Intraspecific trait variation in plants: a renewed focus on its role in ecological processes.

BACKGROUND: Investigating the causes and consequences of intraspecific trait variation (ITV) in plants is not novel, as it has long been recognized that such variation shapes biotic and abiotic interactions. While evolutionary and population biology have extensively investigated ITV, only in the last 10 years has interest in ITV surged within community and comparative ecology. SCOPE: Despite this recent interest, still lacking are thorough descriptions of ITV's extent, the spatial and temporal structure of ITV, and stronger connections between ITV and community and ecosystem properties. Our primary aim in this review is to synthesize the recent literature and ask: (1) How extensive is intraspecific variation in traits across scales, and what underlying mechanisms drive this variation? (2) How does this variation impact higher-order ecological processes (e.g. population dynamics, community assembly, invasion, ecosystem productivity)? (3) What are the consequences of ignoring ITV and how can these be mitigated? and (4) What are the most pressing research questions, and how can current practices be modified to suit our research needs? Our secondary aim is to target diverse and underrepresented traits and plant organs, including anatomy, wood, roots, hydraulics, reproduction and secondary chemistry. In addressing these aims, we showcase papers from the Special Issue. CONCLUSIONS: Plant ITV plays a key role in determining individual and population performance, species interactions, community structure and assembly, and ecosystem properties. Its extent varies widely across species, traits and environments, and it remains difficult to develop a predictive model for ITV that is broadly applicable. Systematically characterizing the sources (e.g. ontogeny, population differences) of ITV will be a vital step forward towards identifying generalities and the underlying mechanisms that shape ITV. While the use of species means to link traits to higher-order processes may be appropriate in many cases, such approaches can obscure potentially meaningful variation. We urge the reporting of individual replicates and population means in online data repositories, a greater consideration of the mechanisms that enhance and constrain ITV's extent, and studies that span sub-disciplines.

Predicting arteriovenous fistula maturation with intraoperative blood flow measurements.

OBJECTIVE: To establish the criteria for intraoperative blood flow measurements taken at the time of autologous arteriovenous fistula (AVF) construction to predict future access maturation and thereby avoid waiting periods for futile fistulas to declare themselves. METHODS: From April 2006 through to March 2007 consecutive patients undergoing native AVF construction at one institution underwent intraoperative measurements of blood flow using transit-time ultrasound technology. No action was taken based upon the flow measurement at the time of surgery. Patients were followed and data collected comprising demographics and AVF maturation. A fistula was considered mature when it was successfully accessed for hemodialysis (HD) at least three times. Statistical analysis was performed including receiver operating characteristics (ROC), ANOVA, and Chi square using the JMP software package. RESULTS: During the 12-month period, 70 autologous AVFs were created including 41 antecubital brachiocephalic, 21 radiocephalic, and 8 basilic vein transpositions in 35 females and 33 males with a mean age of 58+/-1.7 (mean+/-SEM). The group included 37 Hispanic, 17 Native American, 10 Caucasian, 3 African American and 1 Asian patient. The etiology of renal failure comprised 53 diabetics, 13 hypertensives, 1 polycystic kidney disease and 1 congenital abnormality. Complete follow-up was available in 69/70 AVFs in 67 patients. Patients were excluded from analysis if they had not yet started dialysis (n=12), stopped or died (n=4) before their fistula was accessed. Patients whose AVFs were patent, but required a secondary procedure to achieve a functional access were considered non-functional. There was a significant difference between the maximal intraoperative flow rates between functional and non-functional AVFs (573.6+/-103 mL/min vs. 216.8+/-35.8 mL/min; p<0.05). There was no difference between groups in regard to age, gender, race or etiology of renal failure. ROC analysis suggested a threshold value of 140 mL/min for radiocephalic and 308 mL/min for brachiocephalic AVFs to predict maturation to a functional access. CONCLUSION: Intraoperative blood flow measurements obtained at the time of autologous AVF construction can identify fistulas that are unlikely to mature; and therefore, that require immediate revision or abandonment which will ultimately expedite the establishment of a useful access in the HD patient. This is the first study to establish the minimal flow values uniquely needed for both radial artery and brachial artery AVFs to expect primary maturation to a functional access.

Vein adaptation to arterialization in an experimental model.

