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Joseph D Raffetto

Publications and source records attributed to Joseph D Raffetto.

14 recordsLinked to original sources
PubMed2006

Venous ulcer fibroblasts respond to basic fibroblast growth factor at the cell cycle protein level.

Fibroblasts cultured from venous ulcers demonstrate phenotypic characteristics of cellular senescence including slow growth, altered morphology, upregulation of fibronectin, and increased senescence-associated beta-galactosidase activity. In senescent cells, arrest of cell replication is related to overexpression of p21 and underexpression of phosphorylated tumor-suppressor protein retinoblastoma (ppRb). The regulatory mechanisms for cell proliferation in venous ulcer fibroblasts are unknown. In this study, venous ulcer fibroblasts are examined for cell cycle protein expression and modulation by basic fibroblast growth factor (bFGF). Fibroblasts were isolated from the venous ulcer of the distal lower extremity (fb-D) of patients with chronic venous insufficiency. A control biopsy was obtained from the proximal ipsilateral thigh (fb-P). Paired cultures were plated at 100,000 cells/plate and the cells synchronized. After 24 hr, one culture set was treated with bFGF (20 ng/mL) and the other was kept in culture medium only (untreated). All cultures, treated and untreated, were lysed following 24 hr of incubation, and the lysate was used to perform immunoblot analysis for p21, ppRb, and cyclin D1. Immunoblot samples were standardized to protein content. In all patients analyzed (n = 4), at basal levels (untreated) fb-D demonstrated significant overexpression of p21 versus fb-P (p = 0.016). Treatment with bFGF resulted in significant downregulation of p21 levels for fb-D (p = 0.008) and fb-P (p = 0.037) compared to untreated fibroblasts. ppRb was underexpressed in fb-D versus fb-P (p = 0.069). Treatment with bFGF increased ppRb significantly in fb-D (p = 0.030) and in fb-P (p = 0.027) compared to untreated fibroblasts. No differences were observed in cyclin D1 with respect to basal levels in fb-P versus fb-D or in treated versus untreated groups. Venous ulcer fibroblasts show phenotypic similarity to senescent cells, with overexpression of p21 as well as down regulation of phosphorylated pRb. The aberrations seen in the cell cycle proteins in fb-D are similar to those seen in senescent cells; however, bFGF can modulate important cell cycle regulatory proteins, promoting a proliferative environment in fb-D that is not possible in a senescent cell. The role of bFGF may be useful in the clinical treatment of venous ulcer pathology.

Adult↗
PubMed2005

Differences in risk factors for lower extremity arterial occlusive disease.

BACKGROUND: Patients undergoing lower extremity revascularization have associated cardiovascular risks: smoking, hypertension, dyslipidemia, and diabetes. This study evaluated the impact of cardiovascular risk factors on proximal versus distal arterial occlusive disease in patients undergoing lower extremity revascularization as adjusted to a control group without vascular disease. STUDY DESIGN: We performed a retrospective, case-control study that included 151 patients undergoing lower extremity revascularization and 229 patients undergoing knee and hip replacement (controls). Risk factors were determined for each of three separate groups undergoing revascularization for different levels of occlusive disease: aortoiliac, superficial femoral, and popliteal-tibial. Comparisons to controls were tested using t-tests or chi-square tests and multiple logistic regression. RESULTS: Dyslipidemia was associated with a significant risk of aortoiliac (odds ratio [OR]=3.4; p=0.0006) and superficial femoral occlusion (OR=2.8; p=0.01) but was less strongly associated with popliteal-tibial occlusion (OR=2.1; p=0.09). Smoking was strongly associated with aortoiliac (OR=4.5; p=0.004) and superficial femoral disease (OR=4.6; p=0.0007) but not popliteal-tibial disease (OR=1.3; p=0.53). In contrast, diabetes mellitus and chronic renal insufficiency were strong risk factors for popliteal-tibial occlusion (OR=5.4, p=0.0002; OR=3.9, p=0.01, respectively), but were not significant risk factors for aortoiliac or superficial femoral occlusion. CONCLUSIONS: These data, which use revascularization level as a surrogate marker for lower extremity arterial disease, suggest that the risk factor profile for proximal disease differs from that of distal disease. These findings may reflect differences in the biology of disease and indicate that different risk factors have various anatomic influences on arterial disease formation.

