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Biomedical subjects

T A Whitehill

Publications and source records attributed to T A Whitehill.

At least 19 recordsLinked to original sources
PubMed2001

Epithelioid hemangioendothelioma of the common femoral vein: Case report and review of the literature.

A young competitive skier had venous claudication. A stenosis of the left common femoral vein was revealed by means of an examination. Exploration and vein patch angioplasty were performed, and because of both the unusual appearance (focal thickening of vein wall) and the unclear etiology of the lesion, frozen and permanent sections of the wall were obtained. Epithelioid hemangioendothelioma, a rare intravascular sarcoma, was revealed by means of an examination of the permanent sections. Two additional procedures were required to completely excise the epithelioid hemangioendothelioma. We discuss these rare vascular malignancies and include a review of the available literature. Also, oncologic principles important in both the diagnosis and therapy of intravascular sarcomas are discussed.

Adult↗
PubMed2001

Iatrogenic vascular injuries from percutaneous vascular suturing devices.

OBJECTIVE: The purpose of this study was to examine the patterns of injury and the strategies of surgical repair of iatrogenic vascular injuries from a percutaneous vascular suturing device after arterial cannulation. METHODS: We retrospectively reviewed the clinical experience from an academic vascular surgical practice over a 2-year period. The subjects were patients undergoing vascular repair of iatrogenic vascular injury after deployment of a percutaneous vascular suturing device. Interventions were direct repair of arterial injury (with or without device extraction) or arterial thrombectomy and repair. The main outcome variables included patterns of arterial injury, magnitude of arterial repair, limb salvage, hospital stay, and perioperative mortality and morbidity rates. RESULTS: From August 1998 through August 2000, eight patients (4 men, 4 women; median age, 55 years; range, 44-80 years) required vascular operations for complications of percutaneous suturing devices after diagnostic (2) or therapeutic (6) arteriograms through a transfemoral approach. Complications included four pseudoaneurysms (1 infected) due to arterial tear from suture pull through, two entrapped closure devices due to device malfunction, and two arterial thromboses due to narrowing/severe intimal dissection. All patients required operative intervention. Direct suture repair with or without device removal was performed in five patients, arterial debridement with vein patch angioplasty in one patient, and arterial thrombectomy and vein patch angioplasty in two patients. There were no perioperative deaths. The median hospital stay was 5 days (range, 2-33). Limbs were salvaged in all patients with a mean follow-up of 4.8 months (range, 1-13). CONCLUSIONS: Although abbreviated postangiography recovery periods and early ambulation have motivated the widespread use of percutaneous suturing devices, the infrequent occurrence of vascular injuries produced by these devices can be significantly more challenging than simple acute pseudoaneurysms or hemorrhage. In addition, thrombotic complications have a small but finite risk of limb loss.

Adult↗
PubMed2000

Negative impact of cardiac evaluation before vascular surgery.

The optimal preoperative evaluation of cardiac risk in patients with peripheral vascular disease is controversial. In developing a paradigm for preoperative cardiac workup, potential adverse effects of evaluation and cardiac intervention must be considered. This study analyzed the deleterious outcomes of extensive, comprehensive cardiac evaluation and intervention before planned vascular surgery in patients treated at the Denver Department of Veterans Affairs Medical Center. Over a 12-month period between 1994 and 1995, 161 patients were scheduled to undergo major vascular operations; 153 patients came to operation. The decision to pursue a cardiac evaluation was variously made by a combination of surgeons, cardiologists, and anesthesiologists. No defined protocol was followed. Cardiac history, chest X-rays and ECGs were obtained for all patients. Extended cardiac evaluation included these studies plus special tests, including echocardiography (echo), radionuclide ventriculography (RNVG), dipyridamole thallium scintigraphy (DTS), and cardiac catheterization (CC). Extended cardiac evaluations were undertaken in 42 patients. Complications related to percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass grafting (CABG) were also recorded. Cardiac mortality and morbidity after vascular interventions were itemized in all 153 patients. Forty-two male patients, aged 68 +/- 9 years, underwent extended cardiac evaluations before planned vascular operations. The median elapsed time for cardiac workup was 14 days (mean 30 +/- 59 days). The median and mean times from cardiac workup to vascular surgery were 25 days and 76 +/- 142 days, respectively. Eighteen (43%) patients had echo or RNVG; 22 (52%) patients had DTS; 27 (64%) had CC; 9 (21%) had PTCA; 7 (17%) had CABG. Sixteen (38%) patients had untoward events related to cardiac evaluation. Eight patients (19%: one with cerebrovascular disease, and seven with aortic aneurysms) refused vascular surgery after extended cardiac workup. Complications attributable to CC, PTCA, and CABG included prosthetic graft infection, pseudoaneurysms (two), sternal wound infections (two), renal failure and brain anoxia. Two patients with severe limb ischemia who were candidates for revascularization ultimately required amputations because of delay due to cardiac evaluations. Extensive cardiac evaluation prior to vascular operations can result in morbidity, delays, and refusal to undergo vascular surgery. The underlying indication for vascular operations and the local iatrogenic cardiac complication rates must be considered before ordering special studies.

