Biomedical subjects

E Ascher

Publications and source records attributed to E Ascher.

At least 19 recordsLinked to original sources

PubMed2006

Duplex guided balloon angioplasty of failing infrainguinal bypass grafts.

OBJECTIVE: To assess the results of angioplasty and stent placement under duplex guidance for failing grafts. METHODS: Over 22 months, 25 patients (72% males) with a mean age of 74+/-10 years presented to our institution with a failing infrainguinal bypass. The site of the most significant stenotic lesion was in the inflow in four cases, conduit in 18 cases and at the outflow in 11 cases. All arterial (20) or graft (13) entry sites cannulations were performed under direct duplex visualization. Duplex scanning was the sole imaging modality used to manipulate the guide wire and directional catheters from the ipsilateral CFA to a site beyond the most distal stenotic lesion. Selection and placement of balloons and stents were also guided by duplex. In 11 cases (33%), the contralateral CFA was used as the entry site and a standard approach (fluoroscopy and contrast material) was employed. Completion duplex exams were obtained in all cases. RESULTS: The overall technical success was 97% (32/33 cases). In only one case, the outflow stenotic lesion in the plantar artery could not be traversed with the guidewire due to extreme tortuosity. Overall local complications rate was 6% (two cases). One vein bypass pseudoaneurysm caused by rupture with a cutting balloon was repaired by patch angioplasty and one SFA pseudoaneurysm at the puncture site required open repair. Overall 30-day survival rate was 100%. Overall 6-month limb salvage and primary patency rates were 100 and 69%, respectively. CONCLUSIONS: Duplex guided endovascular therapy is an effective modality for the treatment of failing infrainguinal arterial bypasses.

Aged↗

PubMed2005

Activation of p38MAPK signaling cascade in a VSMC injury model: role of p38MAPK inhibitors in limiting VSMC proliferation.

INTRODUCTION: P38 mitogen-activated protein kinase (MAPK) has a crucial role in regulating signaling pathways implicated in the cellular events leading to restenosis. We examine p38MAPK activation in response to vascular cell injury, its biological effects and determine whether selective p38MAPK inhibitors, SB220025/SB203580, decrease vascular smooth muscle cell (VSMC) proliferation. METHODS: Human aortic VSMCs were cultured and wounds made on the monolayers to elicit mitogenic responses and induce p38MAPK activation. P38MAPK inhibitor pretreatment, at varying doses (1-100 microM) and treatment duration was used to block p38MAPK phosphorylation. Cytotoxicity, viability, proliferation and apoptosis were determined and expression of p38MAPK/phospho-p38MAPK was obtained by chemiluminiscent immunoblot analysis. RESULTS: Phosphorylation of p38MAPK depended on injury severity and was inhibited by both p38MAPK inhibitors, but not by SB202474, a specific antagonist of p38MAPK inhibitors. VSMCs treated with p38MAPK inhibitors showed a dose-dependent decrease in viable cell number, apoptosis and proliferation, reversing the deleterious effects of p38MAPK activation comparable to controls (p < 0.05). CONCLUSIONS: This wound injury model activates the p38MAPK-signaling cascade in VSMC and causes cell proliferation that can be abrogated by pre-incubation with p38MAPK selective synthetic inhibitors in a time and dose-dependent manner. SB220025 used here for the first time in VSMC reveals itself to be a stronger p38MAPK inhibitor than SB203580 and being a second generation inhibitor may be the preferred drug for novel therapeutic maneuvers.

Calcium-Calmodulin-Dependent Protein Kinases↗

PubMed2004

The role of the endovascular surgeon for lower extremity ischemia.

