#06#
Revisiones-Clínica-Pronóstico
*** Reviews-Clinical-Prognosis
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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[1]
TÍTULO / TITLE: - A randomized long-term
trial of tacrolimus/sirolimus versus tacrolimus/mycophenolate mofetil versus
cyclosporine (NEORAL)/sirolimus in renal transplantation. II. Survival,
function, and protocol compliance at 1 year.
REVISTA
/ JOURNAL: - Transplantation 2004 Jan 27;77(2):252-8.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000101495.22734.07
AUTORES
/ AUTHORS: - Ciancio G; Burke GW; Gaynor JJ; Mattiazzi
A; Roth D; Kupin W; Nicolas M; Ruiz P; Rosen A; Miller J
INSTITUCIÓN
/ INSTITUTION: - Department of Surgery, Division of
Transplantation, University of Miami School of Medicine, Miami, FL 33101, USA. gciancio@med.miami.edu
RESUMEN
/ SUMMARY: - BACKGROUND: In an attempt to reduce
chronic calcineurin inhibitor induced allograft nephropathy in first cadaver
and human leukocyte antigen non-identical living-donor renal transplantation,
sirolimus (Siro) or mycophenolate mofetil (MMF) was tested as adjunctive
therapy, with planned dose reductions of tacrolimus (Tacro) over the first year
postoperatively. Adjunctive Siro therapy with a similar dose reduction
algorithm for Neoral (Neo) was included for comparison. METHODS: The detailed
dose reduction plan (Tacro and Siro, group A; Tacro and MMF, group B; Neo and
Siro, group C) is described in our companion report in this issue of
Transplantation. The present report documents function, patient and graft
survival, protocol compliance, and adverse events. RESULTS: As mentioned (in
companion report), group demographics were similar. The present study shows no
significant differences in 1-year patient and graft survival but does show a
trend that points to more difficulties in group C by way of a rising slope of
serum creatinine concentration (P=0.02) and decreasing creatinine clearance
(P=0.04). There were more patients who discontinued the protocol plan in group
C. Thus far, no posttransplant lymphomas have appeared, and infectious
complications have not differed among the groups. However, a greater percentage
of patients in group C were placed on antihyperlipidemia therapy, with an
(unexpected) trend toward a higher incidence of posttransplant diabetes
mellitus in this group. Group A required fewer, and group B the fewest,
antihyperlipidemia therapeutic interventions (P<0.00001). CONCLUSIONS: This
1-year interim analysis of a long-term, prospective, randomized
renal-transplant study indicates that decreasing maintenance dosage of Tacro
with adjunctive Siro or MMF appears to point to improved long-term function,
with reasonably few adverse events.
----------------------------------------------------
[2]
TÍTULO / TITLE: - Early outcome after
sirolimus-eluting stent implantation in patients with acute coronary syndromes:
insights from the Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology
Hospital (RESEARCH) registry.
REVISTA
/ JOURNAL: - J Am Coll Cardiol 2003 Jun
4;41(11):2093-9.
AUTORES
/ AUTHORS: - Lemos PA; Lee CH; Degertekin M; Saia F;
Tanabe K; Arampatzis CA; Hoye A; van Duuren M; Sianos G; Smits PC; de Feyter P;
van der Giessen WJ; van Domburg RT; Serruys PW
INSTITUCIÓN
/ INSTITUTION: - Department of Cardiology, Thoraxcenter,
Erasmus Medical Center, Dr Molewaterplein 40, NL-3015 GD Rotterdam, the Netherlands.
RESUMEN
/ SUMMARY: - OBJECTIVES: This study evaluated the early
outcomes of patients with acute coronary syndromes (ACS) treated with
sirolimus-eluting stents (SES). BACKGROUND: The safety of SES implantation in
patients with a high risk for early thrombotic complications is currently
unknown. METHODS: Sirolimus-eluting stents have been utilized as the device of
choice for all percutaneous procedures in our institution, as part of the
Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospital (RESEARCH)
registry. After four months of enrollment, 198 patients with ACS had been
treated exclusively with SES (64% of those treated in the period) and were
compared with a control group composed of 301 consecutive patients treated with
bare stents in the same time period immediately before this study. The
incidence of major adverse cardiac events (MACE) during the first month was
evaluated (death, nonfatal myocardial infarction [MI], or re-intervention).
RESULTS: Compared with control patients, patients treated with SES had more
primary angioplasty (95% vs. 77%; p < 0.01), more bifurcation stenting (13%
vs. 5%; p < 0.01), less previous MI (28% vs. 45%; p < 0.01), and less
glycoprotein IIb/IIIa inhibitor utilization (27% vs. 42%; p < 0.01). The
30-day MACE rate was similar between both groups (SES 6.1% vs. control patients
6.6%; p = 0.8), with most complications occurring during the first week. Stent
thrombosis occurred in 0.5% of SES patients and in 1.7% of control patients (p
= 0.4). In multivariate analysis, SES utilization did not influence the
incidence of MACE (odds ratio 1.0 [95% confidence interval: 0.4 to 2.2]; p =
0.97). CONCLUSIONS: Sirolimus-eluting stent implantation for patients with ACS
is safe, with early outcomes comparable with bare metal stents. N. Ref:: 25
----------------------------------------------------
[3]
TÍTULO / TITLE: - Pregnancy outcome after
cyclosporine therapy during pregnancy: a meta-analysis.
