Thoracic outlet syndrome in children and young adults.

OBJECTIVES: Thoracic outlet syndrome has been well described in the population between 25 and 40 years of age, and is less frequently reported in those in the first two decades of life. The objective of this study was to review results with onset of TOS in the first two decades of life to determine type of presentation and outcomes from surgical intervention. METHODS AND MATERIALS: Charts of all patients in the first two decades of life, operated on for TOS between 1994 and 2006 were reviewed with follow-up by clinic visit and phone survey to assess the patients' current level of activity and relief from symptoms. RESULTS: Twelve patients were identified (13 operations), with a mean age of 16.8 years. Acute ischemic symptoms were the initial presentation for 38%, venous TOS in 24%, and neurogenic symptoms in 38%. All patients had symptom relief with surgery with a mean time to resolution of 10.9 weeks. All patients remained symptom free or improved at follow-up. CONCLUSIONS: Vascular TOS is much more common in TOS presenting in the first two decades of life. Surgical intervention for TOS in this population results in long-lasting symptom relief and should be considered for all subtypes of patients.

Evaluation of a screening protocol to exclude the diagnosis of deep venous thrombosis among emergency department patients.

OBJECTIVE: The purpose of this study was to evaluate the efficacy and cost effectiveness of a deep venous thrombosis (DVT) screening protocol incorporating DVT pretest probability (PTP), selective D-dimer assay, and venous duplex imaging (VDI) to exclude the diagnosis of DVT among emergency department (ED) patients. METHODS: A prospective study of all patients evaluated in the ED for suspected DVT during 1 year was undertaken. Patients were classified into PTP risk category by ED physicians before VDI. Correlation studies were completed using VDI as the gold standard. Charges associated with the protocol were calculated. RESULTS: One hundred fourteen patients were included. The incidence of DVT was 9.6% (11). Thirty-six (55%) patients were classified as high risk, 23 (35%) as moderate, and 7 (10%) as low risk. All patients diagnosed with DVT were in the high-risk group (incidence, 16.7%). The sensitivity and negative predictive value were both 100% when PTP and D-dimer were used, but fell to 80% and 95%, respectively, when only D-dimer was considered. The true negative rates were 23% and 37%, respectively. Based on this study, we propose the following screening: for high-risk patients, use direct VDI (no D-dimer); for low-risk or moderate-risk patients, obtain D-dimer, and if it is positive, use VDI, and if it is negative, no further action is required. The average charge associated with the protocol was 170.50 dollars as opposed to 202.00 dollars for global VDI. CONCLUSION: A screening protocol using PTP along with selective D-dimer and VDI to exclude the diagnosis of DVT among ED patients is efficacious and cost efficient. This screening approach establishes criteria to satisfy billing requirements, can eliminate unnecessary VDI in 23% of ED referrals, and can reduce charges by 16%.

Balloon angioplasty for arteriovenous graft stenosis.

PURPOSE: To retrospectively review the long-term outcome as well as the cost effectiveness of thrombolytic therapy and balloon angioplasty (TBA) versus surgical thrombectomy and balloon angioplasty (SBA) in the treatment of prosthetic dialysis access grafts. METHODS: Between February 1996 and February 1999, 63 hemodialysis patients (35 women; mean age 62.2 years) were treated for 105 thromboses in 6-mm polytetrafluoroethylene straight or loop bridge arteriovenous grafts. Choice of treatment was at the discretion of the surgeon or interventional radiologist: either Fogarty balloon thrombectomy followed by balloon dilation of the venous anastomotic stenosis or urokinase thrombolysis followed by angioplasty. RESULTS: Forty-eight SBAs and 55 TBAs were performed in 63 patients without complications. The primary patency rates in the entire cohort were 34%, 29%, and 17% at 1, 2, and 3 months, respectively. Primary patency after TBA was 29%, 18%, and 11%, and that for SBA, 45%, 45%, and 33% over the same time intervals. The mean graft survival was 10 days for TBA versus 31 days for SBA. Repeat angioplasty performed in 23 grafts produced secondary patency rates of 52% at 1 month, 34% at 3 months, and 5% at 5 months. The Medicare reimbursement for both treatments was identical ($1638 for TBA and $1670 for SBA). CONCLUSIONS: The poor patency rate and high cost of TBA and SBA suggests that these procedures should not be routinely used for salvage of thrombosed arteriovenous grafts with outflow stenosis. Patch angioplasty or creation of simultaneous temporary and new permanent accesses may be a more cost-effective approach in these patients.

