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David L Gillespie

Publications and source records attributed to David L Gillespie.

At least 19 recordsLinked to original sources
PubMed2007

Celecoxib inhibits meningioma tumor growth in a mouse xenograft model.

BACKGROUND: Treatments for recurrent meningiomas are limited. We previously demonstrated universal expression of COX-2 in meningiomas and dose-dependent growth inhibition in vitro with celecoxib, a COX-2 inhibitor. We therefore tested the effects of celecoxib on meningioma growth in a mouse xenograft model. METHODS: Meningioma cell lines (IOMM-Lee, CH157-MN, WHO grade I primary cultured tumor) were transplanted into flanks of nude mice fed mouse chow with celecoxib at varying concentrations (0, 500, 1000, 1500 ppm) ad libitum. Tumors were measured biweekly and processed for MIB-1, Factor VIII, COX-2, and VEGF, and assayed with transferase-mediated dUTP-biotin nick-end labeling (TUNEL). RESULTS: Celecoxib reduced growth of mean tumor volume by 66% (P < .05), 25% (P > .05), and 65% (P < .05) compared with untreated controls in IOMM-Lee, CH157-MN, and benign tumors, respectively. IOMM-Lee tumors removed from celecoxib treatment regained a growth rate similar to the control. Blood vessel density decreased and apoptotic cells increased in treated flank tumors. Diminished COX-2 expression and VEGF were observed in treated IOMM-Lee tumors. Mean plasma celecoxib levels were 845, 1540, and 2869 ng/mL, for low-, medium-, and high-dose celecoxib, respectively. CONCLUSIONS: Celecoxib inhibits meningioma growth in vivo at plasma levels achievable in humans. Celecoxib-treated tumors were less vascular with increased apoptosis. IOMM-Lee tumors treated with celecoxib showed decreased COX-2 and VEGF expression. COX-2 inhibitors may have a role in the treatment of recurrent meningiomas.

Animals↗
PubMed2006

Physiological changes in venous hemodynamics associated with elective fasciotomy.

It has been postulated that lower extremity fasciotomy may disrupt the calf musculovenous pump and predisposes to development of chronic venous insufficiency (CVI). However, studies based on trauma patients who undergo emergent fasciotomy are confounded by the possibility of concomitant vascular and soft tissue injury and use historical controls. This is a prospective study that evaluates venous hemodynamics in young patients undergoing elective fasciotomy for chronic exertional compartment syndrome (CECS), eliminating the problems associated with retrospective study of trauma patients. CECS was diagnosed by history and, when indicated, measurement of compartment pressures. Prior to elective two- or four-compartment fasciotomy, each patient underwent lower extremity air plethysmography (APG) and colorflow duplex ultrasonography. These studies were repeated a minimum of 6 weeks postoperatively. Fifteen patients who had fasciotomies for CECS were studied; two of these patients had bilateral fasciotomies for a total of 17 limbs. There were 13 male and two female patients (average age 31.2 years). APG and colorflow duplex were performed an average of 12 weeks after fasciotomy. Outflow fraction, venous volume, and ejection volume showed no significant changes postoperatively. However, the venous filling index (VFI) increased (0.9 +/- 0.1 vs. 1.1 +/- 0.1 mL/sec; p < 0.05, paired t-test), the ejection fraction tended to decrease (59 +/- 4% vs. 52 +/- 2%; p < 0.08, paired t-test), and the residual volume fraction (RVF) increased (26 +/- 3% vs. 36 +/- 5%; p < 0.05, paired t-test). There were no patients with evidence of deep venous reflux. Two extremities with preoperative greater saphenous vein (GSV) reflux did not worsen, and three extremities developed new GSV reflux following fasciotomy, although VFI remained normal in each extremity. Elective fasciotomy for CECS does not lead to significant venous reflux but likely does diminish calf muscle pump function and increases RVF moderately in young adult patients. With longer follow-up this diminished calf muscle pump function may increase the risk of CVI.

Adult↗
PubMed2006

Delayed evaluation of combat-related penetrating neck trauma.

