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E D Reis

Publications and source records attributed to E D Reis.

32 records · Page 2Linked to original sources

Modulation of apoptosis, proliferation, and p27 expression in a porcine coronary angioplasty model.

Smooth muscle cell (SMC) proliferation is a prominent feature of intimal hyperplasia after percutaneous coronary interventions. p27 is a critical regulator of cell proliferation. Our aims were to analyze the time course of p27 expression, Ki67 proliferative index, and apoptosis after angioplasty in the porcine coronary artery. We also investigated the effects of rapamycin--an antiproliferative drug--on these events. The expression of p27 and Ki67, and apoptosis were determined in porcine coronary arteries harvested at timed intervals from 1 h to 28 days after angioplasty. A gradual increase in p27 expression was observed from 7 to 28 days. Ki67 expression peaked by 7-14 days after angioplasty. By 21-28 days, Ki67 expression decreased, while p27 reached maximal levels. An early apoptotic response was found by 6 h, followed by a gradual return to baseline. Rapamycin induced a reduction in Ki67 proliferative index (2 +/- 0.5%) and an increase in apoptosis (7 +/- 1%) versus untreated animals at the 28-day time point (5 +/- 1 and 1 +/- 0.5%, respectively; P < 0.05). In summary, coronary angioplasty induced a rapid apoptotic response, followed by a progressive increase in proliferation. Later on, as p27 expression increased in the vessel wall, cell proliferation decreased. Modulation of cell cycle progression may be a useful therapeutic approach in the treatment of intimal hyperplasia after angioplasty.

Angioplasty, Balloon, Coronary↗

Inhibition of tissue factor reduces thrombus formation and intimal hyperplasia after porcine coronary angioplasty.

OBJECTIVES: We investigated the in vivo effects of tissue factor (TF) inhibition with recombinant tissue factor pathway inhibitor (rTFPI) on acute thrombus formation and intimal hyperplasia and the in vitro effects on smooth muscle cell migration and proliferation. BACKGROUND: Inhibition of TF with TFPI has been shown to reduce intimal hyperplasia in experimental models. However, its effects after coronary angioplasty and the cellular mechanisms involved have not been investigated. METHODS: Twenty-three swine underwent multivessel coronary angioplasty. Fifteen (n = 25 arteries) were euthanized at 72 h to assess thrombus formation and eight (n = 24 arteries) at 28 days to assess intimal hyperplasia. Animals in the 72-h time point received: 1) human rTFPI (0.5 mg bolus plus 25 microg/kg/min continuous infusion for 3 days) plus heparin (150 IU/kg intravenous bolus) plus acetyl salicylic acid (ASA) (325 mg/day); 2) rTFPI regimen plus ASA and 3) heparin (150 IU/kg intravenous bolus) plus ASA. RESULTS: On histology the control group had evidence of mural thrombus (area 0.8+/-0.4 mm2). Treatment with TFPI plus heparin abolished thrombus formation (mean area: 0.0+/-0.0 mm2, p < 0.05) but was associated with prolonged activated partial thromboplastin time and extravascular hemorrhage. Recombinant TFPI alone inhibited thrombosis without bleeding complications (mean area: 0.03+/-0.02 mm2, p < 0.05 vs. control). Animals in the 28-day time point received continuous intravenous infusion of rTFPI or control solution for 14 days. Tissue factor pathway inhibitor reduced neointimal formation with mean intimal area of 1.2+/-0.3 mm2 versus 3.2+/-0.4 mm2 in the control group; p < 0.01. Recombinant TFPI had no effect on human aortic smooth muscle cell growth but inhibited platelet-derived growth factor BB-induced migration. CONCLUSIONS: Inhibition of TF with rTFPI can prevent acute thrombosis and intimal hyperplasia after injury. Tissue factor plasma inhibitor may prove useful as an adjunct to intracoronary interventions.

Angioplasty, Balloon, Coronary↗

Delayed hemoperitoneum following large-volume paracentesis in a patient with cirrhosis and ascites.

The diagnosis of early or late hemoperitoneum after large-volume paracentesis can be reached easily by a repeat tap, but gastrointestinal bleeding and other common causes of hypotension in cirrhotics must be ruled out first. When the hemoperitoneum is confirmed, imaging studies are often inconclusive and laparotomy should be considered when hemodynamic instability persists despite adequate fluid resuscitation. However, in instances of delayed hemoperitoneum, it must be anticipated that operation may not identify the bleeding site and result in further decompensation of the liver. OLT may well be the best therapeutic option in this rare, high-risk situation.

Ascitic Fluid↗

Accelerated flap prefabrication with vascular endothelial growth factor.

