#14#

 

Revisiones-Ciencias Sociales (todas) *** Reviews-Social Sciences (all)

 

AGENTES INMUNOSUPRESORES *** IMMUNOSUPPRESSIVE COMPOUNDS

(Conceptos / Keywords: Immunosuppressive comp; Muromonab-cd3; Sirolimus; Tacrolimus; Cyclosporine; Mycophenolic acid; Antilymphocyte serum; Immunosuppressive comp. used in oncology, etc).

 

Enero / January 2001 --- Marzo / March 2004

 

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Enlace / Link

 

[1]

TÍTULO / TITLE:  - International Federation of Clinical Chemistry/International Association of Therapeutic Drug Monitoring and Clinical Toxicology working group on immunosuppressive drug monitoring.

REVISTA / JOURNAL:  - Ther Drug Monit 2002 Feb;24(1):59-67.

AUTORES / AUTHORS:  - Holt DW; Armstrong VW; Griesmacher A; Morris RG; Napoli KL; Shaw LM

INSTITUCIÓN / INSTITUTION:  - Analytical Unit, St George’s Hospital Medical School, London, UK. d.holt@sghms.ac.uk

RESUMEN / SUMMARY:  - Issues surrounding the measurement and interpretation of immunosuppressive drug concentrations have been summarized in a number of consensus documents. The Scientific Division of the International Federation of Clinical Chemistry has formed a working group in collaboration with the International Association of Therapeutic Drug Monitoring and Clinical Toxicology. This paper sets out the goals of the working group in light of the developments that have occurred in the field of immunosuppressive drug monitoring since the publication of the last consensus documents.

 

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[2]

TÍTULO / TITLE:  - Treatment of atopic dermatitis and impact on quality of life: a review with emphasis on topical non-corticosteroids.

REVISTA / JOURNAL:  - Pharmacoeconomics 2003;21(3):159-79.

AUTORES / AUTHORS:  - Schiffner R; Schiffner-Rohe J; Landthaler M; Stolz W

INSTITUCIÓN / INSTITUTION:  - Department of Dermatology, University of Regensburg, Regensburg, Germany. jr.schiffner@t-online.de

RESUMEN / SUMMARY:  - Atopic dermatitis (AD) is a chronic skin disease with increasing prevalence and rising costs. Stigmatisation and pruritus are only some aspects of potential quality-of-life (QOL) impairments. AD is not curable and repeated treatments are often necessary. At present, treatment with topically-applied corticosteroids is state-of-the-art for mild to moderate flare-ups. However, many patients are worried about the use of corticosteroids due to the widespread fear of adverse effects. In this review the present literature is analysed concerning impact on quality of life for topically-applicable alternatives to the state-of-the-art treatment. For comparison reasons, data from other treatment modalities are additionally given. Characteristics of studies were analysed using ‘general’ (year and mode of publication, type and aim of study, number of patients, and clinical measurement) and ‘QOL specific’ criteria (type and number of QOL measurements including relevance for study aim and age group, validation in used language, sensitivity to change, and improvement at end of study). QOL data are published only in the minority of studies evaluating treatment efficacy and do not cover the variety of possible therapies. Data are available for tacrolimus, pimecrolimus, UVA/UVB combination and UVB narrowband (topical non-corticosteroidal treatments), as well as for topical corticosteroids, cyclosporin, and inpatient treatment. All studies provided a marked improvement in quality of life after therapy. One study assessed quality of life after a treatment-free follow-up period obtaining a clear increase in impact on quality of life. Since studies used different QOL measurements and vary in inclusion criteria, treatment schedules and presentation of results, a comparison of QOL improvement is not recommended. A single randomised study compared topically applied non-corticosteroidal treatment (UVA/UVB combination) with another treatment modality (cyclosporin) and found no difference in QOL improvement. At present, there is a clear lack of controlled randomised studies evaluating different active treatment modalities and their impact on quality of life. Consensus meetings are desirable to formulate guidelines for the selection and correct use of QOL measurements. Patients’ fear of side effects (e.g. concerning corticosteroids) should be integrated in QOL questionnaires for evaluation of possible compliance problems and real costs. Since relapse after treatment is frequent in AD, QOL measurements should also be performed after a treatment-free follow-up period. At present, we can not answer the question ‘which treatment best improves quality of life in AD?’.  N. Ref:: 128

 

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[3]

TÍTULO / TITLE:  - Kidney transplantation from living-unrelated donors: comparison of outcome with living-related and cadaveric transplants under current immunosuppressive protocols.

REVISTA / JOURNAL:  - Urology 2003 Dec;62(6):1002-6.

AUTORES / AUTHORS:  - Chkhotua AB; Klein T; Shabtai E; Yussim A; Bar-Nathan N; Shaharabani E; Lustig S; Mor E

INSTITUCIÓN / INSTITUTION:  - National Centre of Urology, Tbilisi, Georgia.

RESUMEN / SUMMARY:  - OBJECTIVES: Living-unrelated donors may become an additional organ source for patients on the kidney waiting list. We studied the impact of a combination of calcineurin inhibitors and mycophenolate-mofetil together with steroids on the outcomes of living-related (LRD), unrelated (LUR), and cadaver transplantation. METHODS: Between September 1997 and January 2000, 129 patients underwent LRD (n = 80) or LUR (n = 49) kidney transplantation, and another 173 patients received a cadaveric kidney. Immunosuppressive protocols consisted of mycophenolate-mofetil with cyclosporine-Neoral (41%) or tacrolimus (59%) plus steroids. We compared the patient and graft survival data, rejection rate, and graft functional parameters. RESULTS: LRD recipients were younger (33.6 years) than LUR (47.8 years) and cadaver (43.7 years) donor recipients (P <0.001). HLA matching was higher in LRD patients (P <0.001). Acute rejection developed in 28.6% of LUR versus 27.5% of LRD transplants and 29.7% of cadaver kidney recipients (P = not significant). The creatinine level at 1, 2, and 3 years after transplant was 1.63, 1.73, and 1.70 mg% for LRD patients; 1.48, 1.48, and 1.32 mg% for LUR patients; and 1.75, 1.68, and 1.67 mg% for cadaver kidney recipients (P = not significant), respectively. No difference in patient survival rates was found among the groups. The 1, 2, and 3-year graft survival rates were significantly better in recipients of LRD (91.3%, 90.0%, and 87.5%, respectively) and LUR transplants (89.8%, 87.8%, and 87.8%, respectively) than in cadaver kidney recipients (81.5%, 78.6%, 76.3%, respectively; P <0.01). CONCLUSIONS: Despite HLA disparity, the rejection and survival rates of LUR transplants under current immunosuppressive protocols are comparable to those of LRD and better than those of cadaveric transplants.

 

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[4]

TÍTULO / TITLE:  - Rejection rate in living donor kidney transplantation with and without basiliximab in tacrolimus/mycophenolate mofetil-based protocol.

REVISTA / JOURNAL:  - Transplant Proc 2003 Mar;35(2):653-4.

