Role of matrix metalloproteinases 1, 2, and 9 and tissue inhibitor of matrix metalloproteinase-1 in chronic venous insufficiency.

PURPOSE: Increased transforming growth factor-beta(1) (TGF-beta(1)) activity is associated with chronic venous insufficiency (CVI) disease progression and dermal skin pathology. Because TGF-beta(1) stimulates collagen synthesis and alters the levels of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs), we investigated the hypothesis that increased TGF-beta(1) activity is associated with differences in messenger RNA and protein levels of MMPs and TIMP-1 in patients with CVI. METHODS: One hundred ten biopsies of the lower calf and lower thigh in 73 patients were snap frozen in liquid nitrogen and stratified into six groups according to the clinical etiologic anatomic distribution pathophysiology disease classification. One set of lower-calf and lower-thigh biopsies were analyzed for MMP-1 and TIMP-1 gene expression with quantitative reverse transcription and competitive polymerase chain reaction. A second set of biopsies was analyzed for the active and latent forms of MMP-1, MMP-2, and MMP-9 as well as for TIMP-1 by western blotting, gelatin zymography, and tissue localization by immunohistochemistry (IHC). RESULTS: Compared with the control, MMP-1 messenger RNA was increased in class-4 and class-6 patients (P < or =.01), whereas TIMP-1 was increased in class-6 patients only (P < or =.05). However, there were no differences in total protein between MMP-1 and TIMP-1. Active MMP-2 protein increased in class-4 and class-5 patients compared with active MMP-1 and TIMP-1 (P < or =.01). Western blotting did not identify the active component of MMP-9. Similarly, only the latent form of MMP-9 was observed by gelatin zymography, whereas both the latent and active forms of MMP-2 were observed. IHC demonstrated MMP-1 and MMP-2 in dermal fibroblasts and in perivascular leukocytes. TIMP-1 was observed in basal-layer keratinocytes of the epidermis only. MMP-9 was not detected by IHC. CONCLUSION: MMP synthesis is regulated at both the transcriptional and post-transcriptional levels in CVI. Our data suggest that post-translational modifications are key to functional regulation. Dermal fibroblasts and migrating leukocytes are probable cellular sources of MMPs. Increased active MMP-2 levels in class-4 and class-5 patients indicate tissue remodeling caused by pre-ulcer and postulcer environmental stimuli. These data suggest that alterations in MMP-2 activity, in conjunction with TGF-beta(1)-mediated events, cause an imbalance in tissue remodeling leading to a pro-ulcer-forming environment.

In-stent restenosis after carotid angioplasty-stenting: incidence and management.

PURPOSE: Carotid angioplasty-stenting (CAS) has been advocated as an alternative to carotid endarterectomy (CEA) in patients with restenotic lesions after prior CEA, primary stenoses with significant medical comorbidities, and radiation-induced stenoses. The incidence of restenosis after CAS and its management remains ill defined. We evaluated the incidence and management of in-stent restenosis after CAS. METHODS: Patients with asymptomatic (61%) and symptomatic (39%) carotid stenosis of > or = 80% underwent CAS between September 1996 and May 2000; there were 50 procedures and 46 patients (26 men and 20 women). All patients were followed up clinically and underwent duplex ultrasonography (DU) at 3- to 6-month intervals. In-stent restenoses > or = 80% detected with DU were further evaluated by means of angiography for confirmation of the severity of stenosis. RESULTS: No periprocedural or late strokes occurred in the 50 CAS procedures during the 30-day follow-up period. One death (2.2%) that resulted from myocardial infarction was observed 10 days after discharge following CAS. During a mean follow-up period of 18 +/- 10 months (range, 1-44 months), in-stent restenosis was observed after four (8%) of the 50 CAS procedures. Angiography confirmed these high-grade (> or = 80%) in-stent restenoses, which were successfully treated with balloon angioplasty (3) or angioplasty and restenting (1). No periprocedural complications occurred, and these patients remained asymptomatic and without recurrent restenosis over a mean follow-up time of 10 +/- 6 months. CONCLUSIONS: We recommend CAS for post-CEA restenosis, primary stenoses in patients with high-risk medical comorbidities, and radiation-induced stenoses. In-stent restenoses occurred after 8% of CAS procedures and were managed without complications with repeat angioplasty or repeat angioplasty and restenting.

Venous severity scoring: An adjunct to venous outcome assessment.