OBJECTIVE: The approach to penetrating trauma of the head and neck has undergone significant evolution and offers unique challenges during wartime. Military munitions produce complex injury patterns that challenge conventional diagnosis and management. Mass casualties may not allow for routine exploration of all stable cervical blast injuries. The objective of this study was to review the delayed evaluation of combat-related penetrating neck trauma in patients after evacuation to the United States. METHOD: From February 2003 through April 2005, a series of patients with military-associated penetrating cervical trauma were evacuated to a single institution, prospectively entered into a database, and retrospectively reviewed. RESULTS: Suspected vascular injury from penetrating neck trauma occurred in 63 patients. Injuries were to zone II in 33%, zone III in 33%, and zone I in 11%. The remaining injuries involved multiple zones, including the lower face or posterior neck. Explosive devices wounded 50 patients (79%), 13 (21%) had high-velocity gunshot wounds, and 19 (30%) had associated intracranial or cervical spine injury. Of the 39 patients (62%) who underwent emergent neck exploration in Iraq or Afghanistan, 21 had 24 injuries requiring ligation (18), vein interposition or primary repair (4), polytetrafluoroethylene (PTFE) graft interposition (1), or patch angioplasty (1). Injuries occurred to the carotid, vertebral, or innominate arteries, or the jugular vein. After evacuation to the United States, all patients underwent radiologic evaluation of the head and neck vasculature. Computed tomography angiography was performed in 45 patients (71%), including six zone II injuries without prior exploration. Forty (63%) underwent diagnostic arteriography that detected pseudoaneurysms (5) or occlusions (8) of the carotid and vertebral arteries. No occult venous injuries were noted. Delayed evaluation resulted in the detection of 12 additional occult injuries and one graft thrombosis in 11 patients. Management included observation (5), vein or PTFE graft repair (3), coil embolization (2), or ligation (1). CONCLUSIONS: Penetrating multiple fragment injury to the head and neck is common during wartime. Computed tomography angiography is useful in the delayed evaluation of stable patients, but retained fragments produce suboptimal imaging in the zone of injury. Arteriography remains the imaging study of choice to evaluate for cervical vascular trauma, and its use should be liberalized for combat injuries. Stable injuries may not require immediate neck exploration; however, the high prevalence of occult injuries discovered in this review underscores the need for a complete re-evaluation upon return to the United States.

Adult↗
PubMed2006

Venous thromboembolism among United States soldiers deployed to Southwest Asia.

INTRODUCTION: Military operations may represent a high-risk environment for venous thromboembolism (VTE). We sought to identify and describe cases of venous thromboembolism among US military personnel serving in Southwest Asia, and estimate relative disease rates compared to non-deployed personnel. MATERIALS AND METHODS: Retrospective review of imaging archives, hospital discharge codes, case logs and autopsy records for the diagnosis of deep vein thrombosis or pulmonary embolism occurring from 1 March 2003 through 29 February 2004 among U.S. military personnel deployed to Southwest Asia. Rates of disease in deployed and non-deployed active-duty soldiers were estimated using personnel data and deployment experience obtained from automated rosters. RESULTS: Forty cases of venous thromboembolism were identified. The case-fatality rate was 16% (3/19) among those with pulmonary embolism. Antecedent trauma followed by prolonged air evacuation was present in 55% (22/40). Compared to trauma-associated cases, non-trauma cases were more commonly over 40 years old (44% vs. 5%; p<0.05), assigned to a transportation or quartermaster company (56% vs. 14%; p<0.05), or had a history of remote venous thromboembolism (31% vs. 0%; p<0.05). The overall incidence among deployed active-duty soldiers was 22.1/100,000 person-years. Compared to non-deployed active-duty soldiers, the age-adjusted incidence rate ratio was 1.06 (CI(0.95) 0.68-1.67). CONCLUSIONS: VTE rates among deployed soldiers are relatively low compared to the general population, and are comparable to non-deployed soldiers. Fatalities from PE are not uncommon, and vigilance among clinicians remains warranted. Trauma followed by prolonged air evacuation or ground transport during military operations may represent unique interactive risk factors for venous thromboembolism.

Adult↗
PubMed2006

Upper extremity arterial combat injury management.

