Molecular mechanisms of altered cholesterol metabolism in rats with spontaneous focal glomerulosclerosis

BACKGROUND: Imai rats exhibit spontaneous focal glomerulosclerosis (FGS), which is marked by heavy proteinuria, severe hyperlipidemia, and progressive renal insufficiency beginning at 8 to 10 weeks of age. In an earlier study, we reported severe skeletal muscle and adipose tissue lipoprotein lipase, and very low-density lipoprotein (VLDL) receptor deficiencies, which account for elevated plasma VLDL and triglycerides in Imai rats at 34 weeks of age. In this study, we investigated key factors involved in cholesterol metabolism. METHODS: Male Imai and Sprague-Dawley control rats were fed a regular rat chow and observed from age 8 through 34 weeks. Hepatic 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase, cholesterol 7alpha-hydroxylase, low-density lipoprotein (LDL) receptor and acyl Co A:cholesterol acyltransferase (ACAT) were measured by Western blot and plasma lecithin:cholesterol acyltransferase (LCAT) protein was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: At 34 weeks of age, the Imai rats showed severe proteinuria, hypoalbuminemia, 60% reduction in glomerular filtration rate (GFR), elevated plasma total and LDL cholesterol and LDL/high-density lipoprotein (HDL) ratio. Imai rats showed a twofold elevation of hepatic HMG-CoA reductase, the rate-limiting step in cholesterol biosynthesis, but no significant change in cholesterol 7alpha-hydroxylase, the rate-limiting enzyme in cholesterol catabolism to bile acids. This was accompanied by and largely due to a threefold down-regulation of hepatic LDL receptor, which limits hepatic uptake of LDL; and a threefold up-regulation of hepatic ACAT (P < 0.01), which augments esterification of hepatocyte free cholesterol, thus, limiting cholesterol-mediated feedback regulation of cholesterol synthesis and catabolism. Moreover, plasma LCAT concentration was severely depressed (by fourfold) in Imai rats. This abnormality can impair HDL-mediated cholesterol transport from extrahepatic tissues to the liver. CONCLUSION: The study revealed marked abnormalities of the key proteins involved in regulation of hepatic cholesterol metabolism. These abnormalities can account for severe dysregulation of cholesterol metabolism in Imai rats with spontaneous FGS, which closely resembles FGS in humans.     

Effects of barium concentration on the radiopacity and biomechanics of bone cement: experimental study

Purpose  This study was undertaken to evaluate the changes in the radiopacity and mechanics of polymethylmethacrylate (PMMA) bone cement with the addition of barium. Materials and methods  Barium sulfate powder was added to a PMMA bone cement with an initial 10% barium concentration. The changes in radiopacity and strength were evaluated by testing cement blocks containing four barium concentrations (10%, 20%, 30%, 40%). Radiopacity was evaluated by measuring the computed tomography (CT) values of the bone cement, and strength was evaluated by compressive, three-point bending, and impact load tests. Results  CT values increased in proportion to the barium concentration. The compressive load test showed that cement with a 40% barium concentration was significantly more fragile than cement with lower barium concentrations. The three-point bending load test showed that the cement became more fragile in proportion to the barium concentration. The impact load test showed that cement with 30% and 40% barium concentrations was significantly more fragile than cement with 10% and 20% barium concentrations. Conclusion  Radiopacity is increased and strength is reduced by adding increasing concentrations of barium powder to bone cement. The results of the present study suggest that adding barium permits the radiopacity and strength of bone cement to be adjusted in clinical practice.     

Transition of ventricular function and energy efficiency after a primary or staged Fontan procedure

PURPOSE: The transitional changes of the ventricular function at different time points after total cavopulmonary connection (TCPC) were examined. METHODS: A total of 29 patients were divided into a primary TCPC group and a staged TCPC group. In both groups, phase I was defined as within 2 months after TCPC and phase II as beyond at least a year after TCPC. Changes in ventricular end-diastolic volume (EDV), ventricular end-systolic elastance (Ees), effective arterial elastance (Ea), and ventriculoarterial coupling (Ea/Ees) were evaluated. RESULTS: The results for the primary TCPC group are as follows. Phase I: The EDV decreased (P < 0.05). The Ees and Ea both increased (P < 0.05). Ea/Ees showed a tendency to increase (P = 0.08). Phase II: The EDV decreased (P < 0.05). The Ees increased significantly, and Ea showed no significant change. Ees/Ea showed a tendency to decrease (P = 0.07). The results for the staged TCPC group were as follows. Phase I: The EDV decreased significantly after bidirectional cavopulmonary shunt (BCPS). The Ees showed no significant change after BCPS and TCPC. Although Ea increased after BCPS (P < 0.05), it showed no significant change after TCPC. Ea/Ees showed no significant change. Phase II: The Ees increased (P < 0.05) without significant changes of EDV and Ea. As a result, Ea/Ees showed a tendency to decrease. CONCLUSION: This study suggested improved ventricular function in both groups. These results suggest hemodynamic adaptation to the Fontan circulation. The deleterious effects on ventricular function caused by the Fontan procedure disappeared within a couple of years. This acute effect can be ameliorated by the staged approach to the Fontan circulation.     

