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Biomedical subjects

F O Tio

Publications and source records attributed to F O Tio.

At least 37 records · Page 2Linked to original sources
PubMed1997

Single-dose intramuscular administration of sustained-release Angiopeptin reduces neointimal hyperplasia in a porcine coronary in-stent restenosis model.

BACKGROUND: In-stent restenosis results primarily from neointimal hyperplasia. In a previous study we showed that continuous subcutaneous Angiopeptin infusion for 1 week significantly reduces neointimal hyperplasia in a porcine coronary overstretch in-stent restenosis model. The present study evaluated the relative efficacy of immediate-release and sustained-release Angiopeptin in the same model. METHODS: Thirty pigs (n = 10 in each group) were randomly assigned to three groups: controls receiving no Angiopeptin (Group 1); a sustained-release treatment group receiving one time intramuscular administration of 20 mg of Angiopeptin (Group 2); and a systemic treatment group receiving continuous Angiopeptin over a 1-week period via a subcutaneous osmotic pump (200 micrograms/kg total dose) (Group 3). One oversized Palmaz-Schatz stent (mean stent/artery = 1.25) was subsequently implanted in the left anterior descending coronary artery. The degree of neointimal reaction was evaluated 4 weeks later by angiography (maximal per cent diameter stenosis) and histology (maximal neointimal area corrected for injury score). RESULTS: A trend towards a reduction in diameter stenosis was observed by angiography, despite a similar degree of injury (25 +/- 17% in Group 1, 13 +/- 8% in Group 2, and 14 +/- 9% in Group 3; P = 0.072 by ANOVA). Histology demonstrated that both Angiopeptin treatment strategies significantly reduced in-stent neointimal area compared with the control group (1.65 +/- 0.97 mm2 in Group 1 versus 0.93 +/- 0.41 mm2 in Group 2 versus 0.85 +/- 0.28 mm2 in Group 3; P = 0.016 by ANOVA). Measurement of plasma Angiopeptin levels revealed comparable levels in both treatment groups, which persisted for up to 2 weeks. CONCLUSIONS: This study shows that single-dose intramuscular administration of sustained-release Angiopeptin reduces in-stent restenosis as effectively as the prolonged systemic treatment requiring a subcutaneous pump. Thus, a practical, effective, pharmacologic therapy for preventing in-stent restenosis may be available and should be evaluated in patients.

Animals↗
PubMed1997

A randomized animal study evaluating the efficacies of locally delivered heparin and urokinase for reducing in-stent restenosis.

BACKGROUND: In-stent restenosis is primarily due to neointimal hyperplasia. Results from recent nonrandomized studies suggest that local delivery of heparin or urokinase to the site of angioplasty or stenting results in a lower rate of restenosis. OBJECTIVE: To determine whether local delivery of heparin or urokinase reduces in-stent restenosis. METHODS AND RESULTS: Thirty-three pigs were assigned randomly to one of three groups: controls (n = 9) administered local saline infusion, the heparin group (n = 15) administered local heparin (6000 u/10 min), and the urokinase group (n = 9) administered local urokinase (250000 u/10 min), via a local delivery catheter (Dispatch) at the site of subsequent stent implantation. Prior to local delivery, all of the animals were subjected to balloon injury (balloon:artery diameter ratio approximately or = 1.3) to facilitate intramural drug impregnation. After local therapy, one Palmaz-Schatz stent (mean stent: artery diameter ratio approximately or = 1.25) was implanted within the left anterior descending coronary artery. The degree of neointimal hyperplasia was evaluated 4 weeks later by angiography (as the maximal percentage diameter stenosis) and histology (as the maximal neointimal area stenosis). We found no difference in percentage diameter stenosis (46 +/- 18% control, 42 +/- 27% heparin group, and 37 +/- 20% urokinase group, P = 0.7) and corrected neointimal area (1.06 +/- 0.42 mm2 control, 0.94 +/- 0.29 mm2 heparin, and 0.88 +/- 0.26 mm2 urokinase group, P = 0.7) among groups at follow-up. The activated clotting time rose slightly for heparin-treated animals, suggesting that systemic delivery had occurred, whereas fibrinogen levels did not change in urokinase-treated animals. CONCLUSIONS: Local deliveries of heparin and urokinase via the Dispatch catheter, at the chosen dosages, do not reduce in-stent neointimal hyperplasia in this porcine model.