REVISTA
/ JOURNAL: - Transplantation 2001 Apr 27;71(8):1051-5.
AUTORES
/ AUTHORS: - Bar Oz B; Hackman R; Einarson T; Koren G
INSTITUCIÓN
/ INSTITUTION: - The Motherisk Program, Division of
Clinical Pharmacology/Toxicology, The Hospital for Sick Children, Toronto,
Ontario, Canada.
RESUMEN
/ SUMMARY: - BACKGROUND: Cyclosporine (CsA) therapy
must often be continued during pregnancy to maintain maternal health in such
conditions as organ transplantation and autoimmune disease. This meta-analysis
was performed to determine whether CsA exposure during pregnancy is associated
with an increased risk of congenital malformations, preterm delivery, or low
birthweight. METHODS: Various health science databases were searched to
identify relevant articles. Articles selected for inclusion in the study were
required to be free of any apparent selection bias and report outcomes in at
least 10 newborns exposed to CsA in utero, specifically commenting on the
presence or absence of congenital malformations. Article selection and data
extraction were performed by two independent reviewers, with adjudication in
cases of disagreement. To assess risks of CsA exposure, a summary odds ratio
was calculated. Prevalence of malformations was calculated as a rate for all
cyclosporine-exposed live births and for the subgroups identified. Ninety-five
percent confidence intervals were constructed for both the odds ratio and
prevalence rates. RESULTS: Fifteen studies (6 with control groups of transplant
without use of cyclosporine; total patients: 410) met the inclusion criteria
for major malformations, 10 for preterm delivery (4 with control groups; total
patients: 379) and 5 for low birth weight (1 with control groups; total number
of patients: 314). The calculated odds ratio of 3.83 for malformations did not
achieve statistical significance (CI 0.75-19.6). The overall prevalence of
major malformations in the study population (4.1%) also did not vary
substantially from that reported in the general population. OR for prematurity
[1.52 (CI 1.00-2.32)] did not reach statistical significance although the
overall prevalence rate was 56.3%. The OR for low birth weight [1.5 (CI
0.95-2.44 based on 1 study)]. CONCLUSIONS: CsA does not appear to be a major
human teratogen. It may be associated with increased rates of prematurity. More
research is needed to evaluate whether cyclosporine increases teratogenic risk.
----------------------------------------------------
[4]
TÍTULO / TITLE: - Renal function as a
predictor of long-term graft survival in renal transplant patients.
REVISTA
/ JOURNAL: - Nephrol Dial Transplant. Acceso gratuito
al texto completo a partir de los 2 años de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://ndt.oupjournals.org/
●●
Cita: Nephrology Dialysis Transplantation: <> 2003 May;18 Suppl 1:i3-6.
AUTORES
/ AUTHORS: - First MR
INSTITUCIÓN
/ INSTITUTION: - Research and Development, Fujisawa
Healthcare, Inc., Deerfield, IL 60015, USA. roy_first@fujisawa.com
RESUMEN
/ SUMMARY: - Acute rejection is a major risk factor for
kidney graft failure. However, as acute rejection has been progressively
reduced by recent immunosuppressive regimens, other risk factors are becoming
increasingly important. Evidence is accumulating that early renal function
predicts long-term outcome. A recent registry survey of more than 100 000 kidney
transplants found that 6- and 12-month serum creatinine levels, as well as the
change between 6 and 12 months, are strongly associated with long-term graft
survival. A survey of paediatric renal transplant recipients showed that poor
creatinine clearance (<50 ml/min) as early as 30 days post-transplant
predicted an annual rate of graft loss of 13% compared with <3% in patients
with 30-day clearance >50 ml/min. This association between early renal
function and long-term outcome was confirmed in multicentre studies. Renal
transplant recipients (n=572) with 6-month serum creatinine levels >1.5
mg/dl suffered 3-year graft loss of 19.3% compared with only 8.5% in patients
with levels <1.6 mg/dl (P<0.001). Significantly fewer patients receiving
tacrolimus had 12-month serum creatinine levels >1.5 mg/dl compared with
cyclosporin (42 versus 54%, P<0.05). Interestingly, a single-centre study
(n=436) found that while glomerular filtration rate (GFR) at 6 months
post-transplant had remained stable over the last decade, the rate of loss of
renal function had decreased. A lower rate of GFR loss was associated with
absence of rejection, use of mycophenolate mofetil rather than azathioprine and
use of tacrolimus rather than cyclosporin (P<0.01). In conclusion, early measures
of renal function allow identification of those patients at highest risk of
graft failure and provide an invaluable tool for improving outcomes by tailored
immunosuppression. The choice of such immunosuppression should be guided not
only by its ability to prevent rejection, but also by its impact on renal
function. N. Ref:: 11
----------------------------------------------------
[5]
TÍTULO / TITLE: - Cyclosporin trough
levels: is monitoring necessary during short-term treatment in psoriasis? A
systematic review and clinical data on trough levels.
REVISTA
/ JOURNAL: - Br J Dermatol 2002 Jul;147(1):122-9.