Traumatic hemorrhage and vascular injury management have been concerns for both civilian and military physicians. During the 20th century, advances in technique allowed surgeons to focus on vascular repair, restoration of perfusion, limb salvage, and life preservation. Military surgeons such as Makins, DeBakey, Hughes, Rich, and others made significant contributions to the field of surgery in general and vascular surgery in particular. Casualties from combat in Afghanistan and Iraq confront physicians and surgeons with devastating injuries. The current generation of providers is challenged with applying contemporary care while expanding upon the lessons taught by our predecessors. The objective of this report is to review the historical experience with managing military upper extremity arterial injuries and compare that experience with current management.

Arteries↗
PubMed2006

The management of trauma venous injury: civilian and wartime experiences.

The management of venous trauma continues to be debated. Historically, ligation of injured veins is the most common modality of surgical treatment. In the past half-century, additional techniques have been used, including primary repair, interposition graft, and occasionally endovascular techniques. Venous repair, whether in the acute or chronic setting, is believed to prevent or ameliorate the complications of pain, edema, and phlegmasia. Venous repair in civilian trauma and in wartime is commonplace; however, overall treatment strategies remain largely unchanged since the Vietnam War.

Afghanistan↗
PubMed2006

Calcium channel antagonists augment hydroxyurea- and ru486-induced inhibition of meningioma growth in vivo and in vitro.

OBJECTIVE: Although the chemotherapy drug hydroxyurea (HU) and the antiprogesterone mifepristone (RU486) have been used to treat meningiomas for which surgical and radiation therapies have failed, results have been disappointing. The addition of calcium channel antagonists (CCAs) to chemotherapeutic drugs enhances tumor growth inhibition in other tumor types, and the authors demonstrated that CCAs can block meningioma growth in vitro and in vivo. The purpose of this study was to test the effects of the addition of a CCA to HU or RU486 on meningioma growth. METHODS: Primary and malignant (IOMM-Lee) meningioma cell lines were treated with HU, RU486, or either of these plus diltiazem or verapamil. Assays for cell growth, apoptosis, and fluorescent-activated cell sorting were performed on in vitro cultures. Similar cell lines were implanted into nude mice and were treated with HU or RU486, in combination with a CCA. Tumors were analyzed by light microscopy, MIB-1, and factor VIII immunohistochemical staining studies. RESULTS: The addition of diltiazem or verapamil to HU or RU486 augmented meningioma growth inhibition by 20 to 60% in vitro. In vivo, tumors treated with combination drugs were smaller; and immunohistochemical analysis of the IOMM-Lee tumors showed a 10% decrease in the MIB-1 ratio (from 0.41 to 0.30) and an approximate 75% decrease in microvascular density. CONCLUSION: The addition of diltiazem or verapamil to HU or RU486 augments meningioma growth inhibition in vitro by inducing apoptosis and G1 cell-cycle arrest. The combination of HU and diltiazem inhibited the growth of meningiomas in vivo by decreasing proliferation and microvascular density. These results suggest a possible role for these drugs as an additional adjuvant therapy for recurrent or unresectable meningiomas.

Aged↗
PubMed2005

The endovascular management of recurrent aortic hypoplasia and coarctation in a 15-year-old male.

A 15-year-old male complained of easy fatigability, leg weakness, and pain on exertion with episodes of syncope while playing baseball. His past medical history was significant for aortic coarctation associated with a congenital bovine hypoplastic aortic arch. A recent arteriogram revealed innominate and left common carotid artery stenosis as well as recurrent coarctation. He had previously undergone three Dacron patch aortoplasties. At the age of 7, he underwent a fourth operation for recurrent coarctation and because of extensive scar tissue in the region of his prior procedures, a left subclavian artery-to-descending aortic bypass was performed. An endovascular repair to deal with the recent recurrence was performed because of prior surgical difficulties. Percutaneous balloon-expandable stents were placed in the aortic coarctation, innominate, and the left common carotid arteries. Postprocedure, ankle brachial indices were >1 and the patient remains asymptomatic after 1 year.

Adolescent↗
PubMed2005

What imaging studies are necessary for abdominal aortic endograft sizing? A prospective blinded study using conventional computed tomography, aortography, and three-dimensional computed tomography.

