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Biomedical subjects

J M Isner

Publications and source records attributed to J M Isner.

At least 343 records · Page 19Linked to original sources
PubMed1980

Comparison of degrees of coronary arterial luminal narrowing determined by visual inspection of histologic sections under magnification among three independent observers and comparison to that obtained by video planimetry: an analysis of 559 five-millimeter segments of 61 coronary arteries from eleven patients.

The accuracy of determining degrees of luminal narrowing of 559 histologic sections from 61 human coronary arteries was evaluated by visual inspection under magnification (light microscopy) by three independent observers, and the results were compared to those obtained by video planimetry. With the per cent of cross-sectional area narrowing divided into four categories (0 to 25, 26 to 50, 51 to 75, and 76 to 100), both the extent of agreement between each independent observer and video planimetry, i.e., the accuracy of visual inspection under magnification and the extent of agreement among the independent observers, interobserver agreement, evaluated by the Kappa (K) statistic, were excellent. With a K value of 50 per cent indicating reasonably good agreement and values of greater than or equal to 70 per cent indicating strong agreement, the K values between the results of light microscopy and video planimetry by three observers were 61, 67, and 75 percent, respectively, and the extent of interobserver agreement was 72 per cent.

Arteriosclerosis↗
PubMed1979

Systolic click from a Swan-Ganz catheter: phonoechocardiographic depiction of the underlying mechanism.

Although echocardiographic manifestations of Swan-Ganz catheters have received increasing attention, auscultatory sequelae have not previously been described. In the patient described in this report, insertion of a Swan-Ganz catheter resulted in a loud mid systolic click; removal of the catheter eliminated the click. Simultaneous phonoechocardiograms suggest that the click resulted from crisp contact of the catheter against the ventricular septum. Catheter momentum was enhanced by wide excursion and systemic pressures in the right ventricle; paradoxical motion of the septum during systole may have accentuated the force of its contact with the catheter.

Cardiac Catheterization↗
PubMed1979

Calcific pulmonic stenosis in adulthood: treatment by valve replacement (porcine xenograft) with postoperative hemodynamic evaluation.

Clinical and morphologic features are described in a 56-year-old man in whom severe, isolated pulmonic valve stenosis was treated by valve replacement with a porcine prosthesis. The calcific deposits were located on the ventricular aspect of the pulmonic valve, opposite the location (arterial aspect) of calcific deposits on stenotic aortic valves, and calcific deposits also were present in the tricuspid valve anulus.

Animals↗
PubMed1979

Coronary artery narrowing in coronary heart disease: comparison of cineangiographic and necropsy findings.

Of 10 patients with fatal coronary heart disease undergoing coronary angiography 0 to 69 d (average, 21) before necropsy, the amount of narrowing in 61 coronary arteries observed angiographically (diameter reduction) during life by three angiographers was compared with that observed histologically (cross-sectional area) at necropsy. No overestimations of the degree of narrowing were made angiographically. Of 11 coronary arteries or their subdivisions narrowed 0 to 50% in cross-sectional area histologically, none were underestimated angiographically; of eight narrowed 51% to 75% histologically, seven had been underestimated, and of 42 narrowed 76% to 100% histologically, 17 were underestimated angiographically. The coronary atherosclerotic plaquing was diffuse (greater than 25% cross-sectional area narrowing) in 90% of 467 five-millimetre segments of coronary artery examined (24 cm per patient), and this diffuseness of the atherosclerotic process seems to be the major reason for angiographic underestimation of coronary narrowings.

Adult↗
PubMed1979

Cardiac findings in Charcot-Marie-Tooth disease. A prospective study of 68 patients.

Charcot-Marie-Tooth disease (peroneal muscular atrophy) has been reported to cause cardiac arrthymias and conduction disturbances in association with peripheral muscle atrophy. To establish more accurately the frequency of such cardiac disorders in this disease, 68 patients with Charcot-Marie-Tooth disease were evaluated prospectively for evidence of cardiac involvement. Cardiac findings were limited to five patients with conduction defects, two patients with supraventricular tachycardia, two patients with ischemic heart disease, and 20 with mitral valve prolapse. The frequency of each of the abnormal cardiac findings, with the possibly emalities in the population at large. The low incidence of cardiac involvement in patients with Charcot-Marie-Tooth disease may be helpful in distinguishing this disorder from Friedreich's ataxia, an entity that may mimic Charcot-Marie-Tooth disease but that is frequently associated with heart disease.