Vascular endothelial growth factor (VEGF) is a potent promoter of angiogenesis that has been shown to enhance revascularization of ischemic tissues, including skin flaps. This study was designed to investigate the value of a single topical application of recombinant human VEGF to accelerate flap viability in a rat model of a non-ischemic prefabricated flap. Prefabricated flaps were created in 48 Sprague-Dawley rats. An autologous tail artery loop was anastomosed to the femoral artery and vein, and implanted subcutaneously in the lower abdomen. Flaps were divided into two groups of 24 each. At the time of loop implantation the control group received 0.9 percent NaCl or a 16 percent vol/wet polyvinyl alcohol (PVA) solution: the treatment group received VEGF in 0.9 percent NaCl or VEGF in PVA. The PVA gel was used to facilitate topical application In each group, 3- x 4-cm flaps nurtured by the tail artery pedicle were elevated and resutured into place after 3, 4, and 5 weeks. The percentage of surviving skin of each flap was determined by planimetry 7 days after flap elevation. Mean skin survival areas at 3, 4, and 5 weeks were control group 0 percent. 8 percent and 17.5 percent; and VEGIF-treated group, 6 percent, 40 percent, and 66.7 percent respectively VEGF significantly improved flap survival by 5 weeks (p = 0.02). These results suggest that VEGF can accelerate maturation of prefabricated flaps. This approach could expand the application of flap prefabrication as a resource for reconstructive surgery.

Animals↗

Apoptosis, proliferation, and p27 expression during vessel wall healing: time course study in a mouse model of transluminal femoral artery injury.

OBJECTIVE: The balance between cell death and proliferation in the vessel wall influences neointimal formation, remodeling, and eventual luminal narrowing after arterial injury. In this study, the time course of apoptosis, proliferation, and expression of p27-a critical regulator of cell-cycle progression-is characterized in a mouse model of transluminal arterial injury associated with substantial neointimal formation. METHODS: C57BL/6 mice underwent bilateral femoral artery injury by passage of an angioplasty guidewire. Expression of p27, Ki67 proliferative index, and apoptosis, as well as histomorphometry, were analyzed in cross sections of uninjured arteries and arteries harvested at different time intervals after injury. RESULTS: In the uninjured arteries, no apoptotic cells were detected, and p27 and Ki67 were expressed in less than 5% of medial cells. After injury, apoptosis increased markedly in medial smooth muscle cells from 1 to 24 hours and decreased gradually thereafter. Ki67 proliferative index increased after 1 week, peaked at 2 weeks in both the media and neointima, and decreased thereafter. p27 expression was undetectable from 1 to 48 hours, and increased gradually from 1 to 4 weeks. Well-developed neointima was present at 2 and 4 weeks. CONCLUSIONS: In vivo injury to the mouse femoral artery evokes a rapid apoptotic response and downregulation of p27, followed by gradual increase in proliferation. During later phases of arterial repair, p27 expression increases while a shift of proliferation rates toward baseline occurs. Future experiments using this model in genetically modified mice may help identify specific cell-cycle regulatory molecules as therapeutic targets for control of pathologic arterial healing.

Analysis of Variance↗

Mouse model of femoral artery denudation injury associated with the rapid accumulation of adhesion molecules on the luminal surface and recruitment of neutrophils.

Techniques of arterial injury commonly used in animals to mimic endovascular procedures are not suitable for small mouse arteries. This has limited examination of the response to arterial injury in genetically modified mice. We therefore sought to develop a model of transluminal injury to the mouse femoral artery that would be reproducible and result in substantial levels of intimal hyperplasia. Mice of the C57BL/6 strain underwent bilateral femoral artery denudation by passage of an angioplasty guidewire. Intimal hyperplasia was observed in 10% of injured arteries at 1 week, in 88% at 2 weeks, and in 90% at 4 weeks. The mean intimal-to-medial area ratio reached 1.1+/-0.1 at 4 weeks. No intimal proliferation was found in control sham-operated arteries. One hour after injury, the denuded surface was covered with platelets and leukocytes, predominantly neutrophils. This was associated with the accumulation of P-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1. Expression of these adhesion molecules was not seen in the underlying medial smooth muscle cells. At 24 hours, few neutrophils remained on the denuded surface. At 1 week, macrophages and platelets were present in the vessel wall, partially covered by regenerated endothelium. Transluminal wire injury to the mouse femoral artery induces abundant intimal hyperplasia formation by 2 and 4 weeks and elicits the rapid accumulation of leukocytes and adhesion molecules on the denuded luminal surface. This model will be a valuable tool to study arterial injury in genetically modified mouse models.

Animals↗

Rapid oral endotracheal intubation with a fibre-optic scope in rabbits: a simple and reliable technique.

The orotracheal intubation of rabbits is complicated by their oropharyngeal anatomy. Numerous techniques to intubate rabbits have been described; however, these methods require specialized devices, tracheostomy, or are performed in a blind fashion. We describe a technique for the intubation of the rabbit under direct visualization with a standard, small-bore, fibre-optic laparoscope, which is both rapid and simple to perform.

