Indications of partial hepatectomy for transplantable hepatocellular carcinoma with compensated cirrhosis

BACKGROUND: The appropriate treatment strategy for transplantable hepatocellular carcinoma (HCC) patients with compensated cirrhosis remains controversial. METHODS: Surgical outcomes were reviewed in 136 cirrhotic patients with transplantable HCC who had undergone partial hepatectomy. Transplantable HCC was defined as that corresponding to Milan's criteria. RESULTS: The adverse prognostic factors for both survival and disease-free survival were histologic surgical margin of 5 mm or less, Child-Pugh B, and the presence of hepatitis C virus infection. The overall 5-year survival and disease-free survival rates of patients with 1 or none of the adverse prognostic factors were 73% and 33%, respectively, whereas those of patients with 2 or 3 adverse prognostic factors were 36% and 17%, respectively. CONCLUSIONS: Transplantable HCC patients with 2 or 3 adverse prognostic factors should be considered candidates for liver transplantation, whereas patients with only 1 or none of the adverse prognostic factors are good candidates for partial hepatectomy.     

Clinical outcome assessment of membranous nephropathy

Appropriate treatment of idiopathic membranous nephropathy (IMN) remains a controversial issue. Whereas some authors recommend a conservative approach, based on the considerable rate of spontaneous remissions, others utilize early immunosuppressive treatment for most nephrotic patients with IMN. Our retrospective study consisted of 34 patients who presented with IMN between the period from 1987 to 2002. The patients were divided into two groups based on the type of treatment they received the immunosuppressive group comprised 18 patients who received corticosteroids with/without other immunosuppressive drugs and the supportive group comprised 16 patients who were treated with anti platelet drugs as supportive therapy. The amount of proteinuria at the base line was significantly higher in the immunosuppressive group than in the supportive group(4.7 +/- 2.9 vs. 2.7 +/- 2.7 g/24 h). At the end of the follow-up, complete remission was achieved more frequently in the immunosuppressive group than in the supportive group(9/18 vs. 3/16). This suggests that immunosuppressive treatment has the effect of decreasing proteinuria. At the end of the follow-up, 3 patients in the immunosuppressive group and 2 patients in the supportive group showed renal insufficiency (serum creatinine concentration > or = 1.5 mg/dl). Side effects besides diabetes were not seen as a result of immunosuppressive treatment. Our findings suggest that immunosuppressive treatment in IMN cases appears to be beneficial for decreasing proteinuria, but the effect on prevention of renal failure was not evident.     

Impaired systemic cell-mediated immunity and increased susceptibility to acute respiratory tract infections in patients with COPD

Although it has been reported that chronic obstructive pulmonary disease (COPD) is frequently associated with systemic immune disturbances, negative impact of these disturbances on the increased prevalence of acute respiratory tract infections (aRTIs) has remained unclear. We evaluated circulating levels of interferon-gamma (IFN-gamma), soluble interleukin-2 receptor (sIL-2R), neopterin, and soluble intercellular adhesion molecule-1 (sICAM-1) in 35 clinically stable patients with COPD and in 22 age-matched healthy controls, since these molecules are considered to reflect the in vivo status of systemic cell-mediated immunity (CMI). We found that circulating levels of sIL-2R (1.52+/-1.25 vs. 0.97+/-0.48 ng/ml; P<0.05), neopterin (7.23+/-4.24 vs. 4.95+/-1.52 nmol/l; P<0.05), and sICAM-1 (665+/-302 vs. 328+/-164 ng/ml; P<0.0001), but not IFN-gamma (7.55+/-4.72 vs. 6.65+/-1.13 pg/ml; P=NS) were significantly higher in patients with COPD than in the controls. Importantly, follow-up study for 12 months demonstrated that patients in subgroup with relatively higher circulating levels of sIL-2R (2.20+/-1.44 ng/ml, n=18) had significantly higher risk of developing aRTIs (P=0.0204) than those in subgroup with relatively lower circulating levels of sIL-2R (0.80+/-0.23 ng/ml, n=17). These results may suggest that impaired systemic CMI observed in COPD patients is associated with the increased susceptibility to aRTIs in these patients.     

Clinical and electrophysiological characteristics of Brugada syndrome caused by a missense mutation in the S5-pore site of SCN5A

Brugada syndrome is an inherited cardiac disorder caused by mutations in the SCN5A gene encoding the cardiac sodium channel alpha-subunit, and potentially leads to ventricular fibrillation and sudden death. We report a case of a novel SCN5A mutation associated with Brugada syndrome. A 51-year-old man suffered from recurrent nocturnal syncopal attacks due to polymorphic ventricular tachycardia. His electrocardiogram showed ST-segment elevation in V1-V3 leads, but there was no evidence of structural heart disease. DNA sequence analysis of SCN5A in this patient revealed a missense mutation (R282H) in the S5-pore region of domain I. This mutational change was not present in 100 healthy Japanese controls. In the patient's family, a 36-year-old brother had died suddenly. Genetic analysis identified two other carriers of the R282H mutation, who had ST-segment elevation and slightly increased QRS widths, but they experienced no syncopal episodes or ventricular fibrillation. Electrophysiological investigation of the R282H mutant channel expressed in cultured cells showed a severe reduction in sodium current density and a mild positive shift of activation curve. R282H did not enhance intermediate inactivation. Single-channel conductance of R282H was slightly decreased compared with WT. The electrophysiological characteristics of the R282H channel are suggested to be closely related to the clinical phenotype of Brugada syndrome.     