AUTORES / AUTHORS:  - Rahamimov R; Yussim A; After T; Lustig S; Bar-Nathan N; Shaharabani E; Shapira Z; Shabthai E; Mor E

INSTITUCIÓN / INSTITUTION:  - Department of Transplantation, Rabin Medical Center, Beilinson Campus, Petah-Tiqwa, Israel. rutir@clalit.org.il

 

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[5]

TÍTULO / TITLE:  - The FDA guidelines for the treatment of psoriasis using cyclosporine A: are they adequate?

REVISTA / JOURNAL:  - Cutis 2002 Nov;70(5):288-90.

AUTORES / AUTHORS:  - Zackheim HS

INSTITUCIÓN / INSTITUTION:  - Department of Dermatology, University of California, San Francisco, USA. hszackheim@orca.ucsf.edu

RESUMEN / SUMMARY:  - I present a review of the current US Food and Drug Administration (FDA) guidelines for using cyclosporine A (CSA) to treat psoriasis, with particular emphasis on the period for which CSA may be administered. My concern is that, without violating the guidelines, CSA could be given for a prolonged period with only very brief time-outs. I also review the risks for renal toxicity, malignancy, and other side effects from prolonged administration.  N. Ref:: 18

 

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[6]

TÍTULO / TITLE:  - Role of chiral chromatography in therapeutic drug monitoring and in clinical and forensic toxicology.

REVISTA / JOURNAL:  - Ther Drug Monit 2002 Apr;24(2):290-6.

AUTORES / AUTHORS:  - Williams ML; Wainer IW

INSTITUCIÓN / INSTITUTION:  - Department of Oncology, Leicester University, Leicester, United Kingdom.

RESUMEN / SUMMARY:  - Advances in chiral chromatographic separations have given pharmacologists and toxicologists the tools to examine unexpected clinical results involving chiral drugs. The ability to unravel complex phenomena associated with drug transport and drug metabolism is presented in this manuscript. The relation between the chirality of the drug mefloquine and the intracellular concentrations of the drug cyclosporine is illustrated by examining the effect of the enantiomers of mefloquine on the transport activity of P-glycoprotein (Pgp). These studies were conducted using a liquid chromatographic column containing immobilized Pgp. The results demonstrated that (+)-mefloquine competitively displaced the Pgp substrate cyclosporine whereas (-)-mefloquine had no effect on cyclosporine-Pgp binding. The data suggest that cyclosporine cellular and CNS concentrations can be increased through the concomitant administration of (+)-mefloquine. The use of chirality in clinical and forensic situations is also illustrated by the metabolism of the enantiomers of ketamine (KET). The plasma concentrations of (+)-KET and (-)-KET and the norketamine metabolites (+)-NK and (-)-NK were measured in rat plasma using enantioselective gas chromatography. The separations were accomplished using a gas chromatography chiral stationary phase based on beta-cyclodextrin. The pharmacokinetic profiles of (+)-, (-)-KET and (+)-, (-)-NK were determined in control and protein-calorie malnourished (PCM) rats to determine the effect of PCM on ketamine metabolism and clearance. The results indicate that PCM produced a significant and stereoselective decrease in KET and NK metabolism. The data suggest that the effects of environmental factors (smoking, alcohol use, diet) and drug interactions (coadministered agents) can be measured using the changes in stereochemical metabolic and pharmacokinetic patterns of KET and similar drugs.  N. Ref:: 33

 

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[7]

TÍTULO / TITLE:  - Suggested guidelines for the use of tacrolimus in cardiac transplant recipients.

REVISTA / JOURNAL:  - J Heart Lung Transplant 2001 Jul;20(7):734-8.

AUTORES / AUTHORS:  - Taylor DO; Barr ML; Meiser BM; Pham SM; Mentzer RM; Gass AL

INSTITUCIÓN / INSTITUTION:  - Department of Medicine, Division of Cardiology, University of Utah, Salt Lake City, Utah 84132, USA.  N. Ref:: 11

 

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[8]

TÍTULO / TITLE:  - Tailoring immunosuppressive therapy based on donor and recipient risk factors.

REVISTA / JOURNAL:  - Transplant Proc 2001 May;33(3):2207-11.

AUTORES / AUTHORS:  - First MR

INSTITUCIÓN / INSTITUTION:  - University of Cincinnati Medical Center, Cincinnati, Ohio 45267-0585, USA.  N. Ref:: 35

 

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[9]

TÍTULO / TITLE:  - Maintenance immunosuppression in the renal transplant recipient: an overview.

REVISTA / JOURNAL:  - Am J Kidney Dis 2001 Dec;38(6 Suppl 6):S25-35.

AUTORES / AUTHORS:  - Gaston RS

INSTITUCIÓN / INSTITUTION:  - Division of Nephrology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. rgaston@nrtc.uab.edu

RESUMEN / SUMMARY:  - Managing maintenance immunosuppressive regimens after kidney transplantation is often challenging and confusing, requiring careful attention to efficacy, dosing, adverse effects, and costs of multiple medications. Most protocols combine a primary immunosuppressant (cyclosporine or tacrolimus) with one or two adjunctive agents (azathioprine, mycophenolate mofetil, sirolimus, corticosteroids). Avoiding drug-drug interactions is a major part of effective immunosuppressant management, and special situations (eg, pregnancy, intravenous dosing, caring for minority patients) can prove especially daunting. This review summarizes available data regarding current practices in maintenance immunosuppression, emphasizing issues that arise in day-to-day management of renal transplant recipients.  N. Ref:: 69

 

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[10]

TÍTULO / TITLE:  - Donor specific transfusion in kidney transplantation: effect of different immunosuppressive protocols on graft outcome.

REVISTA / JOURNAL:  - Transplant Proc 2001 Aug;33(5):2787-8.

AUTORES / AUTHORS:  - Barbari A; Stephan A; Masri MA; Joubran N; Dagher O; Kamel G

INSTITUCIÓN / INSTITUTION:  - Department ofNephrology and Transplantation, Rizk Hospital, Beirut, Lebanon.

 

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[11]

- Castellano -

TÍTULO / TITLE:Presente y futuro del trasplante renal. Present and future of kidney transplantation.

REVISTA / JOURNAL:  - Actas Urol Esp. Acceso gratuito al texto completo.

      ●● Enlace a la Editora de la Revista http://www.aeu.es/actas/ 

      ●● Cita: Actas Urológicas Españolas: <> 2002 Nov-Dec;26(10):731-58.

AUTORES / AUTHORS:  - Burgos FJ; Alcaraz A; Castillon I; Gonzalez Martin M; Lledo E; Matesanz R; Marcen R; Montanes P; Pascual J

INSTITUCIÓN / INSTITUTION:  - Servicio de Urologia, Hospital Ramon y Cajal, Universidad Alcala, Madrid.