Aged↗
PubMed2000

Current vena cava filter devices and results.

The critical focus in the acute management of deep vein thrombosis (DVT) continues to be the effective prevention of associated life-threatening pulmonary embolism (PE) and the achievement of survival for those in whom such emboli occur. As such, primary treatment for DVT or PE demands adequate anticoagulation with intravenous heparin followed by maintenance oral warfarin for 3 to 6 months. This centered approach successfully prevents 90% to 95% of cases of associated pulmonary embolism. However, under circumstances in which anticoagulation cannot be used, or in which it fails, there is clear indication for placement of a mechanical filter into the inferior vena cava to provide a protective barrier against the passage of clinically significant emboli from pelvic or lower extremity veins. Considerable technical ingenuity and continued evolution of materials and design have propelled the development and number of vena cava filters available for clinical use. Variable data on safety and effectiveness require physicians to match the best filter to each patient's particular situation and anatomy. However, many interventional radiologists and surgeons often base their filter selection on ease of insertion and device cost. Thus, it is paramount that physician users of these devices remember that the primary objective of vena cava filtration is to provide a safe and effective device for permanent implantation. If this objective is not met, the quality of care in the management of deep venous thrombosis or pulmonary embolism will diminish.

Anticoagulants↗
PubMed1999

Intermediate-term outcome of primary digit amputations in patients with diabetes mellitus who have forefoot sepsis requiring hospitalization and presumed adequate circulatory status.

PURPOSE: The intermediate success and outcome of primary forefoot amputations in patients with diabetes mellitus who have sepsis limited to the forefoot and presumed adequate forefoot perfusion, as determined by means of noninvasive methods, was studied. METHODS: Cases of a university hospital-based practice from January 1984 to April 1998 were retrospectively reviewed. Patients included had diabetes mellitus with forefoot sepsis requiring immediate hospitalization for digit amputations who had adequate arterial circulation for healing based on noninvasive and clinical assessment: palpable pedal pulses (29%), "compressible" ankle pressure of 70 mm Hg or higher (48%), pulsatile metatarsal waveforms (67%), and/or toe pressure higher than 55 mm Hg (36%). All patients underwent a primary single- or multiple-digit amputation (through the interphalangeal joint, metatarsal head, or metatarsal shaft). Additional forefoot procedures (debridement, digit amputation) were performed during the follow-up period as needed for persistent or recurrent infection. The main outcome variables were recurrent or persistent foot infection (defined as requiring rehospitalization for antibiotics, wound care, and/or reoperation), the number of repeat operations and hospitalizations for salvage of limbs with recurrent or persistent infections, and time to complete forefoot healing or foot amputation. RESULTS: Ninety-two patients who had diabetes mellitus with 97 forefoot infections comprised the study group. Ninety-seven primary digit amputations (34 through interphalangeal joints, 28 through metatarsal heads, 35 through metatarsal shafts) were performed. The median length of hospital stay was 10 days. There were no operative deaths. The mean follow-up period was 21 months (range, 3 days to 105 months). The primary amputation healed (without persistent infection) in only 38 limbs (39%), at a mean time of 13 +/- 10 weeks. Twenty-three limbs (24%) had not healed the primary amputation without evidence of persistent infection at last follow-up (mean, 12 weeks). Infection persisted in 35 limbs (36%), and infection recurred in 15 of 38 (40%) healed limbs. An average of 1.0 reoperations (range, 0 to 3) and 1.6 rehospitalizations (range, 1 to 4) were involved in salvage attempts in these recurrent/persistent infections. Five persistent and five recurrent infections ultimately healed (mean, 53 weeks). Complete healing was achieved in only 33 of 97 limbs (34%). Twenty-two foot amputations (20 transtibial, two Syme's) were performed (mean, 49 +/- 74 weeks; 20 for persistent infection). Eighteen persistent/recurrent infections remained unhealed at the last follow-up examination (mean, 105 weeks). CONCLUSION: Patients with diabetes mellitus who have sepsis limited to the forefoot requiring acute hospitalization and undergoing primary digit amputations have a high incidence of intermediate-term, persistent, and recurrent infection, leading to a modest rate of limb loss, despite having apparently salvageable lesions and noninvasive evidence of presumed adequate forefoot perfusion.