Some measure of disease severity is needed to properly compare the outcomes of the various approaches to the treatment of chronic venous insufficiency. Comparing the outcomes of two or more different treatments in a clinical trial, or the same treatment in two or more reports from the literature cannot be done with confidence unless the relative severity of the venous disease in each treatment group is known. The CEAP (Clinical-Etiology-Anatomic-Pathophysiologic) system is an excellent classification scheme, but it cannot serve the purpose of venous severity scoring because many of its components are relatively static and others use detailed alphabetical designations. A disease severity scoring scheme needs to be quantifiable, with gradable elements that can change in response to treatment. However, an American Venous Forum committee on venous outcomes assessment has developed a venous severity scoring system based on the best usable elements of the CEAP system. Two scores are proposed. The first is a Venous Clinical Severity Score: nine clinical characteristics of chronic venous disease are graded from 0 to 3 (absent, mild, moderate, severe) with specific criteria to avoid overlap or arbitrary scoring. Zero to three points are added for differences in background conservative therapy (compression and elevation) to produce a 30 point-maximum flat scale. The second is a Venous Segmental Disease Score, which combines the Anatomic and Pathophysiologic components of CEAP. Major venous segments are graded according to presence of reflux and/or obstruction. It is entirely based on venous imaging, primarily duplex scan but also phlebographic findings. This scoring scheme weights 11 venous segments for their relative importance when involved with reflux and/or obstruction, with a maximum score of 10. A third score is simply a modification of the existing CEAP disability score that eliminates reference to work and an 8-hour working day, substituting instead the patient's prior normal activities. These new scoring schemes are intended to complement the current CEAP system.

Mandibular subluxation for distal internal carotid exposure: technical considerations.

PURPOSE: Carotid endarterectomy (CEA) has become one of the most commonly performed vascular procedures, because of the beneficial outcome it has when compared with medical therapy alone and because of the anatomic accessibility of the artery. In cases of distal carotid occlusive disease, high cervical carotid bifurcation, and some reoperative cases, access to the distal internal carotid artery may limit surgical exposure and increase the incidence of cranial nerve palsies. Mandibular subluxation (MS) is recommended to provide additional space in a critically small operative field. We report our experience to determine and illustrate a preferred method of MS. METHODS: Techniques for MS were selected based on the presence or absence of adequate dental stability and periodontal disease. All patients received general anesthesia with nasotracheal intubation before subluxation. Illustrations are provided to emphasize technical considerations in performing MS in 10 patients (nine men and one woman) who required MS as an adjunct to CEA (less than 1% of primary CEAs). Patients were symptomatic (n = 7) or asymptomatic (n = 3) and had high-grade stenoses demonstrated by means of preoperative arteriography. RESULTS: Subluxation was performed and stabilization was maintained by means of: Ivy loop/circumdental wiring of mandibular and maxillary bicuspids/cuspids (n = 7); Steinmann pins with wiring (n = 1); mandibular/maxillary arch bar wiring (n = 1); and superior circumdental to circummandibular wires (n = 1). MS was not associated with mandibular dislocation in any patient. No postoperative cranial nerve palsies were observed. Three patients experienced transient temporomandibular joint discomfort, which improved spontaneously within 2 weeks. CONCLUSION: Surgical exposure of the distal internal carotid artery is enhanced with MS and nasotracheal intubation. We recommend Ivy loop/circumdental wiring as the preferred method for MS. Alternative methods are used when poor dental health is observed.

Dermal tissue fibrosis in patients with chronic venous insufficiency is associated with increased transforming growth factor-beta1 gene expression and protein production.