UNLABELLED: Since the data investigating endovascular therapy performed by surgeons is scarce, we retrospectively reviewed our experience of endovascular procedures performed by vascular surgeons in the operating room for lower extremity ischemia due to stenotic lesions. METHODS: A total of 14,424 procedures were performed by our division between January 1990--October 2003. Of these, 500 involved a balloon angioplasty. These made up 3.5% of the total caseload. The median age of the patients who underwent these 500 balloon angioplasty was 72+/-0.5 years old; 65% were male; 50% had a history of diabetes mellitus, and 6% had ESRD. Indications for the procedures included acute ischemia (47 cases), critical ischemia (rest pain, gangrene, or ischemic ulcers in 254 cases), failing bypass (64 cases), severe claudication (134 cases), and preoperative for a popliteal artery aneurysm repair. RESULTS: 244 of the procedures were percutaneous, and the remaining 256 were combined with some type of open procedure. Those performed as an open technique were in combination with a bypass (135 cases) and in combination with a patch angioplasty (31cases). Balloon angioplasties were performed of the aorta (5 cases), iliac arteries (281 cases), the superficial femoral artery (SFA) (101 cases), the popliteal artery (44 cases), the tibial vessels (77 cases), the subclavian/axillary artery (5 cases) and failing grafts (26 cases). Balloon angioplasty was attempted in eight cases and failed due to inability to cross the lesion with a guidewire. Intraoperative complications included 4 dissections, inability to dilate the lesion adequately (2 cases), and rupture of two iliac lesions that underwent open repair (1 case) or repair with a stent graft (1 case). Stents were initially used highly selectively but recently are now being deployed more liberally in the iliac arteries (total 251 cases with stents). CONCLUSIONS: Based on these data, we suggest that balloon angioplasty is a useful tool that can be performed by vascular surgeons safely. The advantages to the patients include one combined procedure to treat lower extremity ischemia.

Aged↗

PubMed2004

Carotid endarterectomy in octogenarians and nonagenarians : is it worth the effort?

PURPOSE: The safety, effectiveness and cost issues of carotid endarterectomy (CEA) in the elderly patient have been debated due to the limited life expectancy and presumably increased rate of complications. This is despite multiple reports in the literature of excellent results in this population. To further examine this issue, we compared characteristics of three populations who underwent CEA at our institution: 53-79 year old patients (youngest group), 80-89 years old patients (middle group), and 90-98 year old patients (oldest group). METHODS: Medical and financial data were obtained by retrospective review of hospital charts and billing records. We analyzed 266 random CEAs performed in 251 patients in the youngest group, 280 CEAs performed in 247 patients in the middle group and 19 CEA in 16 patients in the oldest group performed between 2/1/90 and 2/5/01. RESULTS: Comparing each CEA group, there were no differences in gender (males: 56% vs. 51% vs. 53%), incidence of preoperative symptoms (43% vs. 43% vs. 42%), hypertension (68% vs. 60% vs. 42%), combined perioperative death and stroke rate (1.8% vs. 2.1% vs. 10%) or other complications (11% vs. 10% vs. 10%). Significant differences (p<0.05) were noted between the groups in incidence of diabetes (33% vs. 51% vs. 5% in each group), and heart disease (28% vs. 38% vs. 21%). Length of stay for admissions for CEA only were also similar in all three groups (2.37 days vs. 2.67 days vs. 2.36 days). A cost analysis of the earliest 230 patients in the entire series examining hospital cost per case revealed similar data for the < 80 years old and > 80 year old patients ($7,842 vs. $9,400). CONCLUSIONS: Carotid endarterectomy can be performed in the elderly as safely and cost effectively as in the younger population.

Age Factors↗

PubMed2003

Hemodynamics of infrapopliteal PTFE bypasses and adjunctive arteriovenous fistulas.