Preoperative evaluation of a tracheal bronchus by three-dimensional 64-row multidetector-row computed tomography (MDCT) bronchography and angiography: Report of a case

We performed successful surgery for lung cancer after confirming the anatomical abnormality of a tracheal bronchus by three-dimensional multidetector-row computed tomography (3D-MDCT) bronchography and angiography. Tracheal bronchus is unusual, and right upper lobectomy for lung cancer would rarely be performed in a patient with a tracheal bronchus. Most clinicians are unfamiliar with the anatomy of a right upper lobe that includes a tracheal bronchus. Preoperative 3D imaging of the tracheal bronchus and its related vessels familiarized us with the anatomy of this patient before the operation. Thus, we recommend preoperative 3DMDCT bronchography and angiography, especially for patients with a possible bronchial anomaly.     

Total cavo-pulmonary connection without foreign material for asplenic heart associated with partial anomalous pulmonary venous connection

The presented case was a 3-year-old boy diagnosed with asplenia (SLL), double outlet right ventricle, pulmonary stenosis, atrioventricular septal defect, hypoplastic left ventricle and partial anomalous pulmonary venous connection to the superior vena cava. Partial anomalous pulmonary venous connection was repaired by translocation of pulmonary artery to avoid pulmonary venous obstruction when Glenn anastomosis was performed. Total cavo-pulmonary connection was established by re-routing the inferior vena cava to pulmonary artery using the atrial septal remnant and the left atrium free wall flap.     

Spindle epithelial tumor with thymus-like differentiation (SETTLE) of the thyroid

BACKGROUND: Tumors of the so-called intrathyroidal epithelial thymoma type are a rare group of thyroid neoplasm tumors. Of this type of tumor, spindle epithelial tumor with thymus like differentiation (SETTLE) has been reported only 17 times in English literature. METHODS: An 18-year-old woman was initially seen with a 6-cm left thyroid mass that was resected with a left thyroidectomy. Histopathologic features of the excised left thyroid tumor together with an immunohistochemistry and electron microscopy led us to a diagnosis of SETTLE. RESULTS: Most of the specimen was composed of highly cellular spindle cells that formed intersecting and streaming fascicles. The spindle cells showed both vimentin immunoreactivity and cytokeratin immunoreactivity but no immunoreactivity for thyroglobulin or calcitonin. Electron microscopic examination of the spindle cells demonstrated prominent cytoplasmic tonofilaments, desmosomes, and basal lamina consistent with epithelial cell origin. DNA content analysis by flow cytometry revealed DNA diploidy. CONCLUSIONS: SETTLE of thyroid gland is an extremely rare entity. A review of the literature reveals that SETTLE has distinctive morphologic features and an immunohistochemical profile.     

Selected ventriculoplasty for idiopathic dilated cardiomyopathy with advanced congestive heart failure: midterm results and risk analysis

Background: To treat advanced heart failure due to idiopathic dilated cardiomyopathy, surgical ventricular restoration with mitral reconstruction was conducted and evaluated. Methods: In 95 patients (81 men, mean age: 54 years), New York Heart Association class III/IV was 44/51, and 33 patients (36%) were inotropic dependent preoperatively. Mitral regurgitation (≥2+) was noted in all patients. All patients underwent left ventriculoplasty (septal anterior ventricular exclusion in 38, partial left ventriculectomy in 57) and mitral reconstruction (repair 53, replacement 42). Fifty-two patients (55%) had concomitant tricuspid repair. Intra-aortic balloon pumping and left ventricular assist device was used in 24 patients and two patients, respectively. Results: Hospital mortality was 11.6% (11 of 95), with 6.6% (5 of 76) in elective and 31.6% (6 of 19) in emergency operations. The ejection fraction and cardiac index increased from 22.3 ± 6.3% to 27.2 ± 8.0% and from 2.3 ± 0.5 ml/m²/min to 2.8 ± 0.5 ml/m²/min, respectively (p < 0.001). The endodiastolic volume index, endosystolic volume index and diastolic dimension decreased from 232.9 ± 56.1 ml/m² to 160.0 ± 49.8 ml/m², from 178.9 ± 46.7 ml/m² to 113.8 ± 44.7 ml/m² and from 82.0 ± 9.0 mm to 68.9 ± 11.6 mm, respectively (p < 0.001). Late death occurred in 27 patients with 22 cardiac deaths. The mean NYHA class was 1.7 among the survivors. One-, 3- and 5-year survival rates were 72.8%, 61.4% and 50.5%, respectively. In the 62 patients who were non-inotropic dependent preoperatively, 1-, 3-, and 5-year survival rates (81.8%, 73.7% and 62.9%) were significantly better than the inotropic-dependent group (55.3%, 37.3% and 28.0%). Patients with mitral annuloplasty showed a significantly higher 5-year survival rate than patients with mitral valve replacement (59.6% vs 43.6%) in univariate analysis. By application of the exclusion site selection method, the two different ventriculoplasty procedures did not show significant difference in survival rates. Multivariate analysis showed that preoperative inotropes and old age were significant predictors for postoperative mortality. Conclusion: The selected ventriculoplasty in combination with mitral annuloplasty is a useful option for patients with an extremely dilated left ventricle in idiopathic dilated cardiomyopathy. Surgery should be considered before inotropic dependency occurs when prior medical treatment has failed.     

