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A. El Gamel

Bio: A. El Gamel is an academic researcher. The author has contributed to research in topics: Transplantation & Heart transplantation. The author has an hindex of 3, co-authored 4 publications receiving 127 citations.

Papers
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Journal ArticleDOI
TL;DR: The difference in the mean ejection fraction in the first week after transplantation suggests that bicaval orthotopic cardiac implantation is associated with a lower right atrial pressure, a lower likelihood of atrial tachyarrhythmias, less need for pacing, less mitral incompetence, less diuretic dose, and a shorter hospital stay.

101 citations

Journal Article
TL;DR: It is concluded that cyclosporine trough levels above 200 ng/ml in the first 2 years after heart transplantation are associated with reduced cellular rejection without deleterious effects on renal function.
Abstract: BACKGROUND: The introduction of cyclosporine to heart transplantation immunosuppressive protocols has been associated with an improvement in the long- and short-term survival rates. The ideal dose of cyclosporine that maximizes its immunosuppressive properties and minimizes its toxicity has remained an enigma since its introduction. This study was undertaken to evaluate which range of cyclosporine levels provided the most effective protection against graft rejection. METHODS: We studied the correlation between cyclosporine levels and histologic grade of rejection, cardiac function, and renal function by retrospectively analyzing the results of 1407 individual whole blood cyclosporine trough levels. One hundred seven heart transplant recipients were studied within 2 years of undergoing transplantation. As a historical comparison, we also studied 146 individual trough cyclosporine levels from a subgroup of patients (n = 14) who had acute cellular rejection with graft dysfunction or failure. We correlated trough cyclosporine levels with the histologic severity of cellular rejection, cardiac function (right cardiac catheterization), and serum creatinine in both groups. The correlation was performed within patient's own data rather than between patient groups to avoid interpatient variations. RESULTS: The mean cyclosporine level was significantly higher (206 ng/ml) when the patients had grade 0 cellular rejection in comparison to grade 3A, with a mean cyclosporine level of 173 ng/ml (p = 0.005). Patients with graft dysfunction or failure had higher mean cyclosporine level (230 ng/ml) when they had no rejection compared with 3A rejection with a mean cyclosporine level of 153 ng/ml (p = 0.001). Furthermore, lower cyclosporine levels were associated with graft dysfunction. There was no correlation between serum creatinine and cyclosporine levels (r = 0.059, r2 = 0.351%). CONCLUSION: We conclude that cyclosporine trough levels above 200 ng/ml in the first 2 years after heart transplantation are associated with reduced cellular rejection without deleterious effects on renal function.