PURPOSE: Blood flow, pressure and peripheral resistance in patients with established polytetrafluoroethylene (PTFE) grafts and adjunctive arteriovenous fistulas (AVF) have rarely been investigated. To better elucidate the effects of this AVF, we obtained noninvasive measurements of hemodynamic variables in patients with infrapopliteal PTFE grafts and an AVF. METHODS: . Systolic, mean and diastolic arm and toe pressures were measured with an oscillometric technique employed in automatic blood pressure monitors. Peak-systolic velocity, end-diastolic velocity and flow rates at the graft and recipient distal artery were measured with duplex ultrasound. Resistance for the leg and foot in peripheral resistance units ( PRU ) was estimated as mean arm pressure divided by graft flow rate and as mean toe pressure divided by distal artery flow rate respectively. We analyzed data from 21 patients. Toe pressures were measurable in 13 patients. Bypass graft inflow was at the external iliac artery in 11 patients, common femoral in six, common iliac in two and superficial femoral in two. The distal anastomosis was at the anterior tibial artery in 10 patients, peroneal in seven and posterior tibial in four patients. RESULTS: . Graft systolic and diastolic velocities were 91+/-46 (mean+/-sd) and 38+/-31 (mean+/-sd) cm/s respectively. Toe systolic pressure averaged 81+/-28 (mean+/-SD) mmHg with a corresponding toe/brachial index (TBI) of 0.53+/-0.18 (mean+/-SD). The ratio between arm mean pressure, 104+/-20 (mean+/-SD) mmHg, and graft flow rate, 413+/-290 (mean+/-sd) ml/min, yielded an estimated leg resistance of 0.32+/-0.20 peripheral resistance units (PRU) (mean+/-sd). The ratio between mean toe pressure, 51+/-21 (mean+/-SD) mmHg, and distal artery flow rate, 37+/-26 (mean+/-SD) ml/min, produced an estimated foot resistance averaging 1.66+/-1.18 PRU (mean+/-sd). CONCLUSIONS: Average graft flow rate was five times greater than flow reported for standard tibial bypasses. Although distal artery flow rate and graft peak systolic velocity were within reported normal ranges, mean toe pressure and toe-brachial index were below normal. Leg and foot resistances were decreased. These data suggest that bypasses with arteriovenous fistulas have increased flow, desirable for graft patency, but may affect distal perfusion pressure.

Aged↗

PubMed2003

Comparison of Magnetic Resonance Angiography (MRA) and Duplex Ultrasound Arterial Mapping (DUAM) prior to infrainguinal arterial reconstruction.

OBJECTIVE: the purpose of this study is to compare Magnetic Resonance Angiography (MRA) to Duplex Ultrasound Arterial Mapping (DUAM) and intraoperative findings to determine the clinical, accuracy of MRA for planning lower extremity revascularization procedures. METHODS: forty-two patients who underwent lower extremity revascularization procedures had both MRA and DUAM evaluations. These data were analyzed retrospectively and two distinct endpoints were considered. First, we compared the MRA and DUAM findings for aorto-iliac, femoral-popliteal and infra-popliteal segments to intraoperative findings and evaluated the degree to which they agreed. Second, if there was a disagreement between imaging modalities, it was established whether a change in operative procedure would have resulted. RESULTS: MRA and DUAM findings agreed in 26 of 31 cases (83%) of aorto-iliac segments, in 25 of 31 cases (81%) of femoral-popliteal segments, and in 16 of 21 cases (76%) of infra-popliteal segments. In total, DUAM agreed with intraoperative findings in 98% of cases while MRA agreed in 82% (p<.001). Disagreement between intraoperative findings and DUAM lead to an alternate surgical procedure in only one case (2%) while disagreement with MRA lead to a different procedure in 38% of cases (p<.001). CONCLUSIONS: these data show that MRA is not yet adequate to replace conventional angiography and is less accurate that DUAM. Further improvements are necessary before MRA can be used as the sole modality for formulation of a pre-operative plan for lower extremity revascularization.

Angiography↗

PubMed2003

Carotid surgery without external carotid endarterectomy: a 6-year clinical experience with 1027 cases.

PURPOSE: previously we routinely performed endarterectomy of the external carotid artery (ECA) during carotid surgery. However, discouraging experience and lack of supportive data in the literature made us question its necessity. The present report describes our experience with a modified carotid endarterectomy (CEA) technique where the ECA is left undisturbed regardless of its degree of stenosis. METHODS: from January 1996 to June 2001, 1027 CEAs were performed in 905 patients with this technique at our institution. All operations were performed for at least 60% internal carotid artery (ICA) stenosis. A preoperative carotid duplex scan was available for review in 990 cases (96%). Follow-up duplex scans were recovered from 0 to 1 months in 851 cases (83%) and from >1 month in 655 cases (64%). Seventy percent of these cases were performed for asymptomatic lesions. RESULTS: the perioperative (30-day) mortality rate for the entire group of patients was 0.5% and the stroke rate was 0.7%. Mean follow-up was 18 months (range: 2-66 months). Only two ECAs occluded in the first postoperative month. During the follow-up period, 37 additional ECAs (5.6%) were found to progress from mild to severe (>75%) stenosis postoperatively. In addition, 7% of the cases were found to have worsened the degree of stenosis, 8% improved and 85% remained unchanged. CONCLUSION: these data support sparing of the ECA during CEA.

