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Biomedical subjects

D U Kim

Publications and source records attributed to D U Kim.

At least 55 records · Page 3Linked to original sources

Polyglactin 910/polydioxanone bicomponent totally resorbable vascular prostheses.

Previous studies from our laboratory have shown that bioresorbable vascular prostheses woven from lactide-glycolide copolymers and implanted into arteries of several animal models become replaced by cellular tissues; the rate of replacement parallels the kinetics of prosthetic resorption. This study evaluates the efficacy of bicomponent resorbable prostheses as a method of augmenting resistance to dilatation during the resorption period of the more rapidly resorbed component. Bicomponent prostheses (n = 37) were woven from compound yarns containing 74% polyglactin 910 (PG910) and 26% polydioxanone (PDS) and were interposed into adult white New Zealand rabbit infrarenal aortas. Resultant prosthesis-tissue complexes were harvested after 2 weeks to 12 months. Specimens were photographed and sectioned for light, scanning, and transmission electron microscopy. Randomly selected fresh explants at 1 and 3 months and control aortic segments from the same rabbits were simultaneously perfused with culture media (37 degrees C, 100/80 mm Hg, 60 ml/min) and perfusates assayed by means of tritiated radioimmunoassay techniques for the stable prostacyclin metabolite 6-keto-PGF1 alpha before and after the addition of sodium arachidonate (10 micrograms/ml) to the media. Results showed 100% patency, no aneurysms, and stenosis in 1 of 37 prostheses (3%). PG910 was totally resorbed by 2 months and PDS by 6 months. By 1 month inner capsule thickness was 303 +/- 30 microns. In contrast to previous reports this was significantly thicker than that within 100% PDS (230 +/- 40 microns) and significantly less thick than in 100% PG910 (530 +/- 62 microns). Inner capsules in all three groups stabilized at similar thicknesses (417 to 502 microns).(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗

Derivation of neointima in vascular grafts.

Vascular prostheses woven from absorbable lactide/glycolide copolymers are replaced by myofibroblast-laden tissue conduits lined by endothelium. When these prostheses are implanted in arteries of animal models, the absorption-replacement reactions are inhibited by Dacron. To determine whether these reactions resulted primarily from transanastomotic pannus ingrowth, prostheses (30 mm x 4 mm) were constructed of three 10-mm long segments with Dacron segments on both ends and a middle polyglactin 910 (PG910) segment. The prostheses were implanted in the aortas of 15 adult New Zealand White rabbits. Resultant prosthesis/tissue complexes were harvested in triplicate at 2 weeks and at 1, 2, 3, and 4 months after implantation. Explants were photographed and sectioned for light microscopy and for scanning and transmission electron microscopy, which showed 100% patency with no aneurysms or stenoses. Inner-capsule thickness in the PG910 segments increased only during the interval from 2 weeks to 2 months; this thickness was statistically greater than either Dacron segment at 1 and 2 months (p less than or equal to 0.004 and p less than or equal to 0.0001, respectively). Proximal and distal Dacron segments did not differ from each other in thickness. Inner capsules of PG910 segments at 1 month were composed predominantly of myofibroblasts, whereas inner capsules of Dacron segments were composed of fibrin coagulum beyond the initial 2 mm of endothelial pannus ingrowth. These data suggest that transanastomotic pannus ingrowth is not the primary source of cells replacing absorbable vascular prostheses.

Absorption↗

Arterial regeneration over polydioxanone prostheses in the rabbit.

We analyzed histologic, ultrastructural, and functional characteristics of rabbit aortic conduits regenerated over absorbable polydioxanone prostheses. Twenty-eight polydioxanone-elicited prosthesis/tissue complexes harvested two weeks to 12 months following implantation were analyzed grossly; photographed; sectioned for light, scanning, and transmission electron microscopy; and studied for compliance, bursting strength, and prostacyclin and thromboxane metabolite contents. No aortic-related deaths or hemorrhages occurred. Smooth regenerated conduits without stenoses were seen in 27 of 28 specimens, with one small aneurysm. Transprosthetic myofibroblast migration and proliferation paralleled the kinetics of macrophage-mediated prosthetic dissolution, which was consequently delayed compared with polyglycolic acid prostheses. Confluent endothelial-like luminal surfaces were present after two weeks. Progressive inner capsular thickening ended after three months at 420 micron. Ex vivo compliance curves resembled arterial elasticity. Regenerated tissue withstood 1200 mm Hg of systolic pressure, and 6-keto-prostaglandin F1 alpha to thromboxane B2 ratios did not differ from normal control specimens.

