Biomedical subjects

H S Tran

Publications and source records attributed to H S Tran.

14 recordsLinked to original sources

PubMed2001

BioGlue surgical adhesive for thoracic aortic repair during coagulopathy: efficacy and histopathology.

BACKGROUND: We hypothesized that induction of coagulopathy in sheep would model clinical needle hole and surgical bleeding from synthetic graft anastomoses, and that a new tissue bioadhesive (BioGlue) would control postoperative blood loss during surgical repair of the thoracic aorta. METHODS: Sheep were anticoagulated with aspirin and heparin. A bypass was made using end-to-side anastomoses of a graft to a partially occluded descending thoracic aorta. Experimental anastomoses (EXP, n = 9) were treated with BioGlue, and control anastomoses (CON, n = 5) were treated with Surgicel to gain intraoperative hemostasis. RESULTS: EXP animals exhibited significantly reduced postsurgical bleeding (CON median 955 mL versus EXP median 470 mL, p < 0.003), a reduced rate of blood loss over the first 2 postoperative hours (CON median 210 mL/hr versus EXP median 92.5 mL/hr, p < 0.006), and over the entire recovery period (CON median 158 mL/hr versus EXP median 86 mL/hr, p < 0.05), and reduced total blood loss (CON mean 1,497 +/- 691 mL versus EXP mean 668 +/- 285 mL, p < 0.008). On histologic examination of tissues explanted after 3 months, BioGlue was relatively inert and demonstrated a minimal inflammatory response. CONCLUSIONS: The use of BioGlue significantly reduced the volume and rate of postsurgical bleeding in a coagulopathic sheep model for thoracic aortic operations. Histopathologically, BioGlue generated only a minimal inflammatory response. This new surgical tissue bioadhesive should prove extremely beneficial for coagulopathic patients undergoing thoracic aortic or vascular procedures.

Anastomosis, Surgical↗

PubMed2001

Prostacyclin is neither sufficient alone nor necessary to cause pulmonary dysfunction: results from infusions of prostacyclin and antiprostacyclin antibody in porcine septic shock.

OBJECTIVE: This study evaluated whether prostacyclin is a necessary mediator of inflammation in graded bacteremia or is sufficient alone in pathophysiologic concentrations to cause the pulmonary derangement of bacteremic shock. DESIGN: Experimental. SETTING: Laboratory. SUBJECTS: Twenty-three anesthetized adult swine. INTERVENSIONS: Swine were studied in four groups for 4 hrs: a) an anesthesia control group (n = 6); b) a septic control group (n = 6), in which 1010/mL Aeromonas hydrophila was infused intravenously at 0.2 mL.kg-1.hr-1 and increased to 4.0 mL.kg-1.hr-1 over 3 hrs; c) a prostacyclin infusion group (n = 6), which received prostacyclin infusion to match septic control plasma concentrationsclm without bacteremia; and d) an antiprostacyclin antibody group (n = 5), which received continuous Aeromonas hydrophila infusion plus antiprostacyclin antibody infusion. MEASUREMENTS AND MAIN RESULTS: Pulmonary hemodynamics, arterial blood gases, and plasma concentrations of arachidonate metabolites were measured hourly over a 4-hr period. In the septic control group and antiprostacyclin antibody group, elevated pulmonary vascular resistance index and pulmonary artery pressure with decreased Pao2, as well as lower pH, were documented after 1 and 3 hrs of graded bacteremia compared with the anesthesia control group and prostacyclin infusion group (p <.05). Thromboxane B2 concentration increased significantly in all groups during septic shock. In the antiprostacyclin antibody group, leukotriene B4 increased immediately after starting antiprostacyclin antibody infusion and reached significance at 3 hrs compared with the septic control group (p <.05). The prostacyclin infusion group had consistently lower concentrations of leukotrienes C4, D4, and E4 than all other groups. CONCLUSIONS: Prostacyclin does not mediate blood gas changes, alterations of pulmonary hemodynamics, or platelet abnormalities in porcine septic shock, because antiprostacyclin antibody infusion did not change the pulmonary hypertension and hypoxemia, and infusion of prostacyclin to pathophysiologic blood concentrations did not reproduce such changes. Antiprostacyclin blockade during bacteremia significantly increased concentrations of leukotrienes C4, D4, and E4 and leukotriene B4, whereas prostacyclin infusion suppressed concentrations of leukotrienes C4, D4, and E4, suggesting that endogenous prostacyclin may blunt leukotriene release.