Adult↗
PubMed1998

Ovarian ablation alone promotes aortic intimal hyperplasia and accumulation of fibroblast growth factor.

BACKGROUND: Estrogen-mediated cardiovascular protection is incompletely explained by its beneficial lipid-modifying effects. Previous studies interrogating direct vascular effects of estrogens have used models of either diet- or injury-induced atherosclerosis. The purpose of this study was to determine the influence of ovarian ablation alone on vascular remodeling. We hypothesized that estrogens are atheroprotective, independent of their influence on lipid metabolism, by directly influencing the production and effects of a prototypical atherogenic mediator, basic fibroblast growth factor (bFGF). METHODS AND RESULTS: Twenty-five female sheep were randomized to sham operation, ovariectomy, or ovariectomy plus 17beta-estradiol replacement. Serum cholesterol and triglyceride levels were serially measured for 1 year and were similar among groups and in the normal range (30 to 60 mg/dL). At 6, 9, and 12 months, ovariectomy resulted in aortoiliac intimal hyperplasia compared with sham (P<0.01) and hormone replacement (P<0.01) groups. The neointima of ovariectomized animals was characterized immunohistochemically by increased vascular smooth muscle cells (VSMCs). Levels of bFGF protein were determined in adjacent aortic segments. Ovariectomized sheep had 2-fold more FGF than sham or ovariectomized sheep that received hormone replacement. In vitro, estradiol inhibited the mitogenic effect of bFGF on human aortic VSMCs. CONCLUSIONS: Without dietary manipulation, ovarian ablation alone induces aortic intimal hyperplasia in the ewe. Estradiol abrogates this response independently of its effects on serum lipids. Hormone replacement decreases the accumulation of the atherogenic peptide bFGF in vivo and inhibits the mitogenic response of VSMCs to bFGF in vitro. These results suggest that estrogens may provide atheroprotection both by modulating local production and by attenuating the influence of bFGF on VSMC growth.

Animals↗
PubMed1998

Interleukin-10 inhibits human vascular smooth muscle proliferation.

Arterial injury results in the elaboration of pro-inflammatory substances including cytokines and peptide growth factors which act to modify vascular smooth muscle (VSMC) proliferation and migration with resultant vessel stenosis. Produced by T-lymphocytes and macrophages, interleukin-10 (IL-10) is an anti-inflammatory cytokine in several cell lines. We hypothesized that IL-10 may participate in vascular remodeling by inhibiting VSMC proliferation. Human aortic VSMCs were isolated and cultured. Proliferation assays were performed to determine the effect of the effect of IL-10 on (1) unstimulated, (2) cytokine (tumor necrosis factor-alpha: TNF alpha)-stimulated, and (3) growth factor (basic fibroblast growth factor: bFGF)-stimulated VSMC proliferation. Compared to control, both TNF alpha and bFGF-stimulated VSMC proliferation (P < 0.002). IL-10 alone had no effect on cell growth. However, with TNF alpha or bFGF-stimulation, physiologic doses of IL-10 inhibited both VSMC DNA synthesis and VSMC growth (P < 0.001). Furthermore, IL-10 was effective in inhibiting TNF alpha-induced proliferation at a dose as low as 10 fg/ml (P < 0.001) and bFGF-induced proliferation at a dose as low as 1 pg/ml (P < 0.001). In conclusion, TNF alpha and bFGF stimulate human VSMC growth. IL-10 potently abrogates the proliferative response to these atherogenic mitogens. IL-10 might represent an endogenous source of immune-mediated atherprotection and when given exogenously, may prove to be a novel therapeutic agent in regulating vessel wall remodeling following vascular injury.