6-Ketoprostaglandin F1 alpha↗

Biomaterial pretreatment with ECGF to augment endothelial cell proliferation.

ECGF, a polypeptide of bovine hypothalamic derivation, is the most potent endothelial cell mitogen known, with mitogenic and chemotactic effects well demonstrated in vitro on human endothelial cells. These effects are synergized by heparin. In vivo re-endothelialization of blood-contacting biomaterials may be enhanced by bonding ECGF and heparin to prosthetic surfaces. Long woven Dacron (24 mm) and woven PDS vascular prostheses were treated first with human plasma fibronectin (10 micrograms/cm2). Porcine sodium heparin (20 micrograms/cm2) was added by means of fibronectin's heparin affinity. Pure 125I-ECGF (95% alpha, 5% beta; 1 ng/cm2) was next fixed by the heparin affinity of ECGF and followed by a second heparin layer (20 micrograms/cm2) to synergize with and stabilize ECGF. 125I-ECGF adherences were determined by scintillation counts. Attachment efficiency averaged 25%. Prostheses were interposed into rabbit aortas and harvested in triplicate from 0 to 30 days to establish in vivo washout curves. After explantation, residual 125I-ECGF was eluted from prostheses, and intact ECGF was identified by SDS gel electrophoresis. Similarly prepared but nonradioiodinated Dacron and PDS prostheses were explanted after 7 days and their ECGF eluted off for in vitro activity documentation. This ECGF retained its mitogenic properties, causing a 1000% to 1200% increase in 3H-thymidine incorporation into newly synthesized DNA in test murine LE-II cells. Fibronectin-heparin-ECGF fixation to blood-contacting biomaterials may enhance spontaneous re-endothelialization and/or hasten the confluence of transplanted endothelial cells.

Animals↗

Compound polyglactin 910/polypropylene small vessel prostheses.

This study evaluated morphologic and functional characteristics of tissue reactions to compound prostheses of 69% absorbable polyglactin 910 (PG910) and 31% nonabsorbable polypropylene in the rabbit. Forty-two woven PG910/polypropylene prostheses (24 X 4 mm internal diameter) implanted into rabbit infrarenal aortas were harvested after 2 weeks to 12 months. Each explant was photographed and sectioned for light microscopy and transmission and scanning electron microscopy. Randomly selected explants underwent either compliance and bursting strength measurements or assays of production of prostacyclin and thromboxane metabolites by luminal surfaces of both regenerated conduits and normal control aortas in response to administered sodium arachidonate. Results showed 100% patency with no aneurysms and 2% stenoses (1 of 42 prostheses). Confluent endothelial-like cellular luminal surfaces covering oriented smooth muscle-like myofibroblasts comprised the inner capsules whose thicknesses stabilized at 1 to 2 months. Only residual polypropylene remained in the prostheses after 2 months. Compliance studies reflected a 0.65 mm (14%) change over a pressure range of 0 to 160 mm Hg. All regenerated prosthesis-tissue complexes had bursting strengths greater than the proximal perianastomotic native aortas, which burst between 600 and 2000 mm Hg. At 1 month the rate of production of 6-keto-PGF1 alpha per square millimeter of surface area of experimental segments was normal. Production of 6-keto-PGF1 alpha by experimental segments at 3 months had increased fourfold whereas thromboxane B2 (TxB2) production remained unchanged. The 6-keto-PGF1 alpha/TxB2 ratio increased from 1 to 4 months. This study demonstrates clinically efficacious morphologic, mechanical, and biochemical characteristics of PG910/polypropylene-elicited vascular prosthesis-tissue complexes.

6-Ketoprostaglandin F1 alpha↗

Dacron inhibition of arterial regenerative activities.