RESUMEN / SUMMARY:  - Renal transplant is the treatment of choice for the patient with end stage renal disease. España is the country with the highest donation rate (33 ppm). However, at present this figure is stabilized. The development of non-beating heart programmes, living-donor nephrectomy (specially laparoscopic nephrectomy) programmes, and may be xenotransplantation in a non-immediate future could increase the transplantation activity. The knowledge of preservation mechanisms, specially with the use of perfusion machines allows to rescue for transplantation kidneys with a long warm-ischemia time. Furthermore, these machines are useful for analyzing viability markers. The new immunosuppressive drugs: Tacrolimus, Mycophenolate-Mophetil, Rapamycin and monoclonal antibodies against alpha chain of the interleukine-2 receptor (Basoliximab and Dazcizumab) have reduced the incidence of acute rejection in the immediate renal transplant period. However, its effect in the long-term follow-up period is still a matter of controversy. The incidence of tumour in the renal transplant recipient is increased, specially those of lymphoma, skin cancer and Kaposi sarcoma. Periodical exams for detecting the development of tumours are mandatory in this population. Finally, xenotransplantation is an attractive alternative, although immunological, infective and ethical barriers should previously be resolved.  N. Ref:: 92

 

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[12]

TÍTULO / TITLE:  - Pharmacokinetic aspects of treating infections in the intensive care unit: focus on drug interactions.

REVISTA / JOURNAL:  - Clin Pharmacokinet 2001;40(11):833-68.

AUTORES / AUTHORS:  - Pea F; Furlanut M

INSTITUCIÓN / INSTITUTION:  - Institute of Clinical Pharmacology and Toxicology, Department of Experimental and Clinical Pathology and Medicine, Medical School, University of Udine, Italy. federico.pea@med.uniud.it

RESUMEN / SUMMARY:  - Pharmacokinetic interactions involving anti-infective drugs may be important in the intensive care unit (ICU). Although some interactions involve absorption or distribution, the most clinically relevant interactions during anti-infective treatment involve the elimination phase. Cytochrome P450 (CYP) 1A2, 2C9, 2C19, 2D6 and 3A4 are the major isoforms responsible for oxidative metabolism of drugs. Macrolides (especially troleandomycin and erythromycin versus CYP3A4), fluoroquinolones (especially enoxacin, ciprofloxacin and norfloxacin versus CYP1A2) and azole antifungals (especially fluconazole versus CYP2C9 and CYP2C19, and ketoconazole and itraconazole versus CYP3A4) are all inhibitors of CYP-mediated metabolism and may therefore be responsible for toxicity of other coadministered drugs by decreasing their clearance. On the other hand, rifampicin is a nonspecific inducer of CYP-mediated metabolism (especially of CYP2C9, CYP2C19 and CYP3A4) and may therefore cause therapeutic failure of other coadministered drugs by increasing their clearance. Drugs frequently used in the ICU that are at risk of clinically relevant pharrmacokinetic interactions with anti-infective agents include some benzodiazepines (especially midazolam and triazolam), immunosuppressive agents (cyclosporin, tacrolimus), antiasthmatic agents (theophylline), opioid analgesics (alfentanil), anticonvulsants (phenytoin, carbamazepine), calcium antagonists (verapamil, nifedipine, felodipine) and anticoagulants (warfarin). Some lipophilic anti-infective agents inhibit (clarithromycin, itraconazole) or induce (rifampicin) the transmembrane transporter P-glycoprotein, which promotes excretion from renal tubular and intestinal cells. This results in a decrease or increase, respectively, in the clearance of P-glycoprotein substrates at the renal level and an increase or decrease, respectively, of their oral bioavailability at the intestinal level. Hydrophilic anti-infective agents are often eliminated unchanged by renal glomerular filtration and tubular secretion, and are therefore involved in competition for excretion. Beta-lactams are known to compete with other drugs for renal tubular secretion mediated by the organic anion transport system, but this is frequently not of major concern, given their wide therapeutic index. However, there is a risk of nephrotoxicity and neurotoxicity with some cephalosporins and carbapenems. Therapeutic failure with these hydrophilic compounds may be due to haemodynamically active coadministered drugs, such as dopamine, dobutamine and furosemide, which increase their renal clearance by means of enhanced cardiac output and/or renal blood flow. Therefore, coadministration of some drugs should be avoided, or at least careful therapeutic drug monitoring should be performed when available. Monitoring may be especially helpful when there is some coexisting pathophysiological condition affecting drug disposition, for example malabsorption or marked instability of the systemic circulation or of renal or hepatic function.  N. Ref:: 397

 

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[13]

TÍTULO / TITLE:  - Outcomes in kidney transplantation.

REVISTA / JOURNAL:  - Semin Nephrol 2003 May;23(3):306-16.

AUTORES / AUTHORS:  - Djamali A; Premasathian N; Pirsch JD

INSTITUCIÓN / INSTITUTION:  - Department of Medicine and Surgery, University of Wisconsin Medical School, Madison, WI 53792, USA.

RESUMEN / SUMMARY:  - It is estimated that there are greater than 100000 kidney transplant recipients with a functioning graft in the United States. Recent advances in immunosuppression have improved short-term graft survival rates and decreased early mortality by decreasing the incidence and therapy for acute rejection episodes. For those accepted on the waiting list, transplant prolongs patient survival compared with remaining on dialysis. During the 1990s, 3 new immunosuppressive drugs were introduced in clinical kidney transplantation. All were approved for use by the Food and Drug Administration after large, controlled, randomized trials. Mycophenolate mofetil (MMF), when combined with cyclosporine (CSA) and prednisone, lowered acute rejection rates by nearly 50% compared with control. Tacrolimus compared with CSA also significantly reduced acute rejection rates in kidney transplant recipients, but was associated with a significant increase in posttransplant diabetes mellitus (PTDM) in the early trials. When evaluated in combination with MMF, the incidence of PTDM was much lower. At the end of the decade, sirolimus was shown in several randomized trials to lower acute rejection rates and is believed to be less nephrotoxic compared with calcineurin inhibitors. All of the randomized trials were not statistically powered to assess long-term superiority. Registry analyses have been performed that appear to show some long-term benefit of immunosuppressive therapy with MMF. Other outcome assessments in kidney transplant recipients include risk factors for chronic allograft nephropathy, hypertension, hyperlipidemia, and bone disease. Although there are few randomized trials, understanding of the significance of these common complications has progressed and strategies for therapy and intervention have been developed. This article focuses on the randomized trials of immunosuppressive therapy and complications associated with use of these drugs. In addition, we review the current management and intervention for the comorbidities associated with the long-term clinical management of the kidney transplant recipient.  N. Ref:: 78

 

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[14]

TÍTULO / TITLE:  - Evolution of immunosuppression and continued importance of acute rejection in renal transplantation.

REVISTA / JOURNAL:  - Am J Kidney Dis 2001 Dec;38(6 Suppl 6):S2-9.