6-Ketoprostaglandin F1 alpha↗

PubMed2001

A method of endoscopic endotracheal intubation in rabbits.

Endotracheal intubation in rabbits is a formidable task and has led to the devising of a new endoscopic method. Sixty New Zealand White rabbits (2.0-3.5 kg) underwent experimental left thoracotomy requiring mechanical ventilation. After anaesthetic induction was achieved, the animal was placed in a supine position. A rigid 30 degrees endoscope was passed through a 4.5 mm endotracheal tube (ET) and then used to advance, under direct vision, through the oropharynx and vocal cords. Once passing the vocal cords, the ET was advanced into the trachea as the endoscope was withdrawn. All animals were successfully intubated within 30 s to 2 min and then ventilated. No complications or deaths occurred during or after intubation, or postoperatively. No instances of oesophageal intubation occurred. All animals survived long-term. Thirty animals underwent necropsy at 10 days and, 30 at 30 days, with no postoperative evidence of orotracheal injury. We have established a new method of endotracheal intubation in rabbits. It is reliable, effective, non-traumatic, safe, and expeditious.

Animal Welfare↗

PubMed2000

Preoperative chemotherapy-sensitized radiation therapy for cervical metastases in head and neck cancer.

OBJECTIVE: To determine the efficacy of concurrent preoperative cisplatin chemotherapy and radiotherapy (CT/RT) for patients with advanced head and neck cancer and cervical metastatic disease. DESIGN: Retrospective analysis. SETTING: University hospitals. PATIENTS: Eighty-eight patients with operable stage III and IV squamous cell carcinoma of the head and neck and palpable cervical lymphogenous metastases received preoperative concurrent CT/RT followed by planned neck dissection. INTERVENTIONS: All patients undergoing CT/RT received concomitant continuous infusions of cisplatin (20 mg/m2) on days 1 to 4 and 22 to 25 of CT/RT. Thirty-nine patients underwent single-fraction (1.8-Gy) radiotherapy to 45.0 Gy, and 49 patients received 10 single-fraction (1.8-Gy) treatments, which were hyperfractionated (1.2-Gy twice a day) to 46.8 Gy. MAIN OUTCOME MEASURES: The 71 patients for whom complete post-CT/RT data were available were evaluated for clinical response in addition to survival. Histologic complete response (HCR) was confirmed from planned neck dissection specimens (n = 48) after clinical complete response (CCR) from initial CT/RT. Kaplan-Meier statistical analysis for disease-specific survival and overall survival was performed on all 88 patients who received CT/RT. RESULTS: A CCR and an HCR were noted in 78% (18/23) and 59% (10/17) of patients with N1 lesions, respectively, and in 60% (29/48) and 45% (14/31) of patients with N2-3 lesions, respectively. The percentage of patients with CCR who also had HCR was 67% (10/15) for patients with N1 lesions and 54% (14/26) for patients with N2-3 lesions. With a median follow-up of 18.5 months, the Kaplan-Meier disease-specific survival rate at 54 months (n = 88) was 70% (21/30) for patients with N1 lesions, 60% (24/40) for patients with N2 lesions, and 39% (7/18) for patients with N3 lesions. The overall survival and disease-specific survival rates at 5 years for all nodal groups combined were 36% (32/88) and 59% (52/88), respectively. CONCLUSIONS: A CCR to CT/RT was achieved in nearly two thirds of patients with head and neck cervical lymphogenous metastases, independent of nodal tumor load. Most patients (59% [24/41]) with CCR were pathologically tumor free before neck dissection.