These biocompatibility studies evaluate the effects of Dacron, absorbable polymeric, and compound prostheses containing both elements in various constructions on the migration, proliferation, and functional characteristics of regenerating endothelial and smooth muscle-like cells in the rabbit aorta model. Prosthesis/tissue complexes explanted after 2 weeks to 9 months were studied grossly, photographed, sectioned for light microscopy and scanning and transmission electron microscopy, and assayed for 6-keto-PGE1 alpha contents in inner capsular tissues. Polyglycolic acid, polyglactin 910, or polydioxanone prostheses elicited a transinterstitial migration and proliferation of primitive mesenchymal cells that differentiated into smooth muscle-like myofibroblasts and a surface repopulation of confluent endothelial-like cells paralleling the time course of macrophage-mediated prosthetic dissolution. Even small Dacron components (20%) woven into or surrounding the absorbable polymer significantly inhibited these processes, yielding significantly thinner, less cellular inner capsules with lower 6-keto-PGF1 alpha contents. These studies show the augmentation of clinically efficacious arterial regenerative activities by polymers phagocytosed by macrophages and the inhibition of these activities by Dacron.

6-Ketoprostaglandin F1 alpha↗

Arterial regenerative activity after prosthetic implantation.

Factors modifying arterial regenerative activity were evaluated by replacing adult rabbit aortas with either absorbable polyglycolic acid (PGA) or nonabsorbable Dacron prostheses, 3.5 mm in internal diameter by 24 mm in length, woven to identical specifications including pore size, wall thickness, and elastic modulus, and were followed up for 12 months. At death, 48 PGA and 20 Dacron specimens were studied grossly and by arteriography, light microscopy, scanning and transmission electron microscopy, and by bursting strength determinations. There were no aortic-related deaths or transaortic hemorrhages. Both materials elicited a surrounding inflammatory reaction containing macrophages which transgressed the interstices of only the PGA prostheses. Between two and four weeks, circumferentially oriented smooth-musclelike myofibroblasts proliferated in the PGA inner capsule yielding a neointima 3.2 times thicker than Dacron's. Early ultrastructurally primitive cells progressively differentiated into these smooth-musclelike myofibroblasts. The few myofibroblasts later appearing with Dacron were radially oriented. After one month proliferation stopped in both groups and neointimal thickness became constant. The luminal surface in the PGA group was endothelial-like but was fibrinous in the Dacron group. All specimens withstood saline infusion at three to five times systolic pressure. These studies demonstrate great arterial regenerative potential and suggest hemodynamic and intercellular mitogens controlling it.

Animals↗

Video intercom: O.R. consultation and frozen section with screen display of gross and microscopic findings.

Seldom does the pathologist at Saint Barnabas Medical Center, Livingston, NJ, enter the operating room to consult with the operating surgeon. Instead, consultation takes place via an audio-intercommunication system supplemented by video. In this article, the authors explain how and when the system is used, the equipment needed, and the benefits to be derived by pathology residents.

Education, Medical↗

Anticipation of renal transplant failure by postanastomosis biopsy and immunofluorescence.

Ninety-six pre- and postanastomosis allograft biopsies from 48 transplant recipients were studied employing the direct fluorescent antibody procedure. Of the 48 transplants studied, 26 postanastomosis biopsies showed significant blood vessel wall deposits consisting predominantly of 2-4+ staining IgM and C3 deposits. The corresponding preanastomosis biopsies showed only patchy intimal surface staining. All but two of the grafts with positive biopsies had been preserved by the pulsatile perfusion method for various periods of time. Twenty-three of the twenty-six grafts with positive findings failed within 1 month while only 2 of the 19 negative postanastomosis biopsies failed within the 1-month period. Based on these findings actual graft failure occurred in 89% of the patients with postanastomosis transplant biopsies with positive findings. Although crossmatch studies were negative in all cases, further immunologic studies of eluates obtained from positive postanastomosis biopsies revealed the presence of lymphocytotoxic IgM antibodies in three of five cases studied. These findings suggest that rapid deposition of undetected preformed lymphocytotoxic antibodies accumulate in the vessel walls following anastomosis and contribute to transplant failure.

Biopsy↗

Treponemal antigen in immunopathogenesis of syphilitic glomerulonephritis.