Comparative results of conservative treatments for isolated anterior talofibular ligament (ATFL) injury and injury to both the ATFL and calcaneofibular ligament of the ankle as assessed by subtalar arthrography

Background There have been no reports describing the results of conservative treatment of acute lateral ligament injury of the ankle in detail in terms of the severity of the injury, and the results of conservative treatment for injury with severe instability are still controversial. The purpose of this study was to assess the results of nonoperative treatment of acute lateral ligament injury according to its severity. Methods Fifty-five consecutive acute lateral ankle ligament injuries in 54 patients who were treated nonoperatively were followed up as a prospective study. Twenty-seven were male patients and 27 were female patients; the average age was 23.9 years (12–55 years). The patients were divided into two groups according to the extent of the ligament injury: patients with an isolated injury of the anterior talofibular ligament and those with combined injuries of the anterior talofibular ligament and the calcaneofibular ligament. In addition to the routine examinations for inversion ankle sprain, subtalar arthrography was mainly used to assess the condition of the calcaneofibular ligament. The arthrography was performed an average of 3.5 days after the injury (0–5 days). Results Fifty-five ankles of patients who were treated nonoperatively according to the same protocol were included in this study, and were followed up for an average of 5.0 years (37–86 months). At the time of the final follow-up, 22 of 25 (88%) ankles with an isolated injury to the anterior talofibular ligament were asymptomatic; in contrast, only 9 of 30 (30%) ankles with combined injuries of the anterior talofibular and calcaneofibular ligament were asymptomatic. The average American Orthopaedic Foot and Ankle Society score of the isolated injuries was 97.8 points, in contrast to 92.4 points for the combined injuries. Conclusions The results of nonoperative treatment with 1 week immobilization followed by a functional brace were excellent in patients with an isolated injury of the anterior talofibular ligament, but were unsatisfactory in those with combined injuries of the anterior talofibular and calcaneofibular ligaments.     

A novel approach to restore atrial function after the maze procedure in patients with an enlarged left atrium.

OBJECTIVE: Left atrial (LA) volume reduction surgery concomitant with the maze procedure has been reported to facilitate sinus rhythm recovery even in patients with refractory atrial fibrillation (AF) with an enlarged LA. However, it is unknown whether the procedures can also restore effective atrial function of the enlarged LA with over-stretched myocardium. METHODS: The maze procedures in association with mitral valve surgery were performed to 57 AF patients with an enlarged LA (LA diameter >or=60mm). Among them, 32 patients had concomitant LA volume reduction surgery (VR group). Another 25 patients did not have the volume reduction (control group). RESULTS: Three months postoperatively LA end-diastolic volume (LAEDV, ml) assessed by magnetic resonance (MR) imaging was larger in the VR group than that in the control group (291+/-117 vs 223+/-81 ml, p<0.05). Postoperatively, sinus rhythm recovery rate was better (84 vs 68%, p<0.05) and LAEDV was drastically smaller (118+/-48 vs 203+/-76 ml, p<0.001) in the VR group than those in the control group. Among the patients with sinus rhythm recovery in both groups, LA contraction ejection fraction (%) improved in the VR group but not in the control group (22.3+/-7.8 vs 10.3+/-4.7%, p<0.001). CONCLUSIONS: The LA volume reduction surgery concomitant with the maze procedure restored contraction of the enlarged LA; however, the maze procedure alone did not restore LA contraction in spite of successful sinus rhythm recovery. LA volume reduction surgery may be desirable to the patients with refractory AF with over-stretched LA.     

Delayed thromboembolic infarction associated with reconfiguration of Guglielmi detachable coils--case report

A 77-year-old woman presented with delayed thromboembolic infarction of a basilar artery trunk aneurysm that occurred 2 weeks after coil embolization of the unruptured aneurysm. The postoperative course was uneventful until the patient suffered sudden onset of consciousness disturbance 13 days after the treatment. Computed tomography showed no abnormality, but digital subtraction angiography revealed a thrombus extending from the aneurysm neck to a point distal to the basilar artery. Thrombolysis was achieved by the infusion of urokinase. Reconfiguration of the coil at the aneurysm neck was revealed compared with the initial configuration of the coil immediately after embolization. Magnetic resonance imaging obtained after the thrombolysis showed hyperintense areas in the bilateral occipital lobes and thalami. Periprocedural thromboembolic complications associated with coil embolization of an aneurysm are well known. However, delayed thromboembolic complications may occur in some patients after successful coil packing of an aneurysm.