PURPOSE: The events preceding myointimal thickening in vein grafts after vascular reconstructions are not well characterized. Indeed, the injury response associated with vein graft arterialization may be different than that observed in the balloon angioplasty model. Therefore, we used a rat model to study the early cellular response after arterialization of vein grafts. METHODS: Epigastric veins were placed as femoral artery interposition grafts in 37 male Lewis rats (weight range, 350-400 g). Vein grafts and contralateral epigastric veins were harvested at different time points (6 hours, 1 day, 2 days, 3 days, 7 days, 14 days, 21 days, 30 days, and 70 days). Tissue specimens were processed for histology and immunohistochemistry with antibodies for the proliferating cell nuclear antigen (PCNA) and for different cell types. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay was used as a means of determining the presence of apoptosis. Electron microscopy was used as means of assessing the integrity of the endothelial cell surface (SEM) and confirming the presence of apoptosis (TEM). Specimens were also snap frozen in liquid nitrogen for RNA isolation and molecular analysis. RESULTS: At 1 day, endothelial denudation with platelet deposition on the surface was shown by means of SEM. Both apoptosis and necrosis of smooth muscle cells (SMCs) were present in the media, along with monocyte infiltration. Cellular proliferation and apoptosis were most intense within the first week of implantation. PCNA staining was first seen in the adventitial fibroblasts and microvessels, then in the medial SMCs at 3 days. With reverse transcriptase polymerase chain reaction, upregulation of vascular endothelial growth factor (VEGF) messenger RNA (mRNA) was noted at 1 day. Myointimal thickening progressively developed, with no apparent diminution of the luminal area as long as 70 days after implantation. By means of the analysis of the transforming growth factor beta1, mRNA showed expression during intimal thickening and accumulation of extracellular matrix. Reendothelialization was complete at 30 days. CONCLUSIONS: These observations indicate that the cellular composition in our vein graft model is similar to human stenotic explants. Endothelial denudation is observed in rat vein grafts with complete regeneration by 30 days. VEGF mRNA is upregulated at 1 day, followed by proliferation of microvessel endothelial cells in the adventitia. Cellular proliferation and apoptosis are minimal after 21 days, with progressive intimal thickening likely to be the result of matrix accumulation.

The natural history of intermediate and critical vein graft stenosis: recommendations for continued surveillance or repair.

OBJECTIVE: Duplex ultrasound surveillance (DUS) after autogenous lower extremity bypass grafting is controversial. Specific criteria mandating graft revision are not uniform. It has been suggested that grafts harboring critical stenoses undergo revision, whereas those with intermediate stenoses undergo arteriography with selective repair. We sought to define the natural history and determine the risk of graft occlusion associated with unrepaired vein graft stenoses. METHODS: We analyzed serial vascular laboratory and clinical data of 156 autogenous infrainguinal vein grafts in 142 patients. Grafts were categorized into three groups according to the first DUS-detected (index) lesion: (1) normal (peak systolic velocity [PSV] < 200 cm/s, velocity ratio [V(r)] < 2); (2) intermediate stenosis (200 cm/s < PSV < 300 cm/s, 2 < V(r) < 4); and (3) critical (PSV > 300 cm/s, V(r) > 4). Our policy was to repair grafts with critical lesions and monitor all others. The risks of stenosis progression, graft revision, and graft thrombosis for each group were compared. RESULTS: Serial DUS was normal in 100 (64%) grafts. The incidence of graft thrombosis in the normal group was 3% per year (mean follow-up, 27.5 months). Intermediate lesions developed in 32 grafts (20%) and were followed. Among these 32 grafts with intermediate stenoses, 63% progressed to critical and were revised, and 32% resolved or stabilized (mean follow-up, 26 months). Only one graft occlusion occurred in grafts with intermediate lesions subjected to serial DUS monitoring (incidence 1.5% per year, P = not significant). In the third group, 16 of 25 grafts with critical lesions were successfully revised and remain patent. In nine cases, critical lesions were not repaired, resulting in seven (78%) occlusions, all within 4 months of DUS detection. CONCLUSIONS: Serial surveillance is safe and effective for grafts with intermediate stenoses. The graft occlusion rate for such grafts with careful monitoring is no different from grafts without stenosis, and therefore, arteriography is not indicated in the absence of progression to critical stenosis. The short-term risk of graft occlusion in the presence of an unrevised critical stenosis is nearly 80%. These data have important clinical implications concerning the natural history of vein graft lesions.

Preimplant vein intimal thickness is not a predictor of bypass graft stenosis.