AUTORES / AUTHORS:  - Chan L; Gaston R; Hariharan S

INSTITUCIÓN / INSTITUTION:  - Department of Renal Medicine, University of Colorado Health Sciences Center, Denver, CO 80262, USA. Larry.Chan@uchsc.edu

RESUMEN / SUMMARY:  - As steady improvement in short-term kidney graft survival and long-term outcomes prolongs the lives of transplant patients, responsibility for their care is shifting away from transplant specialists and into the hands of community nephrologists. Therefore, community nephrologists need to have a deeper understanding of immunosuppressive therapies than ever before. Pharmacologic immunosuppression has been continuously evolving over the past two decades. Azathioprine was introduced in the early 1960s. Introduction of cyclosporine (CsA) in 1983 revolutionized short-term outcomes after renal transplantation. The first monoclonal antibody immunosuppressant, OKT3, was introduced in 1986. The 1990s saw the introduction of a number of important new agents, including mycophenolate mofetil (MMF), tacrolimus, and a microemulsion CsA, as well as two new monoclonal antibodies. Combinations of these new agents, along with improving clinical care, have produced 1-year patient survival approaching 100% and graft survival exceeding 90%. The newest class of agents, the first of which is sirolimus, is called target of rapamycin (TOR) inhibitors and is used with CsA for maintenance therapy. Immunosuppressive drug therapy after kidney transplantation continues to evolve. There is a variety of pharmacologic combinations from which to choose, based on immunologic risk and side effect profiles. As new regimens are developed, ongoing communications between the transplant center and community nephrologists will be required to implement therapeutic changes and optimize patient care successfully.  N. Ref:: 59

 

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[15]

TÍTULO / TITLE:  - How to manage patients with lupus nephritis.

REVISTA / JOURNAL:  - Best Pract Res Clin Rheumatol 2002 Apr;16(2):195-210.

      ●● Enlace al texto completo (gratuito o de pago) 1053/berh.2001.0221

AUTORES / AUTHORS:  - Esdaile JM

INSTITUCIÓN / INSTITUTION:  - Division of Rheumatology, University of British Columbia, Canada.

RESUMEN / SUMMARY:  - The clinical and renal biopsy predictors of assistance in determining therapy are reviewed. While pulse cyclophosphamide remains the most effective treatment for proliferative nephritis, there is increasing interest in other agents, such as azathioprine, particularly to maintain remission. While lupus membranous nephropathy has attracted limited study, preliminary work suggests a role for cyclophosphamide. Newer therapies, including cyclosporine A, mycophenolate mofetil, immunoadsorption, intravenous immune globulin, LJP-394, high-dose immunoablation and nucleoside analogues require further study but offer hope for those failing conventional treatments.  N. Ref:: 60

 

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[16]

TÍTULO / TITLE:  - Issues of adherence to immunosuppressant therapy after solid-organ transplantation.

REVISTA / JOURNAL:  - Drugs 2002;62(4):567-75.

AUTORES / AUTHORS:  - Chisholm MA

INSTITUCIÓN / INSTITUTION:  - Department of Clinical and Administrative Sciences, University of Georgia College of Pharmacy and Department of Medicine, Medical College of Georgia, Augusta, Georgia, USA. mchishol@mail.mcg.edu

RESUMEN / SUMMARY:  - Nonadherence to immunosuppressant therapy constitutes a major barrier to post-transplant care. Failure of transplant recipients to take prescribed drugs properly may not only be a significant obstacle to optimal graft function but it may also result in decreased quality of life and productivity, increased morbidity and healthcare cost, and death. Despite the obvious importance of adherence to immunosuppressant therapy, nonadherence is frequent among transplant recipients, with rates ranging from 2 to 68%. This manuscript briefly discusses several issues concerning adherence to immunosuppressant therapy of solid-organ transplant recipients; presents a literature review concerning adherence to immunosuppressant therapy by solid-organ transplant recipients; and suggests strategies that may be used to enhance medication adherence. Although many of the studies have results that conflict concerning factors associated with immunosuppressive nonadherence, most of the investigators concluded that nonadherent behaviour is usually not predictable. Because of possible adverse events, emphasis should be placed on increasing medication adherence in all transplant recipients.  N. Ref:: 28

 

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[17]

TÍTULO / TITLE:  - Sirolimus eluting stent: a new era in interventional cardiology?

REVISTA / JOURNAL:  - Curr Pharm Des 2003;9(13):1077-94.

AUTORES / AUTHORS:  - Windecker S; Roffi M; Meier B

INSTITUCIÓN / INSTITUTION:  - Swiss Cardiovascular Center Bern, University Hospital, Bern, Switzerland. Bernhard.Meier@insel.ch

RESUMEN / SUMMARY:  - Coronary artery stents have emerged as the preferred tool for percutaneous coronary interventions during the past decade by eliminating abrupt vessel closure and reducing restenosis compared with balloon angioplasty. While coronary artery stents prevent constrictive arterial remodeling and elastic recoil, the implantation is associated with more severe arterial vascular injury than balloon angioplasty alone. The arterial injury initiates a vasculoproliferative response with smooth muscle cell proliferation and migration as well as extracellular matrix formation, which may lead to severe neointimal hyperplasia with in-stent restenosis in 10-30% of cases. Sirolimus, a naturally occurring macrocyclic lactone, has been identified as a pharmacological cell cycle inhibitor with potent antiproliferative and antimigratory effects on vascular smooth muscle cells in vitro. The systemic administration of sirolimus has been shown to effectively reduce neointimal hyperplasia in experimental restenosis models. Subsequently, sirolimus has been incorporated at therapeutically important doses into biocompatible polymers, which made it suitable for stent-based drug elution. Investigation of sirolimus eluting stents in both experimental and clinical restenosis studies have demonstrated dramatic reductions in neointimal hyperplasia. Accordingly, sirolimus eluting stents offer an attractive mode of local drug delivery by minimizing systemic toxicity and maximizing local dose requirements. In addition, sirolimus eluting stents hold great promise to effectively prevent restenosis.  N. Ref:: 104

 

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[18]

TÍTULO / TITLE:  - Limited sampling strategies for estimating cyclosporin area under the concentration-time curve: review of current algorithms.

REVISTA / JOURNAL:  - Ther Drug Monit 2001 Apr;23(2):100-14.

AUTORES / AUTHORS:  - David OJ; Johnston A

INSTITUCIÓN / INSTITUTION:  - Department of Clinical Pharmacology, St. Bartholomew’s & the Royal London School of Medicine and Dentistry, United Kingdom.

RESUMEN / SUMMARY:  - Cyclosporin, the drug of first choice in transplantation surgery, is characterized by a low therapeutic index and variable absorption, so close monitoring of the drug is required to optimize the dosing. Predose blood cyclosporin levels are measured routinely for therapeutic monitoring, but this approach is not optimal because the area under the concentration-time curve (AUC) correlates better with clinical events. However, conventional methods of measuring AUC require many blood samples, which is not viable in a routine clinical setting. AUC monitoring can be simplified for use in a clinical setting by using a limited sampling strategy (LSS) that allows AUC to be estimated using a small number of blood samples collected at specific times. This article reviews the current literature on estimating cyclosporin AUC using LSS. Thirty-eight papers suggesting the use of specific time points were found. LSS has been developed for different transplant types, with different dosing regimens, and with different assays. Most authors suggested either two- or three-sample equations. Results from authors who validated their models suggest that equations defined on one transplant type may be applicable to other transplant types, to both adults and children, and to early or late after transplantation. Moreover, it seems that there is flexibility in the choice of equations available to clinicians. The number of samples to collect for accurate estimations is a matter of debate, but a wise choice can minimize the number. The choice of the optimal LSS and validation are discussed.  N. Ref:: 102

 

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[19]

TÍTULO / TITLE:  - A view on beta cell transplantation in diabetes.