AUTORES
/ AUTHORS: - Heydendael VM; Spuls PI; Ten Berge IJ;
Opmeer BC; Bos JD; de Rie MA
INSTITUCIÓN
/ INSTITUTION: - Department of Dermatology, Academic
Medical Center, University of Amsterdam, PO Box 22660, the Netherlands.
RESUMEN
/ SUMMARY: - BACKGROUND: Cyclosporin is an effective
treatment for severe plaque psoriasis. Unfortunately, its use may be limited by
time- and dose-related nephrotoxicity. Serum trough levels may be useful for
monitoring the risk of nephrotoxicity. OBJECTIVES: To determine whether
monitoring of trough levels is necessary in psoriasis patients undergoing
short-term treatment with cyclosporin. METHODS: A computerized and manual
literature search identified studies on adults with plaque-type psoriasis
treated with cyclosporin < or = 5 mg kg-1 daily, in which trough levels were
measured in whole blood. Number of patients, treatment duration, formulation
and dosage, renal function tests and trough levels were extracted. The
association between renal function and trough levels was investigated.
Additionally, in a randomized controlled trial on cyclosporin vs. methotrexate
in moderate to severe psoriasis, cyclosporin trough levels were measured
frequently in 20 patients during 12 weeks of treatment. The Pearson correlation
coefficient between serum creatinine and cyclosporin trough levels was
calculated. RESULTS: Fifty-six articles were found concerning cyclosporin
trough level measurements in psoriasis patients, of which eight were analysed.
Many studies were excluded due to inappropriate cyclosporin dosages used. As
data were heterogeneous and lacked various key parameters, a correlation study
and a meta-analysis could not be performed. Instead, a quantitative description
of the literature was given. No high mean trough levels or elevations of serum
creatinine were described. In our clinical study, all the mean trough levels in
17 patients treated with cyclosporin 3 mg kg-1 daily were within the
therapeutic range (< 200 ng mL-1). Elevated trough levels were found in two
of three patients treated with cyclosporin 3-5 mg kg-1 daily. No signs of renal
dysfunction were seen. CONCLUSIONS: The literature does not provide a definitive
answer on whether monitoring cyclosporin trough levels in patients with
psoriasis should be standard practice. Our own data show no need for
cyclosporin trough level monitoring during short-term treatment with
cyclosporin 3 mg kg-1 daily. However, when cyclosporin doses are > 3 mg kg-1
daily, monitoring may be indicated. N.
Ref:: 32
----------------------------------------------------
[6]
TÍTULO / TITLE: - Prospects for treatment
of paraquat-induced lung fibrosis with immunosuppressive drugs and the need for
better prediction of outcome: a systematic review.
REVISTA
/ JOURNAL: - Qjm. Acceso gratuito al texto completo a
partir de los 2 años de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://qjmed.oupjournals.org/
●●
Cita: QJM: <> 2003 Nov;96(11):809-24.
AUTORES
/ AUTHORS: - Eddleston M; Wilks MF; Buckley NA
INSTITUCIÓN
/ INSTITUTION: - Centre for Tropical Medicine, Nuffield
Department of Clinical Medicine, University of Oxford, UK. eddlestonm@eureka.lk
RESUMEN
/ SUMMARY: - BACKGROUND: Acute paraquat self-poisoning
is a significant problem in parts of Asia, the Pacific and the Caribbean.
Ingestion of large amounts of paraquat results in rapid death, but smaller
doses often cause a delayed lung fibrosis that is usually fatal.
Anti-neutrophil (‘immunosuppressive’) treatment has been recommended to prevent
lung fibrosis, but there is no consensus on efficacy. Aim: To review the
evidence for the use of immunosuppression in paraquat poisoning, and to
identify validated prognostic systems that would allow the use of data from
historical control studies and the future identification of patients who might
benefit from immunosuppression. DESIGN:Systematic review. METHODS: We searched
PubMed, Embase and Cochrane databases for ‘paraquat’ together with ‘poisoning’
or ‘overdose’. We cross-checked references and contacted experts, and searched
on [www.google.com] and [www.yahoo.com] using ‘paraquat’, ‘cyclophosphamide’,
‘methylprednisolone’ and ‘prognosis’. RESULTS: We found ten clinical studies of
immunosuppression in paraquat poisoning. One was a randomized controlled trial
(RCT). Seven used historical controls only; the other two were small (n = 1 and
n = 4). Mortality in controls and patients varied markedly between studies.
Three of the seven non-RCT controlled studies measured plasma paraquat;
analysis using Proudfoot’s or Hart’s nomograms did not suggest that
immunosuppression increased survival in these studies. Of 16 prognostic systems
for paraquat poisoning, none has been independently validated in a large
cohort. DISCUSSION: The authors of the RCT have performed valuable and
difficult research, but their results are hypothesis-forming rather than conclusive;
elsewhere, the use of historical controls is problematic. In the absence of a
validated prognostic marker, a large RCT of immunosuppression using death as
the primary outcome is required. This RCT should also prospectively test and
validate the available prognostic methods, so that future patients can be
selected for this and other therapies on admission. N. Ref:: 57
----------------------------------------------------
[7]
TÍTULO / TITLE: - A benefit-risk
assessment of basiliximab in renal transplantation.
REVISTA
/ JOURNAL: - Drug Saf. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://www.csmwm.org/
●●
Cita: Drug Safety: <> 2004;27(2):91-106.