Aorta↗
PubMed1998

Estrogen replacement inhibits intimal hyperplasia and the accumulation and effects of transforming growth factor beta1.

BACKGROUND: The role of estrogens in providing atheroprotection has been well documented in both epidemiologic and experimental studies. This phenomenon has traditionally been attributed to the beneficial lipid-modifying effects of estrogens. Previous studies have used models of either diet- or injury-induced atherosclerosis. As such, the interrelationship between estrogens, lipids, and atherosclerosis remains unclear. We hypothesized that estrogens are atheroprotective independent of changes in serum lipids by directly influencing the accumulation and effects of the peptide growth factor transforming growth factor beta1 (TGF-beta1). MATERIAL AND METHODS: Thirteen female sheep (8 years old) were randomized to sham, ovariectomy, or ovariectomy with 17beta-estradiol replacement. Serum lipid levels were serially measured. At 9 months, necropsy was performed with histologic morphometric analysis of the aortoiliac bifurcation. Levels of TGF-beta1 were determined in serum and aortic tissue. Human aortic smooth muscle cells were isolated and cultured. RESULTS: Serum triglyceride, lipoprotein a, and total, low-density lipoprotein, and high-density lipoprotein cholesterol levels were similar and normal between groups. Ovariectomy resulted in aortoiliac intimal hyperplasia compared with sham (P < 0.001) and hormone replacement (P < 0.001) groups. Compared with ovariectomy, estrogen replacement attenuated aortic accumulation of TGF-beta1 (P < 0.02). In vitro, estradiol potentiated TGF-beta1 inhibition of human vascular smooth muscle cell (VSMC) proliferation and increased TGF-beta1 release in stimulated VSMCs (P < 0.001). CONCLUSIONS: Without dietary manipulation, ovarian ablation induces aortic intimal hyperplasia in the ewe. Estradiol abrogates this response independently of its effects on serum lipids. Hormone replacement decreases the accumulation of TGF-beta1, suggesting that estrogens may provide atheroprotection both by modifying local production and by modulating the influence of TGF-beta1 on VSMC growth.

Animals↗
PubMed1998

Thrombophilia and activated protein C resistance.

In addition to classic vascular insults such as inflammation, trauma, malignancy, and surgery, a number of hereditary coagulation defects predispose patients to a wide array of thrombotic complications. A novel genetic defect in factor V allowing for resistance to its cleavage by activated protein C has recently been implicated in a significant number of cases of familial thrombophilia. A brief case report and review of the literature is presented to familiarize surgeons to this important and quite frequent cause of hypercoagulability.

Activated Protein C Resistance↗
PubMed1998

The biology of estrogen-mediated repair of cardiovascular injury.

Women appear to be protected from cardiovascular disease until the onset of menopause. Considerable evidence supports the atheroprotective effects of endogenous and supplemental estrogens. The beneficial effects of estrogens on lipid metabolism cannot wholly explain this phenomenon. Accumulating data suggest that estrogen may act at the cellular and molecular level to influence atherogenesis. The purpose of this review is to examine lipid-independent mechanisms of estrogen-mediated atheroprotection after cardiovascular injury.

Cardiac Surgical Procedures↗
PubMed1998

Contemporary management of isolated iliac aneurysms.

OBJECTIVE: Because isolated common iliac artery aneurysms are infrequent, are difficult to detect and treat, and have traditionally been associated with high operative mortality rates in reported series, we analyzed the outcomes of operative repair of 31 isolated common iliac artery aneurysms in 21 patients to ascertain morbidity and mortality rates with contemporary techniques of repair. METHODS: A retrospective review study was conducted in a university teaching hospital and a Department of Veterans Affairs Medical Center. Perioperative mortality and operative morbidity rates were examined in 17 men and four women with isolated common iliac artery aneurysms between 1984 and 1997. Ages ranged from 38 to 87 years (mean 69 +/- 8 years). Slightly more than half of the cases were symptomatic, with abdominal pain, neurologic, claudicative, genitourinary, or hemodynamic symptoms. One aneurysm had ruptured and one was infected. There was one iliac artery-iliac vein fistula. All aneurysms involved the common iliac artery. Coexistent unilateral or bilateral external iliac aneurysms were present in four patients; there were three accompanying internal iliac aneurysms. Overall, 52% of patients had unilateral aneurysms and 48% had bilateral aneurysms. Aneurysms ranged in maximal diameter from 2.5 to 12 cm (mean 5.6 +/- 2 cm). No patients were unavailable for follow-up, which averaged 5.5 years. RESULTS: Nineteen patients underwent direct operative repair of isolated iliac aneurysms. One patient had placement of an endoluminal covered stent graft; another patient at high risk had percutaneous placement of coils within the aneurysm to occlude it in conjunction with a femorofemoral bypass graft. Patients with bilateral aneurysms underwent aortoiliac or aortofemoral interposition grafts, whereas unilateral aneurysms were managed with local interposition grafts. There were no deaths in the perioperative period. Only one elective operation (5%) resulted in a significant complication, compartment syndrome requiring fasciotomy. The patient treated with the covered stent required femorofemoral bypass when the stent occluded 1 week after the operation. The patient treated with coil occlusion of a large common iliac aneurysm died 2 years later when the aneurysm ruptured. CONCLUSIONS: Isolated iliac artery aneurysms can be managed with much lower mortality and morbidity rates than aneurysm previously been reported by using a systematic operative approach. Percutaneous techniques may be less durable and effective than direct surgical repair.