PURPOSE: Preimplant vein morphology has been implicated as a risk factor for subsequent vein graft failure. It is controversial whether microscopic intimal thickening in random saphenous vein biopsy specimens is associated with an increased risk of graft failure. The purpose of this study was to determine the incidence of preexisting intimal thickening in a macroscopically normal preimplant vein, and to evaluate whether preimplant vein intimal thickness was predictive of future vein graft stenosis. METHODS: As part of an ongoing protocol, samples of preimplant veins were obtained at the time of the primary leg bypass. Routine duplex surveillance identified 14 patients who required operative revision for severe graft stenosis (n = 12) or graft occlusion (n = 2). Verhoeff's staining of specimens was performed to delineate the internal elastic lamina. Morphometric analysis of preimplant vein specimens was performed. The results were compared to a control group of 13 preimplant vein specimens selected from patients whose grafts have remained patent and stenosis-free by duplex. RESULTS: Preoperative risk factors were identical between the two groups. Mean intimal thickness in all 27 specimens was measured by two blinded observers. Almost 50% of specimens exhibited marked intimal thickening (>0.08 mm). The mean preimplant intimal thickness of the stenosis group was 0.108 mm +/- 0.155 compared to 0.100 mm +/- 0.064 for the control group (P = 0.866, NS). CONCLUSION: Although grossly normal preimplant veins often exhibit prominent microscopic intimal thickening, preimplant vein intimal thickness determined from a random saphenous vein biopsy at the time of primary leg bypass is not predictive to the subsequent development of vein graft stenosis.

Improved patency of infrainguinal polytetrafluoroethylene bypass grafts using a distal Taylor vein patch.

OBJECTIVE: The purpose of this study was to evaluate graft patency and limb salvage rates for infrainguinal polytetrafluoroethylene (PTFE) bypass grafts using distal anastomotic Taylor vein patch in patients lacking suitable vein conduit. METHODS: We reviewed 44 patients who underwent infrainguinal bypass between January 1996 and August 2000 using 6-mm PTFE and a distal Taylor vein patch. Postoperative oral anticoagulation was administered to 80% of patients. Graft patency was confirmed during follow-up with serial graft duplex scanning. RESULTS: Operative indications were rest pain, nonhealing ulcer, or gangrene in 76% of patients, 43% of whom had undergone previous ipsilateral leg bypass. Distal anastomotic sites were the below-knee popliteal (29%) and tibial-peroneal arteries (67%). At 1 month, 1 year, and 2 years, respectively, the primary patencies (SE <10%) were 86%, 71%, and 71%; limb salvage rates were 95%, 75%, and 66%; and mortality rates were 5%, 20%, and 20%. CONCLUSIONS: These early results with PTFE and distal Taylor vein patch are promising, and markedly superior to previous reports of PTFE without anastomotic modification. Further long-term follow-up will be necessary to determine the 3- to 5-year durability of such reconstructions.

The influence of gender on complications of carotid endarterectomy.

PURPOSE: Carotid endarterectomy (CEA) effectively reduces stroke risk in properly selected patients. Subgroup analysis of the Asymptomatic Carotid Artery Study trial noted increased complications in women. Additional studies implicate female gender as a risk factor for perioperative stroke, leading some clinicians to modify the indications for CEA in women. The purpose of this study was to determine the influence of gender on the risk of perioperative complications in patients undergoing CEA. METHODS: The records of all patients who underwent CEA at a university medical center from January 1995 to December 1999 were reviewed. Patient demographics, procedure related risk factors, operative details, and specific complications were entered into a database for statistical analysis. RESULTS: A total of 324 consecutive patients underwent CEA during the study period. There were 199 men (61%) and 125 women (39%). Among the men and women, there were no differences in age, smoking, hypertension, hypercholesterolemia, diabetes, family history, renal insufficiency, or symptomatic versus asymptomatic indications for CEA. More women than men received a carotid patch (90.4% versus 77.9%, P = 0.003). One woman died (0.8%) and no men died for a total combined 30-day mortality of 0.31% (P = not significant). Men and women did not differ in rates of stroke (1.5% versus 2.4%) or perioperative myocardial infarction (1.0% versus 0.8%). In addition, there was no difference when stroke and death rates were combined (2% versus 3.2%). The length of stay (2.2 versus 2.6 days) was also not different. CONCLUSIONS: There are no significant differences in rate of stroke, myocardial infarction, or 30-day mortality, between men and women following CEA. Women should not be excluded from the benefits of CEA based on perceived increased complication rates.

Intimal growth and neovascularization in human stenotic vein grafts.

BACKGROUND: Myointimal thickening and microvessel ingrowth are commonly observed in vein graft stenosis, which complicates a third of infrainguinal bypass procedures. But a direct correlation between these two features has not been established. Our purpose was to analyze the relationship between neovascularity and intimal thickness in human vein grafts. STUDY DESIGN: Twenty-two explant stenotic vein grafts (STVG), 8 nonstenotic arterialized vein grafts (AVG), and 20 age-matched control greater saphenous veins (CGSV) were analyzed histologically and compared morphologically by light microscopy. Digitized computer image analysis was used to measure intimal thickness and quantitate microvessel ingrowth. Immunolocalization of endothelial cells around the lumen and in microvessels was determined using antibodies to factor VIII and to endothelial nitric oxide synthase (eNOS), respectively. RESULTS: Focal areas of endothelial disruption and thrombus deposition were present in 23% (5 of 22) of stenotic vein grafts. The neointima of STVG grafts was two- and fourfold thicker than that of AVG and CGSV, respectively (p < 0.0001). Microvessels were most frequently observed in the adventitia and media of STVG and increased in number with increasing intimal thickness (p < 0.001 by ANOVA). CONCLUSIONS: A fourfold increased neointimal thickness in critically stenotic vein grafts is associated with increased medial and adventitial neovascularization. Remodeling alone with doubling of the intimal thickness in nonstenotic arterialized vein grafts does not appear to be associated with enhancement of the graft microvasculature. More specific observations using an experimental model may allow us to further define the role of angiogenesis in vein graft stenosis and to determine the therapeutic implications of such observations.