Isolated iliac artery aneurysms in patients with or without previous abdominal aortic aneurysm repair.

BACKGROUND: Isolated iliac artery aneurysms (IAA) in patients with or without previous abdominal aortic aneurysm (AAA) repair are rare. We wanted to compare the presentation, distribution, treatment, outcome and patterns of subsequent aneurysm formation in these patients. METHODS: We retrospectively reviewed patients with isolated IAA over a 10-year period. Patients with primary isolated IAA (group 1) were compared with patients who presented with IAA after previous AAA repair (group 2). RESULTS: There were 23 patients in each group. Demographics and comorbidities were similar. No aneurysms were detected outside of the iliac system in group 1; 22% of patients in group 2 had other aneurysms. The mean time after AAA repair to IAA diagnosis was 8.8 +/- 3.2 years for operated on patients. The in-hospital mortality was 0% for elective cases and 50% for emergency cases for both groups. Three patients in group 2 (13%) developed new aneurysms during follow-up, whereas the only new aneurysm in group 1 was a contralateral IAA. CONCLUSIONS: Patients with new IAA after AAA repair have a greater tendency to develop further aneurysms in other sites, synchronously or metachronously. The time to detection of new IAA after AAA repair is at least 5 years in most cases. In both groups, a quarter to a third of patients present with rupture, with a resultant mortality of 30% to 50%, whereas those operated on electively have minimal morbidity and almost no mortality.

The role of thrombolytic therapy in the management of paradoxical embolism.

Paradoxical emboli are considered a rare event, representing less than 2% of all arterial emboli. The most common intracardiac defect associated with paradoxical emboli is a patent foramen ovale. Most commonly, a pulmonary embolism is the cause of the acute increase in right atrial pressure leading to a reversal of intracardiac flow and passage of venous embolic material to the left heart. We present a patient with a pulmonary embolism and paradoxical emboli, and discuss therapeutic approach. We suggest that the treatment of choice for the patient with pulmonary embolism and non-limb-threatening acute ischemia due to a paradoxical emboli should be thrombolytic therapy and intracaval filter placement, followed by patent foramen ovale repair.

Endothelial dysfunction following thrombolysis in vitro.

OBJECTIVES: Thrombolytic therapy is frequently used to manage vascular graft thrombosis. However, long-term patency after thrombolysis remains poor. The purpose of this study was to characterise the morphological and functional response of endothelial cells (EC) exposed to a thrombus and subsequently lytic therapy. METHODS: Human EC were exposed to human whole blood thrombus for 2, 6, 12, and 24 h. The thrombus was lysed with urokinase. Cell morphology was studied with electron microscopy. Northern blot analyses were performed with human c-DNA probes for endothelin-1, thrombomodulin, tissue factor, tissue plasminogen activator, plasminogen activator inhibitor, and triose phosphate isomerase. RESULTS: EC retraction occurred for each period of incubation. Thrombomodulin expression was increased 2.2-fold at 6 h and 2.4-fold at 24 h. t-PA expression was depressed proportionally to the duration of thrombus exposure. PAI and TF expression transiently increased 1.5-fold at 2 h of exposure and returned to baseline at 6 h. Endothelin expression remained unchanged. CONCLUSIONS: Except for a transient increase in TF expression and reversal of the tPA/PAI ratio, EC exposed to thrombus do not appear to become actively procoagulant. The increase in TM expression may reflect enhanced thromboresistance. However, EC retraction may be responsible for an increase thrombogenicity of saphenous vein graft after thrombosis and Urokinase therapy.

