Imaging for carotid stenting.

Carotid artery stenting (CAS) using embolic protection devices (EPD) has emerged as a viable alternative to carotid endarterectomy (CEA) in select patients. Imaging plays a critical role in the selection of patients for CAS. Duplex ultrasonography alone is insufficient to assess patients for CAS suitability. Advancements in computed tomography angiography (CTA) and magnetic resonance angiography (MRA) techniques are helping to identify lesions vulnerable to cerebral embolization during carotid interventions - a more prevalent event during CAS in comparison to CEA. Here we review the relevant data on the various imaging techniques available to improve patient selection and minimize neurologic adverse events during carotid artery stenting.

Carotid artery reconstruction for infected carotid patches.

OBJECTIVES: Infected carotid prosthetic patches (ICPP) are a rare but catastrophic complication of carotid endarterectomy (CEA). Prevention and appropriate surgical management is essential. We report our experience of carotid artery reconstruction for ICPP. DESIGN: Single-center retrospective study. METHODS: 10-year review of the surgical treatment of ICPP. RESULTS: Twelve patients presented with patch infection following CEA. Three patients presented acutely with an expanding hematoma, eight with chronic complications (abscess/discharging sinus n = 5, carotid pseudoaneurysm n = 3). Mean age was 75 years. Replacement conduits included superficial femoral artery (n = 6), cadaveric homograft (n = 3), long saphenous vein (n = 2) and one patient had primary closure. Five patients had muscle flaps fashioned for carotid artery protection. Operative complications included hypoglossal nerve injury (1 patient), superficial skin infection (2 patients) and one patient was returned to the operating room for a neck haematoma. Five surgical specimens were culture positive for: Staphylococcus aureus (n = 3), Corynebacterium propionibacterium (n = 1) and Streptococcus anginous (n = 1). There were no 30-day mortalities. Mean hospital stay was 6 days. Median follow-up was 16 months (range 3-108 months). CONCLUSION: Carotid artery reconstruction in a contaminated wound represents a significant surgical challenge. Unlike previous reports that used venous conduits, this is the first series where cadaveric or autologous arterial conduits were preferred. Arterial conduits achieved durable short term follow-up.

Is color-flow duplex a good diagnostic test for detection of isolated calf vein thrombosis in high-risk patients?

Color-flow duplex scanning (CDS) is a good diagnostic test for lower extremity proximal deep vein thrombosis (DVT). This report aims to evaluate the diagnostic accuracy of CDS in detecting isolated calf DVT in two in-hospital populations. A total of 166 patients had routine DVT testing with both CDS and venography: 99 total joint arthroplasty patients and 67 symptomatic in-hospital patients. Isolated calf DVT was noted in 34% of arthroplasty patients and 12% of symptomatic in-hospital patients. Peroneal DVT was most common. The sensitivity, specificity, positive predictive value, and negative predictive value (with 95% confidence interval [CI]) of CDS in detecting isolated calf DVT in the symptomatic in-hospital group was 39% (16%-62%), 98% (94%-99%), 88% (65%-99%), and 81% (71%-91%), respectively. In the arthroplasty patients these values were 13% (3%-23%), 92% (85%-99%), 60% (30%-90%), and 55% (45%-65%), respectively. CDS has a low sensitivity in detecting isolated calf DVT among hospitalized patients and cannot be deemed an effective tool for identifying clots limited to only one or two tibial vessels.

Long-term fate of the aneurysmal sac after endoluminal exclusion of abdominal aortic aneurysms.