An economic appraisal of lower extremity bypass graft maintenance.

OBJECTIVE: Infrainguinal graft surveillance leads to intervention on the basis of duplex-identified stenoses. We have become increasingly concerned about the high frequency with which such revisions are required to maximize graft patency and limb salvage rates. The economic implications of these procedures have not been carefully analyzed or justified. METHODS: We retrospectively reviewed 155 consecutive autogenous infrainguinal bypass grafts performed for chronic leg ischemia in 141 patients. All patients were enrolled in a prospective surveillance program using color flow duplex imaging. Full economic appraisal (cost analysis, cost-effect analysis, and cost-benefit analysis) was performed for all graft surveillance and limb salvage-related interventions through use of standard accounting and valuation techniques. RESULTS: Mean follow-up was 27 months. Five-year assisted primary patency (72%) and limb salvage rates (91%) were calculated by means of life table analysis. A total of 61 grafts required 86 revisions. Within 1 year of implantation, 36% of the grafts required revision. During this first year, the mean cost per graft enrolled was $9417. Time intervals after the initial year demonstrated a reduced annual revision rate (6%) and cost ($1725 per graft). The mean 5-year cost of graft maintenance ($16,318) approached that of the initial bypass graft ($19,331). The sum of the initial cost of bypass graft and 5-year graft maintenance cost ($35,649) was similar to the cost of amputation ($36,273). Grafts revised for duplex-detected stenoses (n = 46), in comparison with those revised after thrombosis (n = 15), had an improved 1-year patency (93% vs 57%; P <.01), required fewer amputations (2% vs 33%; P <.01), less frequently required multiple graft revisions (P =.06), and generated fewer expenses (at 12 months after revision, $17,688 vs $45,252, P <.01). CONCLUSION: The cost associated with graft maintenance is significant, particularly within the first year, and demands consideration. Revision of a duplex-identified stenosis was significantly less costly than revision after graft thrombosis. Compared with the cost of limb amputation, limb salvage-related expenses appear to be justified.

Characterization of cellular density and determination of neointimal extracellular matrix constituents in human lower extremity vein graft stenoses.

UNLABELLED: Arterial restenosis has been attributed to a hyperproliferative smooth muscle cell response. Paradoxically, studies of human coronary atherectomy and vein graft stenotic lesions have demonstrated a relatively low nuclear proliferative rate with the majority of the neointimal mass consisting of extracellular matrix. The purpose of the present study was to characterize the cellular density and determine the relative composition of the extracellular matrix protein constituents in stenotic, human lower extremity vein-bypass graft lesions. METHODS: Duplex surveillance of 148 consecutive infrainguinal bypass grafts identified 17 patients with 22 preocclusive autogenous vein graft stenoses (mean graft age 7 months). Morphological analyses of these stenotic lesions were compared with excised samples of 20 greater saphenous vein segments taken at the time of graft implantation from matched control patients. Intimal and medial areas were compared and cell density was determined with fluorescent nuclear (Bisbenzimide) staining. Differential light microscopy with pentachrome staining was performed to determine the relative percent composition of intimal matrix constituents by stereological morphometric (point-count) techniques. RESULTS: The intimal areas for control and stenotic vein segments were 1.64 x 10(6) microm2 and 3.85 x 10(6) microm2, P < 0.0001, whereas the intimal nuclear densities (cells/unit volume) were 1.42 x 10(3) and 1.70 x 10(3) cells/microm2, P = 0.03. respectively. The corresponding medial area and medial nuclear densities were 5.01 x 10(6) microm2, 3.31 x 10(6) microm2; P = 0.08, and 2.27 x 10(3), 3.29 x 10(3); P = 0.001, for control and stenotic specimens, respectively. The intima:media area ratios were much greater, whereas the intimal and medial cell densities were only slightly greater in the stenotic compared with control veins. The relative composition of intimal extracellular matrix proteins of stenotic vein graft segments consisted of 21% cellular (fibrous) material, 33% collagen, and 46% glycosaminoglycan ground substance. CONCLUSION: The intimal lesions responsible for lower extremity vein graft stenosis are more hypertrophic than hyperplastic. Therapies aimed at preventing arterial and vein graft restenosis may thus need to inhibit matrix biosynthetic processes in addition to cellular proliferation.