Nicotine and its metabolite cotinine are mitogenic for human vascular smooth muscle cells.

PURPOSE: Intimal hyperplasia caused by smooth muscle cell (SMC) proliferation is the major cause of infrainguinal graft failure within the first 12 months. Tobacco smoking is associated with a twofold increase in graft failure within the first year of extremity bypass surgery, but the mechanism is not clearly understood. This study evaluated the effect of nicotine and its major stable metabolite cotinine on vascular SMC proliferation in vitro. METHODS: SMC were harvested from human arteries and grown in culture with standard methods. Cells were seeded at a density of 1.8 x 10(4) cells/well in 24 multiwell dishes and cell cycle-synchronized. Subsequently the SMC were incubated with media containing 0.1% or 15% fetal bovine serum and nicotine or cotinine at concentrations ranging from 10(-9) mol/L to 10(-6) mol/L. Control samples were incubated with corresponding media but without the drugs. SMC proliferation was determined at 4 days with a cell counter. DNA synthesis was assessed at 24 hours with 3H-thymidine uptake. The results were expressed as a percentage change compared with the control samples (mean +/- SEM). Results were analyzed by analysis of variance and t tests. RESULTS: In the presence of serum both nicotine and cotinine at concentrations of 10(-7) and 10(-8) mol/L were mitogenic for SMC in vitro (p < 0.05). A weak mitogenic effect was observed at a low serum concentration for cotinine but not nicotine. Cotinine at a concentration of 10(-9) mol/L, a level seen among passive smokers, was a statistically significant stimulus for DNA synthesis in both minimum serum and serum-supplemented media. At high concentrations both substances were toxic for the cells. CONCLUSION: We have demonstrated a potential role for nicotine and cotinine in the development of intimal hyperplasia and ultimately failure of the vascular reconstruction.

In vitro endothelialisation of arteriovenous loop grafts for haemodialysis.

OBJECTIVES: To evaluate the feasibility in a pilot study of in vitro endothelialisation of PTFE grafts used as interposition arteriovenous fistulas in uraemic patients. METHODS: Autologous saphenous vein endothelial cells were harvested and cultured on PTFE grafts in seven patients undergoing maintenance haemodialysis. The patients had several previous failures of vascular access sites. The patients were followed with duplex ultrasound, clinical examination and in one case an explanted graft was examined. RESULTS: At the end of follow-up four of the seven patients had patent grafts. One patient occluded the graft immediately postoperatively and another after 3.5 months. The former patient received a second endothelialised graft. In two further patients revision of the outflow was performed. In two patients a functioning graft was excised, in one case because of bleeding of a venous aneurysm and in one case because of suspected infection. The former which was excised 5 weeks postoperatively revealed that 85% of the surface was covered by endothelial cells. CONCLUSIONS: This pilot study shows that in vitro endothelialisation of PTFE grafts used for haemodialysis is possible in uraemic patients. In this highly problematic patient group the results are promising with endothelial cell coverage after 5 weeks of implantation.

Nicotine and cotinine stimulate secretion of basic fibroblast growth factor and affect expression of matrix metalloproteinases in cultured human smooth muscle cells.

