A case of malignant fibrous histiocytoma with metastatic brain tumors after tumorgenic embolism]

A 61-year-old man had been treated for malignant fibrous histiocytoma with the pulmonary and the lymph node metastasis in the department of orthopedics in our hospital. He was admitted to our department because of an acute onset of conscious disturbance and non-fluent aphasia. Diffusion-weighted imaging (DWI) showed high signal intensity areas in the bilateral cerebella, thalami and posterior lobes. T2WI did not show any mass effects. Enhanced CT did not reveal any enhanced lesion. He was diagnosed as having cerebral embolism, and his conscious disturbance was improved after medication. Eight weeks later, he presented dysphagia, dysarthria, and ataxia in his extremities. DWI showed multiple lesions of low signal intensity located at the identical place where had showed high signal intensity in the initial DWI. T2WI showed high signal intensity area with mass effect. It was indicated that cerebral metastasis might grow after tumorgenic embolism. This is a rare case that tumor emboluses were developed to the metastatic brain tumors.     

Glucocorticoid receptor enhancement of pregnane X receptor-mediated CYP2B6 regulation in primary human hepatocytes.

Although the glucocorticoid receptor (GR) facilitates the xenobiotic-induced expression of CYP2B in rodents, its role in the regulation of human CYP2B6 is unclear. In this report, the role of human GR in the regulation of CYP2B6 was evaluated using primary human hepatocytes and transfection assays with Huh7 cells. CYP2B6 expression was not induced in primary hepatocytes treated with dexamethasone (DEX) concentrations (0.01-1 microM) known to activate GR. In contrast, treatment with 0.1 microM DEX enhanced CYP2B6 induction by different pregnane X receptor (PXR) activators, including rifampin, phenytoin, clotrimazole, and phenobarbital. In Huh7 cells, cotransfection of human (h)GR and hPXR with CYP2B6-phenobarbital-responsive enhancer module (PBREM) reporter constructs revealed that all hPXR ligands induce CYP2B6 reporter gene activity, and this ligand-dependent activation is greatly enhanced by activated hGR. CYP2B6 reporter gene expression was not induced in the presence of hPXR ligands when hGR alone was cotransfected with CYP2B6 reporter construct. In hGR and human constitutive androstane receptor (hCAR) cotransfection assays, activated hGR increased the constitutive activation of PBREM reporter constructs by hCAR in the absence of inducers. In the presence of activated hGR and known inducers of CYP2B6, only PB treatment caused a further 2-fold activation of hCAR compared with control. These studies show that hGR is involved synergistically in the xenobiotic-responsive regulation of human CYP2B6 by hPXR and hCAR. Moreover, the results suggest that the GR-enhanced expression of CYP2B6 is mediated through an indirect mechanism that does not require increased expression of nuclear receptor.     

The limitation of staged repair in the surgical management of congenital complex heart anomalies with aortic arch obstruction

OBJECTIVE: Severe aortic arch obstruction including an interrupted aortic arch in congenital complex heart anomalies remains a challenge in surgical management. METHODS: Treatment and outcomes in 75 consecutive patients who underwent an aortic arch repair as the first step of the staged repair protocol between 1975 and 2000 were reviewed. Their ages at repair ranged from 1 day to 8.5 months. RESULTS: Cross-sectional postoperative follow-up data were available in all the patients. The follow-up period ranged from 0 to 27.6 years (mean: 7.3 +/- 7.3 years). There were 20 postoperative hospital deaths (27%) and 7 late deaths. The Kaplan-Meier estimate of survival was 81.3% +/- 4.5% at 1 month, 68.0% +/- 5.4% at 1 year, 65.0% +/- 5.5% at 5 years, 63.1% +/- 5.7% at 10 years, 63.1% +/- 5.7% at 20 years. By Cox regression analysis, body weight of 2.5 kg or less is the only independent determinant of postoperative mortality (p = 0.04, multivariable odds ratio: 2.50, [95% confidence interval: 1.02-6.1]). The aortic arch morphology, the primary cardiac lesion, or date of operation did not reach a statistically significant level to show correlation with mortality. Reintervention to reconstruct the aortic arch was performed at 9 occasions in 8 of the 55 patients who survived the primary operation (14.5%). The Kaplan-Meier estimate of the reintervention-free rate was 91.3% +/- 4.2% at 5 years, 85.5% +/- 5.6% at 10 years, 75.6% +/- 8.2% at 20 years. Using multivariable Cox regression analysis, interrupted aortic arch (versus aortic coarctation) was the only independent predictor of a shorter time to reintervention (p = 0.001, multivariable odds ratio: 16.1, [95% confidence interval: 3.2-80.2]). CONCLUSIONS: The staged repair protocol was associated with significant limitations in patient survival and with the development of recurrent aortic arch obstruction. Thus, a primary repair protocol may serve as an alternate approach, especially in patients with low weight or with an interrupted aortic arch.     