The correlation of early flow disturbances with the development of infrainguinal graft stenosis: a 10-year study of 341 autogenous vein grafts.

PURPOSE: Although duplex surveillance of infrainguinal bypass grafts is widely accepted, the optimal frequency and intensity of graft surveillance remains controversial. Earlier reports have suggested that grafts can be stratified into high-risk and low-risk groups based on the presence or absence of early graft flow disturbances. The purpose of this study was to provide long-term data in determining whether early graft flow disturbances detected by means of duplex scanning can predict the development of intrinsic vein graft stenosis. METHODS: We reviewed a series of patients undergoing prospective duplex graft surveillance after autogenous infrainguinal bypass grafting procedures from 1987 to 1997. Patients included in the study underwent at least one duplex scan within 3 months of graft implantation and were observed for a minimum of 6 months. Grafts were categorized as abnormal when a focal flow disturbance with a peak systolic velocity greater than 150 cm/s was identified within 3 months of graft implantation. RESULTS: Of 341 vein grafts in 296 patients who met inclusion criteria, 89 grafts (26%) required revision for intrinsic stenosis; the mean follow-up period was 35 months (range, 6 months to 10 years). Early flow disturbances were detected in 84 (25%) grafts. Grafts with early flow disturbances were more likely to ultimately require revision (43% vs 21%; P =. 0001) and required initial revision earlier (8 months vs 16 months; P =.019). Eighty-two percent of initial graft revisions occurred in the first 2 postoperative years; 69% occurred in the first year. However, an annual 2% to 4% incidence of late-appearing graft stenosis persisted during long-term follow-up. An additional 24 patients (7% of grafts) required an inflow or outflow reconstruction. CONCLUSION: Grafts with early postoperative flow disturbances detected by means of duplex scanning have nearly three times the incidence of graft-threatening stenosis and an earlier requirement for revision, when compared with normal grafts. This suggests that the biology and etiology of these lesions may differ. These data support not only aggressive efforts to detect early graft lesions to stratify grafts at highest risk, but also continued lifelong graft surveillance to detect late-appearing lesions, inflow and outflow disease progression, and maximize graft patency.

The contribution of inducible nitric oxide and cytomegalovirus to the stability of complex carotid plaque.

BACKGROUND: Although the association between inflammation and atherosclerosis is well established, the biologic events that trigger the local inflammatory response within plaque are not fully understood. Cytotoxic free radicals and infectious agents, both of which are associated with an inflammatory response, have previously been implicated in the initiation and progression of atherosclerosis. In this study, we analyzed carotid plaque for evidence of oxidative vascular injury by determining the presence and distribution of inducible nitric oxide synthase (iNOS) expression and nitrotyrosine formation and for evidence of infection with cytomegalovirus. METHODS: Carotid plaque from 51 patients who underwent endarterectomy for either primary (n = 37) or recurrent (n = 14) stenosis were examined histologically (hematoxylin-eosin staining and Masson's trichrome staining) and with immunohistochemistry with specific antibodies to alpha-smooth muscle actin, macrophages (CD68), T-lymphocytes (CD3), and T-cell activation (human leukocyte antigen-DR). Twenty-eight specimens from patients with primary (n = 15) and recurrent (n = 13) stenosis were examined for the presence of iNOS and nitrotyrosine with immunohistochemistry and in situ hybridization (iNOS). Twenty-three additional specimens (22 primary, and 1 recurrent) were analyzed with antibodies to p53, cytomegalovirus, and the polymerase chain reaction (cytomegalovirus, n = 8). RESULTS: Primary atherosclerotic lesions were either complex heterogenous cellular plaques (n = 29) or relatively acellular fibrous plaques (n = 8). Ten of 14 recurrent plaques were either complex or fibrous lesions, and the remaining four were typical of myointimal thickening. CD68-positive staining cells were detected in all specimens regardless of their structural morphology. CD3-positive cells were interspersed between macrophages in all heterogeneous cellular plaques and only infrequently noted in fibrous plaques. iNOS and nitrotyrosine immunoreactivity were detected in macrophages and smooth muscle cells in all complex and fibrous plaques and in two of four myointimal plaques. The presence of iNOS and nitrotyrosine in plaque correlated with the existence of symptoms in 80% of primary and 62% of recurrent lesions. Cytomegalovirus was detected in only two of 23 carotid specimens (9%). CONCLUSION: The association between ischemic cerebrovascular symptoms and iNOS and nitrotyrosine immunoreactivity in complex primary and recurrent carotid plaque and the infrequent occurrence of cytomegalovirus in primary carotid lesions suggests that ongoing free radical oxidative damage rather than viral infection may contribute to plaque instability in patients with complex and fibrous carotid plaques.