REVISTA / JOURNAL:  - Ann N Y Acad Sci 2002 Apr;958:69-76.

AUTORES / AUTHORS:  - Pipeleers D; Keymeulen B; Chatenoud L; Hendrieckx C; Ling Z; Mathieu C; Roep B; Ysebaert D

INSTITUCIÓN / INSTITUTION:  - Free University of Brussels (VUB), Brussels, Belgium. Daniel.Pipeleers@vub.ac.be

RESUMEN / SUMMARY:  - Organ donors also offer a source of insulin-producing tissue that might be used for the treatment of diabetes. Clinical protocols for transplantation of this tissue aim for the prevention of chronic diabetes complications without introducing new serious side effects. Pancreas and islet cell transplantation are discussed in this perspective. The future of islet cell implants looks favorable but depends on finding ways to induce immune tolerance to the donor beta cells. Clinical trials can take advantage of relevant progress in animal models. In a limited study, recipient treatment with antilymphocyte antibodies and culture of donor cell preparations appeared useful to induce a state of operational immune tolerance in type 1 diabetic patients, as indirectly judged by graft survival and by analysis of auto- and alloreactivities in recipients. Use of cultured beta cell preparations also allows donor cell recruitment from suboptimal donor organs and increases the degree of standardization and quality control of islet cell grafts. The future of these grafts will depend on the development of techniques for the neogenesis of beta cells.  N. Ref:: 47

 

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[20]

TÍTULO / TITLE:  - n-3 Fatty acids and their role in nephrologic practice.

REVISTA / JOURNAL:  - Curr Opin Nephrol Hypertens 2001 Sep;10(5):639-42.

AUTORES / AUTHORS:  - Donadio JV

INSTITUCIÓN / INSTITUTION:  - Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA. donadio.james@mayo.edu

RESUMEN / SUMMARY:  - During the past year, a newly reported clinical trial has strengthened the argument for recommending daily treatment with n-3 polyunsaturated fatty acids in patients with immunoglobulin A nephropathy (the most common form of primary glomerulonephritis in the world) who are at high risk for progression of renal disease. Studies are underway that involve a combination of cyclosporine A, a commonly prescribed immunosuppressive agent in solid-organ transplantation, with a high-potency n-3 polyunsaturated fatty acid to reduce cyclosporine toxicity. Two studies reported during the past year show promise that dietary supplementation with n-3 polyunsaturated fatty acids will substantially decrease vascular access graft thrombosis in patients receiving maintenance hemodialysis, and may reduce hypercalciuria in patients who suffer from kidney stones.  N. Ref:: 26

 

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[21]

TÍTULO / TITLE:  - Solid-state fermentation: a promising microbial technology for secondary metabolite production.

REVISTA / JOURNAL:  - Appl Microbiol Biotechnol 2001 Apr;55(3):284-9.

AUTORES / AUTHORS:  - Robinson T; Singh D; Nigam P

INSTITUCIÓN / INSTITUTION:  - Biotechnology Research Group, University of Ulster, Coleraine, UK.

RESUMEN / SUMMARY:  - Solid state (substrate) fermentation (SSF) has been used successfully for the production of enzymes and secondary metabolites. These products are associated with the stationary phase of microbial growth and are produced on an industrial scale for use in agriculture and the treatment of disease. Many of these secondary metabolites are still produced by submerged liquid fermentations (SmF) even though production by this method has been shown to be less efficient than SSF. As large-scale production increases further, so do the costs and energy demands. SSF has been shown to produce a more stable product, requiring less energy, in smaller fermenters, with easier downstream processing measures. In this article we review an important area of biotechnology, since the recent evidence indicates that bacteria and fungi, growing under SSF conditions, are more than capable of supplying the growing global demand for secondary metabolites.  N. Ref:: 53

 

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[22]

TÍTULO / TITLE:  - Immunosuppressants in advanced clinical development for organ transplantation and selected autoimmune diseases.

REVISTA / JOURNAL:  - Expert Opin Emerg Drugs 2003 May;8(1):47-62.

AUTORES / AUTHORS:  - Kovarik JM; Burtin P

INSTITUCIÓN / INSTITUTION:  - Novartis Pharmaceuticals, 4002 Basel, Switzerland. john.kovarik@pharma.novartis.com

RESUMEN / SUMMARY:  - Immunosuppressants dampen the immune response or restore balance among immune system components. They are primarily used to prevent allograft rejection after organ transplantation and to prevent or treat disease flares in autoimmune diseases. Immunosuppressants available at present include the calcineurin inhibitors (cyclosporin, tacrolimus), antimetabolites (azathioprine, leflunomide, methotrexate, mycophenolate mofetil), antiproliferatives (sirolimus), monoclonal antibodies to T lymphocyte (basiliximab, daclizumab, muromonab-CD3) and anticytokines (anakinra, etanercept, infliximab). The immunosuppressive market grows at a rate of > 10% yearly, with total sales in 2001 of US$2.7 billion. Immunotherapy in transplantation and autoimmune diseases is tending towards the use of multi-drug regimens tailored for the individual patient. At least 23 new immunosuppressants are currently in advanced clinical testing or preregistration, and can be divided into three groups. First, emerging drugs targeting intracellular ligands in immune cells are primarily analogues of currently-marketed agents, which attempt to provide improved pharmaceutical or safety profiles compared with the prototype compound. They are largely being developed in organ transplantation. Second, emerging drugs targeting cell surface ligands on immune cells attempt to antagonise novel molecular sites to interfere with immune cell activation via costimulatory signals, immune cell adhesion to tissues or the vasculature and immune cell trafficking. These agents are being primarily developed in rheumatoid arthritis, psoriasis and/or multiple sclerosis. Finally, emerging drugs acting as anticytokines, which largely follow on from the success of those on the market, by antagonising the function of tumour necrosis factor or a narrow selection of interleukins. All are being assessed in rheumatoid arthritis. Drug development of immunosuppressants is increasingly attempting to intervene in disease progression over the long term. These efforts bring with them trial design and regulatory issues, such as what markers can be used as trial outcome measures, over what duration do trials need to be conducted and what labelling claims are allowed. With the intensive activity in this field, it is likely that several new drugs will reach the market in the coming decade. One caveat, however, is that emerging immunosuppressants that are likely to capture a reasonable share of this increasingly-fragmented market must demonstrate the ability to achieve disease remission or long-term slowing of disease progression.  N. Ref:: 55

 

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[23]

TÍTULO / TITLE:  - Influence of one human leukocyte antigen mismatch on outcome of allogeneic bone marrow transplantation from related donors.

REVISTA / JOURNAL:  - Hematology 2003 Feb;8(1):27-33.

      ●● Enlace al texto completo (gratuito o de pago) 1080/1024533031000072054

AUTORES / AUTHORS:  - Hasegawa W; Lipton JH; Messner HA; Jamal H; Yi QL; Daly AS; Kotchetkova N; Kiss TL

INSTITUCIÓN / INSTITUTION:  - Bone Marrow Transplant Service, Princess Margaret Hospital/University Health Network, Toronto, Ont, M5G 2M9, Canada.

