Pharmacologic preconditioning effects: Prostaglandin E1 induces heat-shock proteins immediately after ischemia/reperfusion of the mouse liver

Prostaglandin E1 (PGE1) has several potential therapeutic effects, including cytoprotection, vasodilation, and inhibition of platelet aggregation. This study investigates the protective action of PGE1 against hepatic ischemia/reperfusion injury in vivo using a complementary DNA microarray. PGE1 or saline was continuously administered intravenously to mice in which the left lobe of the liver was made ischemic for 30 minutes and then reperfused. Livers were harvested 0, 10, and 30 minutes postreperfusion. Messenger RNA was extracted, and the samples were labeled with two different fluorescent dyes and hybridized to the RIKEN set of 18,816 full-length enriched mouse complementary DNA microarrays. Serum alanine aminotransferase and aspartate aminotransferase levels at 180 minutes postreperfusion were significantly lower in the PGE1-treated group than in the saline-treated group. The cDNA microarray analysis revealed that the genes encoding heat-shock protein (HSP) 70, glucose-regulated protein 78, HSP86, and glutathione S-transferase were upregulated at the end of the ischemic period (0 minutes postreperfusion) in the PGE1 group. Our results suggested that PGE1 induces HSPs immediately after ischemia reperfusion. HSPs might therefore play an important role in the protective effects of PGE1 against ischemia/reperfusion injury of the liver.     

Sentinel node sampling limits lymphadenectomy in stage I non-small cell lung cancer.

OBJECTIVE: It is controversial whether a systematic mediastinal lymph node dissection (MLND) needs to be performed in all patients with stage I lung cancer. The present study was done to examine the new sentinel lymph nodes hypothesis based on the lobe of the primary tumor. METHODS: In our first study, the lymph node (LN) metastases were assessed in 291 stage I non-small cell lung cancer (NSCLC) patients who had a major lung resection with a systematic mediastinal lymph node dissection. We evaluated the validity of using our new sentinel lymph nodes method based on the lobe of the primary tumor as follows: the pretracheal (#3), tracheobronchial (#4), and hilar nodes (#10) for right upper lobe tumors; #4, subcarinal (#7), and #10 for middle lobe tumors; the subaortic (#5), paraaortic (#6), and #10 for left upper lobe tumors; and the #7, #10, and interlobar nodes (#11) for tumors in either lower lobes. In the second study, we performed a lobectomy with new sentinel node sampling in 64 patients with preoperative complications. If all of the sampling nodes showed no metastases on frozen section diagnosis, systematic node dissections were not performed. RESULTS: Six of 291 patients in the first study had skip metastases that did not involve the new sentinel nodes; 5 of the 6 patients had macroscopic pleural invasion. Thus, we defined pleural invasion as an exclusion criterion for the second study. In the second study, the median follow-up time was 39 months. Metastatic lymph nodes were detected in 11 of 64 patients. Fifty-three patients (83%) had no metastasis in the sampled nodes, and, therefore, a mediastinal lymph node dissection was not done. The morbidity rate in the sampling group was 36%, and there was no mortality. In the sampling group, local recurrences were observed in two patients, distant metastases in eight, and carcinomatous pleuritis in one; the overall 5-year survival rate was 82%. CONCLUSIONS: We found that it is possible to perform a less invasive lymphadenectomy for patients with stage I lung cancer using intra-operative sampling of new sentinel lymph nodes.     

The Japanese experience with metabolic imaging in the clinical setting

Conclusions  Reduced utilization of fatty acids at rest often is observed in severely ischemic myocardium and possibly postischemic myocardium despite normal perfusion at rest. The role of metabolic imaging in identifying postischemic insult as ischemic memory imaging has been the focus of recent investigations. A number of reports from Japan show quite acceptable diagnostic accuracy of BMIPP imaging for detecting coronary patients without prior MI. In addition, recent data indicate that BMIPP imaging has prognostic value when applied in patients with documented or suspected coronary disease. The major advantage of BMIPP imaging is to demonstrate ischemic myocardium as an area of altered metabolism at rest. Thus this study is of clinical importance for elderly patients or for patients not suitable for a stress study. Furthermore, this radiopharmaceutical tracer may hold promise in demonstrating early alteration of energy metabolism in a variety of myocardial disorders.     

Glial localization of four‐repeat tau in atypical progressive supranuclear palsy

In the present case, a patient in whom limb apraxia and asymmetrical parkinsonism developed suggesting corticobasal degeneration, is reported. Neuropathologic examination revealed numerous tufted astrocytes in the precentral cortex in addition to the characteristic pathologic findings of PSP. Therefore, on the basis of clinicopathologic features, atypical progressive supranuclear palsy was diagnosed. In addition, the brain tissue of the present patient was investigated with an antibody specific for four‐repeat tau (4R‐tau). In the precentral cortex, numerous tau‐positive tufted astrocytes, pretangles, and threads were positive for 4R‐tau. Using a confocal microscopy we demonstrated that tufted astrocytes positive for 4R‐tau were adjacent to astrocytes positive for GFAP. The present findings suggest that accumulation of four‐repeat tau in astrocytes is a degenerative process rather than a reactive process.     

