Associations of radiographic degeneration and pain with daily cumulative hip loading in patients with secondary hip osteoarthritis

The purpose of this study was to investigate the associations of radiographic and clinical variables of hip osteoarthritis (OA) with alterations in gait and joint loading in patients with secondary hip OA. Fifty females with secondary hip OA were participated. The minimum joint space width (mJSW) of the hip as a degenerative sign and Sharp and center edge (CE) angles as morphological variables were measured radiographically. Hip joint pain was assessed using a visual analog scale. As gait variables, walking speed, range of hip motion, hip moment peak, and hip moment impulse were calculated. Daily cumulative hip loading was calculated as the hip moment impulse multiplied by the mean number of steps per day. After bivariate correlation analyses between dependent (mJSW and pain) and independent variables (age, body mass index, sharp/CE angles, steps per day, and gait variables), separate forward‐backward stepwise multiple regression analyses were performed for each dependent variable. Daily cumulative hip loading in the sagittal plane (β = 0.30, p = 0.021) and age (β = ?0.36, p = 0.007) were significantly associated with the mJSW. Walking speed (β = ?0.36, p = 0.008) and age (β = 0.29, p = 0.031) were significantly associated with hip joint pain. Decrease in daily cumulative hip loading in the sagittal plane was associated with mJSW independently of age. Although the causal relationship was not clear, patients with hip OA reduced total exposure to hip joint loading adaptively rather than lowering the hip moment peak concerning worsening of hip degeneration. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1977–1983, 2016.

     

Rare Complication of Takotsubo Cardiomyopathy: Ventricular Septal Perforation with Septal Dissection

We describe a rare case of takotsubo cardiomyopathy complicated by acute ventricular septal perforation with ventricular septal dissection. The ventricular perforation was successfully closed by repairing the dissecting site with a bovine pericardial patch. doi: 10.1111/jocs.12676 (J Card Surg 2016;31:150–153)     

Clinical significance of small, dense LDL cholesterol in patients with hyperlipidemia and type 2 diabetes

We investigated the serum levels of small, dense LDL-cholesterol (sd LDL-C) in patients with hyperlipidemia and type 2 diabetes. An analytical assay was used to determine the levels of sd LDL-C, employing a filter method using a separating agent of polyanion and divalent cation natures. Reference intervals of sd LDL-C in normal healthy subjects (n=113) ranged from 8.0 to 42.0 mg/dl. We found a strong correlation between the levels of sd LDL-C and both the ratio of LDL-C/apolipoprotein B and the LDL migration index. The LDL migration index was analyzed using polyacrylamide gel disk electrophoresis. The levels of sd LDL-C in patients with types IIa, IIb and IV hyperlipidemia were significantly higher than those in normal subjects and in patients with normal lipidemia. The levels of sd LDL-C in patients with type IIb were higher than those with types IIa and VI. Examination of patients with polydisperse LDL showed that the levels of nodular and disrupted type sd LDL-C were higher than the levels of symmetry type sd LDL-C. Moreover, the levels of sd LDL-C in patients with type 2 diabetes were higher than those in normal subjects. A high level of sd LDL-C in patients with type 2 diabetes was found to be an indicator of possible complications of hyperlipidemia and lessly related to glycemic control. Therefore, the determination of sd LDL-C levels can be useful in the diagnosis of patients with hyperlipidemia and polydisperse LDL and in patients with type 2 diabetes with complications of hyperlipidemia and atherosclerosis.     

Distinctive evaluation of nonmucinous and mucinous subtypes of bronchioloalveolar carcinomas in EGFR and K-ras gene-mutation analyses for Japanese lung adenocarcinomas: confirmation of the correlations with histologic subtypes and gene mutations