PURPOSE: Pathologic dermal degeneration in patients with chronic venous insufficiency (CVI) is characterized by aberrant tissue remodeling that results in stasis dermatitis, tissue fibrosis, and ulcer formation. The cytochemical processes that regulate these events are unclear. Because transforming growth factor-beta(1) (TGF-beta(1)) is a known fibrogenic cytokine, we hypothesized that the increased production of TGF-beta(1) would be associated with CVI disease progression. METHODS: Seventy-eight punch biopsy specimens of the lower calf (LC) and the lower thigh (LT) of 52 patients were snap frozen in liquid nitrogen and stratified into four groups according to the Society for Vascular Surgery/International Society for Cardiovascular Surgery CEAP classification (C, clinical; E, etiologic; A, anatomic distribution; and P, pathophysiology). One set of LC biopsy specimens were analyzed for TGF-beta(1) gene expression with quantitative reverse transcriptase-polymerase chain reaction: healthy skin, n = 6; class 4, n = 6; class 5, n = 5; and class 6, n = 7. A second set of biopsy specimens from the LC and LT were analyzed for the amount of bioactive TGF-beta(1) with a certified cell line 64 mink lung epithelial bioassay: healthy skin, n = 8; class 4, n = 23; class 5, n = 13; and class 6, n = 10. The location of TGF-beta(1) was determined at the light and electron microscopy level with immunocytochemistry and immunogold (IMG) labeling. Multiple comparisons were analyzed with a one-way analysis of variance and the Student-Newman-Keuls post hoc tests. The LC and LT comparisons were analyzed with a two-tailed unpaired t test. RESULTS: The TGF-beta(1) gene transcripts for control subjects and patients in classes 4, 5, and 6 were 7.02 +/- 7.33, 43.33 +/- 9.0, 16.13 +/- 7.67, and 7.22 +/- 0.56 x 10(-14) mol/microg total RNA, respectively. The transcripts were significantly elevated in class 4 patients only (P

Sensory impairment: a feature of chronic venous insufficiency.

OBJECTIVE: Clinical and microscopic evidence suggests the existence of sensory neuropathy in patients with severe chronic venous insufficiency (CVI). A clinical evaluation was conducted to determine whether a sensory neuropathy was present and, if so, to determine its extent and distribution. METHODS: The study was performed in a university-affiliated Veterans Affairs Medical Center. Twenty-three limbs were studied in 14 male veterans with mild or moderate CVI. The exclusions included diabetes, previous ipsilateral extremity surgery, or other diseases associated with neuropathy. Sensory thresholds in the limbs with CEAP class 2 disease (n = 11) were compared with the thresholds in the limbs with CEAP class 5 disease (n = 12) at nine different sites on the foot, ankle, calf, thigh, and palm. Thenar and hypothenar thresholds were measured as internal controls. Thresholds were determined by a pressure aesthesiometer consisting of 20 graduated filaments that ranged from 1.65 to 6.65 (log(10)mg)(10) of pressure. A complete, sensory motor assessment of the limb was performed by an experienced neurosurgeon who specialized in peripheral nerve evaluation. The clinical variables assessed were deep tendon reflexes, vibration, proprioception, and light touch. Venous reflux was determined with duplex ultrasound scanning and air plethysmography. RESULTS: Sensory thresholds at the most common site of venous ulceration-just proximal to the medial malleolus--were significantly (P <.05) different between mild (class 2) and severe (class 5) CVI. Sensory abnormalities coincided with the extent of trophic changes and did not reflect specific dermatomal or cutaneous nerve distributions. In addition to light touch or pinprick, vibration sense and deep tendon reflexes were also significantly worse in those with severe CVI. CONCLUSION: Sensory neuropathy is a feature of severe CVI, and its distribution is coincident with trophic changes. Because this is often unappreciated by the patient, it probably contributes to the propensity for deterioration from minor trauma.

Patency and limb salvage for polytetrafluoroethylene bypasses with vein interposition cuffs.

Polytetrafluoroethelene (PTFE) is often utilized in patients with limb-threatening ischemia requiring infrainguinal revascularization in the absence of autologous saphenous vein. To increase long-term patency of PTFE grafts, vein interposition cuffs have been recommended as adjunctive procedures. The purpose of this study was to assess the efficacy of vein interposition cuffs on the long-term patency and limb salvage of patients requiring prosthetic bypass grafts for limb-threatening ischemia. Prosthetic bypass grafts with vein interposition cuffs (PTFE/VC) were performed on 56 limbs in 55 patients (32 men, 23 women; mean age of 67 years) from October 1993 to January 1998. Grafts were prospectively evaluated every 3 months for the first 12 months and biannually thereafter with duplex ultrasonography. PTFE/VC and PTFE bypasses at the popliteal level appear to have comparable patencies. However, PTFE/VC appear to offer an improved patency and limb salvage for infrapopliteal bypasses in patients with critical limb ischemia. When infrapopliteal revascularization is required in the absence of autologous saphenous vein, we recommend the use of PTFE with vein interposition cuffs.

Endoscopic subfascial perforating vein ligation: its complementary role in the surgical management of chronic venous insufficiency.