Adult↗
PubMed1998

Class II cytokine receptor ligands inhibit human vascular smooth muscle proliferation.

BACKGROUND: Vessel injury provokes the release of proinflammatory cytokines and growth factors that influence vascular smooth muscle cell (VSMC) proliferation and migration. Produced by T lymphocytes, interleukin-10 (IL-10) and interferon-gamma (IFN-gamma) both have immunoregulatory functions and act on similar receptors, designated class II cytokine receptors. We hypothesized that the class II cytokine receptor participates in vascular remodeling by inhibiting VSMC proliferation. The purposes of this study were to determine the influence of class II cytokine receptor stimulation on (1) unstimulated, (2) cytokine-stimulated, and (3) growth factor-stimulated VSMC proliferation. METHODS: Human aortic VSMCs were isolated and cultured. VSMCs were treated with IL-10 or IFN with or without tumor necrosis factor-alpha (TNF-alpha) or basic fibroblast growth factor (FGF). Proliferation was quantified by colormetric assay. RESULTS: Compared to control, both TNF and FGF stimulated concentration-dependent VSMC proliferation (P < .005). IL-10 and IFN alone had no effect on unstimulated cell growth. With TNF or FGF stimulation, both IL-10, at a dose as low as 10 fg/ml, and IFN, at a dose as low as 1.0 U/ml, inhibited cell growth (P < .001). CONCLUSIONS: The class II cytokine receptor ligands, IL-10 and IFN, inhibit cytokine-(TNF) and growth factor-(FGF) induced VSMC proliferation. The class II cytokine receptor may provide a novel therapeutic target in regulating vessel wall remodeling after vascular injury.

Aorta, Thoracic↗
PubMed1997

Unusual causes of mesenteric ischemia.

Although complications of generalized atherosclerosis most commonly cause intestinal ischemia, a number of unusual causes may be responsible. These unusual causes can be grouped into six major categories: (1) mechanical, (2) drugs, (3) hematologic, (4) endocrine, (5) vasculopathies, and (6) miscellaneous. Morbidity and mortality rates remain high because these rare diseases frequently go unrecognized until patients suffer adverse outcomes. A high index of suspicion may decrease the delay in diagnosis of mesenteric ischemia caused by these disorders.

Antibodies, Anticardiolipin↗
PubMed1997

Role of revascularization in the treatment of claudication.

Intermittent claudication is a relative indication for vascular reconstruction. Conservative management with a combination of risk factor control, exercise training and medical therapy will relieve or at least improve claudication in some patients. If claudication precludes gainful employment or imposes an unacceptable alteration in lifestyle, surgical revascularization should be considered. Surgical bypass for claudication will produce optimal results in younger patients, in whom near-normalization of the ankle/brachial index can be anticipated. Proximal axial (in-line) reconstructions maintain their patencies longer than more distal, and often technically more challenging, bypasses. These tenets also apply well to percutaneous transluminal angioplasty. Both surgical and catheter-based interventions carry potential risks of short- and long-term morbidity, although overall morbidity associated with surgery for claudication is acceptably low. Interventions are justified only if they are safe, effective and durable, and if they are performed after the long-term prognosis for both life and limb is considered.

Anastomosis, Surgical↗
PubMed1996

Caval interruption methods: comparison of options.