PURPOSE: Shrinkage of an abdominal aortic aneurysm (AAA) is the hallmark of successful endoluminal treatment. Our goal was to prospectively assess the midterm to long-term shrinkage of the AAA sac after endovascular repair. METHODS: A total of 123 patients with AAA underwent endoluminal treatment with the Ancure device at our institution between February 1996 and February 2000. At least a 1-year follow-up was available for 70 of the 123 patients. AAA sac size, presence of endoleaks, calcifications, and outcome data were collected on these patients at 6, 12, 24, and 36 months after repair and compared with the preoperative AAA size and characteristics. All endoleaks found at the 6-month follow-up visit were treated aggressively with embolotherapy. An AAA sac regression of 0.5 cm or more was considered the minimum measurable decrease. Regression of the sac diameter to 3.5 cm or less was considered a complete collapse of the sac. RESULTS: Successful endoluminal repair was accomplished in 119 of 123 patients. The mortality rate was 0.8% (1/123). There was a steady decrease in AAA sac size from baseline (5.56 +/- 0.1 cm), to 6 months (5.0 +/- 0.14 cm, P =.0006), to 12 months (4.65 +/- 0.13 cm, P =.04), and to 24 months (4.26 +/- 0.16 cm, P =.03). At 24 months, 74% (29/39) had a decrease in sac size of 0.5 cm or more, with 28% (11/39) complete collapse. Patients with initial endoleaks had the same likelihood of regression of sac size (> or = 0.5 cm) when compared with the group of patients with no endoleaks at the 24-month evaluation (64% vs 76%, P =.09). CONCLUSION: Endoluminal AAA repair resulted in a significant reduction in sac size that continues up to 2 years. Significant shrinkage occurs as early as 6 months after placement. The initial presence of endoleaks does not predict the lack of sac regression.

Endovascular repair of an aortoduodenal fistula.

PURPOSE: To demonstrate the utility of endovascular stent-graft repair for the management of an unusual aortoduodenal fistula. METHODS AND RESULTS: A 23-year-old man with an aortoduodenal fistula secondary to tumor necrosis was treated with a Corvita endoluminal stent-graft after several failed surgical attempts to repair the defect. At 2-year follow-up, the patient was clinically and radiographically devoid of any evidence of occult stent-graft infection. CONCLUSIONS: This case illustrates the usefulness of endovascular repair for the treatment of a primary aortoduodenal fistula. Endovascular repair should be included in the armamentarium for the management of difficult aortoduodenal fistulas.

Biphasic response to gut manipulation and temporal correlation of cellular infiltrates and muscle dysfunction in rat.

BACKGROUND: Surgical manipulation of the intestine results in the massive movement of leukocytes into the intestinal muscularis at 24 hours. This is associated with muscle inhibition. The aim of this study was to temporally associate leukocyte extravasation with ileus after surgical manipulation. METHODS: Rats underwent a simple manipulation of the small bowel and were killed at various times (0, 0.25, 0.5, 1, 3, 6, 12, and 24 hours) postoperatively. Jejunal circular-muscle contractile activity was assessed in a standard organ bath. Both extravasating and resident leukocytes were immunohistochemically stained in muscularis whole mounts. RESULTS: Contractile activity was significantly reduced immediately after surgery, but rapidly returned to control levels at 3 hours. After recovery, muscle function decreased at 12 and 24 hours (41% and 81%, respectively). The resident muscularis macrophage network demonstrated cellular activation 1 hour postoperatively. The number of leukocytes increased over time (neutrophils, 67.5-fold; monocytes, 98.2-fold; and mast cells, 47-fold at 24 hours). CONCLUSIONS: The functional results demonstrate a biphasic response in the suppression of muscle activity after surgical manipulation. Regression analysis (r2 = 0.998) of the temporal development of leukocyte infiltration and the protracted phase of muscle inhibition provides evidence for a correlation between cellular inflammation and postoperative dysmotility.

Oxygen-dependent chronic obstructive pulmonary disease does not prohibit aortic aneurysm repair.

BACKGROUND: Severe oxygen-dependent chronic obstructive pulmonary disease (COPD) is considered by many to be a contraindication to open abdominal aortic aneurysm (AAA) repair. We reviewed our own experience with this patient population. METHODS: From July 1995 to March 1999, 14 consecutive patients limited by home oxygen-dependent COPD underwent elective open infrarenal AAA repair. Their medical records were reviewed. RESULTS: The mean aortic aneurysm size was 6.3 cm. The mean PaO2 = 70 mm Hg, PaCO2 = 45 mm Hg, forced expiratory volume in 1 second (FEV1) = 34% of predicted, and forced vital capacity (FVC) = 67% of predicted. All 14 patients were extubated within 24 hours, mean length of hospital stay was 5.9 days, and there were no perioperative deaths. CONCLUSIONS: Severe home oxygen-dependent COPD is not a contraindication to safe elective open AAA repair.