RESUMEN / SUMMARY:  - This study compares the clinical outcomes of 60 consecutive patients who received an allogeneic blood or marrow stem cell transplant (BMT) from one Human Leukocyte Antigen (HLA) mismatched related donors with those of 120 matched patients who had HLA identical sibling donors. The control patients were matched for diagnosis, disease status, conditioning regimen, and age at BMT. All patients received standard CYA and MTX for GVHD prophylaxis. The probability of overall survival (OS) at 5 years was 35% in the study group compared to 56% in the control group. The relapse rates and acute GVHD rates did not differ between the two groups. Graft failure was a significant problem in the study group compared to the control group (13 vs. 0%, p < 0.0001). All cases of graft failure occurred in patients with a mismatch in the host-versus-graft direction. BMT-related deaths were also increased in the study group. Forty percent of deaths were caused by infection in the study group vs. 19% in the control group (p < 0.01). In conclusion, the OS of patients receiving marrow/stem cells from one antigen mismatched related donors was inferior to that of controls with HLA-identical related donors. There was an increase in mortality related to infections occurring in the setting of an increased frequency of graft failure in these patients.  N. Ref:: 21

 

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[24]

TÍTULO / TITLE:  - Perspectives of drug-eluting stents: the next revolution.

REVISTA / JOURNAL:  - Am J Cardiovasc Drugs 2002;2(3):163-72.

AUTORES / AUTHORS:  - Moses JW; Kipshidze N; Leon MB

INSTITUCIÓN / INSTITUTION:  - Lenox Hill Heart and Vascular Institute of New York and Cardiovascular Research Foundation, New York, New York 10021, USA. jmoses@lenoxhill.net

RESUMEN / SUMMARY:  - Coronary stent implantation has become a well established therapy in the management of coronary artery disease (CAD). Although the Stent Restenosis Study (STRESS) and Belgium-Netherlands Stent (BENESTENT) trials demonstrated convincingly that stenting is superior to percutaneous transluminal coronary angioplasty with respect to restenosis in de novo lesions, there is, however, still a high incidence (10 to 50%) of restenosis following stent implantation. Improvements in stent design and implantation techniques resulted in an increase in the use of coronary stents and today, in most centers in the US and Europe, stenting has become the predominant form of nonsurgical revascularization accounting for about 80% of all percutaneous coronary intervention procedures. Coronary stents provide luminal scaffolding that virtually eliminates elastic recoil and remodelling. Stents, however, do not decrease neointimal hyperplasia and in fact lead to an increase in the proliferative comportment of restenosis. Agents that inhibit cell-cycle progression indirectly have also been tested as inhibitors of vascular proliferation. When coated onto stents, sirolimus, a macrolide antibiotic with immunosuppressive properties, and paclitaxel and dactinomycin, both chemotherapeutic agents, induced cell-cycle arrest in smooth muscle cells (SMC) and inhibited neointimal formation in animal models. Preliminary clinical studies with drug-eluting stents produced dramatic results eliminating restenosis in large and mid-size arteries. Quantitative coronary angiography and intravascular ultrasound demonstrated virtually complete inhibition of tissue growth at 6 and 12 months after sirolimus-eluting stent implantation. Results are also very encouraging with paclitaxel-coated stents. However, it needs to be proven that current drug-eluting stents will produce similar results in ‘real life’ interventional practice (long lesions, lesions in small vessels, in vein grafts, chronic total occlusions, and bifurcated and ostial lesions). The ongoing randomized, double-blind sirolimus-coated Bx Velocity trade mark balloon expandable stent in the treatment of patients with de novo coronary artery lesions (SIRIUS) trial may answer some of these concerns. With further improvements, including the expansion of drug-loading capacity, double coatings and coatings with programmable pharmacokinetic capacity using advances in nanotechnology (which may allow for more precise and controlled release of less toxic and improved molecules), we think that in the next few years the practice of interventional cardiology may undergo major changes. A new era of dramatic improvements in the treatment of CAD may have dawned. The prospect of approval of this technology should herald a host of clinical trials to revisit basic assumptions about the place of coronary stenting in the contemporary care of obstructive (and nonobstructive) CAD.  N. Ref:: 76

 

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[25]

TÍTULO / TITLE:  - Pyogenic granuloma in a renal transplant patient: case report.

REVISTA / JOURNAL:  - Spec Care Dentist 2001 Sep-Oct;21(5):187-90.

AUTORES / AUTHORS:  - al-Zayer M; da Fonseca M; Ship JA

INSTITUCIÓN / INSTITUTION:  - Department of Orthodontics and Pediatric Dentistry, University of Michigan School of Dentistry, 1011 N. University Ave., Ann Arbor, MI 48109, USA.

RESUMEN / SUMMARY:  - This case report describes a 14-year-old female referred to Pediatric Dentistry for evaluation and treatment of cyclosporine-induced gingival hyperplasia. Examination of the anterior maxillary area showed a red, vascular, exophytic, soft-tissue mass which had been excised a few months earlier without a histopathologic examination being done. The mass did not appear consistent with gingival overgrowth induced by long-term use of medication, and thus an excisional biopsy was performed, which diagnosed the lesion as a pyogenic granuloma. A review of the literature and management recommendations are discussed.  N. Ref:: 20

 

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[26]

TÍTULO / TITLE:  - Annual trends and triple therapy--1991-2000.

REVISTA / JOURNAL:  - Clin Transpl 2001;:247-69.

AUTORES / AUTHORS:  - Nishikawa K; Terasaki PI

INSTITUCIÓN / INSTITUTION:  - Terasaki Foundation Laboratory, Los Angeles, CA, USA.

