Biomedical subjects

Michael D Dake

Publications and source records attributed to Michael D Dake.

44 records · Page 3Linked to original sources

PubMed2002

Prognosis of aortic intramural hematoma with and without penetrating atherosclerotic ulcer: a clinical and radiological analysis.

BACKGROUND: Advances in imaging techniques have increased the recognition of aortic intramural hematomas (IMHs) and penetrating atherosclerotic ulcers (PAUs); however, distinction between IMH and PAU remains unclear. We intended to clarify differences between IMH coexisting with PAU and IMH not associated with PAU by comparisons of clinical features, imaging findings, and patient outcome to derive the optimal therapeutic approach. METHODS AND RESULTS: We performed a retrospective analysis of 65 symptomatic patients with aortic IMH. There were 34 patients with IMH associated with PAU (group 1) and 31 patients with IMH unaccompanied by PAU (group 2). Involvement of the ascending aorta (type A) was more frequent in group 2 (8 of 31, 26%), whereas most of the patients in group 1 had exclusive involvement of the descending aorta (type B) (31of 34, 91%). Patients were subdivided into 2 categories, those with clinical progression and those with stable disease. Forty-eight percent of patients in group 1 and 8% in group 2 were in the progressive category (P=0.002). Clinical and radiological findings were compared between those group 1 patients who had a progressive disease course (n=12) and those who were stable (n=13). Sustained or recurrent pain (P<0.0001), increasing pleural effusion (P=0.0003), and both the maximum diameter (P=0.004) and maximum depth (P=0.003) of the PAU were reliable predictors of disease progression. CONCLUSIONS: This study suggests a difference in disease behavior that argues for the prognostic importance of making a clear distinction between IMH caused by PAU and IMH not associated with PAU. IMH with PAU was significantly associated with a progressive disease course, whereas IMH without PAU typically had a stable course, especially when limited to the descending thoracic aorta.

Aortic Diseases↗

PubMed2002

Inhibition of vascular endothelial growth factor-mediated neointima progression with angiostatin or paclitaxel.

PURPOSE: Therapeutic angiogenesis represents a new paradigm for treatment of ischemic vascular syndromes. However, vascular endothelial growth factor (VEGF) enhances the rate and degree of plaque formation. This study evaluates the potential to block these effects nonspecifically with paclitaxel or specifically with angiostatin. MATERIALS AND METHODS: Recombinant human VEGF(165) (rhVEGF) was administrated intramuscularly (2-microg/kg single injection) in combination with adventitial delivery of paclitaxel, angiostatin, or vehicle alone at the site of femoral arterial balloon overdilation injury in New Zealand White rabbits (n = 5 per treatment). Five additional animals with no rhVEGF and no adventitial delivery served as procedural controls. All rabbits were fed according to a 0.25% cholesterol diet beginning 28 days before angioplasty. Treated arteries were harvested after 7 days and evaluated to determine intima-to-media (I/M) ratios, macrophage infiltrate, and endothelial cell density. RESULTS: On histologic analysis, the rhVEGF/gel control group exhibited a mean I/M ratio of 0.337 +/- 0.028, a 77% increase over procedural controls, which exhibited a mean I/M of 0.190 +/- 0.010. rhVEGF/paclitaxel reduced I/M ratios to 0.151 +/- 0.007. In contrast, specific antiangiogenic therapy (rhVEGF/angiostatin) reduced I/M ratios to 0.032 +/- 0.003, a 91% decrease relative to rhVEGF/gel and an 83% decrease relative to procedural controls (P =.001 for each comparison). Local macrophages and endothelial cells also decreased with treatment. CONCLUSIONS: This study shows that paclitaxel and angiostatin each afford local protection against rhVEGF-mediated increases in neointima. Angiostatin further prevents progression of underlying neointima. These local therapies may allow broader use of therapeutic angiogenesis while avoiding and treating potentially undesirable effects.

Analysis of Variance↗

PubMed2002

In vivo vascular engineering of vein grafts: directed migration of smooth muscle cells by perivascular release of elastase limits neointimal proliferation.