21 citations


Cited by
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Journal ArticleDOI
TL;DR: Institutional Affiliations Chair Costanzo MR: Midwest Heart Foundation, Lombard Illinois, USA Task Force 1 Dipchand A: Hospital for Sick Children, Toronto Ontario, Canada; Starling R: Cleveland Clinic Foundation, Cleveland, Ohio, USA; Starlings R: University of Chicago, Chicago, Illinois,USA; Chan M: university of Alberta, Edmonton, Alberta, Canada ; Desai S: Inova Fairfax Hospital, Fairfax, Virginia, USA.
Abstract: Institutional Affiliations Chair Costanzo MR: Midwest Heart Foundation, Lombard Illinois, USA Task Force 1 Dipchand A: Hospital for Sick Children, Toronto Ontario, Canada; Starling R: Cleveland Clinic Foundation, Cleveland, Ohio, USA; Anderson A: University of Chicago, Chicago, Illinois, USA; Chan M: University of Alberta, Edmonton, Alberta, Canada; Desai S: Inova Fairfax Hospital, Fairfax, Virginia, USA; Fedson S: University of Chicago, Chicago, Illinois, USA; Fisher P: Ochsner Clinic, New Orleans, Louisiana, USA; Gonzales-Stawinski G: Cleveland Clinic Foundation, Cleveland, Ohio, USA; Martinelli L: Ospedale Niguarda, Milano, Italy; McGiffin D: University of Alabama, Birmingham, Alabama, USA; Parisi F: Ospedale Pediatrico Bambino Gesu, Rome, Italy; Smith J: Freeman Hospital, Newcastle upon Tyne, UK Task Force 2 Taylor D: Cleveland Clinic Foundation, Cleveland, Ohio, USA; Meiser B: University of Munich/Grosshaden, Munich, Germany; Baran D: Newark Beth Israel Medical Center, Newark, New Jersey, USA; Carboni M: Duke University Medical Center, Durham, North Carolina, USA; Dengler T: University of Hidelberg, Heidelberg, Germany; Feldman D: Minneapolis Heart Institute, Minneapolis, Minnesota, USA; Frigerio M: Ospedale Niguarda, Milano, Italy; Kfoury A: Intermountain Medical Center, Murray, Utah, USA; Kim D: University of Alberta, Edmonton, Alberta, Canada; Kobashigawa J: Cedar-Sinai Heart Institute, Los Angeles, California, USA; Shullo M: University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Stehlik J: University of Utah, Salt Lake City, Utah, USA; Teuteberg J: University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Uber P: University of Maryland, Baltimore, Maryland, USA; Zuckermann A: University of Vienna, Vienna, Austria. Task Force 3 Hunt S: Stanford University, Palo Alto, California, USA; Burch M: Great Ormond Street Hospital, London, UK; Bhat G: Advocate Christ Medical Center, Oak Lawn, Illinois, USA; Canter C: St. Louis Children Hospital, St. Louis, Missouri, USA; Chinnock R: Loma Linda University Children's Hospital, Loma Linda, California, USA; Crespo-Leiro M: Hospital Universitario A Coruna, La Coruna, Spain; Delgado R: Texas Heart Institute, Houston, Texas, USA; Dobbels F: Katholieke Universiteit Leuven, Leuven, Belgium; Grady K: Northwestern University, Chicago, Illlinois, USA; Kao W: University of Wisconsin, Madison Wisconsin, USA; Lamour J: Montefiore Medical Center, New York, New York, USA; Parry G: Freeman Hospital, Newcastle upon Tyne, UK; Patel J: Cedar-Sinai Heart Institute, Los Angeles, California, USA; Pini D: Istituto Clinico Humanitas, Rozzano, Italy; Pinney S: Mount Sinai Medical Center, New York, New York, USA; Towbin J: Cincinnati Children's Hospital, Cincinnati, Ohio, USA; Wolfel G: University of Colorado, Denver, Colorado, USA Independent Reviewers Delgado D: University of Toronto, Toronto, Ontario, Canada; Eisen H: Drexler University College of Medicine, Philadelphia, Pennsylvania, USA; Goldberg L: University of Pennsylvania, Philadelphia, Pennsylvania, USA; Hosenpud J: Mayo Clinic, Jacksonville, Florida, USA; Johnson M: University of Wisconsin, Madison, Wisconsin, USA; Keogh A: St Vincent Hospital, Sidney, New South Wales, Australia; Lewis C: Papworth Hospital Cambridge, UK; O'Connell J: St. Joseph Hospital, Atlanta, Georgia, USA; Rogers J: Duke University Medical Center, Durham, North Carolina, USA; Ross H: University of Toronto, Toronto, Ontario, Canada; Russell S: Johns Hopkins Hospital, Baltimore, Maryland, USA; Vanhaecke J: University Hospital Gasthuisberg, Leuven, Belgium.

1,346 citations

Journal ArticleDOI
TL;DR: In this article, the authors showed that calcineurin inhibitors, cyclosporin A (CsA) and FK 506 (0.3 mg · kg −1 · d −1 ) or even higher doses of CsA (10 and 20 mg· kg − 1 · d−1 ) were sufficient to prevent the development of pressure-overload hypertrophy in the spontaneously hypertensive rat and aortic banding.
Abstract: —A rapidly emerging body of literature implicates a pivotal role for the Ca 2+ -calmodulin–dependent phosphatase calcineurin as a cellular target for a variety of Ca 2+ -dependent signaling pathways culminating in left ventricular hypertrophy (LVH). Most of the recent experimental support for this hypothesis is derived from in vitro studies or in vivo studies in transgenic mice expressing activated calcineurin or mutant sarcomeric proteins. The aim of the present study was to test whether calcineurin inhibitors, cyclosporin A (CsA) and FK 506, prevent pressure-overload LVH using 2 standard rat models: (1) the spontaneously hypertensive rat (SHR) and (2) aortic banding. The major new findings are 2-fold. First, in SHR, LVH (left ventricular weight to body weight ratio) was unaffected by a dose of CsA (5 mg · kg −1 · d −1 ) that was sufficient to raise blood pressure and to inhibit calcineurin-mediated transcriptional activation in skeletal muscle. Second, in rats with aortic banding, LVH was unaffected by FK 506 (0.3 mg · kg −1 · d −1 ) or even higher doses of CsA (10 and 20 mg · kg −1 · d −1 ) that were sufficient to inhibit 90% of total calcineurin phosphatase activity in the hypertrophied myocardium. In the latter experiments, CsA blocked neither the elevated left ventricular end-diastolic pressures, a measure of diastolic function, nor the induction in atrial natriuretic peptide mRNA in the hypertrophic ventricles. Thus, in numerous experiments, systemic administration of potent calcineurin inhibitors did not prevent the development of LVH in 2 classic models of pressure-overload hypertrophy. These results demonstrate that pressure-overload hypertrophy can arise through calcineurin-independent pathways.