Adult↗
PubMed1978

Vascular complications of thorium dioxide.

Vascular complications occurring late after exposure to thorium dioxide (thorotrast) are described in two patients. One patient had both cerebral andmyocardial infarcts and died at age 25 years. Necropsy disclosed both adventitial and intimal fibrosis of the left carotid artery and greater than 75 per cent cross-sectional area luminal narrowing of both the left main and left anterior descending coronary arteries. The other patient, a 33 year old man, had no cerebral symptoms in life but total obstruction of the right carotid artery secondary to a thorotrastoma was found at necropsy. Vascular complications due to thorotrast appear to represent consequences of chronic alpha irradiation.

Adult↗
PubMedDate not supplied

Cardiac electrophysiologic testing: its role in the selection of antiarrhythmic drug regimens for supraventricular and ventricular arrhythmias.

Cardiac electrophysiology studies use intracardiac recording and programmed stimulation to define the mechanisms and most appropriate therapy for supraventricular and ventricular arrhythmias. Using these techniques, the majority of clinical tachycardias can be reproducibly initiated and terminated in the electrophysiology laboratory, thereby allowing the most appropriate therapy to be selected. With this approach, antiarrhythmic agents can be tested in a systematic, serialized fashion for efficacy, safety and patient tolerance. With both supraventricular and ventricular tachycardias, suppression of arrhythmia induction predicts freedom from recurrence, whereas inducibility carries a poor prognosis in clinical follow-up. Electrophysiology studies provide a safe and effective approach to the treatment of selected patients with cardiac arrhythmias.

Anti-Arrhythmia Agents↗
PubMedDate not supplied

The biology of restenosis.

Recent studies have allowed a better understanding of the biology of restenosis. Neointimal thickening--also referred to as neointimal hyperplasia--occurs in response to experimental arterial injury. This process involves different steps which include smooth muscle cell activation, proliferation, and migration, and the production of extracellular matrix. Neointimal thickening has been identified as one of the mechanisms of restenosis after balloon angioplasty in humans. The factors which control neointimal thickening include growth factors, hormonal factors, and mechanical factors. Delinquent reendothelialization has been shown to have a permissive impact on smooth muscle cell proliferation. In addition to neointimal thickening, arterial remodeling also plays a major role in restenosis. Studies performed on animals and in human subjects have established the potential for "constrictive remodeling" to reduce the vessel lumen after angioplasty. Restenosis thus appears as a multifactorial entity that may be addressed in the future by a combined mechanical and pharmacological approach.

Angioplasty, Balloon↗
PubMedDate not supplied

Multicenter trial of the wallstent in the iliac and femoral arteries.

PURPOSE: To report the results of the FDA phase II, multicenter trial of the Wallstent in the iliac and femoral arteries. PATIENTS AND METHODS: Two hundred twenty-five patients entered the trial. Stents were placed in the iliac system in 140 patients and in the femoral system in 90 (five patients required both iliac and femoral stents). Clinical patency was measured over 2 years by means of life-table analysis with use of clinical and hemodynamic data and the Rutherford scale. Angiographic patency was measured at 6 months. RESULTS: In the iliac system the primary clinical patency was 81% at 1 year and was 71% at 2 years. The secondary clinical patency was 91% and 86%, respectively. The 6-month angiographic patency was 93%. In the femoral system the primary clinical patency was 61% at 1 year and 49% at 2 years. The secondary patency was 84% and 72%, respectively. The 6-month angiographic patency was 80%. CONCLUSIONS: The results are similar to those with the Palmaz stent in the iliac system and with angioplasty alone in the iliac and femoral systems.

Adult↗
PubMedDate not supplied

Expression of tie1 and tie2 proteins during reendothelialization in balloon-injured rat carotid artery.

The novel endothelial cell tyrosine kinase receptors, Tie1 and Tie2, are essential for vascular development and remodeling in the embryo but little is known regarding the regulation of their expression and their role in the maintenance and repair of the adult vascular system. We examined the expression of Tie1 and Tie2 in normal vessels and during reendothelialization following balloon injury of the adult rat carotid artery. Tie proteins were detected in quiescent endothelial cells of the adult rat carotid artery. Tie1 and Tie2 proteins were also detected in human and rat platelets. A weak expression of Tie1 and Tie2 proteins was detected in young endothelial cells which sparsely repopulated the denuded surface by day 14. Protein levels increased in the confluent layer of endothelial cells by day 28. Based on these observations, we tested whether Tie1 and Tie2 mRNA and protein levels are regulated by cell density. Tie1 and Tie2 expression significantly increased with higher density in cultured human endothelial cells, and this upregulation required cell-cell interaction. These data suggest that Tie1 and Tie2 may play a role in the maintenance and repair of the adult vascular system and that the expression of these proteins is regulated by cell density.