Animals↗
PubMed1996

Interleukin-2 receptor-specific fusion toxin inhibits barotrauma-induced arterial atherosclerosis.

Immunocytochemical analyses of human plaques and experimental arterial lesions have implicated activated lymphocytes and monocytes in the pathogenesis of atherosclerosis, as demonstrated by the expression of interleukin-2 (IL-2) membrane receptors and major histocompatibility complex class II epitopes. The objective is to determine if targeting these cells with an IL-2 receptor-specific chimeric toxin, DAB486-IL-2, can inhibit experimental post-angioplasty vascular neointimal thickening. Twenty-two atherogenically modeled rabbits were treated in vivo with DAB486-IL-2 (0.1 mg/kg per day i.v.; n = 11) or placebo (n = 11) for 10 days following aortic balloon angioplasty (4 atm x 30 s each x 2 dilatations). In vitro 3H-leucine incorporation studies of mononuclear leukocyte and vascular smooth muscle cell protein synthesis inhibition by DAB486-IL-2 were also performed. Angioplasty sites were examined for evidence of hyperproliferative atherosclerotic narrowing by quantitative angiography and histomorphometry of neointimal cross-sectional area at baseline and 6 weeks after injury. In vitro Concanavalin-A stimulated rabbit mononuclear leukocyte protein synthesis was 50% inhibited by DAB486-IL-2 at a concentration (IC50) of 6 x 10(-11) M. Rabbit vascular smooth muscle cells were approximately 150-fold less sensitive to DAB486-IL-2 (IC50 = 10(-8) M). In vivo studies showed no change in angioplasty site angiographic minimum luminal diameter at 6 weeks in DAB486-IL-2 treated animals (from 2.96 +/- 0.52 to 2.96 +/- 0.48 mm; percent cross-sectional area reduction = 1 +/- 10%; P = N.S.). In control animals, luminal diameter decreased from 2.79 +/- 0.4 to 2.32 +/- 0.52 mm at 6 weeks, and percent cross-sectional area was reduced by 34 +/- 14% (P < 0.01 vs. placebo). Quantitative histomorphometric angioplasty segmental intimal cross-sectional area reduction of treated and placebo vessels also differed significantly (19 +/- 16% vs. 31 +/- 21%; P < 0.05). DAB486-IL-2 caused no adverse effects on animal survival, weight or hepatic transaminase levels. We conclude that post-angioplasty administration of the chimeric toxin DAB486-IL-2 inhibits angiographic narrowing and neointimal thickening in the atherogenic rabbit model. Although this IL-2 receptor-specific molecule was cytotoxic in vitro for activated mononuclear leukocytes and vascular smooth muscle cells, systemic toxicity did not occur in vivo at a dose comparable to that evaluated in clinical trials of this agent. Potential anti-proliferative effects of this chimeric toxin may be mediated by direct local inhibition of leukocyte-mediated inflammation, or through the indirect modification of vascular cell mitogenesis and cytokine release.

Angioplasty, Balloon↗
PubMed1995

Self-expanding nitinol stents in canine vertebral arteries: hemodynamics and tissue response.

PURPOSE: To evaluate the hemodynamics and tissue response associated with stent placement in low-flow-velocity arteries. METHODS: Six self-expanding nitinol stents (5.5 mm caliber) were implanted transfemorally within the proximal segments of vertebral arteries (2.5 mm diameter) in six adult dogs during anticoagulative protection. RESULTS: Control angiograms demonstrated patency and 20% dilatation of all stented arteries. One artery was partially thrombosed 1 week later and subsequently showed a 50% stenosis. Throughout the observation period (4 to 9 months after stenting), the other five arteries remained patent without significant narrowing (< or = 15%). Small cervical muscle branches originating from the vertebral arteries within the stented segments remained patent. No major branch occlusions of the vertebrobasilar system were detected. Stent migration or kinking did not occur. MR studies of the brain 4 months after implantation revealed no infarcted areas. These findings were confirmed with brain sections. Stented artery specimens showed delayed stent dilatation. A comparison of the total mean thickness of intima covering the five 30- to 40-mm stents removed at 4, 6, and 9 months showed no significant difference (338, 332, and 389 microns, respectively). Histologic findings verified the macroscopic impression of a thicker intima at the inner curve of the stented artery segments and at the junctions of the stent filaments. The shortest (10 mm) stent had the thinnest neointimal growth (155 microns). Stented vessels showed compression of the media with atrophy, but without necrosis or perforation. Scanning electron photomicrographs revealed intact endothelial cell linings with typical elongated cells. CONCLUSIONS: No significant risk of thromboembolic events exists after implanting these nitinol stents in nonatherosclerotic vertebral arteries in dogs. Thicker neointimal growth after stenting may result from either low wall shear stress with possible flow separation or from changes in the shape and size of the stent, or both.

