Thrombin stimulates mitogenesis in pig cerebrovascular smooth muscle cells involving activation of pro-matrix metalloproteinase-2.

Generation of thrombin is associated with vascular remodeling that involves proliferation of vascular smooth muscle cells (SMCs) and activation of pro-matrix metalloproteinases (pro-MMPs). The present study was to investigate whether thrombin would induce mitogenesis and activation of pro-MMPs in cerebrovascular SMCs (CSMCs), and if so, whether MMP activity would contribute to the CSMC mitogenesis. CSMCs were cultured from pig middle cerebral arteries and stimulated with thrombin. Thrombin (0.1-5U/ml), in a dose-dependent fashion, stimulated mitogenesis in CSMCs as detected by bromo-2'-deoxy-uridine (BrdU) incorporation. Additionally, zymographic analyses showed that thrombin stimulated the appearance of the active form of MMP-2 (MMP-2) in a concentration-dependent manner, but not the release of pro-MMP-2. Thrombin did not affect expression of cell-associated pro-MMP-2 protein as evaluated by Western blot analysis. Treatment with the synthetic MMP inhibitor GM6001 or antibodies to MMP-2 significantly reduced thrombin-induced BrdU incorporation in CSMCs. In conclusion, thrombin activates pro-MMP-2 in the absence of elevated pro-MMP-2 expression and secretion in CSMCs, and thrombin induces CSMC mitogenesis involving its action on MMP-2. These findings suggest that thrombin may have relevance in cerebrovascular remodeling associated with brain atherosclerosis and atherothrombotic ischemic stroke through a mechanism involving MMP-dependent CSMC mitogenesis.

Native superficial femoral artery peripheral atherectomy site pseudoaneurysm: a case report.

A 45-year-old woman who presented with blue toe syndrome was treated with atherectomy for a focal plaque located in the superficial femoral artery. She subsequently developed a large pseudoaneurysm at the atherectomy site requiring multiple sequential endovascular procedures in order to maintain in-line blood flow to the foot. Pseudoaneurysm formation at native peripheral artery atherectomy site has not been reported previously. We discuss possible complications of atherectomy and the possible mechanism of pseudoaneurysm formation after atherectomy. We address the importance of understanding risks of these minimally invasive procedures along with planning follow-up duplex and potential bail-out tactics.

Initial experience with routine selective carotid arteriography by vascular surgeons.

We report the results of our first 2 years of experience with routine carotid angiography with an emphasis on technique and complications. We reviewed the hospital records, office charts, and prospective quality-assurance database records of 336 patients undergoing cerebrovascular arteriograms and collected data on the indications, complications, and technical aspects of the procedures. Indications for angiography included carotid stenosis in 331 (95%) patients, subclavian steal syndrome in 9 patients, vertebrobasilar insufficiency in 6 patients, and carotid body tumor in 2 patients. Selective catheterizations were performed on 654 common carotid arteries, 63 subclavian arteries, and 63 vertebral arteries. Both common carotid arteries were not selectively catheterized in 34 (9.8%) patients. Reasons for not selecting one or both common carotid arteries included physician choice to limit contrast administration in patients with renal insufficiency in 16 cases, proximal occlusion in 4 cases, proximal stenosis thought to be at risk of embolization if instrumented in 3 cases, imaging equipment malfunction in 2 cases, and in only 9 (2.6%) cases was selective carotid catheterization attempted but unsuccessful. There were no procedure-related deaths. Complications were documented in six (1.8%) patients, including cerebrovascular accident (CVA) in 1 (0.3%) patient. One hundred forty-two (41%) patients went on to carotid endarterectomy, and we performed 16 carotid bifurcation stents during the study period. Routine selective carotid angiography is a low-risk procedure that can be performed safely by vascular surgeons with catheter/guide wire skills.

The results of superficial femoral, popliteal, and tibial artery stenting for peripheral vascular occlusive disease.

The purpose of this study was to evaluate the patentcy rates and physiological effectiveness of angioplasty and stenting as a primary therapy for superficial femoral (SFA), popliteal (POP), and tibial (TIB) arterial occlusive disease. Seventy-eight patients had stents placed in the infra-inguinal vessels between January 1, 2001, and July 31, 2004. We collected data on patient demographics, symptoms, as well as pre- and postprocedure ankle-brachial index (ABI) and angiographic findings. Patency rates at 6 months, 12 months, and 24 months were analyzed by life table methods. Thirty-one men and 47 women had a mean age of 68 years (range 36-94 years). Risk factors included diabetes in 50 per cent, hypertension in 79 per cent, smoking in 41 per cent, and end-stage renal disease in 10 per cent. The indications for intervention were claudication in 52 per cent and limb salvage in 48 per cent of patients. Stents were placed in the SFA in 54 patients (69%), in the POP in 15 patients (18%), and in the TIB artery in 6 patients (8%). Average follow-up was 11.2 months. The mean postprocedural increase in ABI was 0.29. The 6-month, 1-year, and 2-year primary patency rates were 83 per cent, 58 per cent, and 47 per cent, respectively. Limb salvage was achieved in 66 per cent of patients treated for limb-threatening ischemia. There was one major and three minor complications. Stenting of the infra-inguinal vessels has a low morbidity, high success rate, and acceptable patency and limb-salvage rates.

