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Charles R Handorf

Publications and source records attributed to Charles R Handorf.

9 recordsLinked to original sources
PubMed2006

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Delivery of Health Care↗
PubMed2006

The effect of bacterial contamination on neointimal hyperplasia in vascular grafts.

Neointimal hyperplasia (NH) is the most significant contributing factor to long-term vascular graft failure. Inflammation is known to be important in its development; however, the role of bacterial infection is unclear. We examined the effect of contamination with common organisms on the development of NH in expanded polytetrafluoroethylene grafts. Thirty adult pigs were randomized into one of four groups: no infection, contamination with Staphylococcus aureus, mucin-producing Staphylococcus epidermidis, or Pseudomonas aeruginosa. An expanded polytetrafluoroethylene graft (6 mm x 3 cm) was placed as a common iliac artery interposition graft and was inoculated with 1-2 x 10(8) of the selected organism before closure. Grafts were explanted 6 weeks postoperatively. Microbiologic, histological, and morphometric evaluations were performed. All grafts were patent at the time of euthanasia. The mean areas of NH were 5.45 mm(2) in sterile grafts, 8.36 mm(2) in S. aureus, 7.63 mm(2) in S. epidermidis, and 11.52 mm(2) in P. aeruginosa grafts. Comparison of means via analysis of variance showed that P. aeruginosa grafts had significantly higher formation of NH than sterile grafts (P = 0.025). NH production in infected grafts appears to be organism specific and is significantly higher with P. aeruginosa than common Gram-positive organisms. Increased NH from subclinical infection may be a significant factor contributing to late graft failures.

Anastomosis, Surgical↗
PubMed2005

Rapamycin-coated expanded polytetrafluoroethylene bypass grafts exhibit decreased anastomotic neointimal hyperplasia in a porcine model.

OBJECTIVE: We tested the hypothesis that rapamycin coated onto, and eluted from, expanded polytetrafluoroethylene (ePTFE) grafts would diminish neointimal hyperplasia in a porcine model. METHODS: Rapamycin (also called sirolimus) was coated onto the luminal surface of 6-mm-internal-diameter thin-walled ePTFE grafts by using an adhesive polymer that allows timed release of the drug. An adhesive polymer that allows timed release of rapamycin from ePTFE was developed with commercially available chemicals and applied on 6-mm ePTFE grafts. Graft integrity was characterized by scanning electron microscopy, and rapamycin levels were quantified by using high-performance liquid chromatography. Twenty-two mongrel pigs were randomized into three groups: untreated ePTFE (n = 6), adhesive-only coated ePTFE (n = 6), or adhesive- and rapamycin-coated ePTFE (n = 10). End-to-side unilateral aortoiliac bypasses were performed by using 6-mm-internal-diameter ePTFE grafts and standardized anastomotic lengths. Unilateral end-to-side aortoiliac ePTFE grafts (6-mm internal diameter) were inserted by using polypropylene sutures, 6-0 proximally and 7-0 distally; all anastomoses were 12 mm long. All animals received aspirin (325 mg orally) daily. All animals were given oral aspirin (325 mg) daily beginning on the day before surgery. At 28 days, the animals were killed, and the grafts were explanted in continuity with the adjacent aortic cuff and the outflow iliac artery. Variables compared between groups included graft patency, distal anastomotic length and cross-sectional narrowing, and intimal thickness at the arterial-graft junction indexed to the adjacent graft thickness. Microscopic analysis was performed with hematoxylin and eosin and Masson trichrome stains on paraffin sections. A pathologist blinded to experimental groups graded sections for collagen deposition, neointima formation, inflammatory cellular infiltrates, medial necrosis, and aneurysmal degeneration. RESULTS: All animals survived until they were killed without clinical evidence of limb ischemia or graft infection. Preplanned t tests in the context of one-way analysis of variance showed no difference in outcome measures between the untreated ePTFE and adhesive-only coated ePTFE groups; therefore, they were combined in further comparisons with the adhesive- and rapamycin-coated ePTFE group. The Rapamycine eluting expanded polytetrafluoroethylene group had longer anastomoses (85.6% vs 60.6% of the initial anastomotic length maintained; P < .0001) and less cross-sectional narrowing in the outflow graft (16.2% vs 28.5%; P = .0007) when compared with the other two groups by using two-tailed Student t tests. There was no evidence of medial necrosis or aneurysmal degeneration. All patent grafts had complete endothelialization on hematoxylin and eosin sections. Rapamycin was detectable and quantifiable in the arterial wall at 28 days after implantation. CONCLUSIONS: Rapamycin can be coated onto and eluted from ePTFE by using a nonionic polymer and a simple coating technique. At 4 weeks after implantation, the rapamycin-eluting ePTFE grafts demonstrate gross, pathologic, and morphometric features of diminished neointimal hyperplasia when compared with non-drug-eluting ePTFE. Four weeks after implantation in a porcine model, rapamycin-eluting ePTFE grafts demonstrated gross, pathologic, and morphometric features of diminished neointimal hyperplasia when compared with untreated and adhesive-only coated ePTFE grafts. CLINICAL RELEVANCE: Rapamycin-eluting ePTFE grafts decrease neointimal hyperplasia in a porcine model. Further studies are needed to evaluate whether patency will be improved. Rapamycin-eluting ePTFE grafts may allow the use of prosthetic grafts in situations in which autologous vein is unavailable and in which neointimal hyperplasia is pronounced, such as in small-diameter (<6-mm) vessels typical of infrapopliteal interventions.