LPS-induced muscularis macrophage nitric oxide suppresses rat jejunal circular muscle activity.

Cellular mechanisms of sepsis-induced ileus remain an enigma. The study aim was to determine the role of nitric oxide (NO) in mediating the suppression of rat jejunal circular smooth muscle activity during endotoxemia. Isolated muscularis inducible NO synthase (iNOS) mRNA was measured by RT-PCR, immunohistochemistry was employed to localize iNOS protein, and contractile activity was measured in an organ bath. The low basal expression of muscularis iNOS mRNA expression was increased in a time-dependent fashion after lipopolysaccharide (LPS), resulting in a 20-fold increase over controls 3 h after injection. Immunohistochemistry of muscularis whole mounts and dissociated muscularis cells for iNOS revealed staining only in the muscularis macrophages 12 h after LPS. LPS caused a 68% reduction in spontaneous muscle activity 12 h after injection, which improved by 53% after the in vitro application of the selective iNOS inhibitor L-N(6)-(1-iminoethyl)lysine. Similar results were obtained in C57BL/6 mice but not in iNOS knockout mice. These data demonstrate that macrophage iNOS plays an important role in mediating LPS-induced intestinal circular muscle suppression.

Arterial thromboembolic events in patients with the factor V Leiden mutation.

BACKGROUND: The factor V Leiden mutation affects 6% of the United States population and is known to be associated with venous thrombosis. We identify, herein, 30 individuals with the Leiden mutation and known arterial thromboembolic events. METHODS: The factor V mutation was assessed using polymerase chain reaction. RESULTS: In the 16 patients sustaining a cerebrovascular accident, the mean age was 44.1 and 11 (69%) were younger than 50. Similarly, the 13 patients presenting with an acute myocardial infarction were relatively young with a mean age of 45.5, and 9 (65%) patients presented at less than 50 years of age. Radiographic information was available for 19 patients in this study. No significant arterial atherosclerotic disease was demonstrated in 18 (95%) of these patients. CONCLUSIONS: This study demonstrates an association between the factor V Leiden mutation and the development of unexplained arterial thromboembolic events, especially in younger patients without existing atherosclerotic disease.

Lipopolysaccharide activates the muscularis macrophage network and suppresses circular smooth muscle activity.

Bacterial lipopolysaccharide (LPS) is a causative agent of sepsis-induced ileus. Although it is known that LPS activates macrophages and initiates inflammation, the consequences of LPS on the macrophage network and a potential inflammatory response within the intestinal muscularis have not been investigated. This study was designed to identify cellular and functional changes in rat intestinal muscularis after intraperitoneal LPS. Histo- and immunohistochemistry were used to phenotype leukocytes. Functional alterations were determined using an organ bath. Compared with controls, LPS caused a 21-fold increase in staining for the lymphocyte activation marker-1 (LFA-1) localized to the ED2+ macrophage network 1 h after injection. This was followed by a significant infiltration of neutrophils, mast cells, and monocytes into the muscularis. LPS also caused a 62% reduction in spontaneous circular muscle activity and a 91% suppression of bethanechol-stimulated contractions 12 h after injection. These results demonstrate that endotoxemia 1) acutely activates the muscularis macrophage network, 2) causes the extravasation of leukocytes, and 3) results in circular muscle impairment.

Anti-tumor necrosis factor antibody therapy fails to prevent lethality after cecal ligation and puncture or endotoxemia.