Adult-derived stem cells and their potential for use in tissue repair and molecular medicine.

This report reviews three categories of precursor cells present within adults. The first category of precursor cell, the epiblast-like stem cell, has the potential of forming cells from all three embryonic germ layer lineages, e.g., ectoderm, mesoderm, and endoderm. The second category of precursor cell, the germ layer lineage stem cell, consists of three separate cells. Each of the three cells is committed to form cells limited to a specific embryonic germ layer lineage. Thus the second category consists of germ layer lineage ectodermal stem cells, germ layer lineage mesodermal stem cells, and germ layer lineage endodermal stem cells. The third category of precursor cells, progenitor cells, contains a multitude of cells. These cells are committed to form specific cell and tissue types and are the immediate precursors to the differentiated cells and tissues of the adult. The three categories of precursor cells can be readily isolated from adult tissues. They can be distinguished from each other based on their size, growth in cell culture, expressed genes, cell surface markers, and potential for differentiation. This report also discusses new findings. These findings include the karyotypic analysis of germ layer lineage stem cells; the appearance of dopaminergic neurons after implantation of naive adult pluripotent stem cells into a 6-hydroxydopamine-lesioned Parkinson's model; and the use of adult stem cells as transport mechanisms for exogenous genetic material. We conclude by discussing the potential roles of adult-derived precursor cells as building blocks for tissue repair and as delivery vehicles for molecular medicine.

The natural history of untreated penetrating diaphragm injury: an animal model.

BACKGROUND: Surgical repair of diaphragm injuries is rather straightforward, but diagnosis can be difficult. The natural history of diaphragm injury is quite controversial. Undoubtedly, many diaphragmatic injuries are missed at the initial evaluation. Some theories state that diaphragm injuries do not heal, and that all eventually lead to herniation. Current theories regarding uniform herniation of all diaphragm injuries are not supported by animal models. The authors developed a penetrating diaphragm injury model to study the natural history of this injury. METHODS: This study used 48 male Sprague-Dawley rats weighing 300-425 g. During the study, 24 of the rats received a 16-gauge needle puncture of the left diaphragm mimicking a small penetrating wound, whereas 24 of the rats received an injury produced with a 2.7-mm aortic punch, which created a defect comparable to a much larger penetrating wound. Half of the animals in each group were euthanized at 1 month, and the other half at 10 months. This allowed short- and long-term follow-up of the injuries. Gross inspection of the left diaphragm was performed after the animals were sacrificed via a thoracoabdominal incision. All diaphragms then were removed for examination. RESULTS: All the rats experienced perioperative recovery. None of the 24 rats with a 16-gauge needle injury had an injury at 1 month (n = 12) or 10 months (n = 12). No patent injury was noted in the aortic punch injury group (n = 12) sacrificed at 1 month. At 10 months, 1 of 12 animals had a small hepatic herniation through the aortic punch injury. All the injuries displayed adhesions to the underlying left hepatic lobe. CONCLUSIONS: The authors developed a penetrating diaphragm injury model to understand better the natural history of this injury. Spontaneous healing occurred in 98% of the animals. In this animal model, because the left lobe of the liver is present beneath the left diaphragm, healing without herniation usually occurs. A role may exist for nonoperative treatment of human right diaphragm injuries in clinical practice. This animal model may prove useful in further defining future management for these injuries.

Impact of a surgical oncologist on general surgery residency training program.

BACKGROUND: To assess the impact of adding a surgical oncologist to our faculty we examined the operative experience in our program before and after the addition. METHODS: Operative case numbers reported to the American Board of Surgery over a 10-year period were analyzed. This time period encompassed 5 years before and after the addition of a surgical oncologist to our faculty. All defined category case numbers were examined using t test analysis. Significance was defined as a P value of less than 0.05. RESULTS: The overall caseload increased in the time period after the faculty addition. There was a statistically significant increase in skin/soft tissue, breast, esophagus, small intestine, large intestine, live, spleen, and endocrine cases. No statistical significance was seen in head/neck, stomach, pancreas, and biliary cases. CONCLUSIONS: The addition of a surgical oncologist to our faculty coincides with a statistically significant increase in areas of skin/soft tissue, breast, esophagus, small intestine, large intestine, liver, spleen, and endocrine. Other areas not statistically significant may reflect referral patterns or this particular oncologist's preferences of practice.