Alloys↗
PubMed1995

Severe diarrhea due to Cokeromyces recurvatus in a bone marrow transplant recipient.

Cokeromyces recurvatus, a sporangiola-forming dimorphic fungus, is a rare cause of urogenital infection in humans. We report here a case of severe watery diarrhea due to C. recurvatus, which was treated successfully with high-dose oral nystatin therapy. We speculate that our patient was probably predisposed to infections due to opportunistic organisms, such as C. recurvatus, because of post-transplantation immunosuppression. To our knowledge, our patient represents the first documented case of diarrhea due to C. recurvatus in man, and this case highlights the potential pathogenic capability of this opportunistic organism in immunosuppressed patients.

Bone Marrow Transplantation↗
PubMed1995

Standardization of conjunctival impression cytology.

Lack of standardization limits the potential of conjunctival impression cytology as a clinical and research tool. This may be attributed to the variety of filter paper currently used. MF Millipore membrane filters of pore sizes 8.0, 3.0, 0.45, 0.22, and 0.025 micron were tested. Samples obtained from 30 eyes of rabbits were randomized and scored by four masked observers for cellularity and morphologic preservation. Cellularity was significantly greater with pore sizes 8.0, 3.0, and 0.45 micron versus 0.22 and 0.025 micron (p < or = 0.001), with an 83% correlation among four scorers. In contrast, morphology was better preserved in the smaller pore size papers (0.22 and 0.025 micron) when compared with larger pore sizes (p = 0.048). Using the best two filter papers (0.22 and 0.025 micron) and an ophthalmodynamometer, either 40, 60, or 80 g of pressure was applied for 3 s to each pore size paper to see whether cellularity could be increased. Cellularity was greater with pore size 0.22 than 0.025 micron (42.3 +/- 19.8 versus 8.7 +/- 6.4). Regardless of the pore size of the filter paper, cellularity was significantly improved at 60 g when compared with either 80 or 40 g. The results show that to maximize cell acquisition, a paper with medium pore size (0.22 micron) and a pressure of 60 g may be the best choice.

Animals↗
PubMed1993

Contrast-enhanced MRI of healed pathologic vertebral compression fracture mimicking active disease in a patient treated for lymphoma.

Despite the valuable contribution of MRI, the distinction between benign and malignant compression fractures of the spine is sometimes difficult, and cannot with certainty be based on T1- and T2-weighted signal criteria alone, or on the configuration of the compression fracture. This case report demonstrates that in certain instances neither can gadolinium enhancement specifically make this determination in cases of treated malignancy of the spinal column. Because treated neoplasia having benign histologic characteristics may continue to enhance with IV gadolinium, biopsy evaluation must be undertaken in this setting in order to prove the diagnosis.

Bone Marrow↗
PubMed1993

Primary left atrial myxosarcoma.

A patient in whom rapidly progressive congestive heart failure developed due to the presence of a left atrial myxosarcoma is described. The histologic picture is consistent with the hypothesis that cardiac myxoid tumors are neoplasms derived from undifferentiated cells found in the endocardium. Unfortunately, most cardiac malignancies are detected too late for curative resection, and palliation remains the mainstay of therapy.

Adult↗
PubMed1993

Re-expansion of balloon-expandable stents after growth.