PURPOSE: We have recently shown that nicotine and its metabolite cotinine are mitogenic for smooth muscle cells in vitro. In the present study, we examined the effect of nicotine and cotinine on the production of growth factors and the expression of matrix metallo-proteinases in smooth muscle cells. METHODS: Smooth muscle cells were harvested from human arteries and grown in culture. Subconfluent cultures were incubated for 24 hours in M199 containing 0.1% fetal bovine serum with or without nicotine or cotinine at concentrations ranging from 10(-9) mol/L to 10(-6) mol/L. The supernatants and cell lysates were assayed by enzyme-linked immunosorbent assay for basic fibroblast growth factor (bFGF), tumor necrosis factor alpha (TNF-alpha), platelet-derived growth factor AB (PDGF-AB), and transforming growth factor beta (TGF-beta). Matrix metalloproteinase expression was determined in subconfluent cultures incubated in albumin with or without nicotine or cotinine at 10(-8) mol/L and 10(-7) mol/L for 6, 12, 18, 24 and 36 hours. Northern blot analyses were performed with human cDNA probes for collagenase-1, stromelysin-1, gelatinase A, gelatinase B, and triose phosphate isomerase. Blots were quantified by phosphor-imaging techniques. RESULTS: Both nicotine and cotinine stimulated the production and secretion of bFGF in a dose-dependent manner. PDGF, TNF-alpha, and TGF-beta secretions were not significantly affected by nicotine or cotinine. Collagenase was up-regulated by nicotine at 18 and 24 hours (4.5-fold to 5.8-fold) and by cotinine at 18 hours (from 5.0-fold to 29-fold). Stromelysin-1 was up-regulated by nicotine and cotinine at 12 and 18 hours (1.5-fold to 7.0-fold). Gelatinase A generally peaked at 12 hours and was up-regulated by both agents (2.0-fold to 6.5-fold). CONCLUSION: Nicotine and cotinine enhanced the production of bFGF, a major mitogen for smooth muscle cells, and up-regulated the expression of several matrix metalloproteinases that are critical in cell migration. These data demonstrate mechanisms by which smoking may contribute to the development of intimal hyperplasia, atherosclerosis, and aneurysms.

Phenotypic modulation of smooth muscle cells during the formation of neointimal thickenings in the rat carotid artery after balloon injury: an electron-microscopic and stereological study.

The formation of neointimal thickenings in the rat carotid artery after balloon injury was studied by a combination of electron-microscopic and stereological methods. All smooth muscle cells in the normal media had a contractile phenotype, the cytoplasm being dominated by myofilaments. Seven days after endothelial denudation, the smooth muscle cells in the innermost part of the media had assumed a synthetic phenotype by loss of myofilaments and formation of a large endoplasmic reticulum and Golgi complex. These cells moved through fine openings in the internal elastic lamina and gave rise to a growing neointima by proliferation and secretion of extracellular matrix components. Fourteen days after the operation, the neointima had almost reached its final size, and mitoses were no longer noted. Nevertheless, the cells maintained a synthetic phenotype with prominent secretory organelles, although myofilaments had started to become more abundant again. They were surrounded by an extracellular matrix made up of collagen fibrils and coalescing patches of elastin. Thirty-five days after the operation, an endothelial cell layer had reformed and covered most of the luminal vessel surface. In parallel, the smooth muscle cells in the neointima had returned to a contractile phenotype with a cytoplasm dominated by myofilaments. These findings provide a morphological basis for further analysis of the cellular and molecular interactions involved in the formation of neointimal thickenings after endothelial injury, and for the search for agents interfering with this process.

The small abdominal aortic aneurysm: the eternal dilemma.

In order to evaluate morbidity and mortality after elective resection of abdominal aortic aneurysms (AAA) as it relates to aneurysm size, a retrospective review of 111 elective aneurysmectomies over a 5 year period was undertaken in a VA population. Thirty seven AAA's measured < 5 cm in diameter and 74 were > or = 5 cm by CT scan. Patients with small AAA (S-AAA) were significantly younger (mean 64 years) than those with large AAA (L-AAA) (mean 69 years) (p < 0.003). Both groups were similar with respect to prevalence of cardiovascular, pulmonary and renal disease. Aortic cross-clamping time was significantly shorter in L-AAA, possibly because those with S-AAA had a higher prevalence of associated occlusive disease requiring more femoral anastomoses (p < 0.04). Postoperatively six patients (8%) had a myocardial infarction (MI) in the L-AAA group and four (5%) of these died. In contrast no patient with S-AAA suffered a postoperative MI. The rates of non-cardiac complications and length of hospital stay were not significantly different between the two groups. However, the patients with L-AAA stayed longer in ICU (p < 0.05) and the overall combined morbidity rate was significantly higher in this group (p < 0.02). Our results suggest that resection of S-AAA upon diagnosis in acceptable risk patients appears to be the safest overall therapeutic plan.

