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THORACIC PRESENTATIONS OF POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDERS Michael E. Halkos, MD * ; Joseph I. Miller, MD; Karen P. Mann, MD; Daniel L. Miller, MD; Anthony A. Gal, MD. Emory University School of Medicine, Atlanta, GA PURPOSE: Post-transplant lymphoproliferative disorders PTLD ; are rare, but significant complications following transplantation. Although organ-specific cases have been reported, primary presentation in the thoracic cavity has not been fully characterized. METHODS: 11 cases of PTLD with a primary thoracic presentation were identified among solid organ or bone marrow BM ; transplant patients from 1990-2002. RESULTS: Patients include 8 men and 3 women mean age of 49 years ; . Transplant cases were as follows: 1 heart, 3 lung, 2 kidney pancreas, 3 kidney, 2 BM, and 0 liver. Time to presentation ranged from 1 to 97 months and was 1 year in 6 and 1 year in 5 cases. Pre-transplant EBV and CMV status were negative in 8 10 and 9 10 cases, respectively. Patients presented with mediastinal adenopathy 7 11 ; or pulmonary parenchymal lesions 5 11 ; . also had extra-thoracic involvement. 8 presented with constitutional symptoms. Pathologic diagnosis was achieved by CT-guided fine needle aspiration FNA ; in 8 patients or by an open biopsy procedure in 3 patients. Pathologic analysis revealed B-cell lymphoproliferative disorder in 9 11 cases, anaplastic large cell lymphoma in 1, and Hodgkin's lymphoma in 1. 5 specimens evaluated for EBV were positive by in situ hybridization or immunohistochemistry. All patients were initially treated with reduction in immunosuppresion and 6 received adjuvant chemotherapy. Overall, mortality was 64%: 4 7 patients died from complications of PTLD 1 heart, 1 BM, 2 kidney ; , and 3 7 3 lung ; died from rejection. The mean interval from diagnosis to death was 13 months and famotidine, for example, glucoside estrace.
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739. Coriandrum sativum: Evaluation of its anxiolytic effect in the elevated plus-maze - Emamghoreishi M., Khasaki M. and Aazam M.F. [M. Emamghoreishi, Department of Pharmacology, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran] - J. ETHNOPHARMACOL. 2005 96 3 ; - summ in ENGL The clinical applications of benzodiazepines as anxiolytics are limited by their unwanted side effects. Therefore, the development of new pharmacological agents is well justified. Among medicinal plants, Coriandrum sativum L. has been recommended for relief Section 30 vol 134.2 and finasteride.
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The veteran methadone researcher Dr. Thomas D'A unno has ag ain performed a g reat servic e b y examining dose levels prescribed in a variety of A m erican clinics * . W hile many factors have been shown to influence outc om es, dose level has always been the m ost co ns isten t pred icto r of po sitive outc om es. Methadone treatment started with a "culture" of high doses and a co nc ept o f "bloc kad e" do sing. T he o riginal trials used do ses o f up 180 m g daily and average doses of 90-100 mg Dole 1965, Newman 1979 ; and there we re few if any reports o f s side effects from maintenanc e doses. Con servative elemen ts seem to have in flu en ced dosin g practices in the 1980s for some reason an d only in recen t years h as the p en dulum sw ung ag ain in favour of effective doses, based on c linical criteria. Th ere are several reco mmend ations that 6 0 m app roximate minimum effective daily maintenance d ose for most op ioid dep enden t patients. D'Aunno thus determined the proportion of patients in clinics n 10 0 ; were prescribed above or below this level from 1988 and at 2, 7 and 1 2 year intervals. Orig inally he found that only 20% of patients received 60 mg or mo re. This rose to 65% by 2000, which is most gratifying for those ab le to cess treatmen t in the U S. It must be a disap po intment fo r erican pu blic hea lth that altho ug h d dictio n has increased yearly, there h as been little expan sio n in th num bers in treatmen t in the past 15 years. The study also show ed that clinics with higher proportions of African erican patients prescribed lower doses but those with accreditation and thus add itional education ; prescribed higher do ses. This study at last gives us a va lidated "standard" by which we can measure ou r own agonist pharmacotherapy practices. And it is clear that inad equ ate do ses yield inadequ ate ou tco mes, includ ing u nsa fe injec ting. O f course this d oes not apply to every case and a proportion will be n ew patients or taking dose reductions, and thus may be appropriately treated on less than 60 mg d aily. A minority of main tenan ce p atien ts may also fare perfectly w ell o n lower doses. In a "norm al" practice sample, however, it would be expected that at least 65% were taking 60 mg or mo re for optimal results. Ed itor's No te: W e are tro ubled by the implication that African ericans rec eive in ferior treatm ent--at least wh en it mes to p rop er do sag e--to Cau casians. This begs the question of w he ther o