Self-expanding endovascular graft: an experimental study in dogs

An arterial endovascular graft was constructed by wrapping an expandable nylon mesh around a framework of Gianturco self-expanding metallic stents. The devices were passed through a 12-French Teflon catheter and positioned in the normal abdominal aorta of five dogs, two of which also had a device placed in an external iliac artery. At follow-up (1-6 months), all grafts remained patent, even though slight luminal narrowing due to neointimal encasement was noted. Histologically, all grafts were covered by neointimal proliferation at the time of removal. The graft material expanded with the stents, resulting in a tight fit between the graft and the vessel wall. Side branches narrowed but remained open because of the size of the nylon mesh. No migration of the grafts equipped with a barbed lead stent was noted. Expandable nylon mesh can be used as an endovascular graft material when wrapped around a framework of self-expanding stents. The resulting device can be easily delivered via transcatheter techniques, and once placed in a vessel, the nylon acts as a support for neointimal encasement, which forms a new vascular lumen.     

Both phenolic and acyl glucuronidation pathways of diflunisal are impaired in liver cirrhosis

Summary The pharmacokinetics of diflunisal, a salicylate derivative that undergoes phenolic and acyl glucuronidation as well as sulphate conjugation, has been studied after a single oral dose (250 mg) in patients with cirrhosis (n=5) and in healthy controls (n=5).The plasma clearance of total (bound + unbound) diflunisal was 10.2 ml · min^–1 in the control subjects and it was not affected by cirrhosis (10.9 ml · min^–1). The plasma protein binding of diflunisal was significantly reduced in cirrhosis; the percentage of unbound diflunisal in plasma was 0.089 in the controls and 0.147 in the patients with cirrhosis. Plasma clearance of unbound diflunisal was significantly impaired in cirrhosis: 11.51 · min^–1 in control subjects vs 7.41 · min^–1 in cirrhotics.In cirrhotic patients, the unbound partial clearances to the phenolic and acyl glucuronides were both significantly reduced, by approximately 38%. The unbound partial clearance to the sulphate conjugate was not significantly affected by cirrhosis.The results show that both the phenolic and acyl glucuronidation pathways of diflunisal are equally susceptible to the effects of liver cirrhosis.     

The physiological regulation of toll-like receptor expression and function in humans

Eleven mammalian toll-like receptors (TLRs 1–11) have been identified to date and are known to play a crucial role in the regulation of immune responses; however, the factors that regulate TLR expression and function in vivo are poorly understood. Therefore, in the present study, we investigated the physiological regulation of TLR expression and function in humans. To examine the influence of diurnal rhythmicity on TLR expression and function, peripheral venous blood samples were collected from healthy volunteers ( n = 8) at time points coinciding with the peak and nadir in the endogenous circulating cortisol concentration. While no diurnal rhythmicity in the expression of TLRs 1, 2, 4 or 9 was observed, the upregulation of costimulatory (CD80 and CD86) and antigen-presenting (MHC class II) molecules on CD14⁺ monocytes following activation with specific TLR ligands was greater ( P < 0.05) in samples obtained in the evening compared with the morning. To examine the influence of physical stress on TLR expression and function, peripheral venous blood samples were collected from healthy volunteers ( n = 11) at rest and following 1.5 h of strenuous exercise in the heat (34°C). Strenuous exercise resulted in a decrease ( P < 0.005) in the expression of TLRs 1, 2 and 4 on CD14⁺ monocytes. Furthermore, the upregulation of CD80, CD86, MHC class II and interleukin-6 by CD14⁺ monocytes following activation with specific TLR ligands was decreased ( P < 0.05) in samples obtained following exercise compared with at rest. These results demonstrate that TLR function is subject to modulation under physiological conditions in vivo and provide evidence for the role of immunomodulatory hormones in the regulation of TLR function.     

Treatment of experimentally induced atherosclerosis in swine iliac arteries: A comparison of self-expanding and balloon-expanded stents

Atherosclerosis was induced in 20 Hanford miniature swine. Subsequently, one iliac artery lesion in each of 16 pigs was stented with either a self-expanding (8 pigs) or a balloon-expanded (8 pigs) stent. Immediately after stent placement, 4 animals in each group were taken off the atherogenic diet and continued on normal chow for the remainder of the study. Four months after stents were placed, atherosclerosis and the mural changes associated with the stent were more clearly evident in the arteries of the pigs continued on the atherogenic diet. These pigs also exhibited significantly more neointimal proliferation. In addition, the arteries containing the balloon-expanded stents showed more extensive and complex intimal changes when compared with arteries with self-expanding stents. Although both stent designs were equally effective in maintaining vascular patency, the balloon-expanded stent was more traumatic to the vessel wall which resulted in a significantly greater neointimal thickness.     

A Test to Detect Chest Tube Kinking

Objectives: To determine whether the Mac‐technique test can detect kinking of the chest tube upon thoracostomy tube placement. Methods: This was a prospective observational study that was conducted October 2000 through October 2001 in an urban Level 1 trauma center. There were 103 consecutive nonrandomized adult trauma patients who required immediate tube thoracostomy during their initial resuscitation who were entered into the study. The Mac‐technique test was performed during standard tube thoracostomy insertion to the appropriate depth. The test involved grasping the external portion of the thoracostomy tube, turning it clockwise 180°, and then releasing the tube. If the tube spontaneously spun back to its original position, the test was considered positive, and the tube was considered kinked. If the tube did not spontaneously spin back and stayed in position upon release, the test was considered negative. Regardless of the results of this test, the tube was secured, and a postprocedure chest radiograph was obtained. The criterion standard for determining a kinked chest tube was its appearance on this chest radiograph. Results: A total of 103 chest tubes were placed by using the Mac‐technique test. The test was positive in eight placements; four tubes were kinked on chest radiograph. The Mac‐technique test was negative in 95 placements; four tubes were kinked on chest radiograph. The Mac technique had a sensitivity of 50% (95% confidence interval [CI] = 15.7% to 84.3%), a specificity of 95.8% (95% CI = 89.6% to 98.8%), a positive likelihood ratio of 11.9, a negative likelihood ratio of 0.52, and an odds ratio using Yates correction of 20.3 (95% CI = 4.1 to 102.1). Conclusions: On the basis of this study, a positive Mac‐technique test is useful to detect chest tubes that are likely to be kinked after insertion and before securing.