Adult↗

PubMed2002

Causes of early post carotid endartectomy stroke in a recent series: the increasing importance of hyperperfusion syndrome.

OBJECTIVE: Early stroke occurs in 0.9% to 7% of patients undergoing carotid endarterectomy (CEA). These have been thought to be mostly due to embolization. However, in our recent clinical experience, we noted hyperperfusion syndrome to be a significant cause of postoperative strokes. Therefore, we reviewed our experience and investigated the distribution of causes of early postoperative strokes. MATERIALS AND METHODS: A retrospective chart review of 444 consecutive patients who underwent CEA at our institution between June 1997 and October 1999 (500 operations) was performed to evaluate the incidence and etiology of early postoperative strokes. Indications for operation included history of stroke correlating with the side of ICA stenosis (50 patients or 10%), symptoms of transient ischemic attacks (84 patients or 16.8%), amaurosis fugax (18 patients or 3.6%), or asymptomatic stenosis (348 patients or 69.6%). All patients were evaluated with duplex scan preoperatively and postoperatively. Diagnosis of early postoperative strokes within one month after CEA was made based on clinical examination. Postoperative CT scan of the brain was available in 100% of patients with suspected diagnosis of CVA. RESULTS: Five patients (3 male and 2 female) were diagnosed with strokes postoperatively (1%). These five were symptomatic patients with ICA stenosis > or = 80% and moderate contralateral ICA stenosis. In two of those patients (40%), the reason for the stroke was considered embolization to the cerebral arteries; one patient suffered a shunt injury as a cause of stroke; two patients (40%) were diagnosed with hyperperfusion syndrome. In both patients diagnosis was made clinically, and in only one of those patients the clinical picture correlated with CT scan. Two patients (0.4%) had asymptomatic ICA occlusion at 2 weeks and 18 days postoperatively. CONCLUSION: Embolization to the cerebral arteries remains the leading cause of early postoperative strokes. However, hyperperfusion syndrome also accounts for a significant portion of these postoperative strokes. The percentage of patients with this syndrome might be even higher, once clinical picture is clearly defined. These data warrant further investigation of hyperperfusion syndrome.

Aged↗

PubMed2001

Initial steps in the unifying theory of the pathogenesis of artery aneurysms.

OBJECTIVES: The objective of this study was to investigate the changes in histology and proteolysis and the role of apoptosis in the development of peripheral artery aneurysms. METHODS: Eighteen popliteal, 6 abdominal aortic, 10 iliac, 2 carotid, and 6 femoral artery aneurysm specimens were obtained from patients undergoing elective surgical repair. All were males with ages 48 to 93 (mean 71 years). Normal controls were obtained from patients matched for age, sex, and major risk factors. Vascular smooth muscle cells (VSMC), macrophages, T lymphocytes, and apoptosis-regulating molecules were detected immunohistochemically. Detection of apoptosis was by TUNEL assay. Proteolytic activity was determined by 10% gelatin gel zymography. RESULTS: Paucity of VSMCs, increased amount of inflammatory infiltrate, and fragmentation of elastic lamellae were observed in aneurysmal tissues as compared to normal arteries (P < 0.02). There is increased gelatinolytic activity at 92, 84, 72, and 67 kDa in the aneurysmal tissues. There are fewer CD68+ macrophages and T cells in the media of controls than in the aneurysms (P = 0.01). Apoptosis is significantly high in aneurysm tissues (P < 0.01) and the degree of apoptosis was in the order AAA>FAA>PAA>IAA>CAA. There is increased expression of Bax, CPP-32, Fas, and p53 in PAA specimens as compared to normal popliteal arteries (P < 0.05). CONCLUSIONS: These data confirm the apparent architectural disruption and loss of VSMCs that are hallmarks of aneurysm development, in peripheral artery aneurysms. Apoptosis and signaling molecules capable of initiating cell death may play a significant role in the pathogenesis of all aneurysms. Our data suggest a common etiology between the various types of aneurysms.