141 citations

Journal ArticleDOI
TL;DR: The distribution characteristics of cyclosporin in blood, plasma and various tissues are clinically important and mathematical models that calculate CsAfu, and hence CsAU, from the concentration of plasma lipoproteins may be a more practical option and should provide a more accurate correlate of effectiveness and toxicity of this drug in transplant recipients than do conventional monitoring procedures.
Abstract: Cyclosporin is an immunosuppressive agent with a narrow therapeutic index. The total concentration of cyclosporin in blood is usually monitored to guide dosage adjustment and to compensate for substantial interindividual and intraindividual variability in cyclosporin pharmacokinetics. Cyclosporin is a highly lipophilic molecule and widely distributes into blood, plasma and tissue components. It mainly accumulates in fat-rich organs, including adipose tissue and liver. In blood, it binds to erythrocytes in a saturable fashion that is dependent on haematocrit, temperature and the concentration of plasma proteins. In plasma, it binds primarily to lipoproteins, including high-density, low-density and very-low-density lipoprotein, and, to a lesser extent, albumin. The unbound fraction of cyclosporin in plasma (CsA(fu)) expressed as a percentage is approximately 2%. It has been shown that both the pharmacokinetic and pharmacodynamic properties of cyclosporin are related to its binding characteristics in plasma. Furthermore, there is some evidence to indicate that the unbound concentration of cyclosporin (CsA(U)) has a closer association with both kidney and heart allograft rejection than the total (bound + unbound) concentration. However, the measurement of CsA(fu) is inherently complex and cannot easily be performed in a clinical setting. Mathematical models that calculate CsA(fu), and hence CsA(U), from the concentration of plasma lipoproteins may be a more practical option, and should provide a more accurate correlate of effectiveness and toxicity of this drug in transplant recipients than do conventional monitoring procedures. In conclusion, the distribution characteristics of cyclosporin in blood, plasma and various tissues are clinically important. Further investigations are needed to verify whether determination of CsA(U) improves the clinical management of transplant recipients.

128 citations

Journal ArticleDOI
TL;DR: Results indicate that the largest populations of cardiac ganglia are near the sinoatrial and atrioventricular nodes, and modifications to surgical procedures involving incisions through regions concentrated with ganglia to minimize arrhythmias and related complications.

108 citations

Journal ArticleDOI
TL;DR: A breath test for markers of oxidative stress was more sensitive and less specific for Grade 3 heart transplant rejection than a biopsy reading by a site pathologist, but the negative predictive values of the 2 tests were similar.
Abstract: Background We evaluated a new marker of heart transplant rejection, the breath methylated alkane contour (BMAC). Rejection is accompanied by oxidative stress that degrades membrane polyunsaturated fatty acids, evolving alkanes and methylalkanes, which are excreted in the breath as volatile organic compounds (VOCs). Methods Breath VOC samples ( n = 1,061) were collected from 539 heart transplant recipients before scheduled endomyocardial biopsy. Breath VOCs were analyzed by gas chromatography and mass spectroscopy, and BMAC was derived from the abundance of C4–C20 alkanes and monomethylalkanes. The “gold standard” of rejection was the concordant set of International Society for Heart and Lung Transplantation (ISHLT) grades in biopsies read by 2 reviewers. Results Concordant biopsies were: Grade 0, 645 of 1,061 (60.8%); 1A, 197 (18.6%); 1B, 84 (7.9%); 2, 93 (8.8%); and 3A, 42 (4.0%). A combination of 9 VOCs in the BMAC identified Grade 3 rejection (sensitivity 78.6%, specificity 62.4%, cross-validated sensitivity 59.5%, cross-validated specificity 58.8%, positive predictive value 5.6%, negative predictive value 97.2%). Site pathologists identified the same cases with sensitivity of 42.4%, specificity 97.0%, positive predictive value 45.2% and negative predictive value 96.7%. Conclusions A breath test for markers of oxidative stress was more sensitive and less specific for Grade 3 heart transplant rejection than a biopsy reading by a site pathologist, but the negative predictive values of the 2 tests were similar. A screening breath test could potentially identify transplant recipients at low risk of Grade 3 rejection and reduce the number of endomyocardial biopsies.

106 citations