RESUMEN / SUMMARY:  - 1. Although the number of cadaver donor transplants did not increase substantially over the past 10 years, unrelated living donor grafts increased from 153 in 1991 to 1,661 through 2000. Use of spousal and other unrelated donor organs contributed to this increase. There was a modest increase in living-related donor transplants from 2,328 in 1991 to 3,451 in 2000. 2. Cadaver donor graft survival at one year improved from 84% in 1991 to 90% in 2000. In contrast, one-year graft survival of living donor transplants only improved from 93% in 1991 to 95% in 2000. 3. Throughout the 10-year period, approximately 13% of transplants were repeat transplants from cadaver donors and roughly 8% were regrafts from live donors. 4. Cadaver donor transplants into White recipients declined from 68% in 1991 to 60% in 2000. For living donors, the percentage of White patients remained constant at about 70%. 5. Graft survival in patients of all races was about equal at one year but diverged at 3 years, with Asians having the highest and Blacks having the lowest 3-year graft survival rates. 6. Average donor age increased from 31.7 in 1991 to 36 in 2000 for cadaveric donor transplants and 37.9 in 1991 to 40.4 in 2000 for living donor transplants. Cadaveric kidneys from donors older than 50 years of age yielded significantly lower 3-year graft survival. 7. Average recipient age for cadaveric donor transplants increased from 42.1 in 1991 to 46.8 in 2000. The average recipient age for living donor transplants also increased steadily from 33.7 in 1991 to 42.9 in 2000. There was relatively little effect on graft survival rates for advanced age recipients. 8. The percentage of sensitized recipients receiving cadaver donor grafts declined from 27% in 1991 to 21% in 2000. Similarly, sensitized recipients receiving living donor grafts decreased from 17% in 1991 to 13% in 2000. Graft survival in patients with more than 50% PRA was lower at 3 years for patients receiving cadaveric donor grafts. Highly sensitized patients receiving living donor grafts had graft survival rates similar to those who were not sensitized. 9. Cold ischemia times decreased from an average of 24.2 hours in 1991 to 18.9 hours in 2000. Improved graft survival rates over those 10 years were noted in all groups, and even cold ischemia times more than 36 hours yielded 3-year graft survivals comparable to those with lower cold ischemia times in 1998. 10. The need for dialysis has remained constant at about 23% over the last 10 years for patients receiving kidneys from cadaveric donors. The rate of dialysis for patients receiving kidneys from living donors was about 5% for each of the 10 years examined. First day anuria increased from 11% in 1991 to 16% in 2000 for cadaver donor transplants and 3% in 1999 to 5% in 2000 for living donor grafts. 11. Cadaveric donor patients requiring dialysis had a 3-year graft survival rate of 63% if there was no first day anuria and 56% if they had first day anuria. This is in contrast to 80% 3-year graft survival for those with immediate diuresis and no need for dialysis. The 3-year graft survival rate for those receiving living donor grafts and needing dialysis was 58% if they had first day diuresis and 41% if they ware anuric on the first day. Conversely, those who had first day function and did not require dialysis had 89% 3-year graft survival. 12. Among the patients receiving cadaveric grafts with first day diuresis there was a marked reduction in those with rejection, from 21% in 1991 to 5% in 2000. Similarly, for this type of patient receiving living donor grafts, the reduction was 17% in 1991 to 5% in 2000. However, graft survival among these patients did not change significantly. The greatest improvement was noted in those with first day anuria and no rejection. 13. Patients who did not require dialysis, and had rejection prior to discharge decreased markedly from 17% in 1991 to 3% in 2000 in those receiving cadaveric grafts and 15% in 1991 to 3.9% in 2000 for those receiving living donors. Graft survival of cadaveric transplants in those needing dialysis, with and without rejection, improved the most in the 10 year period. 14. Hospitalization days for cadaveric transplant recipients were reduced from 19 days in 1991 to 10 days in 2000 and 16 days in 1991 to 8 days in 2000 for recipients of living donor grafts. There was an increase in discharge serum creatinine values from 2.3 mg/dl in 1991 to 3.3 mg/dl in 2000 for cadaver donor grafts. 15. Double therapy was utilized for about 15% of cadaveric and living donors. There was a sharp increase in induction therapy, peaking at 51% in 1994 and decreasing to 5% by 2000 for cadaveric donor transplants. Induction did not improve graft survival for either cadaver or living donor transplant recipients. 16. Triple therapy improved graft survival of White and Black patients, but did not affect the half-lives in either race. 17. The lower graft survival from older donors was not affected by triple therapy for cadaver donor transplants. Triple therapy removed the donor age effect for recipients of living donor grafts. 18. Triple therapy practically eliminated the effect of sensitization for cadaveric donor grafts. Both double and triple therapy virtually eliminated the sensitization effect for living donors. 19. Triple therapy significantly improved the survival of kidneys with more than 36 hours cold ischemia time so that 3-year graft survival was 76% at 3 years compared with 81% for kidneys stored 1-12 hours. 20. Triple therapy improved the 3-year graft survival of kidneys with first day anuria from 50% for double therapy to 69% for triple therapy in cadaver donor transplants. For living donor transplants, there was a similar improvement from 57% with double therapy to 72% with triple therapy. 21. Triple therapy improved the 3-year cadaveric graft survival rate of kidneys requiring dialysis from 51% with double therapy to 67% for triple therapy. There was a similar improvement for living donors needing dialysis from 37% to 61% at 3 years.

 

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[27]

TÍTULO / TITLE:  - Non-ribosomal peptide synthetases as technological platforms for the synthesis of highly modified peptide bioeffectors—Cyclosporin synthetase as a complex example.

REVISTA / JOURNAL:  - Biotechnol Annu Rev 2003;9:151-97.

AUTORES / AUTHORS:  - Velkov T; Lawen A

INSTITUCIÓN / INSTITUTION:  - Monash University, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, P.O. Box 13D, Melbourne, Victoria 3800, Australia.

RESUMEN / SUMMARY:  - Many microbial peptide secondary metabolites possess important medicinal properties, of which the immunosuppressant cyclosporin A is an example. The enormous structural and functional diversity of these low-molecular weight peptides is attributable to their mode of biosynthesis. Peptide secondary metabolites are assembled non-ribosomally by multi-functional enzymes, termed non-ribosomal peptide synthetases. These systems consist of a multi-modular arrangement of the functional domains responsible for the catalysis of the partial reactions of peptide assembly. The extensive homology shared among NRPS systems allows for the generalisation of the knowledge garnered from studies of systems of diverse origins. In this review we shall focus the contemporary knowledge of non-ribosomal peptide biosynthesis on the structure and function of the cyclosporin biosynthetic system, with some emphasis on the re-direction of the biosynthetic potential of this system by combinatorial approaches.  N. Ref:: 205

 

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[28]

TÍTULO / TITLE:  - Pharmacoeconomics of drug therapy for atopic dermatitis.

REVISTA / JOURNAL:  - Expert Opin Pharmacother 2002 Mar;3(3):249-55.

AUTORES / AUTHORS:  - Lamb SR; Rademaker M

INSTITUCIÓN / INSTITUTION:  - Leeds Centre of Dermatology, Great George Street, Leeds, West Yorkshire, LS1 3EX, UK.

RESUMEN / SUMMARY:  - Atopic dermatitis is an increasingly prevalent common childhood disease. While the majority of patients have mild disease, atopic dermatitis can cause considerable distress to patients and their caregivers, with significant social and financial cost to families. With a prevalence of 15 - 20% in Western countries, atopic dermatitis also has a considerable health and societal cost to the community. Many new treatments have been shown to be therapeutically effective, particularly in severe disease, including cyclosporin A (Neoral, Novartis AG), interferon, tacrolimus (Fujisawa Pharmaceutical Co. Ltd.) and iv. immunoglobulin. These are expensive when compared to standard treatments like emollients and topical corticosteroids and have significant adverse effects that limit their use. Additional costs related to monitoring are incurred and the long-term safety of these treatments is yet to be determined. However, an advantage over more traditional therapies is their ability to produce benefits even after treatment ceases. Treatments that produce long-term remissions have a greater likelihood of being cost-effective. With monetary constraints on healthcare and the importance governments place on reducing drug costs, economic evaluations are becoming an increasingly important factor for drug acceptance. Those evaluating cost-effectiveness should pay particular attention to the potential reduction in indirect and intangible costs. Unfortunately, there is a dearth of cost-effectiveness studies in atopic eczema and this needs to be addressed with some urgency.  N. Ref:: 43

 

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[29]

TÍTULO / TITLE:  - An update in transplant immunosuppressive therapy.