Aged↗

PubMed2001

Routine preoperative carotid duplex scanning in patients undergoing open heart surgery: is it worthwhile?

It has been reported that carotid screening may be cost-effective in patient populations in which the prevalence of severe carotid stenosis exceeds 4.5%. In order to identify potential patient populations who might benefit from carotid screening, we examined the results of preoperative duplex scanning in patients undergoing open heart surgery. Between January 1995 and July 1998, 3708 patients (59% male, 41% female) underwent open heart surgery at our institution. Of these, 3081 underwent coronary artery bypass grafting (CABG), 364 underwent valve replacement (VR), and 263 underwent CABG and VR. The ages of these patients ranged from 40 years to 98 years (mean 68 +/- 11 years). The risk factors analyzed included hypertension (HTN), 59%; smoking (Smk), 53%; and diabetes (DM), 33%. Patients were divided into three groups according to their age. Group A consisted of the 835 patients who were < or = 60 years old, group B consisted of 2474 patients ranging from 61 years to 80 years old, and group C consisted of 399 patients who were > or = 81 years old. All patients underwent bilateral preoperative carotid duplex scans at an Intersocietal Commission for the Accreditation of Vascular Laboratories (ICAVL)-accredited vascular laboratory. Statistical analyses were performed using chi-squared, Fisher's exact test, linear regression, and multivariate analysis. From our results we concluded that carotid screening is not recommended for patients under 60 years of age who are undergoing CABG unless they present with a minimum of two of the following major risk factors: hypertension, diabetes, or smoking. However, carotid screening is recommended for all patients undergoing open heart operations who are over the age of 60 years old, regardless of the absence of associated risk factors.

Adult↗

PubMed2001

The value and limitations of the arm cephalic and basilic vein for arteriovenous access.

The National Kidney Foundation has identified the use arteriovenous grafts (AVG) and the interventions required to maintain their patency as two major causes of increased expenditure in the management of hemodialysis access in end-stage renal disease patients. They have issued an appeal for the increased use of native arteriovenous fistulae (AVF). Although the radialcephalic AVF is considered to be the procedure of choice for these patients, other veins should be sought after to maintain an all-autogenous AVF policy. We examined our experience of using arm veins that were transposed to the brachial artery. Over the last 2.5 years, 109 brachiocephalic AVF (BCAVF) and 63 brachiobasilic AVF (BBAVF) were placed in 163 patients with chronic renal failure. In each group, 40 and 25 patients were males, respectively. Ages ranged from 29 to 88 years (mean 67+/-1.4 years) and 37 to 84 years (mean 69+/-2.0 years) in each group. Diabetic patients comprised 56 and 65% of each group and hypertensive patients comprised 73 and 75% of each group. Data collection was via chart review, personal interviews, and review of the dialysis records. Patency was assessed by life-table analysis. The log-rank test was performed in conjunction with Kaplan-Meier survival analysis. Our results showed that the use of BCAVF and BBAVF appears to be a viable alternative to prosthetic arteriovenous grafts. On the basis of our experience, an algorithm for placement of AVF is suggested.

Adult↗

PubMed2001

Von Hippel-Lindau gene therapy: a novel strategy in limiting endothelial cell proliferative activity.

There is evidence that loss of function of the von Hippel-Lindau (VHL) gene causes transcriptional activation of the vascular endothelial growth factor (VEGF) gene, which in turn may lead to increased proliferation of vascular endothelial cells. We hypothesized that transfer of VHL gene, a tumor suppressor gene, into vascular endothelial cells could cause loss of viability and suppression of its proliferative ability. Human aortic endothelial cells (HAEC) were grown as monolayers and transfected with varying titers of adenovirus containing the VHL cDNA (AdVHL). The negative controls used were adenovirus containing green fluorescent protein (AdGFP), vector alone (AdNull), and infection medium without virus. Adenovirus encoding p53 (Adp53) was used as positive control. Cell viability and proliferation were determined by trypan blue dye exclusion and by a tetrazolium-based colorimetric assay. All experiments were performed in triplicate. Our results showed that proliferative activity in HAEC can be blocked and viability of HAEC reduced by adenovirus-mediated gene transfer of VHL gene. This is the first time that VHL gene has been effectively transferred to HAEC. VHL gene transfer into the vascular endothelium may have potential in limiting proliferative processes, including intimal hyperplasia.