Animals↗

Nontropical pyomyositis: analysis of eight patients in an urban center.

Nontropical pyomyositis is rare and usually associated with immunodeficiency virus (HIV) infection. This study assessed manifestations and response to treatment of nontropical pyomyositis in an area with a high prevalence of HIV seropositivity. We undertook a chart review of eight consecutive patients treated for pyomyositis - primary infection of skeletal muscles - from 1988 through 1998. All patients complained of myalgia; four (50%) had fever and six (75%) had leukocytosis. Muscles involved were deltoid, quadriceps, gluteus, and psoas. Six (75%) patients had identifiable risk factors for pyomyositis: HIV seropositivity (two), history of intravenous drug abuse (one), chronic paraplegia and malnutrition (one), diabetes and chronic renal failure (one), and leukemia (one). One patient had had streptococcal pharyngitis previously but was otherwise healthy; another, a 2-year-old, had no evidence of underlying disease. Staphylococcus aureus was the most common organism isolated (50%). Four patients were treated with incision and drainage plus antibiotics; the remaining four patients were treated with intravenous antibiotics only; all recovered. Nontropical pyomyositis, which is often associated with HIV seropositivity or chronic illness, has a favorable outcome. Treatment can be effective even without surgical intervention.

Adult↗

[Gene therapy and liver metastases].

Liver metastases occur in approximately 60% of patients with colorectal cancer. Liver resection is currently the only treatment that offers long-term survival. The 5-year survival rates range from 25 to 40%; however, less than 20% of patients are candidates for resection. The prognosis for the remaining patients is grim, since palliative chemotherapy and symptomatic care are the only available options. The ability to transfer therapeutic genes to target cells in vivo has opened up unprecedented possibilities for the management of metastatic liver cancer. A large number of genes with therapeutic potential have been cloned. Families of genes currently used can be classified as "suicide", cytokine, anti-angiogenic, tumour-suppressor, and oncogenes. Physico-chemical and, more commonly, viral vectors can be used to enhance gene transfer into tumours. The delivery systems for gene therapy continue to improve as minimally invasive techniques are combined with recent vector technology. Encouraging results, such as tumour destruction and long-term protective immunity against metastatic disease, have been obtained in different animal models. This article discusses several recent phase I and II clinical trials. The results of these combined laboratory and clinical studies are expected to define optimal means of incorporating gene therapy into the treatment of liver metastasis.

Colorectal Neoplasms↗

Update on gene therapy for intimal hyperplasia.

Trauma to the vessel wall leads to smooth muscle cell (SMC) activation and eventual intimal hyperplasia. This process occurs in restenosis following balloon angioplasty, particularly with stent placement, occlusion of vascular bypasses, and arteriopathy of chronic allograft rejection. Genetic interventions affecting the cell cycle or early postinjury events have been successful in limiting SMC proliferation in vitro and in animal models. Gene therapy strategies have included the use of antisense oligonucleotides to block protein synthesis, transduced genes to cause cytotoxicity, and genetically engineered cells to decrease the response to injury. The clinical application of gene therapy in vascular diseases should follow the evolution of delivery systems that enable efficient local gene transfer to the arterial wall. (Tab. 1, Fig. 1, Ref. 30.)

Animals↗

Intra-abdominal pulmonary sequestration exhibiting congenital cystic adenomatoid malformation. Report of a case and review of the literature.

We describe the fifth case, to our knowledge, of an intra-abdominal pulmonary sequestration that histologically displayed the features of congenital cystic adenomatoid malformation (CCAM) type 2. This mass was found during routine prenatal ultrasound in an infant with no other congenital malformations. A literature search found 13 previously reported cases of CCAM in extralobar pulmonary sequestration (EPS), nine of which were thoracic and only four were intra-abdominal. An analysis of our case and the 13 previously reported cases shows that the clinical features of EPS containing CCAM type 2 do not differ significantly from those of EPS occurring alone. The presence of CCAM type 2 in our patient is consistent with previously reported cases. Extralobar pulmonary sequestrations located in the abdomen are rarely diagnosed prior to excision, and the presence of CCAM type 2 in this situation may further compound diagnostic difficulties. The morphologic features separating CCAM into three distinct types and the exclusive association of CCAM type 2 occurring in EPS are also discussed.

Bronchopulmonary Sequestration↗

Buerger's disease affecting mesenteric arteries: a rare cause of intestinal ischemia--a case report.

Buerger's disease is a recurrent, inflammatory, segmental, vasoocclusive disease. Typically, the disease affects middle-aged male smokers and involves arteries and veins of extremities. Buerger's disease involving visceral vessels is rare. The authors report on a 51-year-old man with peripheral arterial disease and recurrent intestinal ischemia secondary to Buerger's disease. Clinical and histopathologic features of this case illustrate the life-threatening nature of visceral involvement in Buerger's disease.

Humans↗