PURPOSE: Saphenous vein bypass grafting for coronary revascularization procedures remains limited by accelerated neointima formation. It was hypothesized that creation of a modified chemotactic gradient in vivo could guide migration of smooth muscle cells (SMCs) peripherally instead of in a luminal direction and reduce intimal hyperplasia during vein graft arterialization. MATERIALS AND METHODS: Surgical bypass vein grafting to femoral arteries was performed in adult male New Zealand White rabbits (n = 8 per treatment group; five for 7 d and three for 28 d). Controlled-release microspheres delivering elastase or buffered polymer only were administered perivascularly at the vein graft site. At 7 days, five vein grafts per group were harvested and cross-sections were immunostained with anti-proliferating cell nuclear antigen (PCNA) to determine the number and distribution of proliferating SMCs. At 28 days, three vein grafts per group were harvested and intima-to-media (I/M) ratios were calculated after staining with Verhoeff von Gieson-Masson trichrome stain. RESULTS: Significant early outward-directed elastin degradation resulted from elastase treatment. Concurrently, proliferating SMCs migrated peripherally. PCNA(+) cells in the outer half of the wall increased 2.37 fold compared to procedural controls (P <.0001). Directional shifts in SMC migration underlie these results because overall SMC proliferation was not significantly different. At 28 days after vein graft surgery, a 38% reduction (P =.0008) in neointima was observed relative to procedural controls. CONCLUSION: Directional guidance of SMC responses through perivascular elastase release achieves favorable vein graft remodeling characteristics, including limited neointima development. This represents practical evidence that SMC migration can be directionally guided in vivo in a vein graft model and that plaque progression can be prevented by redistributing elastin without decreasing functional vein graft wall stability.

Analysis of Variance↗

PubMed2002

Is medical therapy still the optimal treatment strategy for patients with acute type B aortic dissections?

OBJECTIVE: The optimal treatment of patients with acute type B dissections continues to be debated. METHODS: A 36-year clinical experience of medical and surgical treatments in 189 patients was retrospectively analyzed (multivariable Cox proportional hazards model) with respect to three outcome end points: all deaths, freedom from reoperation, and freedom from late aortic complications or death. Propensity score analysis identified 2 quintiles (quintiles I and II, consisting of 142 comparable patients) for further comparison of the effects of surgical versus medical treatment. RESULTS: Shock (hazard ratio 14.5, 95% confidence interval 4.7-44.5, P <.001) and visceral ischemia (hazard ratio 10.9, 95% confidence interval 3.9-30.3, P <.001) largely predominated as determinants of death, along with 6 other risk factors (arch involvement, rupture, stroke, previous sternotomy, and coronary or lung disease), which roughly doubled the hazard of death. Female sex was a significant but weaker predictor of death. Renal dysfunction, year of presentation, age, and mode of therapy (medical vs surgical) had no important bearing on overall survival. The actuarial survival estimates for all patients were 71%, 60%, 35%, and 17% at 1, 5, 10, and 15 years, respectively, and were similar for the medical and surgical patients. Reoperation and late aortic complications were predicted by the presence of Marfan syndrome. For the propensity-matched patients in quintiles I and II, survival, freedom from reoperation, and freedom from aortic complications were almost identical in the medically treated and surgical subsets. CONCLUSIONS: The prognosis for patients with acute type B aortic dissection is bleak and determined primarily by dissection-related and patient-specific risk factors, which do not appear to be readily modifiable.

Acute Disease↗

PubMed2002

In vivo vascular engineering: directed migration of smooth muscle cells to limit neointima.

Pathologic neointima formation requires directional smooth muscle cell (SMC) migration from media to intima. The very direction of SMC migration thus becomes a potential therapeutic target. Here, we hypothesize that proliferating SMC after injury can be redirected using engineered chemotactic gradients of elastin degradation to limit late pathologic neointima formation. Buffered bioerodible polymeric microspheres (MS) were constructed to provide 4-week sustained release of elastase, heat-killed elastase, or polymer only. In vitro elastase function and timecourse of release at 37 degrees C, physiologic pH, and shear was determined. Curves revealed an initial bolus followed by sustained linear release for elastase MS, while controls exhibited baseline hydrolysis of substrate. We then employ controlled perivascular release of elastase after angioplasty to engineer modified in vivo gradients of elastin degradation in rabbit femoral arteries. NZW rabbits (n = 8 each) underwent balloon angioplasty of the common femoral artery followed by perivascular distribution of MS. Significant early perivascular elastin degradation resulted. Concurrently, proliferating SMC were guided peripherally (further from lumen) with treatment without significant changes in total proliferation or inflammation. At 28 days, treatment significantly reduces neointima by 42% relative to controls. These results confirm that directionally guiding SMC responses after injury achieves favorable arterial remodeling and limits development of pathologic neointima. Thus, a potential class of therapeutics and the paradigm of in vivo vascular engineering emerge from this work.

Angioplasty, Balloon, Coronary↗

PubMed2002

Angiographic classification of ovarian artery-to-uterine artery anastomoses: initial observations in uterine fibroid embolization.