Efficacy of continuous cleansing with teicoplanin on post-CABG methicillin-resistant staphylococcus aureus (MRSA) mediastinitis: report of a case.

The patient was a 48-year-old male who was diagnosed with unstable angina. He had worsening cardiogenic shock during coronary angiography. Emergency coronary artery bypass grafting (CABG) was performed. He had a methicillin-resistant Staphylococcus aureus (MRSA) mediastinitis on day 22 after CABG. Drains were placed in the anterior mediastinum, left thoracic cavity, and abscess cavity, and another drain was placed in the mediastinal space for continuous cleansing with povidone iodine, oxydol. For antibiotics, teicoplanin (TEIC) was administered intravenously and to the local site via the cleansing drain for about one month. No MRSA was detected by culture in discharges from the mediastinal drain. Inflammatory findings were improved, and the patient was discharged and resumed everyday life without recurrence of inflammation as of eight months. Although the number of cases of MRSA mediastinitis is small and accumulation of cases is necessary to investigate therapeutic methods and selection of antibiotics, our department will select closed continuous cleansing and TEIC for antibiotics as the first choice for MRSA mediastinitis, and accumulate cases to investigate its efficacy.     

Involvement of phosphoinositide metabolism in GABA-induced catecholamine release from cultured bovine adrenal chromaffin cells

The effects of GABA on catecholamine release and phosphoinositide metabolism were studied in cultured bovine adrenal chromaffin cells. GABA and muscimol, a specific agonist for the GABAA receptor, each evoked a gradual secretion of catecholamines from the cells in the presence of ouabain, an inhibitor of Na+, K(+)-ATPase. This release was inhibited by bicuculline, a specific antagonist for the GABAA receptor, or by picrotoxin, a blocker of GABA-gated Cl- channels, and was potentiated by diazepam or pentobarbital. GABA or muscimol induced a concentration-dependent formation of inositol phosphates. This accumulation of inositol phosphates was also inhibited by bicuculline, picrotoxin or removal of extracellular Ca2+, and also potentiated by diazepam and pentobarbital. Nicardipine suppressed GABA-induced catecholamine release in the presence of ouabain and accumulation of inositol phosphates, while verapamil, diltiazem, and omega-conotoxin failed to inhibit these responses to GABA. The phosphoinositide-specific phospholipase C inhibitor neomycin also inhibited both GABA-induced accumulation of inositol phosphates and stimulation of catecholamine release in the presence of ouabain. These results taken together indicate that GABA evoked catecholamine release from the chromaffin cells in the presence of ouabain by stimulation of phosphoinositide metabolism in a Ca2(+)-sensitive manner via activation of GABAA receptor-coupled Cl- channels.     