ther m ino rity gro up s rec eive inferior treatmen t as well. Certainly, mo re questions need to be answ ered--such as whether the p ro blem is m ain ly that clinics with higher proportions of African erican patients are gene rally inferior o r that individual physicians are treating African American patien ts diffe rently than other patien ts. It is possible that the discrepancy has more to do with socioeconomics than simple racism e.g ., in gen eral, it may be the case that facilities in poor areas pro vide inferior treatment to facilities in m ore affluent areas ; . Regardless, this issue requires further stud y. W e can on ly hope that accreditation all opiate agon ist treatmen t providers mu st now obtain accreditation, per the new federal regulations ; results in better treatment, eliminating this discrepancy in dosing p ractices. As reported in the Aug ust 20, 02 ; R euter's H e alt h article, "Methadone Care for Ad dicts found Lac king, " the stu dy's findings are not all good . W hile significan t pro gress has been mad e since 1 988 in dosin g practices, "recent studies have shown that the optimal dosage required to block heroin cravings is m o than 80 milligrams o f m ethad one p er day, and only about one-th ird of patien ts are rec eiving this amount the study findings indicate. `Increasing do sag e levels to 8 0 illigram s a da may b e the m ost p ressing current issue, in light of recent clinical evidence and in light of increased heroin pu rity of street d rug s, ' the au tho rs write and fluconazole.
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MIXTURES OF GLUCOSAMINE AND CHONDROITIN SULFATE REVERSE FIBRONECTIN FRAGMENT MEDIATED DAMAGE TO C ARTILAGE MORE EFFECTIVELY THAN EITHER AGENT ALONE LM Ray1, D Guo1, GA Homandberg 1 Biochemistry and Mol ecular Biology, University of North Dak ota, Grand F orks, ND Aim of Study: The effecti veness of glucosamine and chondroiti n sulfate in bloc king or reversing damage in cartilage expos ed to fibronectin frag ments Fn-f ; , an exposur e known to enhance levels of catabolic cytokines and matrix metalloproteinases MMPs ; and to enhanc e degradation of the matrix, was tested. Methods: Phar macol ogic formul ations from Nutramax Labor atories, Inc., glucosamine hydrochloride FCHG49 ; and chondroitin sulfate TRH122 ; , were tes ted si ngly or in combination at 1, 10 or 100 g ml final concentrati on in the presenc e of 0.1 M Fn-f. T o test for bloc king damage in s hort term c ultures i n the absence of s erum growth fac tors or proteinase inhibitors, bovine cartilage explant cultures were established i n DMEM. Explants were then adj usted to Fn-f with agents and pr oteoglycan PG ; content of medi a assayed to obtain rate constants for PG degradation release. Long term 21 day ; cultures in 10% serum were als o studied, c onditions with greater anabolic potenti al. To tes t for effects on steady state PG content, Fn-f and agent were added and every 7 days cartilage removed and PG content measured. To test for repair in 10% serum, c artilage was first damaged in the presence of 0.1 M Fn-f for 7 days, Fn-f removed and media adjus ted to test compounds. Every 7 days, the remaining PG content was meas ured. MMP expression was tested by western bl otting of medi a. Results: In serum-free c onditions , neither of the agents singly nor in c ombination decreased rates of F n-f mediated PG depl etion. When tested in 10% serum, lower c onc entrations of glucosamine alone had no significant effect on PG content in the absence of Fn-f. However, glucosamine at 100 g ml decreas ed PG depleti on caused by Fn-f by 49% p 0.0001 ; from days 7-21. Chondroiti n sulfate alone s howed a trend of enhancing PG c ontent and at 1-100 g ml and at 7 days, decreas ed PG loss by up to 50% p 0.001 ; and slowl y restored PG. Combi nati ons of both agents at all concentrati ons decreas ed PG loss dos e dependentl y fr om 49% to 89% p 0.0005 ; . Cartilage first damaged with Fn-f and then treated with 100 g ml glucos ami ne showed 55% restoration of PG p 0.0005 ; by day 21. Chondroitin sulfate caus ed a tr end of faster and higher PG restoration acti vity than glucosamine. Combi nations from 1-100 g ml s howed muc h greater than additi ve effects with significant effec ts in restoration of PG by day 7 with 100 g ml restoring PG to above normal levels. However, neither agent al one nor in combinati on decreased MMP-1, -3 or -13. Conclusions: While the effects of thes e agents have been tested in in vitro models and in terms of effects on numer ous pathways and meas urable outc omes, there are few studies of direct effects on cartilage tissue PG content in a well defined cartilage damage model, such as that invol ving Fn-f. We report that glucos ami ne and chondroitin sulfate appear to act synergistically in reversing damage and likel y do not do so by affecti ng MMP levels. We propose that these agents enhanc e anabolic effec ts, s uch as PG s ynthesis, which compensates for matri x damage. Reported obser vati ons of effects of these agents on PG s ynthesis or IGF-1 acti vation are c onsistent with our propos al and galantamine.