Bilateral internal mammary artery grafts for coronary artery bypass operations in children

We performed myocardial revascularization with bilateral internal mammary arteries in eight children for coronary artery complications consequent to Kawasaki disease. Subjects included seven boys and one girl, ranging in age from 3 to 13 years (mean age, 8.3 +/- 3.4 years). The body surface area ranged from 0.65 to 1.65 m2 (average, 1.08 +/- 0.35 m2). Three patients had a previous myocardial infarction. The right internal mammary artery was anastomosed to the right coronary artery and the left internal mammary artery was sutured to the left anterior descending artery in all patients. The patients received an average of 2.4 grafts. Magnifying loupes of 3.5 X were used for anastomosis with 8-0 monofilament polypropylene sutures. Subjects were followed up from 12 to 38 months (23 +/- 10.8 months) after operation. All were doing well with no recurrence of angina, and body development was normal, including the sternum and thorax according to chest x-ray films and computed tomography of the chest. Patency of the bilateral internal mammary arteries was 100% in the early (within 1 month) postoperative period and remained so in the late (over 1 year) postoperative period. Anastomotic junctions between the internal mammary artery and the coronary artery developed well angiographically in the late postoperative period. The internal mammary artery is the graft of choice for pediatric myocardial revascularization because of its excellent long-term patency and growth potential. Bilateral internal mammary arteries should be used whenever indicated, and the use of bilateral internal mammary arteries did not adversely influence chest wall development in the children.     

Evaluation of blood flow patterns of true and false lumens in dissecting aneurysms using MR phase-contrast techniques

The magnetic resonance phase-contrast technique for the measurement of flow velocity and volume in true and false lumens was studied in six patients with chronic dissecting aneurysms. Phase-contrast images were obtained at a level perpendicular to the dissecting aneurysms of the descending aorta. As the maximum diameter of aneurysms increased, the ratio of the cross-sectional area of the false to the true lumen increased and the peak average velocity in the true lumen during systole was decreased. This technique proved invaluable for determining prognosis and operability for this condition.     

High Cell-Density Culture System of Hepatocytes Entrapped in a Three-Dimensional Hollow Fiber Module with Collagen Gel

Abstract: A compact three-dimensional (3D) module is needed for hepatocyte culture in order to develop an effective hybrid artificial liver system that can retain hepa-tocellular structure and differentiated functions. We treated the 3D module with collagen gel to entrap rat hepatocytes. This method yielded a high hepatocellular density (2 times 10⁷ cells/ml) over a period of 14 days and maintained the secretion of albumin and ureogenesis at the same level as the control monolayer method. The ammonia removal remained at 43% of the Day 0 value over 8 days of perfusion. Our data show that this approach may be useful for liver support therapy in an ex-tracorporeal circuit.     

Cystic thyroid masses: ultrasonographic and pathologic correlation

Forty-nine patients with 63 cystic thyroid masses who had undergone preoperative sonography were retrospectively reviewed. 52 lesions (83%) were benign and others (17%) were malignant. Among various sonographic findings of cystic thyroid masses, oval cystic lesions with polyp or dome like solid component projecting into the lumen were all diagnosed adenomatous goiter. Irregular cystic structures with more than 2 cm finger like pedunculated mass extended into and/or out of the lumen were all diagnosed papillary carcinoma. Small oval cysts (less than or equal to 1 cm) with strong echo were all diagnosed colloid goiter. The other sonographic type of cystic thyroid masses had somewhat malignancy (12-30%), not having characteristics which differentiate benign from malignant lesions. Pathologic findings of malignant lesions showed that cancer cells existed rather in pericystic portion than in cyst wall except for finger like solid component projecting into the lumen which was papillary carcinoma itself. Ultrasonically guided needle biopsy should be performed to get samples of above portions.     

Hyperthermo-chemo-radiotherapy as a definitive treatment for patients with early esophageal carcinoma.

Ten patients with early stage esophageal carcinoma were treated with hyperthermo-chemo-radiotherapy (HCR) without surgery. The reasons for the inoperability of these patients included medically inoperable unresectable cancers, advanced age, and/or refusal to undergo surgery. The diagnosis of early esophageal carcinoma was determined by esophagograms, endoscopy, and ultrasonography. Squamous cell carcinoma was histopathologically confirmed in each case. Each patient underwent four to nine sessions of hyperthermic treatment combined with external irradiation and chemotherapy using bleomycin; eight of these patients received additional radiation, and two terminated treatment after the HCR therapy. The tumors in all patients showed either a complete response (CR) or a partial response (PR) after HCR therapy; in two patients viable cancer cells remained, but later disappeared after additional radiation. Five patients experienced no local recurrence for 12 to 70 months and are now alive and doing well, three died of other medical conditions without any evidence of esophageal cancer, and two died of recurrent esophageal cancer 20 to 27 months after initial admission. All ten patients tolerated the HCR well without any systemic side effects. However, in two patients, esophageal erosion was recognized endoscopically. HCR therapy therefore deserves serious consideration when treating patients with small malignant lesions of the esophagus who, for various reasons, are unable to undergo surgery.     

Integration of informations gained from heterogeneic world of myocardial function and ischemia]

Currently, heterogeneity is the word to describe any inhomogeneous phenomenon observed in the ever changing living creatures. Myocardial function is dynamic in nature which is a summation of many inhomogeneous components. In fact, heterogenic phenomenon has been observed both at cellular and at ventricular levels during myocardial contraction and relaxation. However, this heterogenic behavior of myocardial activities serves as a source of monitoring parameters by which we can grasp what is happening in the patient. Reliance on only one of those parameters would lead to a wrong diagnosis and judgement in the heterogenic world. We, therefore, need to integrate those parameters to form more realistic image about patient's status. We have to have a cut off point to divide what is right and what is wrong. Although the truth may not be reached eventually from heterogeneous informations, an appropriate method to integrate informations in the heterogenic world will aid us to come closer to the reality.