Endoscopic methods have proven as efficacious as previous open surgical techniques for ligation of calf perforating veins. The reduced incidence of wound complications favors the minimally invasive approach regardless of the technique used. Since isolated disease of the calf perforating veins is rare, most of these procedures are performed in conjunction with superficial venous ablation. These advanced procedures are indicated for patients with skin and subcutaneous manifestations of CVI (CEAP classes 4, 5, and 6). Although the contribution of perforator ligation to the hemodynamic and clinical result is unclear, clinical symptoms and hemodynamics have significantly improved when performed as described.

Hemodialysis access: influence of the human immunodeficiency virus on patency and infection rates.

PURPOSE: The complication rate for patients who are dialysis dependent and infected with the human immunodeficiency virus (HIV) and the role of viral indicators (CD4 counts) as predictors of these complications are poorly characterized. To determine the influence of HIV status and viral activity on graft patency and infection rates, we retrospectively reviewed our results. METHODS: Between June 1993 and March 1997, the charts of 104 patients (HIV+, n = 42; HIV-, n = 62) who required 112 hemodialysis access grafts were reviewed. Of the 112 procedures, 55 (48%) were autologous arteriovenous fistulae (AVF) procedures (HIV+, n = 23; HIV-, n = 32) and 57 (52%) were prosthetic expanded polytetrafluoroethylene grafting procedures (HIV+, n = 27; HIV-, n = 30). Transcutaneous catheter procedures were excluded from the study. The autologous AVF procedures consisted of direct and transposed AVFs. Patency rates were determined by means of life-table analysis. Infection rates and CD4 counts were compared with the chi2 test and the Fisher exact test. Significance was accepted at a P value of.05 or less. RESULTS: The cumulative 12-month and 24-month patency rates for prosthetic grafts in patients who were HIV+ were 49% and 21%, respectively, versus 77% and 45% for patients who were HIV-. The differences in the prosthetic graft patency rates between these two groups were significant (P .05). The mean CD4+ cell counts were 174: CD4+ counts that were less than 200 did not correlate with or predict the development of infection (P >.05). CONCLUSION: Our data showed that prosthetic graft infection rates were increased and patency rates were decreased in patients who were HIV+ as compared with patients who were HIV- and HIV+ with autologous AVFs. There were no differences in patency rates or infection rates in patients who had undergone autologous access procedures. Long-term graft patency rates were not affected by HIV status, and CD4+ lymphocyte counts were not predictive of infection development. Because the prosthetic graft infection rates exceeded those rates of autologous access procedures, we recommend the vigorous use of autologous AVFs in all patients who are HIV+, regardless of CD4+ count.

Surgical intervention in venous ulceration.

The purpose of this article is to review surgical management for dermal ulceration that results from chronic venous insufficiency. Efficacy is gauged by freedom from recurrent ulceration, an objective clinical monitor. Accurate preoperative diagnosis and postoperative assessment of the venous circulation is enhanced by reliable non-invasive examinations. A recently developed clinical classification unifies reporting criteria and has been widely subscribed. Standard surgical ablation of incompetent saphenous and other superficial veins significantly improves clinical and hemodynamic outcome. Perforator incompetence alone is rarely the cause of ulcerative disease, but adjunctive ligation of communicating veins is considered important to the effective elimination of chronic venous insufficiency. New endoscopic techniques reduce morbidity associated with long incisions from the open subfascial procedure. In a more advanced role, deep venous reconstruction is infrequently performed, but is quite durable. Free-tissue transfer appears to be effective after 2 years of observation. Post-thrombotic chronic venous insufficiency continues to confer a more severe prognosis, which emphasizes the importance of accurate and precise diagnosis. Investigation of patients with ulcerative chronic venous insufficiency should be actively pursued, since individualized surgical management will effectively reduce recurrence of ulceration.

Carotid restenosis: operative and endovascular management.