Carcinoma, Squamous Cell↗

PubMed2000

An in vivo evaluation of a chondroitin sulfate solution to prevent postoperative intraperitoneal adhesion formation.

PURPOSE: The goal of this study was to determine the efficacy of a single intraperitoneal administration of a chondroitin sulfate solution in preventing postoperative adhesion formation. METHODS. Twenty-five Sprague-Dawley rats had a 1-cm(2) area of cecal serosa abraded. Controls (CON, n = 5) received no treatment, the chondroitin sulfate group (CS, n = 10) received chondroitin sulfate (0.013 g/kg) in 0.9% NaCl intraperitoneally (ip), and vehicle controls (VC, n = 10) received an equal volume of 0.9% NaCl solution ip before the abdomen was closed. All animals were sacrificed on postoperative day 10. The extent of adhesion was quantified according to Mazuji's adhesion grade (0 to 4: 0 = no adhesion and 4 = very dense adhesion) and quantitated after H&E, trichome, and immunohistochemical staining for fibrin and collagen type I and type III using digital image analysis. RESULTS: The mean Mazuji's adhesion grade in the CON was 4.0 +/- 0.0, in the VC 2.60 +/- 0.37, and in the CS 1.3 +/- 0.42 (P < 0.01 for CS vs CON and P < 0.05 for CS vs VC comparisons). The mean gray-scale intensity (0-255: 0 = dense amount and 255 = none) of adhesion density in the CON was 105. 5 +/- 5.5, in the VC 125 +/- 15.0, and in the CS 178.3 +/- 21.0 (P < 0.01 for CS vs CON and P < 0.05 for CS vs VC comparisons). The mean adjusted intensity stain indices (AISI) for fibrin and collagen type I in the CON were 59 +/- 17 and 53 +/- 19, in the VC 27 +/- 3 and 25 +/- 7, and in the CS 16 +/- 5 and 6 +/- 3, respectively (P < 0.05 between CS and CON comparisons). The AISI of collagen type III was not significant among all the groups (P > 0.1). CONCLUSIONS: The extent of early postoperative intra-abdominal adhesion formation as determined by gross assessment and from quantitation of fibrin and collagen type I deposition was significantly reduced by a single intraperitoneal administration of a chondroitin sulfate solution.

Animals↗

PubMed2000

Predictors of operative outcome in patients with human immunodeficiency virus infection and acquired immunodeficiency syndrome.

BACKGROUND: Plasma viral load has recently been associated with clinical outcome in patients with human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS). We hypothetized that, in addition to CD4 lymphocytes, plasma HIV-1 RNA counts are predictive of postoperative outcome. METHODS: HIV-infected and AIDS patients admitted to a major teaching hospital requiring invasive or surgical procedures were retrospectively analyzed for postoperative outcome. Preoperative and postoperative immune cell counts including plasma HIV-1 RNA counts were recorded. Chi-square analysis, Fisher's exact test, and multivariate regression were performed with statistical significance P </=0.05. RESULTS: Fifty-five consecutive patients between 14 and 62 years of age were admitted in a 1-year period and underwent 64 diagnostic and therapeutic procedures. Fourteen (22%) postoperative infections and 18 (28%) complications other than infection, with an overall mortality of 11%, were documented. Total preoperative white blood cell count ([WBC] P <0.01), preoperative percent lymphocyte count (P <0.01), absolute postoperative CD4 lymphocyte count (P <0.01), and postoperative plasma viral load (P <0.0001) are associated with mortality. Multivariate regression indicated that postoperative percent CD4 lymphocyte count is an independent predictor of both postoperative infection and other complications (P <0.05, R = 0.848, power = 0.9911), while the decrement in percent CD4 lymphocyte count is an independent predictor of postoperative complications other than infection (P <0.05, R = 0.596, power = 0.7838). CONCLUSIONS: In accordance with the medical literature for clinical outcome in HIV-infected and AIDS patients, both immune cell counts and HIV-1 RNA counts were found to associate with postoperative mortality. However, the postoperative and decrement in percent CD4 lymphocyte proved to be the independent predictors of postoperative complications.

