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Xenotransplantation. 2003 Jul;10(4):325-36.
Treatment with a short course of LF 15-0195 and continuous cyclosporin A attenuates acute xenograft rejection in a rat-to-mouse cardiac transplantation model.
Wang H, Hosiawa KA, Garcia B, Shum JB, Dutartre P, Kelvin DJ, Zhong R.
The Multi-Organ Transplant Program, London Health Sciences Center-University Campus, 339 Windermere Road, London, Ontario N6A 5A5, Canada.
Searching for a novel immunosuppressive agent to effectively prevent acute vascular rejection (AVR) is essential for success in clinical xenotransplantation. We previously reported that Lewis rat hearts transplanted into BALB/c mice developed typical AVR in 6 days. The present study was undertaken to determine the efficacy of LF 15-0195, a new immunosuppressive analog of 15-deoxyspergualin in the prevention of AVR in a rat-to-mouse cardiac xenograft model. We transplanted 2-week old Lewis rat hearts into BALB/c mice. Four groups were included in this study: untreated recipients and cyclosporin A (CsA) treated recipients were controls; LF 15-0195 treated recipients or LF 15-0195 combined with CsA treated recipients were experimental groups. Mouse recipients received either LF 15-0195 2 mg/kg subcutaneously from day-1 to post-operative day 14, or CsA 15 mg/kg subcutaneously daily, from day 0 to endpoint rejection, or the two drugs in combination. We observed that high dose CsA did not inhibit AVR and the graft was rejected in 11.3 +/- 1.9 days. Graft histology and immunohistology showed typical AVR, characterized by interstitial hemorrhage, intravascular fibrin deposition, thrombosis, and massive deposition of anti-rat immunoglobulin G (IgG) and immunoglobulin M (IgM). Serum xenoreactive antibodies (xAbs) were markedly elevated in these animals as well. In contrast, we observed that treatment with LF 15-0195 alone significantly prolonged graft survival to 19.3 +/- 0.7 days. Notably, xAbs were significantly decreased and the rejection pattern of these grafts was cell-mediated rejection (CMR), instead of AVR. When CsA was combined with LF 15-0195, the graft mean survival time was further increased to 58.5 +/- 17.3 days. Antibody production and T-cell infiltration were significantly inhibited at the terminal stages of graft survival and pathology showed striking attenuation of both AVR and CMR. Sequential studies on days 6 and 14 demonstrated that LF 15-0195 either alone or combined with CsA completely inhibited antibody production. However, intragraft infiltration by Mac-1 positive cells including natural killer cells, macrophages and granulocytes in LF 15-0195 treated recipients was similar to that of untreated recipients. We conclude that LF 15-0195 effectively prevented AVR by markedly inhibiting the production of anti-donor IgG xAbs. Also, treatment with short course LF 15-0195 and continuous CsA significantly reduced T-cell infiltration. Studies to test this therapy in inhibiting AVR in a pig-to-non-human primate xenotransplantation model are underway.
Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12795681&dopt=Abstract hemorrhage [PubMed - in process]
Xenotransplantation. 2003 Jul;10(4):357-67.
Depletion of anti-Gal antibodies by the intravenous infusion of Gal type 2 and 6 glycoconjugates in baboons.
Teranishi K, Alwayn IP, Buhler L, Gollackner B, Knosalla C, Huck J, Duthaler R, Katopodis A, Sachs DH, Schuurman HJ, Awwad M, Cooper DK.
Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, MGH East, Building 149-9019, Boston, MA 02129, USA.
BACKGROUND: Natural anti-Gal antibodies (NAb) to Gal epitopes play a key role in the rejection of pig cells or organs transplanted into primates. We have investigated the effect on NAb return after extracorporeal immunoadsorption (EIA) of the continuous intravenous (i.v.) infusion of (i) bovine serum albumin conjugated to Gal type 6 oligosaccharides (BSA-Gal) or (ii) a poly l-lysine backbone conjugated to Gal type 2 or 6 oligosaccharides (PLL-Gal). METHODS: Porcine mobilized peripheral blood progenitor cells (PBPC) obtained by leukapheresis from MHC-inbred miniature swine (n = 9) were infused intravenously (i.v.) into baboons: Group 1 baboons (n = 4) received whole body and thymic irradiation, splenectomy, antithymocyte globulin, cobra venom factor, cyclosporine, mycophenolate mofetil, anti-CD154mAb, porcine hematopoietic growth factors, and EIA before transplantation of high doses (2 to 4 x 1010 cells/kg) of PBPC; Group 2 baboons (n = 3) received the Group 1 regimen plus a continuous i.v. infusion of BSA-Gal for up to 30 days; Group 3 baboons (n = 5) received the Group 1 regimen plus a continuous i.v. infusion of PLL-Gal type 2 (n = 2) or both PLL-Gal types 2 and 6 (n = 3) for up to 30 days. RESULTS: Group 1: NAb returned to pre-PBPC levels within 20-30 days, but there was no induction of antibody to Gal or non-Gal determinants; Group 2: NAb was undetectable or at very low level during BSA-Gal therapy. In one baboon, however, IgG to Gal type 2, but not to type 6, returned during BSA-Gal therapy; Group 3: NAb was undetectable or at very low level during PLL-Gal therapy. In two baboons that received PLL-Gal type 2, NAb to Gal type 6, but not to type 2, returned during PLL-Gal treatment. Two of five baboons, however, developed systemic infection. Four of five baboons died within 14 days; autopsy revealed focal hemorrhagic injury to their hearts, lungs, and small intestines, with histologic abnormalities that varied between animals from hemorrhage and/or thrombosis in some organs (heart, lungs, or intestine) to signs of infections (bacteria in intestine, cytomegalovirus in liver). CONCLUSIONS: (i) BSA-Gal and PLL-Gal therapy maintained depletion of NAb. (ii) Some heterogeneity in specificity of NAb was identified, indicating that the infusion of a combination of Gal type 2 and 6 glycoconjugates may be required. (iii) The addition of PLL-Gal to the immunosuppressive regimen was associated with a high incidence of morbidity and mortality without a clear histopathologic entity underlying the cause of death.
Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12795685&dopt=Abstract hemorrhage [PubMed - in process]
J Gen Intern Med. 2003 May;18(5):343-9.
Changes in the use of do-not-resuscitate orders after implementation of the Patient Self-Determination Act.
Baker DW, Einstadter D, Husak S, Cebul RD.
Center for Health Care Research and Policy and Department of Medicine ,Case Western Reserve University at MetroHealth Medical Center, Cleveland, Ohio, USA. dwbakeorthwestern.edu
OBJECTIVE: To determine changes in the use of do-not-resuscitate (DNR) orders and mortality rates following a DNR order after the Patient Self-determination Act (PSDA) was implemented in December 1991. DESIGN: Time-series. SETTING: Twenty-nine hospitals in Northeast Ohio. PATIENTS/PARTICIPANTS: Medicare patients (N = 91,539) hospitalized with myocardial infarction, heart failure, gastrointestinal hemorrhage, chronic obstructive pulmonary disease, pneumonia, or stroke. MEASUREMENTS AND MAIN RESULTS: The use of "early" (first 2 hospital days) and "late" DNR orders was determined from chart abstractions. Deaths within 30 days after a DNR order were identified from Medicare Provider Analysis and Review files. Risk-adjusted rates of early DNR orders increased by 34% to 66% between 1991 and 1992 for 4 of the 6 conditions and then remained flat or declined slightly between 1992 and 1997. Use of late DNR orders declined by 29% to 53% for 4 of the 6 conditions between 1991 and 1997. Risk-adjusted mortality during the 30 days after a DNR order was written did not change between 1991 and 1997 for 5 conditions, but risk-adjusted mortality increased by 21% and 25% for stroke patients with early DNR and late DNR orders, respectively. CONCLUSIONS: Overall use of DNR orders changed relatively little after passage of the PSDA, because the increase in the use of early DNR orders between 1991 and 1992 was counteracted by decreasing use of late DNR orders. Risk-adjusted mortality rates after a DNR order generally remained stable, suggesting that there were no dramatic changes in quality of care or aggressiveness of care for patients with DNR orders. However, the increasing mortality for stroke patients warrants further examination.
Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12795732&dopt=Abstract hemorrhage [PubMed - in process]
Heart Surg Forum. 2003;6 Supp 1:S47.
Is routine use of temporary epicardial pacing wires necessary after either opcab or conventional cabg/cpb?
Puskas JD, Sharoni E, Williams W, Petersen R, Duke P, Guyton RA.
School of Medicine, Emory University, Atlanta, GA, USA.
OBJECTIVES: Placement of temporary epicardial pacing wires (PWs) after CABG is routine in many centers, despite infrequent but significant complications, including hemorrhage, tamponade and death. The resurgence of OPCAB prompted a re-examination of this practice. METHODS: Two-hundred (200) unselected coronary patients were prospectively randomized to have either OPCAB or conventional coronary artery bypass grafting on cardiopulmonary bypass (CABG/CPB). Three patients were excluded after randomization. Management, including placement or avoidance of PWs, followed unbiased, criteria-driven protocols. Patients requiring pacing immediately prior to chest closure (bradycardia with cardiac output <2.2 L/min/m2, nodal or junctional arrhythmias, atrioventricular block) received PWs. All others avoided PWs. Duration of pacing and complications related to PW placement or avoidance were recorded. RESULTS: PWs were placed in 33/197 (17%) patients, 23 of whom were paced after arrival in the ICU and 10 were never paced. 12 OPCAB vs 21 CABG/CPB patients had PWs (p=0.08). Patients with PWs were older, more commonly female, had more COPD and longer length of stay than those not requiring PWs. Preoperative beta blocker use, coronary anatomy and number of grafts performed were not correlated with need for PWs. No patient without PWs required postoperative pacing by any means or suffered any complication attributable to avoidance of PWs. CONCLUSIONS: Need for pacing immediately prior to chest closure accurately and safely identifies coronary patients who will require postoperative pacing after OPCAB or CABG/CPB. Routine use of PWs is unnecessary. OPCAB may be associated with a reduced requirement for PWs.
Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12796005&dopt=Abstract hemorrhage [PubMed - in process]
Ultrasound Obstet Gynecol. 1992 Sep 1;2(5):349-51.
Ovarian cysts during pregnancy: the role of ultrasonically guided transvaginal aspiration.
Aboulghar M, Mansour R, Serour G.
Department of Obstetrics and Gynecology, Faculty of Medicine, Cairo University, Cairo, Egypt.
Three cases of ovarian cysts, with a mean diameter measuring more than 6 cm during the second trimester of pregnancy, were aspirated transvaginally, guided by ultrasound. All cysts were unilocular, thin-walled with no internal echoes. Cytological examination of the aspirated fluid revealed benign luteinized granulosa cells. No complications occurred and the pregnancies continued to full term. It is believed that needle aspiration of simple ovarian cysts of 6 cm diameter or more during pregnancy is a safe and effective treatment that is capable of reducing the risk of torsion, hemorrhage or rupture and avoiding unnecessary laparotomy. 1992 International Society of Ultrasound in Obstetrics and Gynecology
Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12796935&dopt=Abstract hemorrhage [PubMed]
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