PURPOSE: Surgical management of carotid restenosis (CR) after carotid endarterectomy (CEA) has been associated with a higher perioperative complication rate than that of primary CEA. We recently used carotid angioplasty-stenting (CAS) as an alternative to operative management in patients who had undergone CEA within three years, and we retrospectively compared these results with those of operative management of CR and the overall results of CEA. METHODS: CEA was performed on 1065 adult patients (58% symptomatic, 42% asymptomatic), 62% of whom were men (n = 660) and 38% of whom were women (n = 405), from 1989 to 1997. Before our initiation of a program of CAS, 16 operative procedures (1.9% of CEAs) were performed for CR in 14 adult patients (7 women and 7 men). During the last 20 months, CAS was used in the management of 17 CRs (16 patients; 9 women and 7 men). RESULTS: The 30-day stroke morbidity-death rate for all CEAs (n = 1065) was 1.4%; 11 strokes (1. 0%) occurred (4 major strokes with disability and 7 strokes with minor or no disability), and 4 deaths (0.4%) occurred (2 deaths caused by myocardial infarction, 1 caused by intracranial hemorrhage, and 1 caused by stroke). Operative management of CR (n = 16) included patch angioplasty in 12 cases (autologous vein patches in 10 cases and synthetic patches in 2 cases), whereas interposition grafting was used in 4 cases (saphenous vein in 3 instances and synthetic [polytetrafluoroethylene] in one case). No strokes or deaths were observed. One recurrent laryngeal nerve palsy occurred (6.2%). Among the 16 patients undergoing 17 CAS procedures, the technical procedures were accomplished in all patients. No strokes or deaths occurred. No recurrent restenoses (50% or greater) have been identified within or adjacent to the CAS procedures. CONCLUSION: CR caused by myointimal hyperplasia can be managed by operative techniques or CAS with comparable periprocedural complications. Although long-term follow-up will be required to determine the incidence of recurrent restenosis, CAS may become the preferred procedure in these cases. A randomized clinical trial ultimately will be necessary to determine the role of CAS, as compared with that of operative management.

Retinoblastoma protein: a molecular regulator of chronic venous insufficiency.

PURPOSE: Chronic venous insufficiency (CVI) and varicose vein (VV) formation is characterized histologically by the transformation of smooth muscle cells (SMC) from a contractile to a secretory phenotype and by intense collagen deposition. The subcellular regulation point for these processes may be the retinoblastoma protein (pRb), a known inhibitor of cellular proliferation and regulator of differentiation. We hypothesize that pRb phosphorylation is associated with VV formation and functions as a possible subcellular regulator. METHODS: Patients were separated into two groups. Group 1 (n = 6) consisted of vein specimens obtained from patients undergoing coronary artery bypass grafting. Group 2 (n = 6) consisted of patients with symptomatic CVI and duplex confirmed refluxing greater saphenous veins (GSVs) who required GSV stripping. Western blots of GSV protein extracts were performed with anti-human pRb monoclonal antibodies and the degree of nonphosphorylated and phosphorylated pRb was determined. Results were quantified using image analysis of band intensities (computer calibrated intensity units). The ultrastructural appearance of SMCs and the vein wall architecture were qualitatively analyzed with electron microscopy in both groups. RESULTS: Phosphorylated pRb from varicose GSVs exhibited intensities of 523 +/- 188 units, while phosphorylated pRb from normal GSVs demonstrated intensities of 153 +/- 41 units (P < 0.05). SMCs in varicosed GSVs were surrounded by disorganized collagen deposits and displayed a secretory phenotype with spherical vacuolated cells. SMCs from normal GSVs appeared spindle shaped with a purported contractile phenotype and a well-structured extracellular matrix. CONCLUSION: Our data demonstrate that VV formation, in patients with CVI, is associated with phosphorylated pRb and the transformation of SMCs from a contractile to a secretory ultrastructural morphology. The data suggest that SMC dedifferentiation is regulated by pRb and the disinhibition of this protein (phosphorylation) may be an significant factor in the development of lower extremity varicosities.

Patency of infrainguinal polytetrafluoroethylene bypass grafts with distal interposition vein cuffs.

Polytetrafluoroethylene (PTFE) prosthetic bypasses in the lower extremity have poor patency rates, particularly in limb salvage cases. Patency and limb salvage rates of PTFE bypasses supplemented by distal interposition vein cuffs were assessed in patients requiring revascularization for critical limb ischemia, in the absence of a suitable autologous saphenous vein. Between October 1993 and April 1996, 163 patients underwent 185 infrainguinal bypasses. Forty-three limbs in 42 patients (12 women, 30 men; mean age 67 years) did not have a suitable autologous saphenous vein (24%) and had femoropopliteal (20) and infrapopliteal (23) bypasses performed. Patients were examined prospectively at 3-month intervals during the first year and at 6-month intervals thereafter to determine graft patency and limb salvage. Postoperative anticoagulation with warfarin was used in 26 patients. Indications for operation included limb salvage in 41 extremities (21 rest pain/ulceration or gangrene, 20 rest pain alone), and disabling claudication in two. Patients were followed clinically for 2-30 months (mean 10 months). Cumulative 2-year life-table patencies for all grafts, femoropopliteal and infrapopliteal bypasses were 64%, 75% and 62%, respectively. Previous primary patencies at the authors' institution for PTFE bypasses without vein cuffs were 35%, 46% and 12% for the same categories. Cumulative life-table limb salvage for all PTFE/vein cuff bypasses in the present series was 76% compared with 37% in previous PTFE bypasses without vein cuffs. Adjunctive use of distal interposition vein cuffs improves prosthetic graft patency, while producing satisfactory limb salvage. Postoperative anticoagulation did not influence graft patency. PTFE/vein cuff for lower-extremity revascularization shows good 2-year patency and is an acceptable alternate conduit in patients with critical limb ischemia when autologous saphenous vein is absent.