OBJECTIVE: Preoperative imaging modalities for endovascular abdominal aortic aneurysm repair (EVAR) include conventional computed tomography (CT), aortography with a marking catheter, and three-dimensional computed tomography (3D CT). Although each technique has advantages, to date no study has compared in a prospective manner the reproducibility of measurements and impact on graft selection of all three modalities. The objective of this study was to determine the most useful imaging studies in planning EVAR. METHODS: Twenty patients being considered for EVAR were enrolled prospectively to undergo a conventional CT scan and aortography. The CT scans were then reconstructed into 3D images using Preview Treatment Planning Software (Medical Media Systems, West Lebanon, NH). Four measurements of diameter and six of length were made from each modality in determining the proper graft for EVAR. RESULTS: Measurements from all three modalities were reproducible with intraobserver correlation coefficients of 0.79 to 1.0 for aortography, 0.87 to 1.0 for CT, and 0.96 to 1.0 for 3D CT. Measurements between observers were also similar from each modality; interobserver correlations were 0.70 to 0.97 for aortography, 0.76 to 0.97 for CT, and 0.73 to 0.99 for 3D CT. Significant differences ( P < .01) in diameter measurements were noted at D2 with aortography compared with 3D CT, whereas differences in length measurements were found between CT and 3D CT at L4 (nonaneurysmal right iliac) ( P < .01). The correlation between CT and 3D CT for most length measurements was acceptable (0.63 to 1.0). Aortography for diameters correlated poorly (0.35 to 0.67) with 3D CT. When the endograft selected by aortography/CT or 3D CT alone was compared with the actual endograft used, there was agreement in 11 of 11 patients when adjusted for +/- one size in diameter or length. CONCLUSION: Reproducible and comparable measures of diameter and length can be obtained by each of three imaging modalities available for endograft sizing. As a single imaging modality, 3D CT appears to have the best correlation for both diameters and lengths; however, the difference is not sufficient enough to alter endograft selection. Three-dimensional CT may be reserved for challenging aortic anatomy where small differences in measurements would affect patient or graft selection for EVAR.

Aged↗
PubMed2005

Contemporary management of wartime vascular trauma.

OBJECTIVE: The treatment of wartime injuries has led to advances in the diagnosis and treatment of vascular trauma. Recent experience has stimulated a reappraisal of the management of such injuries, specifically assessing the effect of explosive devices on injury patterns and treatment strategies. The objective of this report is to provide a single-institution analysis of injury patterns and management strategies in the care of modern wartime vascular injuries. METHODS: From December 2001 through March 2004, all wartime evacuees evaluated at a single institution were prospectively entered into a database and retrospectively reviewed. Data collected included site, type, and mechanism of vascular injury; associated trauma; type of vascular repair; initial outcome; occult injury; amputation rate; and complication. Liberal application of arteriography was used to assess these injuries. The results of that diagnostic and therapeutic approach, particularly as it related to the care of the blast-injured patient, are reviewed. RESULTS: Of 3057 soldiers evacuated for medical evaluation, 1524 (50%) sustained battle injuries. Known or suspected vascular injuries occurred in 107 (7%) patients, and these patients comprised the study group. Sixty-eight (64%) patients were wounded by explosive devices, 27 (25%) were wounded by gunshots, and 12 (11%) experienced blunt traumatic injury. The majority of injuries (59/66 [88%]) occurred in the extremities. Nearly half (48/107) of the patients underwent vascular repair in a forward hospital in Iraq or Afghanistan. Twenty-eight (26%) required additional operative intervention on arrival in the United States. Vascular injuries were associated with bony fracture in 37% of soldiers. Twenty-one of the 107 had a primary amputation performed before evacuation. Amputation after vascular repair occurred in 8 patients. Of those, 5 had mangled extremities associated with contaminated wounds and infected grafts. Sixty-seven (63%) patients underwent diagnostic angiography. The most common indication was mechanism of injury (42%), followed by abnormal examination (33%), operative planning (18%), or evaluation of a repair (7%). CONCLUSIONS: This interim report represents the largest analysis of US military vascular injuries in more than 30 years. Wounding patterns reflect past experience with a high percentage of extremity injuries. Management of arterial repair with autologous vein graft remains the treatment of choice. Repairs in contaminated wound beds should be avoided. An increase in injuries from improvised explosive devices in modern conflict warrants the more liberal application of contrast arteriography. Endovascular techniques have advanced the contemporary management and proved valuable in the treatment of select wartime vascular injuries.