AUTORES
/ AUTHORS: - Boggi U; Danesi R; Vistoli F; Del Chiaro
M; Signori S; Marchetti P; Del Tacca M; Mosca F
INSTITUCIÓN
/ INSTITUTION: - Division of General Surgery and
Transplants, Department of Oncology, Transplants and Advanced Technologies in
Medicine, University of Pisa, Pisa, Italy. uboggi@med.unipi.it
RESUMEN
/ SUMMARY: - Interleukin-2 (IL-2) and its receptor
(IL-2R) play a central role in T lymphocyte activation and immune response
after transplantation. Research on the biology of IL-2R allowed the
identification of key signal transduction pathways involved in the generation
of proliferative and antiapoptotic signals in T cells. The alpha-chain of the
IL-2R is a specific peptide against which monoclonal antibodies have been
raised, with the aim of blunting the immune response by means of inhibiting
proliferation and inducing apoptosis in primed lymphocytes. Indeed,
basiliximab, one of such antibodies, has proved to be effective in reducing the
episodes of acute rejection after kidney and pancreas transplantation. The use
of basiliximab was associated with a significant reduction in the incidence of
any treated rejection episodes after kidney transplantation in the two major
randomised studies (placebo 52.2% vs basiliximab 34.2% at 6 months, European
study; placebo 54.9% vs basiliximab 37.6% at 1 year, US trial). Basiliximab and
equine antithymocyte globulin (ATG) administration resulted in a similar rate
of biopsy-proven acute rejection at 6 months (19% for both) and at 12 months
(19% and 20%, respectively). The use of basiliximab appears not to be
associated with an increased incidence of adverse events as compared with
placebo in immunosuppressive regimens, including calcineurin inhibitors,
mycophenolate mofetil or azathioprine and corticosteroids, and its safety
profile is superior to ATG. Moreover, a similar occurrence of infections is
noted in selected studies (65.5% after basiliximab vs 65.7% of controls),
including cytomegalovirus infection (17.3% vs 14.5%), and cytokine-release
syndrome is not observed. Finally, economic analysis demonstrated lower costs of
overall treatment in patients treated with basiliximab. Therefore, the use of
basiliximab entails a very low risk, allows safe reduction of corticosteroid
dosage and reduces the short- and mid-term rejection rates. However, the
improvement in the long-term survival of kidney grafts in patients treated
according to modern immunosuppressive protocols is still to be demonstrated.
These conclusions are based on a systematic review of the scientific
literature, indexed on Medline database, concerning the mechanism of action,
therapeutic activity, safety and pharmacoeconomic evaluation of basiliximab in
renal transplantation. N.
Ref:: 62
----------------------------------------------------
[8]
TÍTULO / TITLE: - Conventional treatment
of Crohn’s disease: objectives and outcomes.
REVISTA
/ JOURNAL: - Inflamm Bowel Dis 2001 May;7 Suppl 1:S2-8.
AUTORES
/ AUTHORS: - Rutgeerts PJ
INSTITUCIÓN
/ INSTITUTION: - Inflammatory Bowel Disease Unit,
University of Leuven, Belgium.
RESUMEN
/ SUMMARY: - Despite conventional medical and/or
surgical intervention, endoscopic and symptomatic relapse is common among
individuals with Crohn’s disease (CD). Treatment goals have therefore been
refocused to include achieving control of active disease and maintaining
remission with agents associated with a minimum of toxic adverse effects.
Conventional treatment regimens have been used with varying success in regard
to these therapeutic goals. Traditionally, aminosalicylates have been
considered effective in inducing a response in some patients with
mild-to-moderate CD but have demonstrated little or no long-term benefit in
controlled clinical trials. Glucocorticosteroid therapy is associated with
higher rates of response in patients with active CD; however, clinical benefits
are frequently offset by the common occurrence of corticosteroid-related
toxicity. Oral controlled-release budesonide has demonstrated comparable
efficacy to prednisolone with less risk for adverse effects, although many
questions remain regarding the long-term use of this agent. Response to
standard immunosuppressive agents such as azathioprine and 6-mercaptopurine in
patients with active disease may require 3 to 6 months from initiation of
treatment. These agents are therefore considered most valuable as maintenance therapy,
providing consistent long-term benefit in patients with chronic refractory or
corticosteroid-dependent disease. Although the incidence of allergic adverse
effects is relatively low with azathioprine/6-mercaptopurine, more serious
adverse effects, including bone marrow suppression, hepatotoxicity,
pancreatitis, and infectious complications, can occur. Limited success in the
treatment of perianal disease has been achieved with antibiotics such as
metronidazole and the immunosuppressives cyclosporine and
azathioprine/6-mercaptopurine. Although broader use of immunosuppressive agents
has allowed improvement in the maintenance of remission in patients with CD,
long-term safety data with these agents are lacking, concerns about toxicity
and the potential risk for neoplasia remain, and attenuation of response with
chronic immunosuppressive use can occur. Therefore, innovative therapeutic
approaches are needed to meet key treatment goals often not addressed by
conventional therapies. N.
Ref:: 48
----------------------------------------------------
[9]
TÍTULO / TITLE: - Pharmacokinetic,
pharmacodynamic, and outcome investigations as the basis for mycophenolic acid
therapeutic drug monitoring in renal and heart transplant patients.