A strategy for increasing use of autogenous hemodialysis access procedures: impact of preoperative noninvasive evaluation.

PURPOSE: We studied the efficacy of preoperative noninvasive assessment of the upper extremity to identify arteries and veins suitable for hemodialysis access to increase our use of autogenous fistulas (AF). METHODS: From Sep. 1, 1994, to Apr. 1, 1997, 172 patients who required chronic hemodialysis underwent segmental upper extremity Doppler pressures and duplex ultrasound with mapping of arteries and veins. The following criteria were necessary for satisfactory arterial inflow: absence of a pressure gradient between arms, patent palmar arch, and arterial lumen diameter 2.0 mm or more. The criteria necessary for satisfactory venous outflow were venous luminal diameter greater than or equal to 2.5 mm for AF and greater than or equal to 4.0 mm for synthetic bridging grafts (BG) and continuity with distal superficial veins in the arm. Intraoperative and duplex ultrasound measurements were compared. Contemporary experience was compared with the 2-year period (1992 to 1994) before implementation of the protocol. RESULTS: During the period from Sep. 1, 1994, to Apr. 1, 1997, 108 patients (63%) had AF, 52 (30%) had prosthetic BG, and 12 (7%) had permanent catheters (PC) placed. Early failure was seen in 8.3% of AFs. Primary cumulative patency rates were 83% for AF and 74% for BG at 1 year (p < 0.05), with a mean clinical follow-up of 15.2 months. No postoperative infections were observed with AF, whereas six infections (12%) were observed with BG and two (17%) with PC insertion. During the period from June 1, 1992, to Aug. 31, 1994, 183 procedures were performed with a distribution of 14% AF, 62% BG, and 24% PC. In this earlier period the AF early failure rate was 36%, and the patency rates were 48%, 63%, and 48% for AF, BG, and PC, respectively (mean follow-up, 13.8 months). CONCLUSION: A protocol of noninvasive assessment increased use of AFs. The cumulative patency rate of AFs was improved, and early failure rates were reduced when compared with the preceding institutional experience. Routine noninvasive assessment is recommended to document adequacy of arterial inflow and delineate venous outflow to maximize opportunities for AF.

Morphometric assessment of the dermal microcirculation in patients with chronic venous insufficiency.

PURPOSE: Ultrastructural assessments of the dermal microcirculation in patients with chronic venous insufficiency have been limited to qualitative morphologic descriptions of venous ulcer edges or venous stasis dermatitis. The purpose of this investigation was to quantify differences in endothelial cell structure and local cell type with emphasis on leukocytes and their relationship to arterioles, capillaries, and postcapillary venules (PCVs). METHODS: Two 4.0 mm punch biopsies were obtained from areas of dermal stasis skin changes in the gaiter region of the leg, as well as from noninvolved areas of skin in the ipsilateral thigh, from 35 patients: CEAP class 4 (11 patients), class 5 (9 patients), class 6 (10 patients), and five normal skin biopsies from patients without chronic venous insufficiency. Electron microscopy was performed on sections at 6700x and 23,800x magnification. At 6700x endothelial cell thickness was determined, and the number of fibroblasts, leukocytes, and mast cells were recorded relative to their proximity to arterioles, capillaries, and PCVs. Similarly, at 23,800x endothelial cell vesicle density, interendothelial junctional widths, and basal lamina thickness (cuff width) were measured. Preliminary evaluation for the presence of transforming growth factor-beta 1 (TGF-beta 1) was performed on three patients using reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Quantitative measurements demonstrated increased mast cell content for class 4 and 5 patients around arterioles and PCVs and increased macrophage numbers for class 6 patients around PCVs (p < 0.05). Fibroblasts were the most common cells observed; however, no differences were demonstrated between groups. No differences were observed in interendothelial junctional widths or vesicle densities in arterioles, capillaries, or PCVs. Basal lamina thickness was increased only at the capillary level (p < 0.05). The results of RT-PCR for TGF-beta 1 messenger RNA were positive in the three patients studied. CONCLUSIONS: Our data suggest that (1) mast cells play a role in the pathogenesis of chronic venous insufficiency; (2) the effects of mast cells, macrophages, or both may be mediated in part by TGF-beta 1; and (3) capillary cuff formation is not associated with widened interendothelial gap junctions, but may be a result of enhanced vesicular transport rate or conformational changes in the interendothelial glycocalyx.