Arterial Occlusive Diseases↗
PubMed2004

Aortobifemoral graft infection with Mycobacterium tuberculosis: treatment with abscess drainage, debridement, and long-term administration of antibiotic agents.

Aortic graft infection with Mycobacterium tuberculosis is rare. We report a patient with a Dacron aortobifemoral prosthetic graft infection secondary to tuberculosis. The infection was successfully treated with surgical drainage without removal of the graft, and long-term antimycobacterial medications. A review of the literature contains only 1 other report of tuberculosis graft infection and treatment. We discuss a rare form of aortic graft infection from M tuberculosis and its treatment.

Abdominal Abscess↗
PubMed2004

Vertebral artery dissection following intravascular catheter placement: a case report and review of the literature.

Vertebral artery dissections (VAD) are known to occur as a result of mechanical manipulations of the cervical region, traumatic injury, iatrogenic injury and are also known to arise spontaneously. We report a case of vertebral artery dissection following vertebral artery cannulation during a central line placement and review the literature. The patient underwent intravascular catheter placement that subsequently demonstrated arterial blood. Duplex ultrasound and computed tomographic (CT) scan confirmed vertebral artery cannulation. The catheter was removed at the bedside with pressure, and a subsequent duplex ultrasound scan revealed a vertebral artery dissection. There were no neurological sequelae. The patient was successfully anticoagulated with warfarin but died from unrelated complications. This case report describes the rare iatrogenic event of VAD and reviews its etiology, diagnosis, complications, and management.

Catheterization, Central Venous↗
PubMed2003

bFGF-induced alterations in cellular markers of senescence in growth-rescued fibroblasts from chronic venous ulcer and venous reflux patients.

Fibroblasts cultured from the distal lower extremity of chronic venous insufficiency (CVI) patients exhibit characteristics of cellular senescence. Basic fibroblast growth factor (bFGF) has been shown to improve growth rates in these fibroblasts. In bFGF-treated fibroblasts, levels of fibronectin and matrix metaloproteinase-2 (MMP-2), known to be up-regulated in senescence, were examined to determine whether bFGF induces changes in these markers of senescence with rescue of cellular proliferation. Fibroblasts were isolated from the distal leg of patients with CVI with and without ulcers (fb-D). In all patients, a control was obtained from the proximal ipsilateral thigh (fb-P). Cells were plated at 3000 cells/plate and treated with bFGF (20 ng/mL) on days 1, 5, 8, and 11. Total cell number was obtained on days 5 and 12 using the Coulter particle counter, and concurrently cells were plated at 10,000 cells/plate and treated with bFGF on the same schedule; cell lysate was harvested on day 12 for immunoblot analysis for MMP-2 and fibronectin. In all patients (n = 7), fb-P grew faster than fb-D (p = 0.039). fb-D showed a mean 3.3-fold increase in growth in response to bFGF, and immunoblot analysis demonstrated an up-regulation of fibronectin and MMP-2 in response to bFGF. This represents the possibility that by stimulating growth, bFGF may drive cells toward senescence. This suggests clinical implication for the use of bFGF and other growth factors in general.

Adult↗
PubMed2003

Incision and abdominal wall hernias in patients with aneurysm or occlusive aortic disease.

INTRODUCTION: Patients undergoing midline incision for abdominal aortic reconstruction appear to be at greater risk for postoperative incision hernia compared with patients undergoing celiotomy for general surgical procedures. Controversy exists as to whether incidence of abdominal wall hernia and increased risk for incision hernia is higher in patients with abdominal aortic aneurysm (AAA) than in patients operated on because of aortoiliac occlusive disease (AOD). We conducted a prospective multi-institutional study to assess frequency of incision hernia after aortic surgery through a midline laparotomy and of previous abdominal wall hernia. METHODS: Patients with AAA (n = 177) or AOD (n = 82) from three major institutions were prospectively enrolled in the study and examined. Data collected included demographic data, cardiopulmonary risk factors, smoking status, history of previous or current abdominal wall hernia (incision, inguinal, umbilical, femoral), previous midline incision, suture type, and postoperative complications. At a minimum of 6 months after laparotomy, patients were evaluated clinically for a new incision hernia. Differences were tested with the unpaired t test, X(2) test, or Fisher exact test, and multiple logistic regression was used to control for confounding variables. RESULTS: Mean follow-up of the cohort was 32.8 +/- 2.3 months. Rate of abdominal wall hernia and inguinal hernia in patients with AAA versus AOD was 38.4% versus 11% (P =.001) and 23.7% versus 6.1% (P =.003), respectively. Rate of postoperative incision hernia in patients with AAA was 28.2%, and in patients with AOD was 11.0% (P =.002). Adjusting for age, smoking, chronic obstructive pulmonary disease, body mass index, diabetes, bowel obstruction, and suture type, patients with AAA had almost a ninefold risk for postoperative incision hernia formation (odds ratio [OR], 8.8; P =.0049). CONCLUSION: Compared with patients with AOD, patients with AAA have a higher frequency of abdominal wall hernia and inguinal hernia, and are at significant increased risk for development of incision hernia postoperatively. The higher frequency of hernia formation in patients with AAA suggests the presence of a structural defect within the fascia. Further studies are needed to delineate the molecular changes of the aorta and its relation to the abdominal wall fascia.