Anastomosis, Surgical↗
PubMed2004

Small intestinal submucosa for vascular reconstruction in the presence of gastrointestinal contamination.

INTRODUCTION: Surgical options for vascular reconstruction in a contaminated field are limited and include prosthetic reconstruction or ligation with extra-anatomic bypass. With prosthetic insertion, rates of graft infection and failures (pseudoaneurysms and thrombosis) are high. In the emergent situations, extra-anatomic bypass is time-consuming and complex, and it produces marginal long-term results. Small intestinal submucosa (SIS) is a cell-free collagen matrix derived from porcine small intestine. Preliminary studies have demonstrated its ability to be remodeled into host tissue. In this study, we compared SIS to polytetrafluoroethylene (PTFE) as a vascular patch for arterial repair in the presence of massive gastrointestinal contamination to evaluate graft patency, incorporation, infection, and aneurysm formation. METHODS: Adult mongrel pigs underwent general anesthesia with Isoflurane and were then randomized to 1 of 3 groups: control, contamination (colon puncture with stool contamination of the pelvis), or shock + contamination (40% blood volume for 1 hour, then resuscitation with shed blood and crystalloid, plus contamination). All groups then underwent a left common iliac arteriotomy and further randomized to a 1 x 3-cm patch angioplasty with either SIS or PTFE. All received cefotetan for 24 hours. All animals were sacrificed between 2 and 4 weeks, and necropsy was performed. Grafts were cultured, and microscopic analysis with hematoxylin and eosin and trichrome was performed. Outcomes included pulse quality (normal or diminished) compared with opposite side, graft infection, and pseudoaneurysm; all were determined by a blinded investigator. RESULTS: Forty animals were randomized, and 1 died of abdominal sepsis. All control animals had normal distal pulses, no pseudoaneurysms, and no patch infections. The pseudoaneurysm rate for the contaminated PTFE patches was 25% compared with 0% in the SIS group (P = 0.09). Patch infection occurred in 73% of all PTFE patches compared with 8% of SIS patches (P < 0.03). Organisms present in the infected grafts included Escherichia coli, Bacteroides species, and other Gram-negative enterics. Histopathology demonstrated the presence of neointima in both SIS and PTFE. Only SIS was completely incorporated, with infiltration of collagen fibrils and lymphocytes. CONCLUSIONS: SIS was associated with improved graft patency, less infection, complete incorporation, and no false aneurysm formation when compared with PTFE. This may be due to its ability to provide a durable scaffold for cellularization and tissue remodeling. This material may offer a superior alternative to more complex vascular reconstruction techniques in contaminated fields.

Animals↗
PubMedDate not supplied

Skin basement membrane zone: a depository for circulating microbial antigen evoking psoriasis and autoimmunity.

BACKGROUND: Elevated levels of antibody to streptococcal exoenzymes have been found in patients with psoriasis or psoriatic arthritis. Research on the role of streptococcal antigen in psoriasis has been hampered by a potential molecular mimicry between streptococcal epitopes and human epidermal keratin. OBJECTIVE AND METHODS: Evidence of microbial product was sought in skin biopsies of psoriasis patients thought clinically to have either streptococcal carrier state or gastrointestinal candidal colonization. A polyclonal antibody to streptococcal-derived exoenzymes unlikely to share antigenic structures with normal human skin, and an anticandidal antibody, were used with linked streptavidin biotin amplification stain. RESULTS: The predicted microbial product appeared heavily in lesional epidermis, but unexpectedly also as a thin deposit along the skin basement membrane zone (SBMZ) of apparently unaffected skin. Staining was negative for nonpsoriatic subjects. CONCLUSIONS: The findings support a direct effect of microbial antigen in psoriasis. They also suggest an important role for SBMZ as a very large adhesive surface in the first step of a process of percutaneous epidermal elimination of foreign antigens and microbial toxins. The many autoimmune phenomena seen so often at the SBMZ are probably a physiologic part of this important immune function. Efforts to enhance the adhesive properties of SBMZ should be exploitable for both diagnostic and therapeutic benefit.

Antigens, Bacterial↗