Adult↗
PubMed2005

Ubiquitous expression of cyclooxygenase-2 in meningiomas and decrease in cell growth following in vitro treatment with the inhibitor celecoxib: potential therapeutic application.

OBJECT: Meningiomas are the second most common symptomatic primary central nervous system tumor in adults. Findings of epidemiological studies link meningiomas with a history of head trauma, indicating a causal relationship between the inflammatory response and meningioma tumorigenesis. Cyclooxygenase-2 (COX-2), an inducible inflammatory enzyme, converts arachidonic acid to prostaglandins, which have angiogenic, cell-proliferative, and antiapoptotic effects. The authors investigated COX-2 expression in meningiomas and the effects of celecoxib, a COX-2 inhibitor, on meningioma cell growth in vitro. METHODS: Four meningioma surgical specimens were immunohistochemically stained and graded (0 to 4) for COX-2. In addition, a Western blot analysis was performed to detect the presence of COX-2. Human meningioma cells grown in cell culture were treated with vehicle or celecoxib (0.25-1 mM). An immunohistochemical analysis of COX-2, a methylthiotetrazole cell proliferation assay, a TUNEL apoptosis assay, and a Western blot analysis for the proapoptotic protein BAX were performed in vitro. One hundred eleven (87%) of 128 benign meningiomas and six (86%) of seven atypical meningiomas displayed a high COX-2 immunoreactivity (Grade 4 staining). In the Western blot analysis all four surgical specimens (100%) stained positive for a 70-kD band consistent with COX-2. Celecoxib inhibited cell growth in a dose-dependent fashion and induced apoptosis by Day 2, with no change noted in the expression of the BAX protein. CONCLUSIONS: The COX-2 enzyme is universally expressed in meningiomas. Celecoxib inhibits meningioma growth in vitro in a dose-dependent fashion, with evidence of apoptosis. Inhibitors of COX-2 may have a role in the treatment of recurrent meningiomas.

Adult↗
PubMed2003

Endovascular management of a peroneal artery injury due to a military fragment wound.

A healthy 29-year-old male suffered bilateral lower extremity fragment wounds resulting in a tense right calf shortly following a wound that required a four-compartment fasciotomy. During treatment of other injuries after medical evacuation he complained of increasing right calf pain. A peroneal pseudoaneurysm (PSA) with a concomitant arteriovenous fistula (AVF) was diagnosed. The distal one-third of the peroneal artery was not visualized, and the posterior tibial and anterior tibial arteries were normal. The patient underwent percutaneous coil embolization of the pseudoaneurysm. Completion arteriography demonstrated no evidence of the PSA and AVF. The patient's bruit and pain resolved.

Adult↗
PubMed2003

Aberrant right subclavian artery syndrome: a case of chronic cough.

A young, otherwise healthy man had chronic cough of 16 months' duration. Evaluation revealed an aberrant right subclavian artery. Kommerell's diverticulum without aneurysmal degeneration was present. Imaging studies showed compression of the esophagus but not the trachea. Results of methacholine challenge test were negative for evidence of reactive airway disease, but suggested mild variable intrathoracic obstruction. While aberrant right subclavian artery syndrome most commonly involves dysphagia, our patient's only symptom was cough. Right subclavian artery to right common carotid artery transposition was performed, with oversewing of the subclavian artery stump to the left of the esophagus through a right supraclavicular incision. This treatment was curative, with complete resolution of symptoms.

Adult↗
PubMed2003

Endovascular assisted in situ bypass grafting: a simplified technique for saphenous vein side branch occlusion.