REVISTA
/ JOURNAL: - Clin Biochem 2001 Feb;34(1):17-22.
AUTORES
/ AUTHORS: - Shaw LM; Korecka M; DeNofrio D; Brayman KL
INSTITUCIÓN
/ INSTITUTION: - Departments of Pathology & Laboratory
Medicine and Surgery, University of Pennsylvania Medical Center, Philadelphia,
PA, USA. shawlmj@mail.med.upenn.edu
RESUMEN
/ SUMMARY: - Mycophenolate mofetil is widely used in
combination with either cyclosporine or tacrolimus for rejection prophylaxis in
renal and heart transplant patients. Although not monitored routinely nearly to
the degree that other agents such as cyclosporine or tacrolimus, there is an
expanding body of experimental evidence for the utility of monitoring
mycophenolic acid, the primary active metabolite of mycophenolate mofetil,
plasma concentration as an index of risk for the development of acute
rejection. The following are important experimentally-based reasons for
recommending the incorporation of target therapeutic concentration monitoring
of mycophenolic acid: (1) the MPA dose-interval
area-under-the-concentration-time curve, and less precisely, MPA predose
concentrations predict the risk for development of acute rejection; (2) the
strong correlation between mycophenolic acid plasma concentrations and
expression of important cell surface activation antigens, whole blood
pharmacodynamic assays of lymphocyte proliferation and median graft rejection
scores in a heart transplant animal model; (3) the greater than 10-fold
interindividual variation of MPA area under the concentration time curve values
in heart and renal transplant patients receiving a fixed dose of the parent
drug; (4) drug-drug interactions involving other immunosuppressives are such
that when switching from one to another (eg, from cyclosporine to tacrolimus or
vice-versa) substantial changes in MPA concentrations can occur in patients
receiving a fixed dose of the parent drug; (5) significant effects of liver and
kidney diseases on the steady-state total and free mycophenolic acid area under
the concentration time curve values; (6) the need to closely monitor
mycophenolic acid when a major change in immunosuppression is planned such as
steroid withdrawal. Current investigations are focused on determination of the
most optimal sampling time and for mycophenolic acid target therapeutic
concentration monitoring. Further investigations are needed to evaluate the
pharmacologic activity of the newly described acyl glucuronide metabolite of
mycophenolic acid which has been shown to inhibit, in vitro, inosine monophosphate
dehydrogenase. N.
Ref:: 37
----------------------------------------------------
[10]
TÍTULO / TITLE: - Cryptococcus neoformans
infection in organ transplant recipients: variables influencing clinical
characteristics and outcome.
REVISTA
/ JOURNAL: - Emerg Infect Dis. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://www.cdc.gov/
●●
Cita: Emerging Infectious Diseases: <> 2001 May-Jun;7(3):375-81.
AUTORES
/ AUTHORS: - Husain S; Wagener MM; Singh N
INSTITUCIÓN
/ INSTITUTION: - Veterans Affairs Medical Center and
University of Pittsburgh, Thomas E. Starzl Transplantation Institute,
Pittsburgh, Pennsylvania 15240, USA.
RESUMEN
/ SUMMARY: - Unique clinical characteristics and other
variables influencing the outcome of Cryptococcus neoformans infection in organ
transplant recipients have not been well defined. From a review of published
reports, we found that C. neoformans infection was documented in 2.8% of organ
transplant recipients (overall death rate 42%). The type of primary immunosuppressive
agent used in transplantation influenced the predominant clinical manifestation
of cryptococcosis. Patients receiving tacrolimus were significantly less likely
to have central nervous system involvement (78% versus 11%, p =0.001) and more
likely to have skin, soft-tissue, and osteoarticular involvement (66% versus
21%, p = 0.006) than patients receiving nontacrolimus- based immunosuppression.
Renal failure at admission was the only independently significant predictor of
death in these patients (odds ratio 16.4, 95% CI 1.9-143, p = 0.004).
Hypotheses based on these data may elucidate the pathogenesis and may
ultimately guide the management of C. neoformans infection in organ transplant
recipients. N. Ref:: 74
----------------------------------------------------
[11]
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.
----------------------------------------------------
[12]
TÍTULO / TITLE: - Controlling the
incidence of infection and malignancy by modifying immunosuppression.
REVISTA
/ JOURNAL: - Transplantation 2001 Dec 27;72(12
Suppl):S89-93.
AUTORES
/ AUTHORS: - Soulillou JP; Giral M
RESUMEN
/ SUMMARY: - Long-term outcomes in renal
transplantation have improved over the years but are still a matter of concern.
Because patients typically require lifelong immunosuppression, the risks of
cancer and infection associated with immunosuppressive agents continue to
demand attention. Physicians strive endlessly to find the right balance between
the level of immunosuppression required to prevent rejection and the level that
will minimize dose-dependent side effects. Data presented in this paper suggest
that some renal transplant recipients might have more than necessary
immunosuppression during maintenance therapy and that reducing the
immunosuppressant dose can decrease cancer incidence, without worsening
long-term patient or allograft survival. Additionally, data were examined
suggesting that immunosuppressive agents might be associated with different
risks for cancer, specifically, the potential advantage of reduced cancer risk
for sirolimus and sirolimus derivatives in comparison with standard
immunosuppressive agents. Although promising, these preliminary results are
from preclinical studies, and further study is warranted. N. Ref:: 42
----------------------------------------------------
[13]
TÍTULO / TITLE: - St John’s wort
(Hypericum perforatum): drug interactions and clinical outcomes.