A novel missense mutation in the SCN5A gene associated with Brugada syndrome bidirectionally affecting blocking actions of antiarrhythmic drugs

Brugada syndrome is an inherited cardiac disorder caused by mutations in the SCN5A gene encoding the cardiac sodium channel alpha subunit, which can lead ventricular fibrillation and sudden death. Inattentive use of antiarrhythmic drugs potentially triggers fatal cardiac arrhythmias through further reduction of sodium current (I(Na)). We studied the molecular mechanism underlying a case of Brugada syndrome that showed no response to a class Ic antiarrhythmic drug. Molecular genetic studies of a patient with Brugada syndrome identified a novel mutation in SCN5A, which causes substitution of serine for asparagine (N406S) in S6 of domain I (IS6). The provocation test with pilsicainide, a class Ic antiarrhythmic drug, failed to exacerbate ST-segment elevation in this case. Electrophysiological analyses of the N406S-mutant channel expressed together with the beta1 subunit in HEK293 cells showed that the voltage dependence of activation was positively shifted by 16 mV and that intermediate inactivation was enhanced. Whereas tonic block by pilsicainide was not changed in the N406S channel, use-dependent block by pilsicainide was almost completely abolished, consistent with the clinical findings of the negative provocation test. In contrast, the N406S channel showed stronger use-dependent block by quinidine than the wild-type channel. We demonstrate a novel Brugada mutation N406S, which is associated with the discordant effects on blocking actions of antiarrhythmic drugs as well as the multiple channel gating defects. We emphasis that an antiarrhythmic drug may exert unpredicted effects in patients with channel mutations.     

Exercise training enhances tumor necrosis factor-alpha-induced expressions of anti-apoptotic genes without alterations in caspase-3 activity in rat epididymal adipocytes

The effect of exercise training on tumor necrosis factor-alpha (TNF-alpha) signaling was investigated in rat epididymal adipocytes. Incubation of isolated adipocytes with TNF-alpha (20 ng/ml) for 5 h enhanced the expression of the inhibitor apoptosis protein 2 (IAP2) gene without any enhancement of caspase-3 activity in both the sedentary control (C) and exercise-trained (TR) groups. However, the ability of TNF-alpha to enhance IAP2 gene expression was significantly greater in TR than in C rats. The basal expression of the IkappaB kinase beta (IKK beta) gene and that of the BCL-x(L) gene were also higher in TR than in C rats. Mn-superoxidedismutase contents in adipocytes were higher in TR than in C rats. Moreover, no apoptotic nucleuses of adipocytes in response to acute exercise were observed in either group at least up to 5 h after exercise. Exercise training also enhanced the inhibitory effect of TNF-alpha on the gene expression of the fatty acid synthase (FAS), a lipogenic enzyme, suggesting that fatty acid synthesis may be reduced. Thus, exercise training enhanced TNF-alpha signaling directed toward the expressions of survival signals and the suppression of FAS gene expression.     

GLUT1 is highly expressed in cementoblasts but not in osteoblasts

Cementum is a specialized mineralized tissue covering root surface of the tooth. Although the tissue's composition resembles bone, there are distinct structural and functional differences between the two mineralized tissues. In this study, the genes that are differentially expressed in putative cementoblasts (human cementum-derived cells [HCDCs]) compared with preosteoblastic cells (human bone marrow stromal cells [BMSCs]) were screened by two independent microarray systems, and some of the selected genes were further analyzed by quantitative real-time RT-PCR. The gene encoding glucose transporter 1 [GLUT1], which showed the greatest difference between the two groups by the latter analysis, was subjected to further analyses. High levels of the GLUT1 protein in HCDCs, but not in BMSCs, were detected by Western blotting and immunocytochemistry. Furthermore, intense immunoreactivities for GLUT1 were observed in cementoblasts and cementocytes but not in osteoblasts or osteocytes in human periodontal tissues. These results indicate that GLUT1 may play a role in cementogenesis and could serve as a biomarker to differentiate between cells of cementoblastic and osteoblastic lineage.     

Effects of expiratory rib-cage compression on oxygenation, ventilation, and airway-secretion removal in patients receiving mechanical ventilation

BACKGROUND: Expiratory rib-cage compression, a chest physiotherapy technique, is well known as the "squeezing" technique in Japan. OBJECTIVE: To determine the effects of rib-cage compression on airway-secretion removal, oxygenation, and ventilation in patients receiving mechanical ventilation. SETTING: An intensive care unit of an emergency and critical care center at a tertiary-care teaching hospital in Tokyo, Japan. METHODS: Thirty-one intubated, mechanically ventilated patients in an intensive care unit were studied in a randomized, crossover trial. The patients received endotracheal suctioning with or without rib-cage compression, with a minimum 3-hour interval between the 2 interventions. Rib-cage compression was performed for 5 min before endotracheal suctioning. Arterial blood gas and respiratory mechanics were measured 5 min before endotracheal suctioning (baseline) and 25 min after suctioning. The 2 measurement periods were carried out on the same day. RESULTS: There were no significant differences in the ratio of arterial partial pressure of oxygen to fraction of inspired oxygen, P(aCO2), or dynamic compliance of the respiratory system between the 2 periods (before and after endotracheal suctioning). Moreover, there were no significant differences in airway-secretion removal between the 2 periods. CONCLUSIONS: This study suggests that rib-cage compression prior to endotracheal suctioning does not improve airway-secretion removal, oxygenation, or ventilation after endotracheal suctioning in this unselected population of mechanically ventilated patients.