Acquired Immunodeficiency Syndrome↗

PubMed2000

The cardiovascular hemodynamics and leukotriene kinetics during prostacyclin and anti-prostacyclin antibody infusions in septic shock.

This study evaluated whether or not prostacyclin (PGI2) was necessary or sufficient by itself in a pathophysiologic concentration to mediate the cardiovascular dysfunction of septic shock. Anesthetized adult swine received anesthesia only (ANESTHESIA CONTROL, n = 6); graded Aeromonas hydrophila, 10(10)/mL, infusion at 0.2 mL/kg/h that increased to 4.0 mL/kg/h over 3 h (SEPTIC SHOCK CONTROL, n = 6); pathophysiologic prostacyclin infusion to match septic shock control plasma levels without bacteremia (PGI2 INFUSION, n = 6), or graded Aeromonas hydrophila plus anti-prostacyclin antibody infusion (ANTI-PGI2-Ab INFUSION, n = 5). This graded porcine bacteremia model was 100% lethal after 4 h. Cardiovascular hemodynamics, arterial blood gases, and plasma levels of arachidonate metabolites were measured at baseline and hourly over a 4-h period. The results showed that PGI2 was not a necessary mediator of impaired cardiovascular hemodynamics in graded bacteremia, as anti-PGI2 antibody infusion did not improve the cardiac index, systemic vascular resistance, or peripheral oxygen balance in septic animals. Also, PGI2 was not sufficient alone to cause the cardiovascular dysfunction of sepsis, as pathophysiologic infusion of PGI2 did not reproduce such changes in normal animals. PGI2 blockade during bacteremia significantly increased LTC4D4E4, and LTB4 whereas PGI2 infusion suppressed LTC4D4E4 concentration, suggesting that endogenous PGI2 may blunt leukotriene release during septic shock. These results indicate a complex dynamic equilibrium among prostacyclin and leukotrienes in septic shock.

6-Ketoprostaglandin F1 alpha↗

PubMed1999

Site-specific immunosuppression using a new formulation of topical cyclosporine A with polyethylene glycol-8 glyceryl caprylate/caprate.

PURPOSE: Dermal application of immunosuppressants can be an effective means of achieving site-specific immunosuppression (SITE) on skin allografts in burn wound management and in the treatment of various immune skin disorders. We have previously reported success with topical cyclosporine A (tCsA) in the treatment of skin allograft rejection in rats. Using a new tCsA formulation with a penetration enhancer (PE), polyethylene glycol-8 (PEG-8) glyceryl caprylate/caprate (Labrasol, Gattefossé, St. Priest, France), in a trinary drug delivery system, we hypothesized that we would induce SITE and significantly delay rejection of dual skin allografts in rats. METHODS: Dual rat skin allografts from Lewis x Brown-Norway (LBN) donors were grafted to Lewis (Lew) recipients. Experimental animals (EXP, n = 7) received a 10-day course of systemic cyclosporine (sCsA, 8 mg/kg/day) followed by topical application. One of the two allografts on each experimental animal received tCsA/PE application (5 mg/kg/day) until sacrifice (tCsA/PE-treated). The other allograft received vehicle only (vehicle-treated). Allogeneic controls (ALLO-CON, n = 9) received no sCsA or tCsA. First signs of rejection were determined based on the initial observation of erythema, hair loss, flakiness, and/or scabs. RESULTS: The mean time to rejection for ALLO-CON allografts was 6.3 +/- 0.7 days (t test, P = 0.0013); for vehicle-treated allografts, 12.3 +/- 3.8 days (paired t test, P = 0.0146); and for tCsA/PE-treated allografts, 25.6 +/- 5.4 days. The disparity of days to rejection between dual allografts in the ALLO-CON group was 0.0 +/- 0.0 day and that between the tCsA/PE- and vehicle-treated dual allografts was 13.3 +/- 3.9 days (t test, P = 0.0016). CONCLUSIONS: A new formulation of tCsA in a trinary drug delivery system is successful at delaying the onset of rejection in dual skin allografts in rats by SITE, and PEG-8 glyceryl caprylate/caprate may represent a potentially effective transdermal penetration enhancer.