The in situ bypass procedure for lower extremity limb salvage requires a long continuous incision or multiple interrupted incisions over the greater saphenous vein to ligate the saphenous vein side branches. This can result in wound complications that frequently prolong hospital stay and threaten the graft. In an effort to reduce the incidence of wound complications, alternate methods of occluding the vein side branches have been used. One method is to deliver coils under angioscopic vision into the saphenous vein side branches. This report details a simplified technique that uses widely available catheter-based equipment to perform saphenous vein side branch occlusion under fluoroscopic guidance.

Embolization, Therapeutic↗
PubMed2003

Microthrombectomy reduces postsclerotherapy pigmentation: multicenter randomized trial.

OBJECTIVE: Postsclerotherapy pigmentation occurs in nearly 30% of patients. Hemosiderin, from degradation of the venous thrombus, is the possible cause. The hypothesis that early removal of the thrombus may eliminate or decrease the incidence of pigmentation has not been proved or documented. The objective of this study was to investigate the effects of early microthrombectomy on incidence of postsclerotherapy pigmentation. MATERIAL AND METHODS: This multicenter, randomized, controlled study involved 101 patients with varicose veins (100 women, 1 man; mean age, 46 years [range, 25-68 years]). Patients were divided into two groups, with veins 1 mm or less in diameter (group 1, n = 50) or veins 3 mm or less in diameter (group 2, n = 51). Group 1 was treated with Sotradecol (STD) 0.25%, and group 2 with STD 0.50%. In each patient, an area of varicosities was selected and divided into halves. One half was randomized to microthrombectomy and the other half served as control. Microthrombectomy was performed 1 to 3 weeks after treatment in the randomized half. Standard photographs were obtained before and 16 weeks after treatment, and were evaluated by three independent reviewers who were blinded to treatment assignments. Each reviewer received an identical set of pretreatment and posttreatment 10 x 15-cm color photographs of the study area, and completed a scoring sheet. Average of the scores was used to evaluate primary (pigmentation) and secondary (overall clinical improvement) end points. The paired t test and chi-square test were used for statistical analysis. RESULTS: In group 1, microthrombectomized areas had statistically significant less pigmentation (P =.0047) and better overall clinical improvement scores (P =.0002) compared with the control side. In group 2 there was no significant difference between the two areas, but patients reported significant relief of pain and inflammation associated with postsclerotherapy thrombophlebitis. CONCLUSION: In veins 1 mm or smaller, microthrombectomy reduced pigmentation and improved overall clinical results. In veins 3 mm or smaller, statistical significance was not achieved, but thrombectomy resulted in faster resolution of the postsclerotherapy pain and inflammation. On the basis of these results, microthrombectomy after sclerotherapy is recommended.

Adult↗
PubMed2002

Preoperative risk stratification using electron beam computed tomography in elective vascular surgery: relationship to clinical risk prediction and postoperative complications.

We studied the utility of electron beam computed tomography as a screening test for the cardiovascular risk of elective vascular surgery. In 45 patients undergoing principally carotid and aortic surgical procedures, coronary artery calcification was prevalent and severe, and related to the clinically predicted cardiovascular risk of the procedure. However, only the clinically predicted surgical risk, and not coronary artery calcification, was related to the incidence of perioperative cardiovascular complications.

Aged↗
PubMed2002

Endovascular management of renal ischemia in a patient with acute aortic dissection and renovascular hypertension.

We report the endovascular management of a patient with a type B aortic dissection complicated by renal ischemia and resultant severe hypertension. A 69-year-old male presented with acute type B aortic dissection with proximal extension complicated by severe renovascular hypertension secondary to left renal ischemia. Endovascular management consisted of imaging with intravascular ultrasound and left renal artery stenting with balloon-expandable stents. His hypertension subsequently resolved and he was discharged on his baseline two-drug regimen. Management of the ischemic complications of type B aortic dissections may be primarily approached using endovascular methods in stable patients, with open surgery reserved for those patients refractory to these methods. Patients with evidence of decreased renal perfusion represent a select group with an increased risk of associated morbidity and mortality and should therefore be aggressively managed. Accurate information and assessment of anatomy can be obtained with intravascular ultrasound and is therefore an important adjunct to the armamentarium of endovascular specialists managing complications of aortic dissection.

Aged↗