Antithrombin III inhibits thrombin-induced proliferation in human arterial smooth muscle cells.

Thrombin has attracted increasing attention as a possible mitogen for vascular smooth muscle cells in lesion development both after vascular injury and in atherogenesis. In this study, the ability of antithrombin III to inhibit alpha-thrombin-induced DNA synthesis and cell proliferation in human arterial smooth muscle cells was analyzed. We demonstrate a concentration-dependent initiation of DNA synthesis and cell proliferation by alpha-thrombin. This effect was abolished when complex formation with antithrombin III was allowed before thrombin was added to the cell cultures. Addition of alpha-thrombin and antithrombin III simultaneously at the beginning of the incubation period also resulted in an inhibition of thrombin-induced DNA synthesis, but to a lower degree. The inhibitory activity of antithrombin III was enhanced in the presence of heparin, which on its own had no inhibitory effect on thrombin-induced DNA synthesis. In contrast, the mitogenic activity of alpha-thrombin could be inhibited by heparin in the presence of low concentrations of serum. This inhibition was dependent on the presence of antithrombin III in serum, since heparin lacked effect if antithrombin III was depleted from serum by immunoaffinity chromatography. Analysis of the enzymatic activity of thrombin showed that the influence on catalytic activity of thrombin corresponded to the mitogenic activity of thrombin in the presence of heparin, antithrombin III, and serum. The results suggest that the mitogenic activity of thrombin is regulated by antithrombin III. Therefore, antithrombin III may serve dual functions by inhibiting thrombin in the coagulation cascade and by neutralizing its growth-promoting effects on vascular smooth muscle cells.

Acidic fibroblast growth factor promotes vascular repair.

Intravascular injury to arteries can result in thickening of the intimal smooth muscle layer adjacent to the lumen by migration and proliferation of cells from the underlying medial smooth muscle layer accompanied by deposition of extracellular matrix. This pathological response, which decreases lumen diameter, might, in part, be the result of the access of smooth muscle cells to plasma and platelet-derived growth factors as a consequence of denudation of the overlying confluent monolayer of vascular endothelial cells. Injured rat carotid arteries were treated by i.v. administration of acidic fibroblast growth factor, a heparin-binding protein that is chemotactic and mitogenic for vascular endothelial cells. The growth factor treatment resulted in dose-dependent inhibition of intimal thickening with parallel promotion of endothelial regeneration over the injured area. Therefore, acidic fibroblast growth factor might be efficacious in the prevention of restenosis caused by intimal thickening following angioplasty in humans.

Evaluation of a prostacyclin analog, iloprost, and a thromboxane A2 receptor antagonist, daltroban, in experimental intimal hyperplasia.

This study evaluated the efficacy of a prostacyclin analog, iloprost, and a thromboxane A2 receptor antagonist, daltroban, as inhibitors of experimental intimal hyperplasia. The vascular injury model used is based on an endothelial injury induced by a brief infusion of air into an isolated segment of the common carotid artery in the rat. Iloprost and daltroban were administered by continuous IV infusion for two weeks. The infusion rates were 0.1 micrograms/kg/min for iloprost and 0.1 mg/kg/hr for daltroban; these dosing rates are associated with significant alterations in eicosanoid-related pharmacologic effects. The animals were sacrificed at two weeks and the carotid arteries fixed in situ for light microscopy. The myointimal thickening was measured as the intima to media area (I/M) ratio. The control animals developed marked intimal thickening, with an I/M ratio of 0.76 +/- 0.12 (mean +/- SEM; N = 7). There was no inhibition of intimal hyperplasia (P greater than 0.05) after either iloprost (I/M ratio: 1.04 +/- 0.13; N = 8) or daltroban (I/M ratio: 0.70 +/- 0.04; N = 6). It is concluded that neither of these two modulators of eicosanoid activity, iloprost and daltroban, inhibit intimal hyperplasia following experimental endothelial injury.