Topography of cell replication in human vein graft stenoses.

BACKGROUND: Analysis of the cellular composition of human autogenous vein graft lesions at the time of revision provides an opportunity to identify the cellular processes leading to the development of stenosis in humans after vascular reconstruction. METHODS AND RESULTS: Human vein graft-threatening stenotic lesions were identified by duplex scanning within 3 to 18 months after infrainguinal bypass and surgically removed. They were serially studied by immunocytochemistry for expression of the proliferating cell nuclear antigen (PCNA) in different cell types: alpha-actin-positive smooth muscle cells (SMCs), endothelial cells (ECs), monocytes, and macrophages. Proliferation indexes were separately obtained for each layer of the vessel wall by determining the mean percentage of PCNA-positive nuclei among the total number of nuclei present within the intima, the media, and the adventitia, respectively. The percentage distribution of the replicating cell types was also determined. We report that in autogenous vein graft (n = 14) the intima of the lesion displayed fewer PCNA + nuclei (1.03 +/- 0.88) than the underlying media (3.14 +/- 0.74) or the adventitia (3.01 +/- 0.74). Replicating SMCs were predominantly in the medial layer (68% of PCNA + cells) of stenotic vein grafts. In the adventitia, the proliferation was most intense in the endothelium of microvessels (65% of PCNA + nuclei). CONCLUSIONS: Our findings reveal a 3-fold greater proliferative activity in the media and the adventitia as compared with the intima of autogenous vein graft lesions, in contrast to cellular proliferation identified in recurrent coronary stenotic plaques. Moreover, there are distinctive patterns of distribution of the different cell populations among the 3 layers. The results indicate a proliferative response of the media and the adventitia of autogenous vein grafts transplanted into the arterial circulation, in addition to the cellular proliferation observed in the intima of the lesion.

Treatment of patients with venous thromboembolism and malignant disease: should vena cava filter placement be routine?

PURPOSE: It has been proposed that inferior vena cava filter placement should be the initial treatment of deep venous thrombosis (DVT) or pulmonary embolus (PE) in patients with coexisting malignant disease. We have chosen instead to selectively place filters only in patients with either a contraindication to anticoagulation therapy or a subsequent complication from anticoagulation therapy. The treatment efficacy and mortality rates in patients with concomitant malignant disease and venous thromboembolism using this approach was determined. METHODS: We retrospectively reviewed all patients at our institution with malignant disease in whom venous thromboembolism developed between August 1991 through August 1996 and identified 166 patients with PE (n = 8), DVT (n = 147), and DVT/PE (n = 11). Of these patients, 138 (83.1%) were initially treated with anticoagulation therapy, and 28 (16.9%) had primary filter placement because of contraindications to anticoagulation therapy (10 for intracranial tumors, 11 for recent or upcoming operations, 6 for recent hemorrhage, and 1 for a malignant bloody pericardial effusion). RESULTS: Thirty-two (23%) of the 138 patients who initially underwent anticoagulation therapy subsequently required a filter for the following reasons: bleeding (n = 15, 10.9%); recurrent thromboembolism (n = 6, 4.3%); heparin-induced thrombocytopenia (n = 1, 0.7%); and perceived high risk for bleeding with continued anticoagulation therapy (n = 11, 8%). Both bleeding and recurrent thromboembolism developed in 1 patient. Sixty patients (36%) received filters. No major technical complications occurred from filter placement. Major recurrent thromboembolic complications developed in 10 patients: DVT (n = 6, 10%), PE (n = 2, 3.3%), inferior vena cava thrombosis and phlegmasia cerulea dolens (n = 1, 1.7%), superior vena cava thrombosis (n = 1, 1.7%). Venous gangrene developed in 1 patient with DVT. The 1-year actuarial survival rates for patients treated with filter and anticoagulation therapy were 35% and 38%, respectively (P = NS). CONCLUSION: In summary, our experience suggests that 64% of patients with malignant disease and venous thromboembolism are effectively treated with anticoagulation alone; 17% require primary filter placement for standard indications, and an additional 19% require subsequent filter placement because of complications (primarily bleeding) or failure of anticoagulation therapy. Although technical complications of filter placement are low, serious life-threatening or limb-threatening thromboembolic complications developed in 17% of patients. Survival was poor in all patients, regardless of treatment. These data support a conservative approach of routine anticoagulation therapy with selective filter placement.

Antibiotic prophylaxis for intracranial pressure monitors.