Aged↗
PubMed2003

Primary aortoduodenal fistula: a case report and review of the literature.

Abdominal aortic aneurysms (AAAs) can cause aortoenteric fistulae (AEF). AEF can either be primary, arising from the aneurysm or other diseases, causing the aorta to erode into the bowel, or secondary, from previous aortic grafting. Primary aortoduodenal fistula (ADF) is a rare clinical entity that usually presents with gastrointestinal bleeding that can be occult, intermittent, or massive. We report a 71-year-old woman with acute onset of abdominal pain and massive hematemesis. Esophagogastroduodenal endoscopy (EGD) and arteriography were nondiagnostic. The patient's condition became unstable, and she was brought emergently to the operating room where the diagnosis of an ADF was made. The ADF and AAA were surgically repaired, and the patient recovered without complications. This case represents an example of a rare complication of AAA with the unusual presentation of multiple aortic aneurysms. We will address the pathophysiology, diagnostic evaluation, and management of AEF.

Aged↗
PubMed2002

Bovine pericardium vs dacron for patch angioplasty after carotid endarterectomy: a prospective randomized study.

HYPOTHESIS: Bovine pericardium (BP) demonstrates improved intraoperative hemostasis and equivalent perioperative morbidity compared with Dacron when used as patch material for angioplasty following carotid endarterectomy. OBJECTIVE: To prospectively compare BP and Dacron patch angioplasty after carotid endarterectomy in a randomized fashion. METHODS: Ninety-five consecutive primary carotid endarterectomies were performed in a prospective randomized fashion in 92 patients. Fifty-one procedures were performed using BP and 44 using Dacron. Intraoperative suture line bleeding was subjectively evaluated by observing bleeding at 3 and 4 minutes following carotid cross-clamp removal and then objectively weighing the sponge used to tamponade bleeding during these time intervals. Perioperative morbidity, including cervical wound hematoma, transient ischemic attack, and stroke, and perioperative mortality were recorded. Statistical analysis was performed using paired t tests, chi(2) analysis, Fisher exact test, or multiple linear regression as appropriate. RESULTS: Suture line bleeding at 3 minutes was present in 7 (14%) of 51 patients in the BP group and 24 (55%) of 44 patients in the Dacron group (P<.001). Suture line bleeding evaluated at 4 minutes was present in 2 (4%) of 51 patients in the BP group and 13 (30%) of 44 patients in the Dacron group (P =.001). Net +/- SEM sponge weight (total intraoperative suture line bleeding) was 6.25 +/- 0.55 g in the BP group and 16.34 +/- 1.85 g in the Dacron group (P<.001). Total suture line bleeding was significantly affected by activated clotting time; however, multivariate analysis demonstrated that bleeding was significantly less with BP (P<.001) even after adjusting for differences in activated clotting time. CONCLUSIONS: Bovine pericardium demonstrated a statistically significant decrease in intraoperative suture line bleeding compared with Dacron. Handling characteristics were judged by the surgeons to be superior for BP. Therefore, we believe BP may be an alternative to Dacron when performing patch angioplasty of the carotid artery after endarterectomy.

Aged↗
PubMed2002

Factors that predict site of outflow target artery anastomosis in infrainguinal revascularization.