OBJECTIVES: The purpose of this study was to evaluate the feasibility of re-expansion of balloon expandable intravascular stents and to examine the gross and histologic effects of re-expansion on vascular integrity. BACKGROUND: Intravascular stents have been used successfully as an adjunct to balloon dilation of congenital pulmonary artery branch stenosis and postoperative stenosis of the pulmonary arteries in children. However, use of rigid stents in children could result in development of relative stenosis at the site of stent implantation with subsequent growth of the child. METHODS: Stainless steel "iliac" stents were placed in the thoracic aorta of 10 normal juvenile swine by a transcatheter technique. Angiography and re-expansion were performed at a mean of 11 weeks (n = 9) and again at 18 weeks (n = 5). After euthanasia, the aortic specimens were removed for gross and histologic examination. RESULTS: Stents were successfully implanted in 10 swine. Re-expansion was successfully performed in each animal at 11 weeks and at 18 weeks. Aortic growth produced a relative constriction of the aorta of 20% +/- 10% (mean +/- SD) at the site of stent implantation at both 11 and 18 weeks. Re-expansion produced a significant increase in mean stent diameter from 10.1 +/- 1 mm to 12.3 +/- 1.2 mm at 11 weeks and from 11.2 +/- 0.7 to 13.5 +/- 1.1 mm at 18 weeks after implantation (p < 0.001). Balloon dilation produced a relative increase in stent diameter of 21% +/- 7% at 11 weeks and 18% +/- 4% at 18 weeks. Stent re-expansion was accompanied by plastic deformation of the neointima without neointimal dissection. Where neointima was thick, there was no evidence of neointimal abrasion, but where neointima was thin, areas of localized neointimal abrasion were observed with focal fibrin and platelet adherence to the stent struts. There was no evidence of medial or adventitial hemorrhage or dissection produced by re-expansion. CONCLUSIONS: Re-expansion of intravascular stents is feasible after growth in juvenile swine without significant injury to neointima, media or adventitia. The results of this study support careful and selective use of intravascular stents as an adjunct to balloon dilation of congenital stenoses in children.

Animals↗
PubMed1992

Intraluminal bypass of abdominal aortic aneurysm: feasibility study.

This study evaluated the feasibility of treatment of abdominal aortic aneurysm (AAA) by means of intraluminal bypass. Artificial aortic aneurysms with fusiform Dacron conduits were created at surgery , a weft-knit Dacron tube with balloon-expandable stents attached at both ends was inserted transfemorally through a 14-F introducer sheath and expanded at the aneurysmal level by means of inflation of a coaxial balloon. The transluminal bypass successfully excluded the aneurysmal lumen immediately after placement. In two dogs, a postplacement aortogram revealed torsion of the graft that caused early occlusion. The six other dogs had a patent bypass at 6 months follow-up. Four of these dogs had evidence of kinking of the graft as a result of shrinkage of the prosthetic aneurysm. Histopathologic studies revealed that endothelialization was complete on the stents and partial on the graft surface. It is concluded that transluminal bypass of AAA is feasible in the dog model.

Animals↗
PubMed1991

Luminal surfaces of fetal rat alveolar type II and Clara lung cells react with antibody to Heymann nephritis antigen.

We have used affinity purified antibody, which reacts with the renal antigen gp600, to examine the immunoreactivity of pulmonary cells in the quick frozen lung tissue of fetal rats. On immunoelectron microscopy, we found that the reaction was specifically localized to the luminal surfaces of Clara cell and, as previously reported, to alveolar type II cell (ATII) membranes. No immunoreaction was seen on or in type I cells, endothelial cells or any other lung or blood cell. These studies suggest that the anti-gp600 immunoselection can be used as a marker to identify and quantify Clara and ATII cells in rat lung tissue.

Animals↗
PubMed1991

Resolution of microsporidial epithelial keratopathy in a patient with AIDS.

A patient with a positive human immunodeficiency virus (HIV) titer and cryptococcal meningitis suffered bilateral epithelial keratopathy caused by Encephalitozoon, which did not respond to sulfas, erythromycin, bacitracin, tobramycin, neomycin, polymyxin B, or fluconazole. Eventual administration of itraconazole for the meningitis apparently produced resolution of the long-lasting (2-month) ocular infection. This new oral triazole antifungal may be valuable against the increasingly prevalent microsporidial infections in patients with acquired immune deficiency syndrome. Debulking of the infection by corneal scraping may have contributed to the authors' success.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Isolation and characterization of a new human microsporidian, Encephalitozoon hellem (n. sp.), from three AIDS patients with keratoconjunctivitis.