To determined the safety and efficacy of prophylactic antibiotics in head-injured patients requiring intracranial pressure monitors, the files of 30 consecutive patients with isolated, severe head injuries admitted over a 1-year period were reviewed. Patients .15 years with severe closed-head injury who did not have severe concomitant, extracranial injury (Abbreviated Injury Score, 3) and survived .48 hours following hospital admission were included. Fourteen patients underwent intracranial pressure monitor placement and received prophylactic antibiotics for the duration of monitoring and the remaining 16 patients were neither monitored nor given prophylactic antibiotics. Length of hospital stay, length of intensive care stay, overall and septic complication rate, and death rate were compared for the two treatment groups. The groups were similar with regard to patient characteristics, associated injuries, and injury severity. Patients who received prophylactic antibiotics demonstrated statistically higher septic morbidity rates (78.6% versus 31.3%) and statistically higher pneumonia rates (57.1% versus 18.8%) compared with patients who did not. No patient developed central nervous system infection related to the monitor itself. These results indicate that the administration of prophylactic antibiotics to head-injured patients for the duration of intracranial pressure monitoring is unnecessary and potentially detrimental. Antibiotics, if given at all, should be limited to the period immediately surrounding intracranial pressure monitor placement.

Current trends in the detection and management of carotid body tumors.

PURPOSE: Because the natural history of carotid body tumors is believed to be unpredictable, immediate surgical removal has been recommended. The present study reviews our experience in the diagnosis and treatment of these uncommon lesions. METHODS: The medical records of patients who appeared for treatment with carotid body tumors between 1981 and 1997 were reviewed. Patients demographics, mode of presentation, imaging and treatment modalities, Shamblin classification, and neurologic complications (stroke, cranial nerve injuries) were analyzed. RESULTS: Over the past 16 years, 31 patients with 32 carotid body tumors have been evaluated, with an average follow-up of 3.2 years. The patients were arbitrarily classified into two groups on the basis of the mode of detection. Seventy percent (23 of 32) of the tumors discovered on clinical or self-examination were classified as Group 1; 28% (9 of 32) of the tumors detected during duplex scanning for carotid artery disease (8) or MRI (1) were classified as Group 2. The mean size of chemodectomas found on palpation (4.3 +/- 1.7 cm) was larger than that of those detected by duplex ultrasound (2.7 +/- 1.0 cm; p < 0.05, by paired t test). Preoperative embolization was successfully performed in 5 of 6 instances of large tumors; the remaining patient suffered a procedure-related stroke. Thirty-one carotid body tumors were resected. In one case, the tumor was felt by the primary surgeon to be too small (0.9 x 0.7 cm on duplex scan) to warrant immediate excision; this patient is being followed by periodic duplex scanning. Five neurologic complications were noted in Group 1, one after preoperative embolization and four after surgery. One cranial nerve injury occurred in Group 2. One patient had a large recurrent chemodectoma with clinical evidence of metastatic disease. CONCLUSION: The increasing use of sophisticated imaging modalities may allow earlier discovery of carotid body tumors before they can be clinically detected. Resection of carotid body tumors of all sizes in appropriate surgical candidates remains the standard of care. Unfortunately, resection of even small tumors is associated with a low but constant incidence of neurologic complications.

The histologic characteristics of primary and restenotic carotid plaque.

BACKGROUND: Although smooth muscle cell proliferation is a prominent feature of restenosis in experimental models, the role of cellular proliferation in the initiation and progression of carotid restenosis is not well documented. METHODS: Between 1985 and 1995, 35 carotid endarterectomies (CEA) in 34 patients were performed for restenosis. Patient risk factors, cerebrovascular symptoms, and operative findings were recorded. Tissue specimens from 29 of these cases and 14 original specimens from the same patient were examined by light microscopy (H&E, trichrome, elastochrome, and Alcian blue) and immunohistochemistry (alpha actin, CD 68, vWF, and proliferating nuclear cell antigen (PCNA)) in order to determine the morphologic characteristics and cellular proliferative activity of the plaque. RESULTS: Hemodynamically significant recurrent stenosis occurred in the 29 patients (69% symptomatic) between 2 months and 30 years after their initial CEAs. Eleven of 29 (38%) lesions were removed early (< 3 years). Recurrent lesions were characterized based on their components as neointimal thickening, 24% (7/29), neointimal thickening and atherosclerosis, 55% (16/29), or atherosclerotic, 21% (6/29). Nineteen of 29 (66%) plaques were complicated by mural thrombus or intraplaque hemorrhage. An inflammatory cell infiltrate consisting of macrophages and T lymphocytes was observed adjacent to areas of recurrent atherosclerosis and macrophages in regions of intimal thickening. Although infrequently present (generally 1-3% of cells) PCNA-positive cells were detected in 41% (12 of 29) of recurrent and 14% (2 of 14) of primary plaques. No PCNA-positive cells were detected in the remaining 67% (29 of 43) of specimens. There was no statistical difference in the number of PCNA-positive cells in early recurrent lesions compared to those recurring after 3 years (36% vs 44%). PCNA immunoreactivity when present was most commonly noted in macrophages associated with thrombus or atheroma rather than smooth muscle cells. CONCLUSIONS: Although evidence of cellular proliferation was observed in 40% of recurrent carotid endarterectomy lesions, the proliferation rate was low (1-3%) and unrelated to the time interval of recurrence. Proliferative activity was most pronounced in macrophages associated with intraplaque hemorrhage or atheroma. The contribution of inflammatory cells to the biologic behavior of restenotic lesions requires further investigation.