REVISTA
/ JOURNAL: - Br J Clin Pharmacol 2002 Oct;54(4):349-56.
AUTORES
/ AUTHORS: - Henderson L; Yue QY; Bergquist C; Gerden
B; Arlett P
INSTITUCIÓN
/ INSTITUTION: - Pharmacovigilance Group, Medicines Control
Agency, UK. leigh.henderson@mca.gsi.gov.uk
RESUMEN
/ SUMMARY: - AIMS: The aim of this work is to identify
the medicines which interact with the herbal remedy St John’s wort (SJW), and
the mechanisms responsible. METHODS: A systematic review of all the available
evidence, including worldwide published literature and spontaneous case reports
provided by healthcare professionals and regulatory authorities within Europe
has been undertaken. RESULTS: A number of clinically significant interactions
have been identified with prescribed medicines including warfarin,
phenprocoumon, cyclosporin, HIV protease inhibitors, theophylline, digoxin and
oral contraceptives resulting in a decrease in concentration or effect of the
medicines. These interactions are probably due to the induction of cytochrome
P450 isoenzymes CYP3A4, CYP2C9, CYP1A2 and the transport protein P-glycoprotein
by constituent(s) in SJW. The degree of induction is unpredictable due to
factors such as the variable quality and quantity of constituent(s) in SJW
preparations. In addition, possible pharmacodynamic interactions with selective
serotonin re-uptake inhibitors and serotonin (5-HT(1d)) receptor-agonists such
as triptans used to treat migraine were identified. These interactions are
associated with an increased risk of adverse reactions. CONCLUSIONS: In Sweden
and the UK the potential risks to patients were judged to be significant and
therefore information about the interactions was provided to health care
professionals and patients. The product information of the licensed medicines
involved has been amended to reflect these newly identified interactions and
SJW preparations have been voluntarily labelled with appropriate warnings. N. Ref:: 44
----------------------------------------------------
[14]
TÍTULO / TITLE: - Risk factors for
bronchiolitis obliterans: a systematic review of recent publications.
REVISTA
/ JOURNAL: - J Heart Lung Transplant 2002
Feb;21(2):271-81.
AUTORES
/ AUTHORS: - Sharples LD; McNeil K; Stewart S; Wallwork
J
INSTITUCIÓN
/ INSTITUTION: - Medical Research Council (MRC)
Biostatistics Unit, University Forvie Site, Papworth Everard, Cambridge, United
Kingdom. linda.sharples@mrc-bsu.cam.ac.uk
RESUMEN
/ SUMMARY: - BACKGROUND: Obliterative bronchiolitis
remains the major limitation to long-term survival after lung transplantation.
A thorough understanding of the factors that confer high risk of developing
obliterative bronchiolitis or its physiologic surrogate bronchiolitis
obliterans syndrome is important to help define therapeutic strategies. METHODS:
We performed a systematic review of studies published since the beginning of
1990. The review excluded non-human studies, publications before 1990, small
(less than 25 patients) studies that were predominantly concerned with
investigating the pathogenesis of obliterative bronchiolitis, studies solely
concerned with diagnosis or treatment of obliterative bronchiolitis, and
overlapping studies from the same center. Onset of bronchiolitis obliterans
syndrome or obliterative bronchiolitis was the outcome of interest. RESULTS:
Acute rejection plays an important role in obliterative bronchiolitis and
bronchiolitis obliterans syndrome onset, and late rejection is a significant
risk factor. Lymphocytic bronchitis/bronchiolitis is also a risk factor, with
some evidence that late onset is associated with greater risk. The effects of
cytomegalovirus, other infectious organisms, and human leukocyte antigen
matching are less clear and require further confirmation. There is little
evidence that recipient and donor characteristics play a major role.
CONCLUSIONS: This systematic review supports the view that obliterative
bronchiolitis arises from alloimmunologic injury marked by clinically apparent
acute rejection episodes and that inflammatory conditions, including viral
infections or ischemic injury, may also play a role. Implications for therapy
are discussed. N.
Ref:: 28
----------------------------------------------------
[15]
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.
----------------------------------------------------
[16]
TÍTULO / TITLE: - Therapeutic drug
monitoring of immunosuppressant drugs in clinical practice.
REVISTA
/ JOURNAL: - Clin Ther 2002 Mar;24(3):330-50;
discussion 329.