INTRODUCTION: Lower extremity revascularization is indicated for limb salvage and incapacitating leg claudication. Many risk factors (age, hypertension, diabetes, tobacco use, dyslipidemia, etc) have been associated with atherosclerosis and the development of peripheral arterial occlusive disease. However, whether these risk factors or the surgical indication (claudication or limb salvage) influences the extent and location of infrainguinal disease and hence the target artery (distal anastomosis) is unclear. This study examines the risk factors and indication for infrainguinal revascularization with respect to the type of bypass performed. METHODS: Three hundred fifty-two infrainguinal revascularizations in 282 patients were retrospectively reviewed. Patient data, including demographics, cardiovascular risk factors, indications, types of revascularization, and perioperative complications and mortality, were collected. Data were analyzed with t test, chi(2) test, Fisher exact test, and multiple logistic regression. RESULTS: The indication for surgical revascularization was claudication in 70 patients and limb salvage in 282. The likelihood of a popliteal anastomosis (above or below knee) versus a tibial or pedal anastomosis was decreased with increasing age (P =.002) and diabetes (P =.0001), and smoking increased the likelihood (P =.056). However, popliteal bypass also was strongly associated with claudication as the surgical indication (odds ratio [OR], 8.7; P =.0001), and 90% of the claudicant group had undergone popliteal anastomosis. Claudication and popliteal anastomosis were both linked to smoking; 97% of subjects who underwent operation for claudication were smokers compared with 75% of subjects who underwent tibial or pedal anastomosis for limb salvage (P =.001). After adjustment for indication, the likelihood of popliteal anastomosis was still decreased with diabetes (OR, 0.46; P =.002), and age had a borderline significant effect (P =.077). When the analysis was stratified by indication for surgery, the likelihood of popliteal bypass among patients who underwent operation for claudication was not influenced by age, diabetes, or smoking. However, within the subset of patients who underwent operation for limb salvage, the likelihood of any popliteal anastomosis was diminished by diabetes (OR, 0.50; P =.007), age (OR, 0.968 per year; P =.01), and chronic renal insufficiency (OR, 0.476; P =.04). CONCLUSION: Infrainguinal peripheral arterial occlusive disease is not a homogenous disease entity. Claudication and limb salvage are associated with two distinct patterns of vascular disease with different risk factors. Patients who undergo operation for claudication are seen at an earlier age, have a high prevalence of smoking, and have proximal disease and a greater likelihood of a popliteal anastomosis. In contrast, patients for limb salvage are less likely to have a popliteal bypass, favoring a more distal target outflow anastomosis that is strongly influenced by advanced age, diabetes, and chronic renal insufficiency.

Aged↗
PubMedDate not supplied

Acute thrombosis of abdominal aortic aneurysms--report of two cases and review of the literature.

An acutely thrombosed abdominal aortic aneurysm (AAA) is a rare but devastating complication of aortic aneurysms. Incidence in reported series is approximately 0.7-2.8% of surgically managed AAA cases with an associated mortality rate of 50%. To date there have been only 46 cases of acutely occluded AAAs reported in the literature. We present our experience of 2 additional cases of acute AAA thrombosis and discuss the mechanism of thrombosis and management. The size of the aneurysm seems to be a better predictor of rupture than of thrombosis. Strong risk factors for thrombosis are the presence of concomitant iliac artery and cardiac disease. Although this complication is rare, its high mortality rate makes it an important disease to understand, recognize, diagnose, and treat for a successful outcome.

Acute Disease↗
PubMedDate not supplied

Noninfectious saccular abdominal aortic aneurysm--a report of two cases.

Saccular aortic aneurysms are eccentrically shaped and are commonly thought to be the consequence of infection of the aorta. However, saccular-type aneurysms can be found independent of any clinical or subclinical infection and can be associated with a penetrating aortic ulcer. Moreover, penetrating aortic ulcers have been described in the thoracic aorta, but there is a paucity of any documentation of this clinical and pathologic entity occurring in the abdominal aorta. The authors describe 2 cases of symptomatic, penetrating atherosclerotic ulcers of the abdominal aorta causing saccular, noninfectious abdominal aortic aneurysms.

Aged↗
PubMedDate not supplied

Proliferative capacity of venous ulcer wound fibroblasts in the presence of platelet-derived growth factor.