Although adenocarcinomas of the lung are associated with epidermal growth factor receptor (EGFR) gene mutations and sensitivity to EGFR tyrosine kinase inhibitors, it remains unclear whether bronchioloalveolar carcinoma (BAC) components and/or subtypes affect these associations. We aimed to clarify correlations between EGFR gene mutations and BAC components and to establish the histologic features as reliable predictors for the mutations. We examined 141 non-small cell lung cancers (NSCLCs), including 118 adenocarcinomas, for mutations in exons 19 and 21 of the EGFR gene together with mutations in codon 12 of the K-ras gene using loop-hybrid mobility shift assays, a highly sensitive polymerase chain reaction-based method. Adenocarcinomas were subdivided into subtypes with a nonmucinous or mucinous BAC component and those without BAC components. In NSCLCs, EGFR mutations were detected in 75 cases (53.2%) and were significantly associated with adenocarcinoma, female sex, and never smoking. Among adenocarcinomas, nonmucinous and mucinous BAC components were significantly associated with EGFR and K-ras gene mutations, respectively. Because EGFR mutations were detected even in most pure nonmucinous BACs, ie, lung adenocarcinoma in situ, EGFR mutation is considered a critical event in the pathogenesis of nonmucinous BAC tumors.     

Asymptomatic colorectal cancer detected by screening

PURPOSE: Colorectal cancer screening has become prevalent. To discuss the efficacy of screening, we studied the characteristics of asymptomatic Colorectal cancer detected by screening. METHODS: This is a retrospective review of patients with colorectal cancer treated at our institution. During the past 20 years, 96 of 1,046 cases of colorectal cancer were asymptomatic and detected by screening. Sixty-one of these cases were detected in the recent five years. The initial screening procedures were fecal occult blood test in 51 cases, sigmoidoscopy or colonoscopy in 18, barium enema in 9, and other tests in 18. RESULTS: Thirteen lesions (14 percent) were smaller than 1.0 cm and 32 (33 percent) were 1–2 cm in size. There were 34 Tis, 21 T1, and 8 T2 tumors. Of the 55 Tis or T1 lesions, 14 showed nonpolypoid growth (5 flat-elevated, 7 flat-elevated with depression, 1 flat, 1 depressed), and 12 of these were detected on endoscopy. Thirty-four cases were TNM Stage 0, 25 were Stage I, 16 were Stage II, 12 were Stage III, and 9 were Stage IV. Sixty-one percent of those detected by screening were in either Stage 0 or Stage I compared with 16 percent in the symptomatic group. Cumulative five-year disease-free survival rates were 100 percent for both Stage 0 and Stage I, 94 percent for Stage II, and 52 percent for Stage III. Overall cumulative five-year survival rate was 87 percent for those detected by screening, compared with 57 percent in symptomatic patients. CONCLUSIONS: Asymptomatic cancers detected by screening were at a less advanced stage. In particular, many nonpolypoid early cancers were detected by endoscopic screening.Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Montreal, Quebec, Canada, May 7 to 12, 1995.     

Noc2 is essential in normal regulation of exocytosis in endocrine and exocrine cells

Rab3 is a subfamily of the small GTP-binding protein Rab family and plays an important role in exocytosis. Several potential effectors of Rab3, including rabphilin3 and Rims (Rim1 and Rim2), have been isolated and characterized. Noc2 was identified originally in endocrine pancreas as a molecule homologous to rabphilin3, but its role in exocytosis is unclear. To clarify the physiological function of Noc2 directly, we have generated Noc2 knockout (Noc2(-/-)) mice. Glucose intolerance with impaired insulin secretion was induced in vivo by acute stress in Noc2(-/-) mice, but not in wild-type (Noc2(+/+)) mice. Ca(2+)-triggered insulin secretion from pancreatic isles of Noc2(-/-) mice was markedly impaired, but was completely restored by treatment with pertussis toxin, which inhibits inhibitory G protein Gi/o signaling. In addition, the inhibitory effect of clonidine, an alpha(2)-adrenoreceptor agonist, on insulin secretion was significantly greater in Noc2(-/-) islets than in Noc2(+/+) islets. Impaired Ca(2+)-triggered insulin secretion was rescued by adenovirus gene transfer of wild-type Noc2 but not by that of mutant Noc2, which does not bind to Rab3. Accordingly, Noc2 positively regulates insulin secretion from endocrine pancreas by inhibiting Gi/o signaling, and the interaction of Noc2 and Rab3 is required for the effect. Interestingly, we also found a marked accumulation of secretory granules in various exocrine cells of Noc2(-/-) mice, especially in exocrine pancreas with no amylase response to stimuli. Thus, Noc2, a critical effector of Rab3, is essential in normal regulation of exocytosis in both endocrine and exocrine cells.     