PURPOSE: To prospectively study and classify the anastomoses between the ovarian and uterine arteries in women undergoing uterine fibroid embolization, and to compare the presence of such with procedural failures and premature menopause. MATERIALS AND METHODS: Angiographic ovarian artery-to-uterine artery anastomoses were studied in 76 consecutive patients undergoing uterine fibroid embolization. Mean patient age was 44.7 years (range, 29-56 years). Clinical follow-up consisted of a standard questionnaire. Procedural failure and complications were compared with the presence of various types of ovarian artery-to-uterine artery connections. RESULTS: Three types of anastomoses were identified. In type I (33 [21.7%] of 152 arteries), flow from the ovarian artery to the uterus was through anastomoses with the main uterine artery. In type II (six arteries [3.9%]), the ovarian artery supplied the fibroids directly. In type III (10 arteries [6.6%]), the major blood supply to the ovary was from the uterine artery. Seven patients (9%) were considered to have clinical failure, with three of the six women with type II anastomoses being in this group. Three of the five women who experienced menopause after fibroid embolization had bilateral ovarian artery-to-uterine artery anastomoses that were classified as high risk. CONCLUSION: Delineation of ovarian artery-to-uterine artery anastomosis is of practical relevance in avoiding nontarget ovarian embolization, in identification of those who would be at risk of uterine artery embolization or ovarian failure, and in those in whom the ovarian artery can be embolized safely.

Adult↗

PubMed2002

Occurrence of secondary ischemic events among persons with atherosclerotic vascular disease.

BACKGROUND AND PURPOSE: Few data exist for large managed care populations on the occurrence of subsequent acute ischemic events in persons with established atherosclerotic vascular disease. We estimated the occurrence of secondary stroke, acute myocardial infarction (AMI), and vascular deaths among 2 large, managed care samples. METHODS: With the use of International Classification of Diseases, Ninth Revision, Clinical Modification codes, patients aged > or =40 years and with stroke, AMI, or peripheral arterial disease (PAD) were identified from administrative data of UnitedHealthcare plans during 1995-1998. Stroke, AMI, and PAD cohorts were identified within a commercial insurance sample and a Medicare sample. Cumulative occurrences of subsequent stroke, AMI, or vascular death were estimated by survival analysis. RESULTS: In the stroke commercial cohort (n=1631; mean age, 62.1 years), cumulative occurrence of subsequent events was 4.2%, 6.5%, 9.8%, and 11.8% at 0.5, 1, 2, and 3 years, respectively; cumulative secondary event occurrence in the AMI commercial cohort (n=6458; mean age, 56.0 years) was 3.5%, 4.8%, 7.3%, and 8.5% and in the PAD commercial cohort (n=5813; mean age, 59.2 years) was 1.5%, 2.8%, 4.8%, and 6.5%, respectively. Cumulative secondary event occurrences were even higher in stroke (n=1518; mean age, 79.5 years), AMI (n=2197; mean age, 76.2 years), and PAD (n=5033; mean age, 76.6 years) cohorts of the Medicare sample: 18.1%, 17.0%, and 8.7%, respectively, at 3 years. More than 75% of each stroke cohort's secondary events were strokes; more than 75% of each AMI cohort's secondary events were AMIs. Of the PAD cohorts' secondary events, 27% to 39% were strokes, 48% to 57% were AMIs, and 13% to 16% were vascular deaths. CONCLUSIONS: Among these managed care enrollees with existing atherosclerotic vascular disease, subsequent ischemic events represent a significant symptomatic disease burden. Given these findings, it is very important to determine whether secondary prevention strategies are being effectively used to manage patients with diagnosed atherosclerosis.

Adult↗

PubMed2002

Initial clinical results of tenecteplase (TNK) in catheter-directed thrombolytic therapy.

PURPOSE: To investigate the safety and immediate efficacy of 2 different doses of tenecteplase (TNK) in peripheral catheter-directed thrombolytic therapy of arterial occlusions and deep vein thrombosis (DVT). METHODS: Over a 20-month period, 63 nonconsecutive patients underwent catheter-directed thrombolytic therapy with either 0.25 mg/h or 0.50 mg/h of TNK in a nonrandomized, open-label study. Of these, 55 patients (60 limbs) were treated for DVT (36 limbs in 16 men and 15 women; mean age 41 years, range 21-73) or peripheral arterial occlusions (24 limbs in 16 men and 8 women; mean age 63 years, range 32-91). The primary endpoints were major bleeding complications and angiographic reduction in clot burden. RESULTS: The mean duration of infusion was 18 +/- 4 hours in patients with arterial occlusions and 30 +/- 13 in those with DVT. Twenty-one (87.5%) patients with occlusive disease had marked or complete lysis of clot. Thirty (83.3%) limbs with DVT had either marked or complete resolution of thrombus. There were 4 (7.3%) episodes of minor bleeding with 1 (1.8%) major hemorrhagic event. Fibrinogen levels dropped by an average of 23%. CONCLUSIONS: Preliminary evidence suggests that TNK doses of 0.25 mg/h to 0.50 mg/h appear to be safe and effective. The potential benefits of TNK therapy warrant further investigation.

Adult↗