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Paul W White

Publications and source records attributed to Paul W White.

6 recordsLinked to original sources

Hypoxia attenuates insulin-induced proliferation and migration of human diabetic infrapopliteal vascular smooth muscle cells.

The proliferative effects of insulin on infrapopliteal vascular smooth muscle cells (VSMCs) have been established. We examined the effect of hypoxia in the presence and absence of insulin on the proliferation and migration of human diabetic infrapopliteal VSMCs in vitro. VSMCs isolated from the infrapopliteal arteries of male diabetic patients of identical disease and clinical patterns undergoing below-knee amputation were harvested and grown to subconfluence. Cells were then exposed to control medium (M199/1% fetal bovine serum/2% antibiotic-antimycotic) or control medium with 100 ng/mL insulin in oxygen concentrations of 17% (normoxia), 5%, and 1%. Cellular proliferation was assayed using [methyl-3H]-thymidine incorporation. Migration assays were performed using the Corning Costar Transwell system. Lactate dehydrogenase was assayed and compared among groups as a marker for cytotoxicity. VSMCs in normoxic conditions (17%) had a significant increase in both proliferation (100 +/- 6.5% vs. 124 +/- 4.7%, p = 0.007) and migration [73.2 +/- 9.3 vs. 118.1 +/- 14.9 cells/4 high-power fields (HPF), p = 0.03] when exposed to insulin. Of cells exposed to insulin, those at both 5% (75.9 +/- 7.9%, p = 0.0001) and 1% (73.6 +/- 4%, p < 0.0001) hypoxia proliferated at a significantly decreased rate compared with cells at normoxia (124 +/- 4.7%). Migration of these insulin-exposed cells was significantly decreased at 1% hypoxia (63.1 +/- 9.0 cells/4HPF) compared to those at normoxia (118.1 +/- 14.9 cells/4HPF, p = 0.006) and 5% hypoxia (101.2 +/- 10.0 cells/4HPF, p = 0.01). There were no significant differences in migration between cells at normoxia and 5% hypoxia. Finally, hypoxia and insulin exerted no significant effect on cytotoxicity. The proliferative and promigratory effects of insulin on diabetic VSMCs are attenuated in hypoxic conditions in a manner unrelated to cytotoxicity.

Cell Hypoxia↗

Aortic angiosarcoma presenting as distal arterial embolization.

Aortic angiosarcoma is a rare, malignant neoplasm of the vasculature, with 24 case reports in the literature. Patients usually present with either aneurysmal or occlusive disease. Treatment consists of en bloc resection of the vessel and contiguous structures with postoperative chemoradiation therapy. Despite surgery and adjunctive measures, prognosis remains dismal as a result of early metastasis and late diagnosis. We report a case of aortic angiosarcoma that presented with distal thromboembolic phenomenon.

Aged↗

Venous hypertension associated with arteriovenous hemodialysis access.

Venous hypertension is a significant problem for the patient on chronic hemodialysis. This condition can result in impairment of arteriovenous access function, disabling upper extremity edema with bluish discoloration and pigmentation of the skin, and, in advanced cases, ulceration of the finger tips and neuralgias. Venous hypertension usually results from central vein stenosis or valvular incompetence in the arteriovenous access outflow vein. A high index of suspicion is required to identify patients at risk for venous hypertension. A history of ipsilateral central venous catheter placement, or physical signs such as visible distended shoulder venous collaterals, and upper extremity edema are suggestive. Diagnosis is confirmed with Duplex ultrasound or contrast venography. The primary goal of diagnosis and therapy of venous hypertension is symptomatic relief while maintaining the functionality of the access. Treatment includes percutaneous catheter-based and open surgical techniques. Open surgical techniques, while more invasive, remain the gold standard as long-term patency after angioplasty, with or without covered stents, remains unproven.

Arteriovenous Shunt, Surgical↗

Medical factors affecting patency of arteriovenous access.

Arteriovenous access failure is multifactorial in nature with contributions from both medical and surgical etiologies. Medical causes of arteriovenous access failure are rare, and therefore infrequently identified as a major contributing source of malfunction. Although they account for only 10-15% of all cases of access failure, their importance should not be underestimated, especially in cases where a surgical source cannot be identified. Most medical causes are derived from Virchow's triad of endothelial cell injury, stasis, and hypercoaguability. Endothelial cell injury occurs through oxidative stress, activated platelets, increased levels of circulating tumor necrosis factor-alpha, and preexisting intimal hyperplasia. Stasis can occur through prolonged access compression, hypotension, or hypoalbuminemia. Finally, patients with renal failure requiring hemodialysis are frequently at increased risk for hypercoaguable states, except for situations of platelet dysfunction, and therefore access failure. Potential treatments include identifying and removing the offending source, as well as innovative, new medications to prevent their reoccurrence. Treatment is aimed at improving quality of life, as well as decreasing morbidity and hospital admissions in this difficult patient population.

Anticoagulants↗

The effect of changing gamma count threshold on sentinel lymph node accuracy.

PURPOSE: Sentinel lymph node (SLN) biopsy has been increasingly accepted in many centers as an alternative to axillary lymph node dissection in the nodal staging of breast cancer. The goal of SLN biopsy is to accurately stage the axilla while minimizing postoperative morbidity. Theoretically, the continuing search for SLNs disrupts additional lymphatics and impacts on operative time. The gamma count threshold is a predefined threshold percentage of the ex vivo count of the "hottest" SLN, which when applied to each individually excised lymph node determines whether a given lymph node is the SLN or a non-SLN. The higher the threshold percentage, the less the number of lymph nodes will meet the criteria of being an SLN. This study examines the hypothesis that changing the gamma count threshold from 10% to 50% will not significantly affect accuracy or the false-negative rate. METHODS: We retrospectively reviewed the charts of patients who underwent SLN biopsy with or without completion axillary lymph node dissection from March 1995 to January 2001 at Walter Reed Army Medical Center. Data were collected on gamma counts for each SLN and histopathology of each SLN. For each SLN ex vivo gamma count, percentage of the ex vivo gamma count of the "hottest" SLN was calculated. RESULTS: The SLN identification success rate was 94% (163 out of 174 patients). On average, 2.07 SLNs were removed per patient and 58% of patients had more than 1 SLN removed (94 out of 163 patients). Only 10% had 4 or more SLNs removed (17 out of 163 patients). Sentinel lymph node metastasis was found in 21% of patients (35 of 163 patients). Of these 35 patients with positive SLNs, 8 patients had a negative "hottest" SLN when a less radioactive SLN was positive for metastasis. Changing the gamma count threshold from 10% to 50% lowers the extrapolated accuracy from 98% to 95% and increases the extrapolated false-negative rate from 8% to 21%. CONCLUSIONS: The accuracy and false-negative rate of SLN biopsy varies based on the lower limit gamma threshold. Maintaining our 10% gamma count threshold results in acceptable accuracy and false-negative rates comparable to reported literature.

Journal Article↗