Gregory Simonian

Dermal tissue fibrosis in patients with chronic venous insufficiency is associated with increased transforming growth factor-β1 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 </=.05). The amount of active TGF-beta(1) in picograms/gram of tissue from LC and LT biopsy specimens as compared with healthy skin biopsy specimens were as follows: healthy skin, <1. 0 pc/g; class 4: LC, 5061 +/- 1827 pc/g; LT, 317.3 +/- 277 pc/g; class 5: LC, 8327 +/- 3690 pc/g; LT, 193 +/- 164 pc/g; and class 6: LC, 5392 +/- 1800 pc/g; LT, 117 +/- 61 pc/g. Differences between healthy skin and the skin of the patients in classes 4 and 6 were significant (P </=.05 and P </=.01, respectively). Differences between the LC and LT biopsy specimens within each CVI group were also significant: class 4, P </=.003; class 5, P </=.008; and class 6, P </=.02. Immunocytochemistry results of healthy skin showed TGF-beta(1) staining of epidermal basal cells only. CVI dermal biopsy results demonstrated positive staining in epidermal basal cells, fibroblasts, and leukocytes. Many leukocytes had positive staining of intracellular granules, which appeared morphologically similar to mast cells. IMG labeling results demonstrated gold particles in the leukocytes and collagen fibrils of the extracellular matrix. CONCLUSION Our study indicated that activated leukocytes traverse perivascular cuffs and release active TGF-beta(1). Positive TGF-beta(1) staining results of dermal fibroblasts were observed and suggest that fibroblasts are the targets of activated interstitial leukocytes. Increased protein production, despite normal levels of gene transcripts in patients in classes 5 and 6, suggests that alternate mechanisms other than gene transcription regulate protein production. A potential mechanism for quick access and release is storage of TGF-beta(1) in the extracellular matrix. IMG labeling to collagen fibrils support this possibility. Furthermore, TGF-beta(1) was exclusively elevated in areas of clinically active disease, indicating a regionalized response to injury. These data suggest that alterations in tissue remodeling occur in patients with CVI and that dermal tissue fibrosis in CVI is regulated by TGF-beta(1).

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.

A Comparison Of Survival At Different Degrees Of Hemorrhagic Shock In Germ-free And Germ-bearing Rats

ABSTRACT We have previously reported superior survival after one level of hemorrhagic shock in germ-free (GF) rats compared with germ-bearing (GB) rats. The objective of this study was to determine the effect of the GF state on survival at different degrees of hemorrhagic shock. GF and GB rats were bled to a mean arterial blood pressure of 30 mmHg. Shock was terminated after 10, 20, 40, or 80% of the maximum shed blood volume was reabsorbed spontaneously. Both shock time and time to decompensation were significantly longer in GF rats (p < .05). Comparative survival was greater for GF rats at most levels of shock (p < .01). This superiority in survival was greatest at moderate shock levels and decreased at severe shock levels. There may be several reasons for the increased tolerance of GF animals to hemorrhagic shock such as metabolic or immunologic variations. It is hard to avoid the fact, however, that the most notable difference between the GF and GB rat is the presence or absence of bacteria.

TCT-805 Use of Orbital Atherectomy to Aid in Endovascular Aortic Endograft Delivery in Patients with Severe Iliac Artery Occlusive Disease

Stent grafts for repair of abdominal aortic aneurysms are continuing to evolve to lower profile designs to facilitate easier endograft delivery. Despite improvements in design, a subset of patients undergoing endovascular abdominal aortic aneurysm repair (EVAR) exist with severely calcified iliac

Adjunctive Use of Thoracic Stent Cuffs to Treat Infrarenal Aortic Necks Too Large for Standard EVAR

Objectives: To evaluate early outcomes and short-term durability of thoracic stent cuffs in patients with abdominal aortic aneurysms (AAA) and infrarenal necks too large for standard endovascular aneurysm repair (EVAR) who were symptomatic, not suitable for open surgery, and could not wait for a custom fenestrated device to be created. Methods: From July 2010 to December 2012, 13 patients with juxtaor pararenal AAA underwent endovascular repair with thoracic aortic endografts as proximal aortic cuffs in conjunction with standard EVAR devices. The patients were symptomatic and were deemed unfit for open surgery due to severe cardiopulmonary and/or renal comorbidities. All patients had infrarenal neck diameters greater than the indications for use for standard aortic endografts. Primary end points were technical success (as defined by aneurysm exclusion without endoleak), follow-up aneurysm exclusion by computed tomographic angiogram, and 30-day and longterm mortality. Results: Thirteen patients (10 men, 3 women) with a mean age of 77.1 years underwent EVAR who presented with symptomatic juxtaor pararenal abdominal aortic aneurysms. The mean aneurysm size was 7.2 cm, and the mean infrarenal aortic neck diameter was 35.5 mm measured by centerline analysis. Technical success was achieved in 100% of cases. The 30-day mortality was 8% (one of 13 patients). At a mean follow-up of 524 days, there have been no endoleaks or other aneurysm related mortalities. There was one death due to stroke at 605 days postop. Conclusions: Complex endovascular repair of juxta and pararenal AAA using thoracic stents cuffs can be safely and successfully performed in symptomatic patients medically unfit for open repair. Using thoracic stent cuffs below the visceral vessels may reduce the complexity and possibly the risk of repair when compared with fenestrated endografts. These techniques can be used for urgent and emergent cases where the wait time for fenestrated technology is prohibitive. Although our results have demonstrated short-term success, long-term durability of this technique with further evaluation is required.