Adenoviridae↗

PubMed2001

Changing characteristics of carotid endarterectomy.

We have noted significant differences in terms of our preoperative work-up, length of stay, morbidity, and mortality of patients undergoing carotid endarterectomy (CEA) from findings reported in large published randomized clinical trials. To further investigate these differences, we have reviewed our recent experience. CEA has proved to be the most effective approach to avert stokes caused by significant atherosclerotic disease of the carotid bifurcation. Between January 1, 1996 and December 31, 1998, 552 patients underwent CEA at our institution. Forty percent were performed in symptomatic patients with stenotic lesions > 60% in diameter by duplex ultrasonography. The remainder were performed for asymptomatic lesions > 60% in diameter. No patient underwent contrast angiography. Fifty-two percent of the patients were males. The mean age was 74 +/- 8 years old. General anesthesia was used in 97% of the cases and regional block, in 3%. All patients underwent routine postoperative measurement of serum creatinine phosphokinase (CPK) isoenzymes. Patients were discharged when deemed clinically stable. The patients' follow-up visits at 1 week and at 3-5 months after the procedure (mean, 3.4 months) included a neurological exam and duplex exam. Patient results suggest that CEAs can be performed in the modern era without contrast arteriography. Most patients can be discharged on the first postoperative day. In addition, previously acceptable rates of postoperative morbidity and mortality should perhaps be revised to meet current standards. Contrary to the previous concept that most postoperative strokes are due to embolic phenomena, hyperperfusion syndrome played an increasingly important role in this review.

Aged↗

PubMed2001

Posterior transverse plication technique for treatment of redundant internal carotid artery during endarterectomy.

PURPOSE: Posterior transverse plication (PTP) has gained popularity as a technique to correct redundancy of the internal carotid artery during endarterectomy. The safety of this technique in large series of patients has not been extensively studied. We investigated 876 primary carotid endarterectomies (CEAs) performed at our institution over the last six years to determine the safety of this technique. METHODS: Indication for surgery was carotid stenosis >/=70% in 341 (39%) symptomatic and 535 (61%) asymptomatic cases. Preoperative imaging consisted of duplex ultrasound alone or combined with magnetic resonance angiography. Patients were divided into four groups related to surgical technique: CEA+PTP+8mm patch (group Ia), CEA+PTP+10mm patch (group Ib), CEA+patch (group II) and CEA+primary closure (group III). There were 43, 39, 581 and 213 patients in groups Ia, Ib, II and III, respectively. No statistical differences in age, sex or risk factors for atherosclerotic disease were noted among the groups. Postoperative duplex ultrasonography was used at 2weeks and every 6months thereafter to evaluate the adequacy of the repair and presence of complications such as pseudoaneurysm formation and extrinsic compression by the excluded carotid segment. RESULTS: The 30-day mortality was 1.2%, 0.6% and 0.3% for groups I, II and III, respectively. Stroke rates for the same period were 0%, 0.6% and 0.8% for groups I, II and III, respectively. Duplex ultrasonography demonstrated significant stenosis (>/=50%) in two (5%) patients in group Ia at 12months. No restenosis was observed in group Ib. For groups II and III the rates of restenosis were 1.5% and 0.8%. One patient in group II developed a pseudoaneurysm after 7months. CONCLUSION: Posterior transverse plication safely corrects redundancy of the internal carotid artery during endarterectomy without causing early significant restenosis. Continued follow-up in a larger group of patients to determine long-term efficacy and correlation between patch size and restenosis rate is warranted.

Aged↗

PubMed2001

Combined upper and lower extremity deep venous thrombosis.