Cytokines have been studied intensively to delineate their role in the altered pathophysiology observed in septic shock. We studied the role of TNF in the lethality of two well characterized models of septic shock by inhibiting TNF's activity with a specific antibody. In the first model, sepsis was induced by cecal ligation and puncture (CLP), and in the second model sepsis was induced by either an i.p. or i.v. injection of LPS. After CLP, plasma endotoxin was detectable within 4 h and reached a peak at 8 h (136 +/- 109 ng/ml). TNF bioactivity peaked at 12 h (528 +/- 267 pg/ml) at a significantly higher level than sham-operated control mice (64 +/- 31 pg/ml). After i.p. LPS, TNF peaked much more quickly (90 min) compared with CLP and at a significantly higher level (107,900 +/- 25,000 pg/ml). Another cytokine studied in septic shock, IL-6, peaked at 12 h after CLP at 1011 +/- 431 pg/ml, and at 90 min after lethal LPS at 16,300 +/- 3,700 pg/ml. Mice were treated with an anti-TNF antibody that has been shown previously to inhibit in vivo TNF activity. Antibody treatment of mice subjected to CLP significantly reduced TNF bioactivity but did not reduce mortality or pulmonary neutrophilic infiltration. In the i.v. LPS model, anti-TNF antibody treatment concomitant with LPS injection reduced plasma TNF activity from 80,000 +/- 20,000 pg/ml to undetectable levels. However, anti-TNF treatment immediately before either i.v. or i.p. LPS did not reduce mortality. Additionally, when the antibody was administered 4 h before the lethal i.v. LPS, there was no reduction in lethality. These data show that in two separate models of septic shock blockade of TNF biologic activity will not prevent lethality.

Interleukin 2 induces tumor necrosis factor gene expression in vivo.

Interleukin 2 (IL-2) treatment of malignancies is often associated with severe toxicity, and the alterations observed after high dose administration of IL-2 are similar to those induced by recombinant tumor necrosis factor (TNF). We therefore examined the hypothesis that IL-2 induces TNF gene expression in vivo. Purified, recombinant human IL-2 was injected intraperitoneally into mice which had been previously primed with complete Freund's adjuvant (CFA). Biologically-active TNF was detected in the ascites fluid of CD-1 mice; it was detectable 30 minutes after IL-2 and peaked at 1 hour (500 +/- 158 units/ml). Plasma levels of TNF also peaked at 1 hour at 32 +/- 4 units/ml. Similar kinetics were observed in CBA/J mice. TNF specific mRNA was also present in the ascites cells, and peaked 30 minutes after IL-2 injection into CBA/J mice. Injection of vehicle containing 10 times the maximum contaminating dose of endotoxin did not induce TNF above background levels. As a further control for potential endotoxin contamination, IL-2 was injected into endotoxin hyporesponsive C3H/HeJ mice. These mice also demonstrated the rapid upregulation of biologically-active TNF in the ascites, with peak production occurring at 1 hour (125 +/- 47 units/ml). The induction of biologically-active TNF in the C3H/HeJ mice was associated with a peripheral blood neutrophilia and lymphopenia, pathophysiologic alterations that have been attributed to TNF. These data show that a single injection of purified, recombinant IL-2 induces TNF gene expression in vivo.

WEHI 164 subclone 13 assay for TNF: sensitivity, specificity, and reliability.

Tumor necrosis factor alpha (TNF) is a peptide monokine involved in a number of immune reactions. To further understand the role of TNF in disease states it is critical to have an inexpensive, yet sensitive and specific assay. Additionally, the effects of prostaglandin E2 (PGE2), dexamethasone (dex), and cyclosporine A (CsA) on TNF gene expression have been studied, although little is known of the effects these compounds have on TNF containing samples. The aim of this study is to determine the sensitivity and specificity of a highly sensitive cell line to the actions of TNF, and to elucidate parameters which affect the stability of TNF in biological fluids. Dex and PGE2 at concentrations of 10(-5), 10(-7), and 10(-9) M, were shown not to effect the WEHI assay, and neither did CsA (10 ng/ml-1 ug/ml). The cells were not lysed by recombinant murine IL-1 alpha or beta, human recombinant IL-1 alpha or beta, human recombinant IL-2 or human recombinant IL-6 at concentrations ranging from 0.02 pg/ml to 1.0 ug/ml, or murine gamma-IFN from 100 pg/ml to 10 ng/ml. TNF containing samples with 1%-10% fetal calf serum maintained their cytolytic activity even after three freeze-thaw cycles. Serum samples did not lose any cytolytic activity with up to 11 cycles of freezing and thawing whereas, tissue culture media, containing TNF, lost significant activity with freeze-thawing. The WEHI assay has successfully detected cytolytic activity from lipopolysaccharide stimulated specimens from a number of different species. These data show the utility of this highly sensitive and specific assay. Furthermore, the WEHI assay showed a high degree of reproducibility in repeated assays.