Hepatocellular carcinoma: Efficacy of transcatheter oily chemoembolization in relation to macroscopic and microscopic patterns of tumor growth among 100 patients with partial hepatectomy

Purpose: To evaluate the efficacy of transcatheter oily chemoembolization (TOCE) for hepatoceliular carcinoma (HCC) on the basis of microscopic and macroscopic findings postembolization. Methods: HCCs ranging in size from 0.5 to 13 cm (mean 3.6 cm) were obtained from partial hepatectomies of 100 consecutive patients who had undergone TOCE between 20 and 246 days (mean 59.5 days) prior to surgery. The efficacy of TOCE was assessed on the basis of the necrotic to live cell ratio of the tumors. The microscopic pattern of tumor growth was grouped into expanding type (complete capsule formation) and replacing type (incomplete or no capsule). There were five types of macroscopic groupings: single nodule, single nodule with extranodular growth (SNE), contiguous and noncontiguous multinodular, and massive growth type. Results: Among 79 cases with the expanding type, 29 (37%) had 100% HCC necrosis, but none with 100% necrosis were in the replacing type. By macroscopic grouping, the efficacy of TOCE decreased from the single nodule type (50% of patients had 100% necrosis) to the SNE type (21%), and the other types (9%).     

Effect of halothane and enflurane on hepatic blood flow and oxygen consumption in dogs

We investigated the relative effects of 0.5, 1.0, 1.5, 2.0 MAC halothane and enflurane, and concurrent noxious stimulus on hepatic blood flow and oxygen consumption in 14 mongrel dogs randomly divided into groups of seven each. Hepatic arterial and portal venous blood flow (HABF and PVBF, respectively) were measured continuously using ultrasonic transit time flow meter. Mean arterial blood pressure (MAP), cardiac index (CI), hepatic oxygen supply, and hepatic oxygen consumption (H _{O 2}) were measured. Halothane significantly deceased HABF, but not PVBF in a dose dependent manner. Enflurane did not affect HABF and PVBF significantly. MAP and CI decreased in both groups, with halothane producing more marked decreases than enflurane. H _{O 2} did not change with enflurane, but did with halothane, producing significant differences, with halothane being greater at 1.5, 2.0 MAC. A noxious stimulus only caused minor change in blood flow. The results suggest that liver blood flow and oxygen consumption are affected differently by halothane and enflurane and that halothane has a stronger tendency to cause an imbalance between liver oxygen supply and consumption than dose enflurane.(Masaki E, Yasuda N, Tanifuji Y et al.: Effect of halothane and enflurane on hepatic blood flow and oxygen consumption in dogs. J Anesth 3: 118–122, 1989)     

Effects of nitrendipine on the autoregulation of regional cerebral blood flow in the pithed rabbit

Summary Effects of the calcium-channel antagonist, nitrendipine, on the autoregulation of regional cerebral blood flow were studied by analysing the pressure-flow relationship in the cortex, subcortex and thalamus in pithed anesthetized rabbits. Arterial pressure was altered from 50 to 125 mm Hg by electrical stimulation of the spinal nerve roots. Regional blood flow was measured with the hydrogen clearance technique. Under control conditions, regional blood flow in the cortex, subcortex and thalamus did not change significantly within the range of mean arterial pressures of 50 to 100 mm Hg. Vascular resistance in each region rose significantly (P < 0.05) in a pressure-dependent manner. During the intravenous infusion of nitrendipine (0.3 and 1 g · kg^–1 · min^–1), blood flow to the three regions of the brain increased in a pressure-dependent manner when mean arterial pressure was increased from 50 to 125 mm Hg. The autoregulatory increase in regional vascular resistance was abolished. In addition, nitrendipine produced a blood pressure-dependent decrease of the vascular resistance in the subcortex and thalamus but not in the cortex. These results indicate that nitrendipine increases regional cerebral blood flows and suppresses regional autoregulations simultaneously. The autoregulatory adjustment in the cortex is more resistant to nitrendipine than that in the subcortex and thalamus. The observation that the action of nitrendipine was not the same in the three brain regions may be due to the vascular beds of these regions differing in their calciumchannel equipment.