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%.

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.

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.

Influence of nicotine and cotinine on the expression of plasminogen activator activity in bovine aortic endothelial cells.

The effects of nicotine and its major metabolite, cotinine, were evaluated on the secretion of plasminogen activator (PA) and plasminogen activator inhibitor (PAI) in cultured bovine aortic endothelial cells. Both compounds increased PA secretion, determined by 125I fibrin plate assay, in a time- and dose-dependent manner. Maximum effects after 24 hr incubation were observed for nicotine at 10(-8) M and for cotinine at 10(-7) M, which corresponded to about 2.6-fold increases over control for both compounds. The pharmacological PA stimulation required both RNA and protein syntheses, as evidenced by inhibition by actinomycin D and cycloheximide. Both control and treated cells produced multiple forms of PA, as evaluated by SDS-PAGE zymography, and a single form of PAI, as evidenced by reverse fibrin autography. Although activities of all species of PA were enhanced by nicotine and cotinine, these compounds had no significant effects on the release of PAI. These results thus suggest that nicotine and cotinine may have fibrinolytic activity in vivo.

Inhibition of intimal hyperplasia after arterial injury by heparins and heparinoid.

The efficacies of standard heparin (SH), low molecular weight heparin (LMWH), and a mixture of sulfated glycosaminoglycans (Org 10172) were investigated with respect to their inhibitory effects on intimal thickening after endothelial injury in the common carotid artery of the rat. The injury was induced by air infusion into an isolated segment of the artery; the pharmacologic agents were administered by continuous intravenous infusion. After 2 weeks the animals were killed and the arteries examined. The control animals developed a marked intimal thickening. A dose-dependent decreases in the intima to media area (I-M) ratio was seen after SH, with approximately 50% and 90% inhibition of intimal thickening at doses of 5 and 50 USP U/kg/hr, respectively. At these effective doses, the effect of SH was associated with reendothelialization of the injured area. The effects of LMWH and Org 10172 were similar to that of SH at doses of 50 anti-Xa U/kg/hr, but these agents had only about 40% inhibition at doses of 15 anti-Xa U/kg/hr. The activated partial thromboplastin times were slightly prolonged in the animals treated with 50 USP/anti-Xa U/kg/hr of SH, LMWH, and Org 10172, whereas significant anti-Xa levels were observed at doses higher than 15 USP/anti-Xa U/kg/hr. It is concluded that SH, LMWH, and Org 10172 have significant inhibitory effects of intimal thickening after injury even at nonanticoagulant levels, with SH being the most potent.

Interaction of thrombin and factor Xa with bovine vascular endothelial cells, smooth muscle cells and rat hepatoma cells.

The aims of the present investigation were to characterize the binding and inhibition of thrombin and factor Xa to bovine vascular endothelial cells (EC), bovine smooth muscle cells (SMC), and rat hepatoma cells (RHC), and to evaluate the effects of plasma constituents on their inhibition. The enzymatic activities of bovine thrombin and factor Xa were assayed using chromogenic substrates. After 10 min incubation with the cells, thrombin activity in the solution had decreased by about 20% and was subsequently recovered on the cell surfaces. When the cells with the surface-bound thrombin were incubated with defibrinogenated plasma or antithrombin III (AT-III) for 30 sec only about 10% and 20-40%, respectively, of the initial activity could be recovered. In similar experiments with factor Xa, initial activity in the solution had decreased by 10% after 10 min incubation, and was subsequently recovered from the cell surfaces. After 30 sec incubation with AT-III, no cell surface-bound factor Xa activity was detected, whereas 10% of the bound factor Xa activity was recovered after incubation with defibrinogenated plasma. It is concluded that thrombin and factor Xa are taken up and inhibited by EC, SMC and RHC cell surfaces in similar ratios, suggesting that cell surface-mediated inhibition of clotting factors is not restricted to vascular wall cells. The inactivation of factor Xa was dependent on AT-III, however, the inactivation of thrombin was further promoted by an additional unidentified plasma constituent.

Acute nontraumatic extremity ischaemia in Sweden. A one-year survey.

An attempt was made to evaluate the results of treatment for acute nontraumatic extremity ischaemia in Sweden during one year. A questionnaire was sent to all surgical units, and 61% replied. Of the total 586 evaluated cases, 497 were classified as embolism and 89 as acute thrombosis. Patient age strongly influenced results in both groups as regards limb salvage and mortality rates. The site of embolic occlusion also influenced mortality, with greatly heightened rate in aortic occlusion. Delay of operation for more than 12 hours after onset of symptoms was associated with increase in amputation rate and mortality. Adequate heparin therapy significantly improved results after embolectomy, but had no such effect after surgical treatment of thrombosis. The amputation rate was higher after acute thrombosis than after embolism. The authors conclude that patient age should be considered in comparisons between different case series of acute ischaemia, that embolus site and time of surgery are important determinants of mortality and amputation rate, and that heparin significantly improves results of embolectomy.

Acute ischemia of the extremities in a metropolitan area during one year.

All acute extremity ischemias during one year (1980) in the greater Stockholm area (population 1.5 million) were evaluated. One hundred and thirty eight cases were found. The incidence figures varied from 0.4/100,000 in the age group 20 to 30 years to 182/100,000 in the ages above 90 years. 81% of the cases were classified as emboli and 19% as acute thrombosis. Over all mortality was 19.5%. In the embolism group mortality was 21%, amputation rate 28% and limb salvage rate 51%. Limb salvage rate was significantly higher in patients receiving heparin therapy (61%) as compared to those who received no heparin (32%). Delay of treatment also caused an increase in amputation rate. Patients with acute thrombosis had a lower mortality (12%) and an amputation rate of 42%. It is concluded that the results of acute extremity ischemia may be less favourable than previously reported when results from institutions not specialised in vascular surgery are also included. Among other possible factors explaining the high amputation rate may be the proportion of older patients.