Role of tumor necrosis factor-alpha in lipopolysaccharide-induced pathologic alterations.

Tumor necrosis factor-alpha (TNF) has been implicated strongly as a principal mediator in the pathogenesis of septic shock. The authors investigated the in vivo production of TNF in CBA/J and CD-1 mice that had been primed by an intraperitoneal injection of complete Freund's adjuvant followed 2 weeks later by an intraperitoneal injection of lipopolysaccharide (LPS). TNF bioactivity peaked in both the ascites and plasma one hour after challenge, and TNF mRNA expression in the ascites cells peaked 30 minutes after LPS. After the induction of bioactivity, an interstitial pulmonary neutrophilic infiltrate occurred that was quantitated both morphometrically and by a myeloperoxidase (MPO) assay. Peripheral blood neutrophilia and lymphopenia developed after the LPS injection (PMNs: control, 46 +/- 2%; LPS, 65 +/- 3%; Lymphs control, 53 +/- 2%; LPS, 37 +/- 3%). Treatment with dexamethasone (Dex) completely inhibited the pulmonary neutrophilic infiltrate as measured by the (MPO) assay. Because Dex will inhibit the production of several cytokines, anti-TNF antiserum was given to mice at the same time as the LPS challenge to assess specifically the role of TNF in inducing these changes. This antiserum partially blocked the pulmonary neutrophil infiltrate, and completely blocked the peripheral blood changes at one hour after LPS. These data demonstrate that TNF plays an important role in the early pathophysiologic alterations that occur after systemic exposure to LPS.

Cyclosporine A inhibits TNF production without decreasing TNF mRNA levels.

The role of cytokines in health and disease has received increasing attention and numerous investigations have explored the regulation of cytokine gene expression. Tumor necrosis factor-alpha (TNF) has received particular attention because of its central role in septic shock and more recent work has shown its participation in transplant immunology. We explored the mechanism of cyclosporine A (CsA) modulation of complete Freunds adjuvant macrophage (CFA-MO) TNF gene expression. From 0.001 to 1 microgram/ml, CsA dose-dependently inhibited lipopolysaccharide (LPS) induced secreted bioactivity; at doses above 10 micrograms/ml CSA was directly toxic to CFA-MO. However, there was no suppression of TNF mRNA levels, and CsA also did not inhibit the accumulation of cell-associated TNF. Thus, CsA modulates TNF gene expression in a previously undescribed manner.

Effects of arachidonic acid metabolites and other compounds on the CTLL assay for interleukin-2.

Interleukin-2 (IL-2) is a peptide lymphokine which plays a central role in many immune responses. Production of IL-2 is blocked in the presence of various chemical constituents including arachidonic acid (AA) metabolites, however, the effects of these compounds on preformed IL-2 is less clear. This study was designed to observe whether commonly employed drugs and AA metabolites will inhibit the ability to measure IL-2 in a standard bioassay. We measured cytotoxic T lymphocyte (CTLL) proliferation in response to IL-2 in the presence of increasing concentrations of drugs or AA metabolites. Our data provides clear evidence that no suppression of cell replication occurs with PGE2, PGF2 alpha, LTB4, LTC4, LTD4, and LTE4 at concentrations of 10(-5)-10(-9) M. At high concentrations, both dexamethasone (10(-5)M) and indomethacin (10(-5) and 10(-6) M) resulted in a suppressive effect on CTLL proliferation, while low concentrations of either compound (10(-7)-10(-9) M) had no effect. This study shows that AA metabolites will not block the ability of IL-2 to induce CTLL proliferation, and neither will dexamethasone or indomethacin at low concentrations.