In order to elucidate the natural history of upper extremity deep venous thrombosis (UEDVT), we compared the morbidity and mortality of patients with UEDVT and that of patients with both UEDVT and lower extremity deep venous thrombosis (LEDVT). Between 1993 and 1996, 21 patients presented to our institution with both LEDVT and UEDVT (Group 1). During the same time period, 144 patients were diagnosed with UEDVT alone (Group 2). The diagnosis was confirmed by duplex scanning in all patients. In Group 1, there were 14 females (67%) and 7 males (23%) with ages ranging from 25 to 97 yr old [mean 73 yr old +/-17 yr (SD)]. In Group 2, there were 84 females (58%) and 60 males (42%) with ages ranging from 9 to 101 yr old [mean 67 yr old +/-17 yr (SD)]. Differences in age and sex between the two groups were not statistically significant. In Group 1, systemic anticoagulation was implemented in 17 patients (81%). Two patients (9.5%) required placement of a SVC and IVC filters due to contraindication to anticoagulation. One patient did not receive anticoagulation, and one patient was only started on aspirin. In Group 2, treatment consisted of systemic anticoagulation in 94 patients (65%). The remainder of the patients were treated with aspirin in three patients (2%) or no anticoagulation in 31 patients (19%). Sixteen patients (11%) underwent placement of a SVC filter either due to failure of anticoagulation to prevent pulmonary embolism (two patients) or contraindication to anticoagulation (14 patients). Pulmonary emboli were documented by ventilation/perfusion lung scan in two patients (9.5%) in Group 1 and in 16 patients (11%) in Group 2. In the first group, 8 of the 21 patients (38%) were dead within 1 month of the diagnosis of UEDVT, and 11 of 21 patients (52%) were dead within 2 months of the diagnosis of UEDVT. In the second group, 20 of 144 patients (14%) were dead within 1 month of the diagnosis of UEDVT and 38 of 144 patients (26%) were dead within 2 months of diagnosis (P<0.02). Our data suggest that patients with both UEDVT and LEDVT have a higher mortality than patients with UEDVT alone. As the risk for pulmonary embolism is similar in both groups, we speculate that the severity of medical illness in patients with both UEDVT and LEDVT may contribute to the higher mortality. This is the first study to examine the mortality of this group of patients.

Adolescent↗

PubMed2001

Examination of the apoptotic pathway and proteolysis in the pathogenesis of popliteal artery aneurysms.

OBJECTIVES: to investigate the role of apoptosis, expression of death-promoting molecules and mediators of apoptosis in the development of popliteal artery aneurysms. METHODS: ten popliteal artery aneurysm (PAA) specimens were obtained from patients undergoing elective surgical repair. Normal controls were popliteal arteries obtained from patients without PAA undergoing infrainguinal bypass surgery (n=8). Standard histochemistry techniques were used to assess elastic lamellae fragmentation and inflammatory infiltrate in PAA. Vascular smooth muscle cells (VSMC), macrophages, T lymphocytes, death-promoting molecules, CPP-32, Fas, p53, perforin, apoptosis-mediating Bcl-2 family proteins and apoptotic death substrate, poly(ADP-ribose) polymerase (PARP) were detected immunohistochemically. Detection of apoptosis was by TUNEL assay. Proteolytic activity was determined by 10% gelatin gel zymography. RESULTS: there is a conspicuous disruption and fragmentation of elastic lamellae in PAA as compared to normal arteries. Increased gelatinolytic activity was observed at 92, 84, 72 and 67 kDa in PAA tissues. There is a significant decrease of VSMCs in the PAA walls (p=0.02). The control arteries had fewer CD68+ macrophages and CD3+ T cells in their media (p<0.01). There was a significant increase in the number of cells undergoing apoptosis in aneurysmal tissue than in the normal vessels, (p<0.02) as well as an increased expression of Bax, CPP-32, Fas, p53 and perforin. CONCLUSIONS: the data confirm the architectural disruption of the PAA wall and illustrate an apparent biological response involving inflammatory infiltrate, apoptosis and signalling molecules capable of initiating cell death. In addition to compromising the mechanical integrity of the vessel wall, VSMC loss may contribute to imbalance in the protein profile, accelerating extracellular matrix degradation that could favour PAA development.

Aged↗

PubMed2001

Glycine preserves function and decreases necrosis in skeletal muscle undergoing ischemia and reperfusion injury.