Carotid arterial trauma: assessment with the Glasgow Coma Scale (GCS) as a guide to surgical management.

Management of carotid arterial injuries associated with focal neurological deficit or altered state of consciousness (SCON) remains unresolved. Experience with these injuries in one particular hospital was reviewed and the Glasgow Coma Scale (GCS) utilized to assist with clinical stratification of these patients. A literature review was also conducted to better define indications for repair or ligation of carotid injuries. From 1978 to 1990, 34 patients with carotid arterial injuries were reviewed with reference to the GCS, focal deficit, hypotension, anatomic site and mechanism of injury. The literature from 1952 to 1993 was surveyed for carotid artery injuries (1316 patients). Outcome of treatment with or without repair was compared with pre-operative neurologic status. Thirty-four patients with injuries of the common (24) or internal (10) carotid arteries were managed with repair (68%), ligation (24%) or observation (9%). The SCON was normal in 18 patients; 16 patients (88%) underwent repair and all remained normal. All patients with GCS 9-14 regained a normal SCON after surgical repair, while 10 patients with GCS < 8 had repair (5), ligation (3), and non-operative management (2); five returned to normal, four died and one remained comatose. However, outcomes correlated poorly with management. Of 1316 patients cited in the surgical literature, patients with no deficit and patients with pre-operative deficits did significantly better after repair as compared with ligation (P<0.001). In comatose patients, management did not affect outcome. It is concluded that carotid arterial injuries should be repaired in patients with normal neurologic evaluation, focal pre-operative neurologic deficits and in patients with GCS > 9. Comatose patients with GCS < 8 do poorly regardless of management. The GCS provides an objective for stratification of patients with altered SCON who benefit from repair of carotid arterial injuries.

Outcome of complex venous reconstructions in patients with trauma.

PURPOSE: The role of complex venous reconstructions (CVRs) in patients with major trauma remains a controversial topic. This study evaluates the patency and clinical outcome of CVRs in a major urban trauma center. METHODS: Between 1979 and 1994 the records of 92 patients with 100 injuries to the iliac, femoral, and popliteal venous system were reviewed. The incidence of edema, pulmonary embolism, and limb loss was documented in 75 men and 17 women (mean age of 27 years, range 14 to 59 years). The 30-day patencies were assessed in all patients with either impedance plethysmography (n = 16), venography (n = 40), or duplex scan (n = 36). Long-term patencies were assessed in 14 patients monitored for 0.5 to 9 years (mean 3.2 years). RESULTS: Mechanisms of injury consisted of 58 gunshot wounds, 23 stab wounds, 6 shotgun wounds, and 5 blunt injuries. There were 112 associated injuries, 41 of which were concomitant arterial injuries. Forty-five of the 100 venous injuries were repaired with CVRs and included 6 (13%) spiral vein grafts, 8 (18%) panel vein grafts, 8 (18%) reversed saphenous vein interposition grafts, 8 (18%) end-to-end repairs, and 15 (33%) vein patch repairs. Thirty-day patency rates for these repairs were 50%, 50%, 75%, 88%, and 87%, respectively, and an overall patency rate of 73% was observed. The remaining 55 injuries were treated with ligation (n = 27) or lateral venorrhaphy (n = 28). The cumulative 30-day patency rate for all venous repairs was 81% (59 of 73). Fourteen patients, nine of whom had CVRs, were available for long-term follow-up. In this group CVRs demonstrated a 100% patency. One patient with a spiral vein graft repair of the common femoral vein had severe reflux causing intermittent edema and mild lipodermatosclerosis. No pulmonary emboli, limb loss, or deaths were identified in patients undergoing CVRs. CONCLUSION: Patients with CVRs had a 30-day patency rate of 73%. Of this group panel and spiral vein grafts were less successful, exhibiting only a 50% 30-day patency rate, whereas end-to-end and vein patch repairs were successful in 88% and 87% of cases, respectively. Our overall evaluation suggests that use of CVRs results in successful venous repair; however, the postoperative patency of interposition panel and spiral grafts suggests selective use of these techniques.