AUTORES
/ AUTHORS: - Kahan BD; Keown P; Levy GA; Johnston A
INSTITUCIÓN
/ INSTITUTION: - Division of Immunology and Organ
Transplantation, University of Texas Health Science Center at Houston Medical
School, 77030, USA. Barry.D.Kahan@uth.tmc.edu
RESUMEN
/ SUMMARY: - BACKGROUND: Therapeutic drug monitoring
(TDM) is essential to maintain the efficacy of many immunosuppressant drugs
while minimizing their toxicity. TDM has become more refined with the
development of new monitoring techniques and more specific assays. OBJECTIVE:
This article summarizes current data on TDM of the following immunosuppressant
drugs used in organ transplantation: cyclosporine, tacrolimus, sirolimus,
everolimus, and mycophenolate mofetil. METHODS: Published data were identified
by a MEDLINE search of the English-language literature through March 2001 using
the terms therapeutic drug monitoring, cyclosporine, tacrolimus, sirolimus,
everolimus, and mycophenolate mofetil. Relevant conference abstracts were also
included. RESULTS: TDM of cyclosporine has been well studied, and recent
findings indicate that monitoring of drug levels 2 hours after dosing is a more
sensitive predictor of outcome than trough (C0) monitoring. C0 levels are being
used more widely in TDM of tacrolimus; however, the relationship between C0 and
area under the curve has varied widely in clinical trials, with correlations
ranging from 0.11 to 0.92. The use of TDM of sirolimus, everolimus, and
mycophenolate mofetil is evolving rapidly. CONCLUSIONS: TDM of
immunosuppressant drugs that have a narrow therapeutic index is an increasingly
useful tool for minimizing drug toxicity while maximizing prevention of graft
loss and organ rejection. N.
Ref:: 85
----------------------------------------------------
[17]
TÍTULO / TITLE: - Therapeutic monitoring
of mycophenolate mofetil in organ transplant recipients: is it necessary?
REVISTA
/ JOURNAL: - Clin Pharmacokinet 2002;41(5):319-27.
AUTORES
/ AUTHORS: - Mourad M; Wallemacq P; Konig J; de Frahan
EH; Eddour DC; De Meyer M; Malaise J; Squifflet JP
INSTITUCIÓN
/ INSTITUTION: - Department of Kidney and Pancreas
Transplantation, University Hospital Saint Luc, Universite Catholique de
Louvain, Brussels, Belgium. Michel.Mourad@chir.ucl.ac.be
RESUMEN
/ SUMMARY: - Adequate immunosuppression minimising the
risk of organ rejection with acceptable tolerability of the used drugs is a
crucial step in organ transplantation. The primary goal is to maintain a
consistent time-dependent target concentration by tailoring individual dosage
leading to the best efficacy and tolerability combination. The use of
therapeutic drug monitoring (TDM) to optimise immunosuppressive therapy is
routinely employed for maintenance drugs such as cyclosporin and tacrolimus.
The question whether therapeutic monitoring of mycophenolic acid (MPA) in organ
transplant recipients treated with mycophenolate mofetil is necessary is not
definitely answered. The correlation of mycophenolic acid pharmacokinetic
parameters with efficacy and toxicity makes the therapeutic monitoring of this
drug promising. However, further studies are mandatory to draw the best
guidelines in order to achieve higher levels of evidence that MPA-TDM may
improve patient outcome. N.
Ref:: 63
----------------------------------------------------
[18]
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
----------------------------------------------------
[19]
TÍTULO / TITLE: - Long-term kidney
transplant survival.
REVISTA
/ JOURNAL: - Am J Kidney Dis 2001 Dec;38(6 Suppl
6):S44-50.
AUTORES
/ AUTHORS: - Hariharan S
INSTITUCIÓN
/ INSTITUTION: - Froedert Memorial Hospital, Medical
College of Wisconsin, Milwaukee, WI 53226, USA. hari@mcw.edu
RESUMEN
/ SUMMARY: - With improvements in short-term kidney
graft survival, focus has shifted towards long-term survival. There has also
been a substantial improvement in long-term survival as measured by kidney
half-life. Long-term graft failure is secondary to chronic allograft
nephropathy (CAN), recurrent disease, and death with a functioning graft. CAN
is secondary to a combination of chronic rejection, chronic cyclosporine
toxicity, and/or donor kidney disease. Risk factors for chronic rejection have
been attributed to both immunological and nonimmunological causes. With a
marked reduction in acute rejection rates-an important risk factor for
CAN-there is a substantial improvement in kidney half-life. There are still
nonimmunological factors, such as donor age, that adversely affect long-term
graft survival. In addition, African-American recipients continue to have a
shorter graft half-life. Recurrent disease is becoming an important cause of late
graft failure. Despite the introduction of various potent immunosuppressive
agents, there has been little or no impact on the prevalence as well as
progression of recurrent diasease. With the reduction of acute rejection rates
and improved short- and long-term graft survival, further improvements of
long-term graft survival will be an important focus in the 21st
century. N. Ref:: 45
----------------------------------------------------
[20]
TÍTULO / TITLE: - Studies of Pediatric
Liver Transplantation (SPLIT): year 2000 outcomes.
REVISTA
/ JOURNAL: - Transplantation 2001 Aug 15;72(3):463-76.
INSTITUCIÓN
/ INSTITUTION: - c/o The EMMES Corporation, 401 N.
Washington Street, Suite 700, Rockville, MD 20850, USA. splitpub@emmes.com
RESUMEN
/ SUMMARY: - BACKGROUND: Initiated in 1995, the Studies
of Pediatric Liver Transplantation (SPLIT) registry database is a cooperative
research network of pediatric transplantation centers in the United States and
Canada. The primary objectives are to characterize and follow trends in
transplant indications, transplantation techniques, and outcomes (e.g.,
patient/graft survival, rejection, growth parameters, and immunosuppressive
therapy.) METHODS: As of June 15, 2000, 29 centers registered 1144 patients,
640 of whom received their first liver-only transplant while registered in
SPLIT. Patients are followed every 6 months for 2 years and yearly thereafter.