BACKGROUND: Glycine (GLY) is a neutral amino acid that has been shown to be cytoprotective in the kidneys of dogs and rabbits undergoing ischemia-reperfusion injury. To investigate whether GLY exhibits a protective effect on skeletal muscle subjected to ischemia and reperfusion injury, we used a well-described gracilis muscle model in canines. METHODS: Twelve adult mongrel dogs were subjected to 6 hours of ischemia in 1 randomly selected side. The dogs were randomized into 2 groups: group 1 (6 animals) underwent 15 minutes of perfusion with 2.2% GLY, and group 2 (6 animals) underwent 15 minutes of perfusion with normal saline solution (NS) only. Both groups had normothermic reperfusion for 1 hour along with the corresponding perfusate. Muscle biopsy specimens were taken, frozen in liquid nitrogen, and stored at -70 degrees C. Muscle injury was evaluated at 48 hours by measuring weight gain (edema), maximal contractile force, and percent of muscle necrosis. Adenosine triphosphate (ATP) and phosphocreatine (Pcr) (an energy store for ATP synthesis) levels were determined by using high performance liquid chromatography. RESULTS: In group 1, the average weight gain was 57% +/- 11.27% while in group 2 it was 100% +/- 12.48%. Maximal muscle contractile force was 712.5 +/- 68 g for group 1 and 511 +/- 27.91 g for group 2. The amount of muscle necrosis was 30 +/- 3.7% in group 1, as opposed to 63 +/- 10% in group 2. The ATP content was 0.07 +/- 0.03 nmol/mg wet tissue weight (post-ischemia with NS) and 0.21 +/- 0.08 nmol/mg wet tissue weight (post-ischemia with GLY). Pcr content was 0.19 +/- 0.04 mmol/mg wet tissue weight (post-ischemia with NS) and 0.27 +/- 0.04 micromol/mg wet tissue (post-ischemia and infused with GLY) (P <.05). CONCLUSIONS: These data show that GLY preserves muscle function, decreases edema and the amount of muscle necrosis and preserves energy stores in this canine model. Because GLY can be safely given systemically in human beings in higher concentrations than that given in our model, as it is given in parenteral nutrition, its mechanism of action should be further investigated for its potential use in the clinical setting of ischemia and reperfusion injury.

Adenosine Triphosphate↗

PubMed2001

Thiamine reverses hyperglycemia-induced dysfunction in cultured endothelial cells.

BACKGROUND: High levels of glucose have previously been shown to inhibit endothelial cell migration and increase secretion of the von Willebrand factor (vWF), a marker of endothelial cell damage. This study investigates whether thiamine, an important coenzyme in intracellular glucose metabolism, improves endothelial cell migration and decreases von Willebrand factor secretion under hyperglycemic conditions. METHODS: Bovine aortic endothelial cells (BAECs) were grown under physiological glucose (5.5 mmol/L) and hyperglycemic (13.8 mmol/L and 27.7 mmol/L) conditions with or without thiamine (200 micromol/L) supplementation. Endothelial cell migration was investigated in monolayers of BAECs that were wounded by scraping. The distance of migration, the number of migrating cells, and the surface area covered by the migrating cells were measured. Secretion of vWF by BAECs under physiological glucose and high glucose conditions with or without thiamine (200 micromol/L) supplementation was studied with enzyme-linked immunosorbent assay. RESULTS: Under hyperglycemic conditions, there was a significant decrease in the number of endothelial cells and an increase in the secretion of vWF (P <.001). Thiamine treatment limited this inhibitory effect of elevated glucose levels on BAECs. Glucose (27.7 mmol/L) significantly decreased the migration distance of BAECs into the wounded area to 4.0 +/- 1.4 cm, as compared with 6.2 +/- 0.3 cm in the control. Thiamine supplementation restored the migration distance by BAECs (6.94 +/- 0.7 cm) and the wound surface area covered (47.7 +/- 5.6 cm(2)) (P <.001). CONCLUSIONS: Hyperglycemia activates BAECs and promotes secretion of vWF, a marker of endothelial cell damage. Thiamine inhibits this endothelial cell activation and the effects of hyperglycemia on endothelial cell migration. This beneficial effect of thiamine limiting endothelial cell dysfunction is possibly through the diversion of glucose flux from anaerobic to aerobic pathways. The data from this study lead to the speculation that thiamine intake may mitigate or delay vascular complications of diabetes.

Animals↗