A new human microsporidian was isolated from cultures of Madin-Darby canine kidney cells incubated with conjunctival scrapings or corneal tissues from three AIDS patients with keratoconjunctivitis. The three isolates were morphologically similar to Encephalitozoon cuniculi. The spores averaged 1 x 1.5-2.0 microns, had six to eight polar filament coils, displayed monokaryotic nuclei, and possessed relatively thick endospores with irregularly shaped exospores. Organisms developed within a parasitophorous vacuole. By SDS-PAGE analysis, the three isolates appeared to be identical but were different from E. cuniculi. Identical banding patterns on Western blots of the three isolates were expressed by each patient's serum. By Western immunoblotting, murine antisera to E. cuniculi reacted to several antigens of the new AIDS-related microsporidian, whereas murine antisera bound weakly to Nosema corneum. The name Encephalitozoon hellem (n. sp.) is proposed to identify this new human microsporidian.

Acquired Immunodeficiency Syndrome↗
PubMed1991

In vivo technetium-99m S12 antibody imaging of platelet alpha-granules in rabbit endothelial neointimal proliferation after angioplasty.

To examine the specificity of technetium-99m monoclonal antibody (S12) imaging for identifying activated platelets at interventional injury sites in atherosclerotic rabbit arteries, subgroups of unheparinized rabbits (n = 39) underwent serial percutaneous transluminal aortic angioplasty (PTA) procedures (with or without intravascular stent placement) followed by in vivo and then ex vivo gamma camera imaging, scanning, and immunoelectron microscopy to determine the intravascular loci of S12 Fab' antibody binding. Despite angiographic vessel patency, image-derived ratios of in vivo S12 binding in injured versus uninjured vascular segments were significantly increased (p less than 0.05) after one PTA (1.3 +/- 0.17, n = 7), PTA twice at 6-week intervals (1.4 +/- 0.22, n = 7), and PTA plus stent placement (1.6 +/- 0.28, n = 7) compared with control experiments (1.1 +/- 0.13, n = 7). Ex vivo imaging of blood-free excised aortas confirmed S12 localization at PTA (2 +/- 0.4, n = 3) and PTA plus stent placement (5 +/- 3.8, n = 7) sites (both p less than 0.05 versus controls). S12 antibody uptake decreased significantly (p less than 0.05) at 1 week after PTA plus stent placement in vivo (1.1 +/- 0.10, n = 4) and ex vivo (1.6 +/- 0.7, n = 3). Electron microscopic studies confirmed dense platelet, fibrin, and red blood cell deposition in regions of acute injury, with endothelial neointimal proliferation at 1 week after PTA. Immunoelectron microscopic studies confirmed specific in vivo S12 binding (22:1 versus nonrelevant IgG) at sites of alpha-granule GMP-140 expression in activated platelets. Therefore, S12 studies may be useful to localize sites of platelet-derived mitogen release at arterial PTA injury sites.

Angioplasty, Balloon↗
PubMed1989

Definition of an immunologic marker for type II pneumocytes.

Based on our previous finding in lung parenchyma of high concentration of the shared epitopes of gp600, a well characterized kidney glycoprotein, we attempted to identify the anatomic site of these epitopes and characterize them biochemically. Affinity-purified polyclonal anti-gp600 antibody was used as the probe. Immunocytochemically in lung on light and electron microscopy the probe reacted exclusively with type II pneumocytes and no other lung cell. The reaction was also demonstrated on freshly isolated and cultured type II pneumocytes. Both approaches showed the reaction to localize on the cell membrane of type II pneumocytes. Immunoprecipitation of radiolabeled type II pneumocyte cell membranes identified two 270- to 290-kDa polypeptides as the reactive proteins. We conclude that the reactive epitopes for anti-gp600 in lung parenchyma are exclusively localized on type II pneumocytes and have a Mr of approximately 270 to 290 kDa and that anti-gp600 may be used as a specific immunologic marker for the type II pneumocytes. Finally, it is possible that the differences in the molecular forms of the cross-reactive proteins in lung and kidney identified in this report are the reason for the known non-nephritogenicity of rat lung for the induction of Heymann nephritis in rat.

Animals↗
PubMed1989

Primary adrenal lymphoma.

A case of non-Hodgkin's lymphoma (large cell immunoblastic sarcoma) arising as a primary malignancy in the adrenal gland is reported and the literature concerning this unusual tumor is reviewed. Although extremely rare, it is possible to make the diagnosis preoperatively. Therefore, primary adrenal lymphoma should be included in the differential diagnosis of a suprarenal mass.

Adrenal Gland Neoplasms↗