Administration, Topical↗

PubMed1997

Quantitation of an orally available thrombin inhibitor in rat, monkey and human plasma and in human urine by high-performance liquid chromatography and fluorescent post-column derivatization of arginine.

An assay for the quantification of plasma and urine levels of CVS 1123, an orally bioavailable thrombin inhibitor, and its desmethyl form. CVS 738, was developed to support clinical and toxicology studies. This assay uses solid-phase extraction, reversed-phase HPLC separation, and post-column fluorescent derivatization with ninhydrin. An internal standard is added to correct for recovery. In aqueous solution, the arginine aldehyde structures of CVS 1123 and CVS 738 exist in multiple forms which can be separated under standard reversed-phase HPLC conditions. HPLC conditions were optimized to give rapid interconversion of the forms on the separation time scale, and consequently a single chromatographic peak. Extraction conditions were modified for quantitative extraction of drug compounds from large volumes of human plasma. The assay was shown to be accurate and precise, with a quantification limit of 17 ng CVS 1123/ml human plasma.

Acetonitriles↗

PubMedDate not supplied

A sheep model for thoracic aortic surgery in the presence of systemic coagulopathy.

Surgical repair of aneurysms, traumatic injuries, or congenital anomalies of the thoracic aorta are associated with high morbidity and mortality mainly as a result of excessive and uncontrollable hemorrhage from diffuse coagulopathy. We developed a model in sheep that simulates this coagulopathic state for experimentation with thoracic aorta surgery. This experimental animal model involves administering a 600-mg aspirin suppository once a day for the 2 days preceding surgery and a final dose on-call to surgery. Prior to cross-clamping the aorta, an intravenous (i.v.) bolus of heparin (400 IU/kg) was administered. Thirty minutes later, the i.v. heparin bolus was repeated. Pre- and intraoperative activated clotting time was 101 +/- 10 s and >1500 s (p < .0001); prothrombin time, 21 +/- 1 s and >100 s (p < .0001); and activated partial thromboplastin time, 20 +/- 1 s and >50 s (p < .0001), respectively. We utilized a partial cross-clamp-and-sew technique to anastomose a woven, gelatin-impregnated, 16-mm tube graft end-to-side to the descending thoracic aorta. Mean total blood loss was 1367 +/- 282 mL, which included mean blood loss from time of release of aortic cross-clamp to close (422 +/- 135 mL) and mean total blood output from chest tube drain (945 +/- 203 mL). The mean time to achieve hemostasis at suture lines after aortic cross-clamp release was 15.5 +/- 6.6 min. In conclusion, a sheep model with induced coagulation defects was successfully developed and reproducible for experimentation involving thoracic aortic surgery.

Anastomosis, Surgical↗

PubMedDate not supplied

Transmyocardial laser revascularization: current status.

Transmyocardial laser revascularization (TMLR) has been widely evaluated for treatment of the ischemic myocardium either in conjunction with coronary artery bypass grafting or as sole therapy. Clinically, it has shown significant improvement for angina symptoms, but the mechanism by which this modality works is unknown at this time. The original premise on which transmyocardial revascularization was established depended on its ability to essentially generate channels that would directly carry blood from the ventricle into the ischemic myocardium. This theory, however, has not been substantiated, so other mechanisms have been postulated. This article gives a historical perspective on the advent of transmyocardial revascularization and the many animal and human studies that have paved the way for its clinical use. Current controversies are examined, along with the new advances in laser technology and where the future of TMLR is headed.

Animals↗

PubMedDate not supplied

A novel technique in a sheep model for evaluating prosthetic heart valve performance.