A patient with syphilitic glomerulonephritis had a renal biopsy and was treated for secondary syphilis. Light, electron, and immunofluorescence microscopic studies revealed an acute proliferative glomerulonephritis with subepithelial, intramembranous, and subendothelial immune complex deposits containing IgG, IgA, IgM, C4, and C3. Similar local deposits containing predominantly IgM were noted in areas of mesangial proliferation. Indirect fluorescent antibody studies employing rabbit treponemal antibody and sheep antirabbit globulin conjugate revealed the presence of treponemal antigen in the glomerular deposits. This finding provides strong evidence for the immunopathogenesis of the glomerular lesion as well as a causal link with Treponema pallidum.

Adult↗

Albumin impregnated vascular grafts: albumin resorption and tissue reactions.

This study aimed to determine the kinetics of albumin resorption from and the healing of two types of albumin impregnated Vasculour II (Bard Cardiovascular) Dacron grafts (ACG-A and ACG-B) using whole blood preclotted Vasculour II Dacron grafts (without albumin) as controls (PCC). Prostheses measuring 4 mm ID x 50 mm length were implanted in the aortoiliac position in 24 dogs (ACG-A n = 12, ACG-B n = 24, PCC n = 12) and explanted after 1, 2 4, and 6 months. Platelet count, platelet aggregometry to 10(-5) M ADP, prothrombin time (PT), and partial thromboplastin time (PTT) were determined preoperatively and at explantation. Sections of the explanted grafts were assayed for human albumin by immunohistochemical techniques utilizing a rabbit polyclonal mono-specific antibody for human albumin followed by the addition of a biotinylated goat anti-rabbit IgG. Immunoperoxidase staining was then performed using Avidin D horse-radish peroxidase. Histology of the grafts (light microscopy, scanning electron microscopy, and transmission electron microscopy) as well as percent thrombus free surface area (TFSA) by computerized planimetry were also determined. Seven of 48 grafts were occluded (85.4% patency) with no difference among the three groups. Platelet aggregometry was not predictive of graft patency. No change in PT or PTT occurred nor was there any difference among the three groups. Retained albumin was detected in every one-month explant but not beyond that time, with the sensitivity for detecting human albumin in this assay being 20 mg albumin per gram of Dacron. All ACG explants at one month revealed inner capsular fibrin coagula not present in PCC specimens.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗

Kinetics of collagen deposition within bioresorbable and nonresorbable vascular prostheses.

This study compares the kinetics of collagen deposition within the prosthesis/tissue complexes formed following implantation of either polyglactin 910 (PG910), polydioxanone (PDS), or Dacron prostheses into rabbit infrarenal aortas. The grafts were explanted in triplicate at 1, 3, and 12 months, and then processed for spectrophotometric hydroxyproline quantitation. A 2 mm longitudinal strip from each sample was processed for histologic evaluation by light and electron microscopy. Results showed more extensive collagen deposition within the prosthesis/tissue complexes of both PG910 and PDS continuing throughout 3 months, as compared to less collagen deposition in Dacron grafts at all time points. Differences between PG910 and Dacron, and between PDS and Dacron at each time point were statistically significant. When correlated with previous related studies done in our laboratory, data showed that in resorbable grafts the rate of collagen deposition parallels the kinetics of cellular proliferation, tissue thickening, and graft resorption.

Animals↗

Prostacyclin production by blood-contacting surfaces of endothelialized vascular prostheses.

This study examines prostacyclin production by blood-contacting surfaces within woven vascular prostheses of polydioxanone (PDS), polyglactin 910 (PG910), or Dacron interposed into rabbit infrarenal aortas. Grafts and normal aortic segments were explanted after 1, 3, and 6 months for pulsatile perfusion with Medium-199 for 60 minutes. Aliquots were removed serially for 6-keto-PGF1 alpha assay. After 30 minutes sodium arachidonate (10 micrograms/ml) was added. Specimens were studied by light microscopy, SEM and TEM. Patency in all three groups exceeded 90%. All three showed re-endothelialization at one month. Normal aorta produced low basal 6-keto-PGF1 alpha with a marked evanescent post arachidonate increase. Dacron did not differ from normal aorta. PG910 and PDS both produced significantly less 6-keto-PGF1 alpha post arachidonate at one month but both increased to normal by three months.

6-Ketoprostaglandin F1 alpha↗