Angioplasty, Balloon↗
PubMedDate not supplied

Vascular endothelial growth factor/vascular permeability factor enhances vascular permeability via nitric oxide and prostacyclin.

BACKGROUND: Vascular endothelial growth factor (VEGF), an endothelial cell mitogen that promotes angiogenesis, was initially identified as a vascular permeability factor (VPF). Abundant evidence suggests that angiogenesis is preceded and/or accompanied by enhanced microvascular permeability. The mechanism by which VEGF/VPF increases vascular permeability (VP), however, has remained enigmatic. Accordingly, we used an in vivo assay of VP (Miles assay) to study the putative mediators of VEGF/VPF-induced permeability. METHODS AND RESULTS: VEGF/VPF and positive controls (platelet-activating factor [PAF], histamine, and bradykinin) all increased vascular permeability. Prior administration of the tyrosine kinase inhibitors genistein or herbimycin A prevented VEGF/VPF-induced permeability. Placenta growth factor, which binds to Flt-1/VEGF-R1 but not Flk-1/KDR/VEGF-R2 receptor tyrosine kinase, failed to increase permeability. Other growth factors such as basic fibroblast growth factor (FGF), acidic FGF, platelet-derived growth factor-BB, transforming growth factor-beta, scatter factor, and granulocyte macrophage-colony stimulating factor (8 to 128 ng) failed to increase permeability. VEGF/VPF-induced permeability was significantly attenuated by the nitric oxide (NO) synthase inhibitors N(omega)-nitro-L-arginine (10 mg/kg) or N(omega)-nitro-L-arginine methyl ester (20 mg/kg) and the cyclooxygenase inhibitor indomethacin (5 mg/kg). The inactive enantiomer N(omega)-nitro-D-arginine methyl ester (20 mg/kg) did not inhibit VEGF/VPF-induced permeability. In vitro studies confirmed that VEGF/VPF stimulates synthesis of NO and prostaglandin metabolites in microvascular endothelial cells. Finally, NO donors and the prostacyclin analogue taprostene administered together but not alone reproduced the increase in permeability observed with VEGF/VPF. CONCLUSIONS: These results implicate NO and prostacyclin produced by the interaction of VEGF/VPF with its Flk-1/KDR/VEGF-R2 receptor as mediators of VEGF/VPF-induced vascular permeability. Moreover, this property appears unique to VEGF/VPF among angiogenic cytokines.

Animals↗
PubMedDate not supplied

Gene therapy for myocardial angiogenesis: initial clinical results with direct myocardial injection of phVEGF165 as sole therapy for myocardial ischemia.

BACKGROUND: We initiated a phase 1 clinical study to determine the safety and bioactivity of direct myocardial gene transfer of vascular endothelial growth factor (VEGF) as sole therapy for patients with symptomatic myocardial ischemia. METHODS AND RESULTS: VEGF gene transfer (GTx) was performed in 5 patients (all male, ages 53 to 71) who had failed conventional therapy; these men had angina (determined by angiographically documented coronary artery disease). Naked plasmid DNA encoding VEGF (phVEGF165) was injected directly into the ischemic myocardium via a mini left anterior thoracotomy. Injections caused no changes in heart rate (pre-GTx=75+/-15/min versus post-GTx=80+/-16/min, P=NS), systolic BP (114+/-7 versus 118+/-7 mm Hg, P=NS), or diastolic BP (57+/-2 versus 59+/-2 mm Hg, P=NS). Ventricular arrhythmias were limited to single unifocal premature beats at the moment of injection. Serial ECGs showed no evidence of new myocardial infarction in any patient. Intraoperative blood loss was 0 to 50 cm3, and total chest tube drainage was 110 to 395 cm3. Postoperative cardiac output fell transiently but increased within 24 hours (preanesthesia=4.8+/-0.4 versus postanesthesia=4.1+/-0.3 versus 24 hours postoperative=6. 3+/-0.8, P=0.02). Time to extubation after closure was 18.4+/-1.4 minutes; average postoperative hospital stay was 3.8 days. All patients had significant reduction in angina (nitroglycerin [NTG] use=53.9+/-10.0/wk pre-GTx versus 9.8+/-6.9/wk post-GTx, P<0.03). Postoperative left ventricular ejection fraction (LVEF) was either unchanged (n=3) or improved (n=2, mean increase in LVEF=5%). Objective evidence of reduced ischemia was documented using dobutamine single photon emission computed tomography (SPECT)-sestamibi imaging in all patients. Coronary angiography showed improved Rentrop score in 5 of 5 patients. CONCLUSIONS: This initial experience with naked gene transfer as sole therapy for myocardial ischemia suggests that direct myocardial injection of naked plasmid DNA, via a minimally invasive chest wall incision, is safe and may lead to reduced symptoms and improved myocardial perfusion in selected patients with chronic myocardial ischemia.

