老年大鼠松质骨骨重建的组织形态计量学研究

目的：研究老年大鼠及在促骨合成药前列腺素E2（PGE2）作用下松质骨骨重建和骨建造的形态计量学改变，探讨动物骨重建形态学新参数测量方法及其意义。方法：50只20月龄雄性Wistar大鼠随机分成5组，年龄对照组（基础组、10d和30d年龄对照组），PGE2给药组（分别10d和30d给予3mg/kg/d处理组）。用体内双荧光标记，不脱钙组织切片，粘合线（cement line）染色，骨组织形态计量学方法，测定骨重建和骨建造参数。结果：20月龄雄性大鼠胫骨近端松质骨的形成表面大多数为骨重建单位（占63．3％），少部分为骨建造单位（占26．7％）；PGE2用药后骨重建单位增加1．5倍，骨建造单位增加4倍，比值倒置，成骨细胞10d时明显增多。说明PGE2通过刺激成骨细胞骨合成而介民导骨建造性骨增加和骨重建性骨量增加，并以前为主。结论：老年雄性大鼠 松质骨以骨重建活动为主，仍有骨建造活动。PGE2主要通过刺激成骨细胞骨建造而增加骨量。     

Focal liver masses: differential diagnosis with pulsed Doppler US

Duplex Doppler ultrasound (US) was used in 68 consecutive patients with focal liver lesions, including 12 hepatocellular carcinomas, one cholangiocarcinoma, 37 metastases, 15 hemangiomas, one hemangioendothelioma, and two focal nodular hyperplasias. Of the hepatocellular carcinomas, six were diffusely hyperechoic, two were hypoechoic, two were single hyperechoic lesions, and two were multifocal and hyperechoic. All ten tumors with Doppler shifts of 5 kHz or above proved to be hepatocellular carcinomas. The other two hepatocellular carcinomas showed Doppler shifts of 3 kHz. In contrast, no hemangioma showed shifts above 0.7 kHz, and ten of the 15 gave no detectable signal. Of the metastases, 20 gave no signal and 17 had signals of up to 4 kHz. Three-kilohertz signals were also obtained from a cholangiocarcinoma, a hemangioendothelioma, and focal nodular hyperplasia. Correlation with angiographic findings suggested that the high-velocity Doppler signals were associated with large pressure gradients due to arteriovenous shunting. Duplex Doppler US can therefore aid in the differential diagnosis of diffuse and focal liver lesions.     

Unintended consequences of policy change to watchful waiting for asymptomatic inguinal hernias

Introduction

In 2009 the Department of Health instructed McKinsey & Company to provide advice on how commissioners might achieve world class National Health Service productivity. Asymptomatic inguinal hernia repair was identified as a potentially cosmetic procedure, with limited clinical benefit. The Birmingham and Solihull primary care trust cluster introduced a policy of watchful waiting for asymptomatic inguinal hernia, which was implemented across the health economy in December 2010. This retrospective cohort study aimed to examine the effect of a change in clinical commissioning policy concerning elective surgical repair of asymptomatic inguinal hernias.

Methods

A total of 1,032 patients undergoing inguinal hernia repair in the 16 months after the policy change were compared with 978 patients in the 16 months before. The main outcome measure was relative proportion of emergency repair in groups before and after the policy change. Multivariate binary logistic regression was used to adjust the main outcome for age, sex and hernia type.

Results

The period after the policy change was associated with 59% higher odds of emergency repair (3.6% vs 5.5%, adjusted odds ratio [OR]: 1.59, 95% confidence interval [CI]: 1.03–2.47). In turn, emergency repair was associated with higher odds of adverse events (4.7% vs 18.5%, adjusted OR: 3.68, 95% CI: 2.04–6.63) and mortality (0.1% vs 5.4%, p<0.001, Fisher’s exact test).

Conclusions

Introduction of a watchful waiting policy for asymptomatic inguinal hernias was associated with a significant increase in need for emergency repair, which was in turn associated with an increased risk of adverse events. Current policies may be placing patients at risk.     

Reversible oxidant-induced increases in albumin transfer across cultured endothelium: alterations in cell shape and calcium homeostasis

To determine whether reactive oxygen molecules could directly and reversibly increase the transfer of albumin across an endothelial barrier, we measured albumin transfer across monolayers of endothelium cultured on micropore filters before and after exposure to xanthine and xanthine oxidase. Xanthine and xanthine oxidase increased endothelial albumin transfer in a dose-dependent fashion. Parallel phase contrast and fluorescence microscopy demonstrated retraction of adjacent cells from one another and disruption of the actin filaments. The oxidant- induced increases in albumin transfer and changes in cell shape were reversed by removing xanthine oxidase and then incubating the monolayers for 3 1/2 hours in tissue culture media enriched with fetal bovine serum. However, incubation in tissue culture media without serum resulted in progressive injury and cell death. Hence, the brief exposure to oxidants initiated a progressive injury process that was reversed by incubation in serum. Because intracellular and extracellular calcium are important determinants of cell shape, and because some oxidized membrane lipids act as calcium ionophores, we asked whether oxidants altered endothelial calcium homeostasis. Xanthine-xanthine oxidase increased release of 45Ca++ from preloaded cells. The calcium antagonist lanthanum chloride prevented xanthine- xanthine oxidase increases in endothelial albumin transfer and prevented the changes in cell shape; chelation of extracellular calcium inhibited lysis of endothelium by xanthine-xanthine oxidase; and the calcium ionophore A23187 increased endothelial albumin transfer and mimicked the oxidant-induced changes in cell shape. Lanthanum chloride inhibited these effects of A23187. These data suggest that oxygen radicals can reversibly increase endothelial permeability to macromolecules, that this is associated with reversible changes in endothelial cell shape and actin filaments, and that the changes in cell shape are related to oxidant-induced changes in endothelial calcium homeostasis.