Factors affecting the prognosis of patients with hepatocellular carcinoma invading the portal vein--a retrospective analysis using 952 consecutive HCC patients

BACKGROUND/AIMS: Hepatocellular carcinoma with portal venous invasion has a very poor prognosis. The aim of this study is to clarify the factors contributing to the survival of hepatocellular carcinoma patients with portal venous invasion. METHODOLOGY: Out of 952 patients with hepatocellular carcinoma admitted to Tokyo University hospital and its affiliated hospitals from 1987 to 1999, 53 patients developed portal venous invasion until December 2000. The main portal vein was invaded in 33 patients, and the first branch was invaded in the 20 patients. The factors contributing to the prognosis of hepatocellular carcinoma patients with portal venous invasion were determined by univariate and multivariate analyses using 19 clinicopathological parameters. RESULTS: Overall survival rates of the 53 patients at 6 months, and 1 and 2 years were 40%, 18%, and 12%, respectively. Univariate analysis indicated that the serum albumin level, Child classification, number of tumor foci, portal venous invasion-targeted irradiation, and percutaneous tumor ablation of the parenchymal main tumor were significant. Multivariate analysis showed that percutaneous tumor ablation (P = 0.033; risk ratio = 0.28) was the most important factor contributing to a favorable prognosis followed by number of tumor foci (P = 0.048; risk ratio = 0.41). CONCLUSIONS: This study showed the significance of treatment for the parenchymal main tumor in addition to portal venous invasion in patients with hepatocellular carcinoma involving portal venous invasion. Therefore, the efficacy of combined therapy using portal venous invasion-targeted irradiation and percutaneous tumor ablation for the parenchymal main tumor on survival of hepatocellular carcinoma patients with portal venous invasion is suggested.     

Theoretical validity of predicting right ventricular systolic pressure by a quantitative index of interventricular septal displacement in acute right ventricular pressure overload

A leftward shift of the interventricular septum (IVS) of the heart is observed in patients with right ventricular pressure overload (RVPO). We simulated the leftward displacement of IVS in a modified ellipsoidal model on the assumption that the IVS generates the same tension as the left ventricular (LV) free-wall in acute RVPO, and derived the relational equations between ventricular pressures (RVP, LVP) and eccentricity index (EI = LVAPD/LVSLD, LVAPD: left ventricular anterior-posterior diameter, LVSLD: left ventricular septal-lateral diameter). The equations indicate that RVP/LVP correlates with simultaneous EI, independent of the absolute LV wall tensions and the LV size. To confirm this result, we undertook recurrent pulmonary embolizations in anesthetized open-chest dogs, and analyzed the relationship between RVP/LVP and EI at four phases in systole through the course of RVPO and shock. The advance of RVPO shifted the peak of RVP toward late-systole and made the values of RVP/LVP and EI significantly greater at late-systole than at early-systole. There were significant linear relationships between instantaneous EI and RVP/LVP at each phase, expect for the early systole in the shock stage, and the regression lines on all phases were similar to one another. These results are consistent with our theoretical ones. Therefore we conclude that it is reasonable to predict RVP by using EI, theoretically and experimentally.     

Differential regulation of gene expression and insulin-induced activation of phosphodiesterase 3B in adipocytes of lean insulin-resistant IRS-1 (-/-) mice

Phosphodiesterase (PDE) 3B, a major isoform of PDE in adipocytes, mediates the antilipolytic action of insulin. PDE3B gene expression is generally reduced in adipocytes of either monogenic or polygenic rodent models of obese, insulin-resistance. An increased fat cell size, a common feature of obesity, could account for this reduction. Insulin receptor substrate-1 (IRS-1) (-/-) mice are lean with a reduced fat cell size and have insulin resistance due to a primary defect of insulin signaling. To determine whether the regulation of PDE3B gene expression is correlated with fat cell size, we examined this gene expression in adipose tissues of IRS-1 (-/-) mice. In IRS-1 (-/-) mice, PDE3B mRNA and protein levels were increased 1.24- and 1.35-fold those in C57BL/6J control mice, respectively. Independently, the fold induction of PDE activity by insulin (insulin-induced/basal) was 1.7-fold in control mice, but was reduced to 1.35-fold in IRS-1 (-/-) mice. Thus, PDE3B gene expression may be inversely correlated with a fat cell size, whereas insulin-induced PDE3B activation is mediated through IRS-1.