REVISTA / JOURNAL:  - Med Health R I 2002 Apr;85(4):131-3.

AUTORES / AUTHORS:  - Thursby MA; Yango AF; Gohh RY

INSTITUCIÓN / INSTITUTION:  - Rhode Island Hospital, Division of Renal Diseases, 593 Eddy Street, Providence, RI 02903, USA. Mthursby@lifespan.org  N. Ref:: 10

 

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[30]

TÍTULO / TITLE:  - Kidney transplantation from living donors: comparison of results between related and unrelated donor transplants under new immunosuppressive protocols.

REVISTA / JOURNAL:  - Isr Med Assoc J 2003 Sep;5(9):622-5.

AUTORES / AUTHORS:  - Chkhotua AB; Klein T; Shabtai EL; Yussim A; Bar-Nathan N; Shaharabani E; Lustig S; Mor E

INSTITUCIÓN / INSTITUTION:  - National Center of Urology, Tbilisi, Georgia.

RESUMEN / SUMMARY:  - BACKGROUND: Recent advances in immunosuppressive therapy have led to a substantial improvement in the outcome of kidney transplantation. Living unrelated donors may become a source of additional organs for patients on the kidney waiting list. OBJECTIVES: To study the impact of the combination of calcineurin inhibitors and mycophenolate-mofetile, together with steroids, on outcomes of living related and unrelated transplants. METHODS: Between September 1997 and January 2000, 129 patients underwent living related (n = 80) or unrelated (n = 49) kidney transplant. The mean follow-up was 28.2 months. Immunosuppressive protocols consisted of MMF with cyclosporine (41%) or tacrolimus (59%), plus steroids. Patient and graft survival data, rejection rate, and graft functional parameters were compared between the groups. RESULTS: LUD recipients were older (47.8 vs. 33.6 years) with a higher number of re-transplants (24.5% vs. 11.2% in LRD recipients, P < 0.05). Human leukocyte antigen matching was higher in LRD recipients (P < 0.001). Acute rejection developed in 28.6% of LUD and 27.5% of LRD transplants (P = NS). Creatinine levels at 1, 2 and 3 years post-transplant were 1.6, 1.7 and 1.7 mg/dl for LRD patients and 1.5, 1.5 and 1.3 mg/dl for LUD recipients (P = NS). There was no difference in patient survival rates between the groups. One, 2 and 3 years graft survival rates were similar in LRD (91.3%, 90% and 87.5%) and LUD (89.8%, 87.8% and 87.8%) recipients. CONCLUSIONS: Despite HLA disparity, rejection and survival rates of living unrelated transplants under current immunosuppressive protocols are comparable to those of living related transplants.

 

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[31]

TÍTULO / TITLE:  - Evolution of biologic therapies for the treatment of psoriasis.

REVISTA / JOURNAL:  - Skinmed 2003 Sep-Oct;2(5):286-94.

AUTORES / AUTHORS:  - Gordon KB; McCormick TS

INSTITUCIÓN / INSTITUTION:  - Department of Medicine, Division of Dermatology, Loyola University, Stritch School of Medicine, Maywood, IL 60153, USA. kgordon@lumc.edu

RESUMEN / SUMMARY:  - Over the past three decades, laboratory and clinical research findings have shown that T cells are the primary mediators of psoriasis pathogenesis and that psoriasis can be treated by eliminating these T cells or interfering with their activation or activity. Based on these observations, many new biologic therapies to treat psoriasis are now in development. These agents, developed primarily through recombinant DNA techniques, are designed to target T cells and the immunologic cascade associated with their activation. Four basic strategic approaches that focus on the steps involved in the immunopathology of psoriasis are: 1) elimination of the pathogenic T cells; 2) inhibition of T-cell activation, proliferation, and migration; 3) immune deviation to down-regulate the type 1 (TH1) response predominant in psoriasis; and 4) blockade of cytokine production. The goal of these new therapies is to improve the treatment of psoriasis, particularly moderate to severe disease, with agents that are well tolerated and safe for long-term use.  N. Ref:: 52

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[32]

TÍTULO / TITLE:  - An evidence-based pilot study exploring relationships between psychologic and physiologic factors in post-lung-transplant adolescents with cystic fibrosis.

REVISTA / JOURNAL:  - J Pediatr Nurs 2003 Jun;18(3):216-20.

      ●● Enlace al texto completo (gratuito o de pago) 1053/jpdn.2003.41

AUTORES / AUTHORS:  - Sredl D; Werner T; Springhart D; Watkins D; Shaner M; McBride G

INSTITUCIÓN / INSTITUTION:  - St. Louis Children’s Hospital, St. Louis, MO, USA.

RESUMEN / SUMMARY:  - After using an evidence-based approach to address clinical practice questions, a pilot study was designed to explore the relationships among anxiety and depression self-report data, cyclosporine (CSA) trough values, and biopsy rejection grades within a posttransplant sample of adolescents with cystic fibrosis. Thirteen study participants completed the Revised Children’s Manifest Anxiety Scale (RCMAS) and the Children’s Depression Inventory (CDI), and had CSA trough levels and biopsy data collected. There was a statistically significant correlation between depression and inflammatory rejection levels. Adolescents with benign rejection scores had lower depression scores than adolescents with higher levels of rejection scores. The data also showed a statistically significant inverse correlation between CSA trough levels and inflammatory rejection levels. Posttransplant success depends on compliance with a strict, antirejection regimen. Adolescence is a turbulent time when many stressors can result in risk-taking behavior such as medication noncompliance and anxiety and depression. Regular psychologic monitoring of posttransplant adolescent patients may be warranted to identify increasing psychologic distress and proactive opportunities for health care intervention. This pilot study is an example of a clinical research question that evolved from a practice situation in which nurses caring for posttransplant adolescents with cystic fibrosis surmised that there were many psychologic issues influencing successful transplant outcomes. Nursing observations suggested a strong connection between poorer medication control, greater risk for rejection, and signs of depression and/or anxiety. The nurse researchers were interested in identifying significant relationships between psychologic factors and physiologic factors, and in discovering objective ways to better assess the psychologic needs of this patient population. A thorough search was conducted of the research literature, and the best clinical practices of other institutions were investigated. There was a lack of transplant research literature on adolescents, and although excellent ideas were generated from inquiries to other institutions, there was a lack of best evidence to answer the clinical questions about this group of patients. The initial clinical question became a research question to determine more about this specific patient population. This article is an example of a clinical research pilot study that resulted from an evidence-based practice process. Pilot studies are springboards for other, more refined research: They help to point the way, or to clarify what the real issues may be. For nurses, they serve as an opportunity to hone critical thinking skills and to contribute to the scientific foundation of our profession.

 

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[33]

TÍTULO / TITLE:  - More economical use of cyclosporine through combination drug therapy.

REVISTA / JOURNAL:  - J Am Anim Hosp Assoc 2002 May-Jun;38(3):205-8.

AUTORES / AUTHORS:  - Daigle JC

INSTITUCIÓN / INSTITUTION:  - Veterinary Specialists of South Florida, Cooper City 33024, USA.  N. Ref:: 30

 

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