDCT images of 10 healthy volunteers were obtained with an incremental axial technique in the expiration phase during normal breathing. Multiplanar reformations (MPR) were then performed. On the basis of the precision of these reconstructions, two radiologists then assessed the accuracy and applicability of the system. RESULTS: Coronal and sagittal MPR images from these prospective respiratory-gated examinations were found to be accurate. In particular, the continuity of borders and surfaces of scanned organs proved the exactness of the previously acquired respiration-correlated axial source images. CONCLUSION: This prototype is feasible to perform prospective respiratory-triggered abdominal MDCT examinations during normal respiration without breathhold. This system may be useful for patients with reduced compliance in holding their breath.     

MR appearances of radiofrequency thermal ablation region: histopathologic correlation with dog liver models and an autopsy case

RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate the utility of magnetic resonance (MR) imaging for indicating the extent of true tissue necrosis of the liver after radiofrequency (RF) ablation in comparison with histopathologic findings in dog models and an autopsy case. MATERIALS AND METHODS: RF ablation of the liver parenchyma was performed on three dogs under general anesthesia. MR appearances of the RF-ablated regions on T1-weighted fast-low angle shot (FLASH; repetition time/echo time [TR/TE]/flip angle: 120/3.8/70),T2-weighted turbo spin echo (3000/80/echo train = 25) and contrast-enhanced T1-weighted images were compared with histopathologic findings. An autopsy case with hepatocellular carcinoma was also enrolled in this study. RESULTS: All ablated regions showed three zones on T1-weighted FLASH images: a central zone with low intensity, a broad hyperintense middle zone, and a surrounding hypointense band. The central and middle zones corresponded to the degrees of coagulation necrosis observed during histopathologic examination, whereas no viable cells were seen in these zones during the microscopic examination using nicotinamide adenine dinucleotide diaphorase stain. The surrounding hypointense band corresponded to sinusoidal congestion in the acute phase and to fibrotic change in the subacute phase. CONCLUSION: MR imaging using the FLASH sequence can accurately determine the extent of the necrotic area after RF ablation.     

Single photon emission computed tomography and statistical parametric mapping analysis in cirrhotic patients with and without minimal hepatic encephalopathy

OBJECTIVE: The early diagnosis and treatment of cognitive impairment in cirrhotic patients is needed to improve the patients' daily living. In this study, alterations of regional cerebral blood flow (rCBF) were evaluated in cirrhotic patients using statistical parametric mapping (SPM). The relationships between rCBF and neuropsychological test, severity of disease and biochemical data were also assessed. METHODS: 99mTc-ethyl cysteinate dimer single photon emission computed tomography was performed in 20 patients with non-alcoholic liver cirrhosis without overt hepatic encephalopathy (HE) and in 20 age-matched healthy subjects. Neuropsychological tests were performed in 16 patients; of these 7 had minimal HE. Regional CBF images were also analyzed in these groups using SPM. RESULTS: On SPM analysis, cirrhotic patients showed regions of significant hypoperfusion in the superior and middle frontal gyri, and inferior parietal lobules compared with the control group. These areas included parts of the premotor and parietal associated areas of the cortex. Among the cirrhotic patients, those with minimal HE had regions of significant hypoperfusion in the cingulate gyri bilaterally as compared with those without minimal HE. CONCLUSIONS: Abnormal function in the above regions may account for the relatively selective neuropsychological deficits in the cognitive status of patients with cirrhosis. These findings may be important in the identification and management of cirrhotic patients with minimal HE.     

Oral Administration of Uracil-Tegafur (UFT) Inhibits Liver Micrometastasis of Human Colon Cancer in an Orthotopic Nude Mouse Model and Its Early Detection System

Purpose To evaluate the effect of UFT (an oral antineoplastic drug combining uracil and tegafur) as an adjuvant chemotherapy.Methods We examined whether UFT inhibits micrometastasis of the liver from colon cancer implanted into the cecum of nude mice in an orthotopic model. Moreover, we studied whether our early detection system using a polymerase chain reaction (PCR) of the human -globin gene would be useful in this model.Results The administration of 20mg/kg UFT p.o., which is a relatively small dose compared with 65mg/kg of the maximum tolerated dose of this drug in mice, inhibited liver metastasis completely when started immediately after a cecectomy (micrometastasis present at this time), but did not inhibit liver metastasis significantly when started at 4 weeks after a cecectomy (gross tumor present at this time). There were no severe toxicities at this dose. In our PCR study, all livers in 10 mice to which therapy was given immediately after a cecectomy and without liver metastasis showed no PCR-amplified fragment, while 7 of 10 livers in the nontreatment group in which gross liver metastases were not observed demonstrated this fragment.Conclusions These findings indicate that UFT is useful for either adjuvant chemotherapy or the inhibition of micrometastasis, and our system to detect micrometastasis by examining the human -globin gene is useful for the early evaluation of the efficacy of these drugs.