Data are submitted to a central coordinating center. RESULTS: One/two-year patient
survival and graft loss estimates are 0.85/0.82 and 0.77/0.72, respectively.
Risk factors for death include: in ICU at transplant (relative risk (RR)=2.63,
P<0.05) and height/weight deficits of two or more standard deviations
(RR=1.67, P<0.05). Risk factors for graft loss include: in ICU at transplant
(RR=1.77, P<0.05) and receiving a cadaveric split organ compared with a
whole organ (RR=2.3, P<0.05). The percentage of patients diagnosed with
hepatic a. and portal v. thrombosis were 9.7% and 7%, respectively; 15% had
biliary complications within 30 days. At least one re-operation was required in
45%. One/two-year rejection probability estimates are 0.60/0.66. Tacrolimus, as
primary therapy posttransplant, reduces first rejection risk (RR=0.70, P<0.05).
Eighty-nine percent of school-aged children are in school full-time, 18 months
posttransplant. CONCLUSIONS: This report provides one of the first descriptions
of characteristics and clinical courses of a multicenter pediatric transplant
population. Observations are subject to patient selection biases but are useful
for generating hypothesis for future studies.
----------------------------------------------------
[21]
TÍTULO / TITLE: - New strategies to
optimize clinical outcomes with cyclosporine in liver transplantation.
REVISTA
/ JOURNAL: - Gastroenterol Hepatol. Acceso gratuito al
texto completo a partir de los 2 años de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://db.doyma.es/
●●
Cita: Gastroenterología & Hepatología: <> 2002 Apr;25(4):289-93.
AUTORES
/ AUTHORS: - Levy GA
INSTITUCIÓN
/ INSTITUTION: - Toronto General Hospital, University of
Toronto, Toronto, Ontario, Canada. N.
Ref:: 25
----------------------------------------------------
[22]
TÍTULO / TITLE: - Incidence and spectrum
of infections in lung transplanted patients: comparison of four different
immunosuppressive protocols.
REVISTA
/ JOURNAL: - Transplant Proc 2001
Feb-Mar;33(1-2):1620-1.
AUTORES
/ AUTHORS: - Treede H; Reichenspurner H; Meiser BM; Kur
F; Furst H; Vogelmeier C; Briegel J; Reichart B
INSTITUCIÓN
/ INSTITUTION: - University Hospital Grosshadern, Munich,
Germany.
----------------------------------------------------
[23]
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.
----------------------------------------------------
[24]
TÍTULO / TITLE: - Strategies to reduce
toxicities and improve outcomes in renal transplant recipients.
REVISTA
/ JOURNAL: - Pharmacotherapy 2002 Mar;22(3):316-28.
AUTORES
/ AUTHORS: - Lo A; Alloway RR
INSTITUCIÓN
/ INSTITUTION: - Department of Surgery, University of
Cincinnati Medical Center, Ohio 45267-0585, USA.
RESUMEN
/ SUMMARY: - Ongoing improvements in immunosuppression
and posttransplantation care have dramatically improved patient and graft
outcomes after transplantation. The frequency of graft loss due to acute
rejection has declined considerably as a result of the availability of a
variety of more potent immunosuppressive agents and probably also because of
refined clinical care and follow-up. Complications of long-term administration of
corticosteroids (steroids) and calcineurin inhibitors, however, have become
increasingly apparent as patients live longer with their transplant, and
attention is shifting to long-term issues. Use of both steroids and calcineurin
inhibitors is associated with metabolic toxicities such as hypertension,
hyperlipidemia, diabetes, bone loss, and cataracts. These contribute to
posttransplantation morbidity and may negatively affect patient and allograft
survival. A variety of troublesome cosmetic side effects, such as hirsutism,
gingival hyperplasia, alopecia, obesity, and cushingoid appearance, also are
associated with these drugs. These effects can detract from patient self-esteem
and compliance with the immunosuppressive regimen. In the past 2 decades, the introduction
of second-generation immunosuppressive drugs, such as tacrolimus, mycophenolate
mofetil, sirolimus, and anti-interleukin-2 receptor monoclonal antibodies, has
provided some alternatives to classic immunosuppressant choices. Patients
experiencing undesirable adverse events now can be converted to another
immunosuppressive regimen that ultimately will improve graft and patient
survival rates and improve quality of life after transplantation. N. Ref:: 99
----------------------------------------------------
[25]
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
----------------------------------------------------
[26]
TÍTULO / TITLE: - Promising early
outcomes with a novel, complete steroid avoidance immunosuppression protocol in
pediatric renal transplantation.
REVISTA
/ JOURNAL: - Transplantation 2001 Jul 15;72(1):13-21.
AUTORES
/ AUTHORS: - Sarwal MM; Yorgin PD; Alexander S; Millan
MT; Belson A; Belanger N; Granucci L; Major C; Costaglio C; Sanchez J; Orlandi
P; Salvatierra O Jr
INSTITUCIÓN
/ INSTITUTION: - Department of Surgery, Stanford University
Medical Center, 703 Welch Road, Suite H-5, Palo Alto, CA 94304, USA.
RESUMEN / SUMMARY: <