The Stainless Steel and Titanium Greenfield filters, the Venatech filter, and the Bird's nest filter are most commonly used in the United States. A comparison of contemporary experience with these filters along with that of Simon-Nitinol filter is shown in Table 1. The published experience with each device is minimal compared with actual clinical use. The published reports available do not often examine experience with a view toward unbiased and accurate comparison of results. Each filter has an acceptably low rate of recurrent PE, but each has experienced the range of complications associated with vena caval filters or partitions. The reviewed case series are too small and the complication rates too similar for any of the newer designs to claim unequivocal superiority. Except for the Stainless Steel Greenfield filter, comparison is further complicated by the lack of standardized, quantitative follow-up of patients over a period long enough for possible extremity venous complications to be observed. Each of the currently available filters has at least one specific attribute that may recommend it for a particular situation. Detailed and comparable examination of IVC filtration is becoming more important as the indication for and use of these devices increase. Clearly, the search for the perfect device to prevent PE should continue.90 Any filtration device plays only a small role in the overall management of the patient with thromboembolic disease. It is incumbent upon the physician who treats this patient to assume the responsibility for the diagnosis of and long-term follow-up of the underlying disorder. Considerable technical ingenuity and continued evolution of materials and design have propelled the development and number of available vena cava filters for clinical use. Without objective clinical data, many interventional radiologists and surgeons base their filter selection on ease of insertion and device cost. Variable data on safety and effectiveness demand that physicians match the best filter to each patient's particular situation and anatomy. The primary objective of vena cava filtration is to provide a safe and effective device for permanent implantation. If this objective is not kept in sight, quality of care in the management of deep venous thrombosis and/or pulmonary embolus will be lost.

Clinical Trials as Topic↗
PubMed1994

Transplantation of lac-Z-transduced microvascular endothelial cells into the skeletal muscle capillary bed of the rat hindlimb occurs independent of the duration of femoral artery occlusion after injection of cells.

The skeletal muscle capillary bed may be an ideal recipient site for transplantation of genetically modified autologous endothelial cells and thus provide a basis for a technique of somatic gene therapy that would be applicable to a variety of acquired and inherited human diseases. The purpose of this study was to test the hypothesis that adhesion of lac-Z-transduced microvascular endothelial cells (MVEC) in the skeletal muscle capillary bed in vivo is dependent on the duration of arterial occlusion after injection of the transduced MVEC. MVEC derived from the abdominal fat pad of syngeneic rats (Wistar F-455) were transfected with the BAG vector, a replication-incompetent retroviral vector containing the lac-Z gene for beta-galactosidase and the Tn5 gene for selection of the transduced cells by the neomycin analogue, G418. lac-Z-transduced MVEC were radiolabeled with 125I-PKH-95, and, after the femoral artery was occluded for 10 min, these cells (1 to 2 x 10(6)) were injected intraarterially into the rat hindlimb. In the experimental groups the femoral artery clamp was removed at 0, 60, or 120 min after injection. A control group without pre- or postinjection femoral arterial occlusion was also studied. Adhesion of MVEC in the skeletal muscle capillary bed (mean percentage of injected 125I activity) was determined in groups of 4 rats at 1 day, 1 week, and 1 month after injection. Adhesion of the transduced MVEC did not increase as the duration of femoral artery occlusion after injection was increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Adhesion and incorporation of lacZ-transduced endothelial cells into the intact capillary wall in the rat.

Use of the capillary bed of skeletal muscle as an in vivo recipient site to transplant autologous endothelial cells that have undergone gene transfer ex vivo has considerable potential as a technique of somatic gene therapy. Here we document a previously unrecognized capacity of endothelial cells to adhere and incorporate spontaneously into confluent endothelial cell monolayers in vitro and in vivo. This spontaneous adhesion and incorporation of endothelial cells enabled us to seed lacZ-transduced endothelial cells into the wall of skeletal muscle capillaries of the hindlimb of the rat. Certain transduced endothelial cells became incorporated within the capillary wall, whereas others remained within the capillary lumen where they formed focal, electron-dense, contacts with host endothelium. lacZ expression in the capillary bed was documented for up to 1 month after transplantation. Use of the intact capillary bed of skeletal muscle as an in vivo recipient site for transduced, autologous endothelial cells holds promise as a strategy for somatic gene therapy to treat various genetic and acquired human diseases.

Animals↗