Free tissue transfer to extend the limits of limb salvage for lower extremity tissue loss.

BACKGROUND: The extent of tissue loss amenable to primary healing after revascularization is unknown. Salvage of limbs with large soft-tissue defects with exposed tendon, joint, or bone lies beyond the limits of conventional techniques. We report our results using free tissue transfer as an adjunct to lower extremity vascular reconstruction in patients with complex ischemic or infected wounds. METHODS: Retrospective chart review of patient and wound characteristics. RESULTS: From January 1992 to June 1996, 585 procedures were performed in 544 patients, including 27 free flaps in 26 patients: 17 free flaps combined with distal bypass (7 staged, 10 simultaneous) and 10 isolated free flaps. Flap donor sites included radial forearm (8), latissimus dorsi (7), rectus abdominus (9), and scapula (3). Surgical indications included extensive ischemic/neurotrophic ulcers, and nonhealing vein graft harvest incision or transmetatarsal amputation site. Mean area of tissue loss was 70 cm2, mean ulcer duration was 5 months, and 92% of patients had exposed tendon, joint, or bone. During a mean follow-up of 14 months, 2 patients died of cardiopulmonary disease and 3 flaps failed, resulting in below-knee amputation. Six flaps were revised for graft stenosis (1), venous thrombosis (1), or flap edge necrosis (4). Limb salvage rate was 70% at 24 months by life-table analysis. Functional ambulation was achieved in 21 of 24 (88%) patients, including 7 of 8 with diabetes, end-stage renal disease, and heel ulcers. CONCLUSION: In select ambulatory patients with large soft-tissue defects and exposed deep structures, functional limb salvage is obtainable in more than 80% of patients. For lesions not amenable to vascular reconstruction with conventional methods of wound coverage, free tissue transfer extends the limits of limb salvage and is a viable alternative to amputation.

Distal revascularization-interval ligation for limb salvage and maintenance of dialysis access in ischemic steal syndrome.

PURPOSE: Traditional options for treating ischemic steal syndrome related to a functioning dialysis access graft or fistula include banding or ligation. Unfortunately, these techniques usually result in inconsistent limb salvage, loss of a functional access, or both. We report our experience with an alternative method of limb revascularization that eliminates steal while maintaining continuous dialysis access. METHODS: Patients who had critical limb ischemia and functioning arteriovenous fistulae (AVF) underwent color-flow duplex scanning, digital photoplethysmography, and arteriography. Arterial ligation distal to the AVF origin eliminated the steal physiologic mechanism while arterial bypass grafting from above to below the AVF revascularized the extremity (distal revascularization-interval ligation [DRIL] procedure). RESULTS: From March 1994 through December 1996, 21 patients with functioning extremity AVFs presented with critical ischemia and steal syndrome. Eleven patients had chronic ischemia with rest pain, paresthesias, or ulcerations related to nine native fistulae (six brachiocephalic, two basilic vein transpositions, one radiocephalic) and two prosthetic bridge grafts (one upper arm, one lower extremity). Acute ischemia developed in 10 patients related to three native fistulae (two brachiocephalic, one radiocephalic) and seven prosthetic bridge grafts (three forearm, three lower extremity, one upper arm). All 21 patients were treated with the DRIL technique. Three of these patients required treatment for ischemia at the time of AVF construction. Nineteen of 21 bypass procedures were performed with autogenous vein, including nine brachial-brachial, three brachial-radial, two radial-radial, two brachial-ulnar, one popliteal-popliteal, one femoral-popliteal, and one femoral-peroneal. Polytetrafluoroethylene grafts were used for one external iliac-popliteal bypass graft and one axillary-brachial bypass graft. Limb salvage and maintenance of a functional fistula were achieved in 100% and 94%, respectively, at 18 months by life-table analysis. CONCLUSION: The DRIL technique reliably restores antegrade flow to the ischemic limb, eliminates the potential pathway for the steal physiologic mechanism, and maintains continuous dialysis access in these difficult patients.