Aged↗
PubMedDate not supplied

Restoration of E2F expression rescues vascular endothelial cells from tumor necrosis factor-alpha-induced apoptosis.

BACKGROUND: Normally, quiescent endothelial cells (EC) line the inner surface of arteries and protect against thrombosis and neointimal growth. A variety of noxious stimuli, including balloon angioplasty, may compromise EC integrity, thereby initiating proliferation and triggering the local release of cytokines, including tumor necrosis factor-alpha (TNF-alpha). METHODS AND RESULTS: In vivo blockade of TNF-alpha using a soluble receptor molecule results in accelerated reendothelialization at sites of balloon angioplasty, suggesting an important physiological role of TNF-alpha in attenuating regrowth of endothelium after balloon angioplasty. Our studies reveal that TNF-alpha, an apoptosis-inducing cytokine, induces G1 cell-cycle arrest in proliferating EC. Quiescent EC are relatively immune to TNF-induced apoptosis versus proliferating EC, which display repression of the E2F transcription factor coincident with TNF-induced apoptosis and cell-cycle arrest. We also show that in this setting, E2F overexpression exerts a survival effect in proliferating EC and restores cell-cycle progression, in direct contrast to results of prior reports, which revealed that deregulated expression of E2F in normally cycling cells induces apoptosis. CONCLUSIONS: These data demonstrate that TNF-induced apoptosis is highly dependent on cell-cycle activity and that E2F can function as survival factor under certain conditions.

Angioplasty, Balloon↗
PubMedDate not supplied

Age-dependent impairment of angiogenesis.

BACKGROUND: The effect of aging on angiogenesis in ischemic vascular disease has not been studied. Accordingly, we investigated the hypothesis that angiogenesis is impaired as a function of age. METHODS AND RESULTS: Forty days after the resection of 1 femoral artery, collateral vessel development was significantly impaired in old (aged 4 to 5 years; n=7) versus young (aged 6 to 8 months; n=6) New Zealand White (NZW) rabbits on the basis of reduced hindlimb perfusion (ischemic: normal blood pressure ratio=0.58+/-0.05 versus 0.77+/-0.06; P<0.005), reduced number of angiographically visible vessels (angiographic score=0.48+/-0.05 versus 0.70+/-0.05; P<0.01), and lower capillary density in the ischemic limb (130.3+/-5.8/mm2 versus 171.4+/-9.5/mm2; P<0.001). Angiogenesis was also impaired in old (aged 2 years) versus young (aged 12 weeks) mice as shown by reduced hindlimb perfusion (measured by laser Doppler imaging) and lower capillary density (353.0+/-14.3/mm2 versus 713.3+/-63.4/mm2; P<0.01). Impaired angiogenesis in old animals was the result of impaired endothelial function (lower basal NO release and decreased vasodilation in response to acetylcholine) and a lower expression of vascular endothelial growth factor (VEGF) in ischemic tissues (by Northern blot, Western blot, and immunohistochemistry). When recombinant VEGF protein was administered to young and old rabbits, both groups exhibited a significant and similar increase in blood pressure ratio, angiographic score, and capillary density. CONCLUSIONS: Angiogenesis responsible for collateral development in limb ischemia is impaired with aging; responsible mechanisms include age-related endothelial dysfunction and reduced VEGF expression. Advanced age, however, does not preclude augmentation of collateral vessel development in response to exogenous angiogenic cytokines.

Aging↗