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Scientific Innovation Today for a Healthy Tomorrow With funding of $18 million by the Canada Foundation for Innovation CFI ; and the Alberta Science and Research Investments Program ASRIP ; , the newly created Institute of Infection, Immunity and Inflammation III ; is attracting the world's top scientists and clinicians to Calgary. These researchers are working together to better understand the cellular processes and clinical consequences of infection, immunity and inflammation with an eye to taking their new-found knowledge from the laboratories directly to the bedside of patients the world over. The Institute has four interlocking areas of focus: Emerging infectious diseases Autoimmunity Pain and intestinal disease Inflammatory lung disease Researchers in the III, like Dr. Pierre-Yves von der Weid, are also exploring key elements of infection, immunity and inflammation. Swelling, for example, is a hallmark feature of inflammation. Swelling occurs as a result of the increased accumulation of fluid from the vasculature to the surrounding tissue. Such swelling can lead to tissue dysfunction and pain, long-term disability, and sometimes even death. While most investigators study the ways in which fluid leaks out of the blood vessels, Dr. von der Weid is focusing on the other side of the equation how fluid leaves the tissue via the lymphatics. By using sophisticated microscopy and electrophysiology technology, he has begun to identify the pumping actions of the lymphatics and the effects of inflammatory mediators on these vessels. Investigations like this, and others in the III, may one day lead to new therapeutic treatments for alleviating, or eliminating inflammation. Trainees are the future of health research in Canada and the III is committed to providing the best training opportunities for young researchers. Dr. John Hwang, a surgery resident, joined our Canadian Institutes for Health Research Training Program: Immunology, Immunopathogenesis and Inflammation and completed a Masters project.
Innate immunity is an immune mechanism that is contrasted with acquired immunity.15 It has long been known that lipopolysaccharide LPS ; acts as an endotoxin and induces dramatic immune reaction, sometimes causing shock and other responses. It was found in 1997 that the true nature of this response is the reaction mediated by toll-like receptors TLR ; . Innate immunity is the immune mechanism working in the important early stage before the characteristic establishment of acquired immunity. It is a defense system against infection consisting of non-lymphatic immune cells such as neutrophils, macrophages, and dendritic cells. TLR is the receptor for pathogen-associated molecular patterns PAMP ; occurring in pathogens such as bacteria, fungi, and viruses. The subtypes from TLR1 to TLR10 have been identified in humans. For example, TLR2 recognizes the peptidoglycan PGN ; of Gram-positive bacteria, TLR2 recognizes viral dsRNA, TLR4 recognizes lipopolysaccharide LPS ; in the outer membrane of Gram-negative bacteria, TLR5 recognizes a structural protein of bacterial flagella called flagellin, TLR7 recognizes imidazoquinolines, which are synthetic compounds with antiviral activity no ligands of biological origin have been identified ; , and TLR9 recognizes CpG DNA of microorganisms. On the other hand, acquired immunity is an immune mechanism that exists only in vertebrate animals. It depends on antigen-specific reactions.
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