Vein transposition in the forearm for autogenous hemodialysis access.

PURPOSE: We describe a technique of superficial venous transposition in the forearm used for the formation of an arteriovenous fistula for hemodialysis access. These modifications of the single-incision radiocephalic fistula are designed to increase options for arteriovenous fistulas by using veins and arteries that are suitable for use but are not in immediate proximity. METHODS: Arteries and veins suitable for a primary arteriovenous fistula were identified and mapped using duplex ultrasound in 89 patients. Separate incisions were used in the majority of cases, and the selected forearm vein was mobilized, angiodilated, and transposed into a subcutaneous tunnel on the volar aspect of the forearm. Before initiation of hemodialysis, duplex ultrasound scanning was performed, and the location that was most suitable for cannulation was identified. Repeat scans were performed at 3-month intervals for analysis of patency. RESULTS: Superficial venous transpositions were performed using a single incision in 13 instances in which the vein was in immediate proximity to the radial artery (type A). Dorsal-to-volar forearm transposition (type B) was performed in 30 veins with anastomoses to the radial (n = 26), ulnar (n = 2), or brachial (n = 2) arteries. Volar-to-volar forearm transposition (type C) was performed in the remaining 46 veins, with anastomoses to the radial (n = 42), ulnar (n = 2), or brachial arteries (n = 2). Successful hemodialysis was accomplished in 81 of 89 patients (91%). The primary cumulative patency rate was 84% at 1 year and 69% at 2 years. The mean duration of follow-up was 14.3 months. CONCLUSIONS: The use of superficial venous transposition for the formation of autogenous hemoaccess was associated with ease of cannulation by dialysis personnel, high maturation rates, reduced early failure rates, and enhanced patency rates. We recommended the use of these technical modifications to increase the use of autogenous fistulas in the forearm.

A program of operative angioplasty: endovascular intervention and the vascular surgeon.

PURPOSE: Vascular surgeons are ideally suited to select and perform endovascular interventions either as primary therapy or as an adjunct to bypass surgery. Attaining proficiency in endovascular techniques is an important goal in the training of vascular surgeons. We report our initial experience with a program of endovascular intervention performed in the operating room by vascular surgeons. METHODS: During the previous three years, we performed 109 angioplasty procedures, 60 aortoiliac (55%), 32 femoropopliteal (29%), and 17 popliteal/tibial (16%), using guidewires and angioplasty balloons directed by intraoperative digital subtraction C-arm arteriography with road-mapping capabilities. Indications for angioplasty included disabling claudication in 59 patients (54%), rest pain in 18 (17%), and tissue loss in 32 (29%). Angioplasty was accompanied by stent placement in 39 of 60 aortoiliac procedures (65%) and in two of 32 femoral procedures (6%). In 16 cases (15%), the endovascular procedure was performed in conjunction with a bypass procedure. In selected cases (15, 14%), duplex scanning was the sole diagnostic method used before surgery to identify the lesion, eliminating the need for preoperative arteriographic scans. Segmental pressure measurements, duplex ultrasound scans, and treadmill exercise testing as indicated were performed before and after surgery. The efficacy of the endovascular intervention was assessed at 3-month intervals during the first year and at 6-month intervals thereafter. RESULTS: A successful results was defined using criteria recommended by the Ad Hoc Subcommittee on Reporting Standards for Endovascular Procedures from the Society for Vascular Surgery/International Society for Cardiovascular Surgery. This included the combination of symptomatic improvement, obtaining an anatomically successful result with < 30% residual lumen stenosis, and elimination of the translesion gradient with an improvement in high thigh-brachial index or ankle-brachial index greater than 0.15. Initial success was achieved in 55 of 60 aortoiliac (92%), 28 of 32 femoropopliteal (88%), and 16 of 17 popliteal/tibial (94%) angioplasty procedures. Clinical follow-up has been achieved in all cases, with continued clinical success rates of 80%, 75%, and 82% for aortoiliac, femoropopliteal, and popliteal/tibial angioplasty procedures, respectively, with a mean follow-up of 15.7 months. CONCLUSION: These results confirm the value of a program in which C-arm technology was used by vascular surgeons in the performance of angioplasty and stenting procedures in the operating room. This experience in therapeutic endovascular intervention will facilitate the credentialing process for future vascular surgeons.