There have been many various animal studies to evaluate the structural integrity and antithrombogenicity of prosthetic heart valves. We were interested in developing a novel sheep model to study the thrombogenicity of mechanical heart valves placed into the systemic circulation but without the need for cardiac bypass. Also, we wanted to minimize the risk ofparaplegia from complete thoracic aortic clamping. Six sheep underwent left lateral thoracotomy for placement of a mechanical heart valve in parallel with the descending thoracic aorta. A valved conduit with a dacron tube graft sutured to the back end was fashioned. Employing partial aortic occlusion with a side-biting clamp, the proximal and distal ends were anastomosed in an end-to-side fashion. Once flow was confirmed through the graft, the native aorta was occulded with umbilical tape. The sheep received no postoperative anticoagulation. The median operative time and estimated blood loss (EBL) was 170 min and 250 cc, respectively. Patency of the valved conduits was confirmed during the initial procedure, and there was no incidence of paraplegia postoperatively. Two animals expired shortly after extubation and at necropsy the valved conduits were patent with preserved valve function. The four survivors were sacrificed a median of 37 days postoperatively. Prior to euthanasia, the valved conduits were evaluated in situ with ultrasound. In all cases, the valves had clot formation at the hinges, which prevented active movement of the leaflets. This novel in vivo technique provides an alternative in testing the thrombogenicity of prosthetic heart valves without cardiac bypass or the risk of paraplegia in an animal that is extremely sensitive to complete aortic cross-clamp.

Anastomosis, Surgical↗

PubMedDate not supplied

Diamond-like carbon coating and plasma or glow discharge treatment of mechanical heart valves.

All mechanical heart valves (MHV) are thrombogenic. Application of surface modification technology to reduce the incidence of thrombus formation on MHV is a novel undertaking. This requires collaboration within the bioengineering and cardiothoracic surgery fields. From reviewing results of recent and past investigations, and our own preliminary study with diamond-like carbon coating (DLC) and plasma or glow discharge treatment (GDT) of MHV, we identify and discuss several potentially beneficial effects that may reduce the extent of valve-related thrombogenesis by surface modification. DLC and GDT may affect the surfaces of MHV in many ways, including cleaning of organic and inorganic debris, generating reactive and functional groups on the surface layers without affecting their bulk properties, and making the surfaces more adherent to endothelial cells and albumin and less adherent to platelets. These different effects of surface modification, separately or in combination, may transform the surfaces of MHV to be more thromboresistant in the vascular system.

Animals↗

PubMedDate not supplied

Site-specific immunosuppression: mechanisms of cellular immunosuppression that are operative at local and systemic levels.

The cellular mechanisms by which topical cyclosporine A (tCsA) induces site-specific immunosuppression were investigated. Experiments were designed to elucidate how cyclosporine A (CsA) suppresses activated immunocytes in animals that are undergoing local alloactivation and concomitant tCsA immune suppression. Lewis rats received dual Lewis x Brown Norway rat skin allografts; the rats were treated with systemic CsA (sCsA) at 8 mg/kg/day for 10 days after grafting and then tCsA and vehicle thereafter. CsA added to mixed lymphocyte reactions 24 hours after culture initiation modeled the local effects of CsA on alloactivated immunocytes, and tCsA in conjunction with limited sCsA prolonged local skin allograft survival. CsA inhibited both antigen-specific and nonspecific activated alloresponses of immunocytes from animals that had received allografts and that underwent limited sCsA treatment only in a dose-dependent manner. When tCsA had been applied, immunocyte responses to a nonspecific antigen were extremely CsA-resistant as compared with those induced by antigen-specific suppression. However, this nonspecific alloresponse was fully suppressible with the use of elevated CsA doses (66 microg/mL); thus alloresponding immunocytes were significantly more sensitive to CsA if they were challenged with the donor antigen and preexposed to limited sCsA followed by tCsA in vivo.

Administration, Topical↗