Growth factors have been demonstrated to increase the proliferation of wound fibroblasts. Platelet-derived growth factor (PDGF) is a potent cell mitogen. However, the role of PDGF in chronic venous ulcers is inconclusive. This study investigated whether PDGF stimulates venous ulcer fibroblasts to proliferate. Fibroblasts (fb) were isolated from 8 venous ulcers wounds (w-fb) and normal skin (n-fb) of the ipsilateral thigh via punch biopsies. Fibroblasts were plated at 1,500 cells/dish in Dulbecco's Modified Eagle Medium + 10% calf serum (CM) and treated with/without PDGF-alphabeta (10 ng/mL) for 15 days. Growth rates were calculated. Western blotting and immunocytochemistry staining determined basal levels for PDGF-alpha and -beta receptors, respectively. Growth rates were significantly lower in w-fb than in n-fb (1,579 +/-546 vs 13,782 +/-5,882 cells/day, p=0.019). PDGF-alphabeta treatment caused n-fb to increase their proliferative capacity relative to complete media (20,393 +/-6,572 vs 13,782 +/-5,882 cells/day, p=0.005). However, PDGF-alphabeta had no significant effect on w-fb proliferation over CM (1,030 +/-264 and 1,579 +/-546 cells/day, p=0.15). In the presence of PDGF-alphabeta, w-fb had a significantly attenuated growth rate over n-fb (1,030 +/-264 vs 20,393 +/-6,572 cells/day, p=0.019). Western blot and immunocytochemistry analysis revealed diminished basal levels of PDGF-alpha and -beta receptors, respectively, in ulcer fibroblasts. Venous ulcer fibroblasts had decreased proliferation. PDGF-alphabeta had no effect on the growth rate of venous ulcer fibroblasts. In venous ulcers, decreased basal levels of fibroblast PDGF-alpha and -beta receptors may explain reduced proliferation. Further clinical studies are needed to elucidate the role growth factors may play in venous ulcers.

Cell Division↗
PubMedDate not supplied

Mitogen-activated protein kinase pathway regulates cell proliferation in venous ulcer fibroblasts.

Venous ulcer fibroblasts have been demonstrated to have low growth rates in response to platelet-derived growth factor (PDGF). Mitogen-activated protein kinase (MAPK) is an important signal transduction mechanism that regulates growth, differentiation, and apoptosis in eukaryotic cells. PDGF binds PDGF receptors that activate a multitiered signaling cascade involving MAPK. We hypothesize that the growth regulation in venous ulcer fibroblasts is dependent on the MAPK extracellular signal-regulated kinase (ERK) pathway in the presence of PDGF. Fibroblasts (fb) were isolated from 8 patients with venous ulcers (w-fb) and the normal skin (n-fb) of the ipsilateral thigh via punch biopsies. Fb were plated at 1,500 cells/dish and treated with PDGF-AB (10 ng/mL) for 15 days. Growth rates were determined. Immunoblot analysis of MAPK ERK for n-fb and w-fb were analyzed. To determine if PDGF-stimulated w-fb and n-fb utilized the MAPK ERK pathway in a dependent manner, the upstream kinase MAPK kinase 1 (MEK 1) was inhibited by PD 98059. In addition, fb were treated with chronic venous ulcer wound fluid (WF) to study its effect on MAPK ERK. In the presence of PDGF, growth rates were substantially lower in w-fb than in n-fb, and MAPK was activated in 6/8 w-fb and in only 2/8 n-fb. Fibroblasts expressing MAPK had significantly reduced cell proliferation compared to fibroblasts not expressing MAPK (p = 0.023). PD 98059 significantly inhibited w-fb and n-fb cell proliferation from basal level, which was reversible with addition of PDGF. In neonatal fibroblasts WF demonstrated inhibition of MAPK ERK over time and addition of PD98059 was not additive. This study suggests that the MAPK ERK pathway is important for cell proliferation in venous ulcer fibroblasts. In the presence of PDGF, fibroblasts with decreased growth rate express MAPK, and proliferation is further abrogated with addition of MEK 1 inhibitor, suggesting the importance of the MAPK ERK pathway regulating w-fb and n-fb proliferation. Although the majority of w-fb activated the MAPK ERK pathway in the presence of PDGF, proliferation was significantly attenuated, indicating that other MAPK inhibitory pathways are competing. Venous ulcer wound fluid directly inhibits the MAPK ERK pathway, suggesting that the venous ulcer wound environment has negative trophic factors that effect fibroblasts proliferation and ulcer healing.

Adult↗