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C Cardella

Publications and source records attributed to C Cardella.

At least 19 recordsLinked to original sources
PubMed2002

Should moderate acute rejection of a cardiac transplant graft be treated?

UNLABELLED: Histologically proven, moderate acute rejection after orthotopic heart transplantation (OHT) is commonly treated with intravenous steroids. This regimen may result in severe metabolic and infectious side-effects. The purpose of this study was to assess and compare outcomes in treated (T) versus not treated (N-T) biopsy proven 3A rejection episodes in cardiac transplant recipients. METHODS: A retrospective analysis was conducted to identify all biopsy proven 3A rejection episodes that occurred over the time period 1995-2000 in patients (patients) >or= 6 months after OHT (n=48 episodes in 35 patients). Of the 48 episodes, 19 were N-T and 29 were T. Decision to treat 3A rejection was based on time after transplant, haemodynamic and/or clinical compromise and left ventricular (LV) dysfunction measured by 2D echo. Most N-T episodes received an increase in background immunotherapy. RESULTS: Time from transplant to index 3A episode in N-T patients was 4.2 versus 2.7 yr for the T patients (p=0.06). There were no differences seen between T and N-T groups for the first and second post-3A biopsy results or LV function post-3A. Presence of coronary disease or death were not different between groups. Of the 29 patients with T episodes, no differences in outcomes (death, first and second post-3A biopsy score, coronary disease, myocardial infarction, or LV function) were seen based on use of treatment with intravenous versus oral steroid. CONCLUSION: In patients more than 6 month after OHT, there were no differences in outcomes (ongoing rejection or LV function) between N-T episodes of 3A rejection and T episodes. In T patients the use of oral steroids was equally as effective for treatment of 3A episodes as intravenous steroids.

Adolescent↗
PubMed2001

Pediatric heart transplantation: improving results in high-risk patients.

OBJECTIVES: Our institutional experience with 73 pediatric patients undergoing cardiac transplantation between January 1, 1990, and December 31, 1999, was reviewed to determine the impact of unconventional donor and recipient management protocols implemented to extend the availability of this therapy. METHODS AND RESULTS: The introduction of donor blood cardioplegic solution with added insulin was associated with a significant improvement in patient and graft survival (hazard ratio [Cox] = 0.25, P =.08), despite significantly longer ischemic times with this protocol compared with the use of crystalloid-based donor procurement techniques (P <.01). Eleven patients underwent intentional transplantation of ABO-incompatible donor hearts with the aid of a protocol of plasma exchange on bypass. In this subgroup, there were 2 early deaths caused by nonspecific graft failure (n = 1) and respiratory complications with mild vascular rejection (n = 1), and there was 1 late death caused by lymphoma. ABO-incompatible transplantation was not a risk factor for death by multivariate analysis. The postoperative course in these patients suggests minimal reactivity directed against incompatible grafts on the basis of low anti-donor blood group antibody production, in association with a favorable rejection profile. Ten of 13 patients requiring preoperative support with an extracorporeal membrane oxygenator survived transplantation; there were 3 additional late deaths in this subgroup (hazard ratio = 2.88, P =.05). CONCLUSIONS: The results with pediatric cardiac transplantation continue to improve as a result of changes in both surgical and medical protocols permitting successful treatment of patients conventionally considered at high risk or unsuitable for transplantation.

ABO Blood-Group System↗
PubMed1999

Outcome of kidney transplantation from high-risk donors is determined by both structure and function.

METHOD: Despite the need to expand the donor pool, it is unclear what parameters should be used. The value of donor renal pathology and calculated creatinine clearance (CrCl) in determining recipient outcome was assessed in 57 kidney transplants from 34 donors in whom pretransplant renal biopsies were performed because of age > or =60, hypertension, and/or vascular disease. We retrospectively compared clinical outcomes in these recipients and 57 control recipients selected to have the same baseline demographics but receiving transplants from low risk donors who were significantly younger (32+/-13.9 vs. 61+/-7.3 years) and lighter weight (71+/-18.1 vs. 84+/-20.2 kg) than the high-risk donors (P<.001 for both). RESULTS: Recipients of high-risk kidneys had a higher incidence of delayed graft function, defined by a <10% fall in serum creatinine (Cr) in the first 24 hr, (56% vs. 30%, P<.01), a higher incidence of rejection (60% vs. 37%, P = .02) and a higher Cr level (197+/-64 vs. 144+/-54 micromol/L at 18 months, P<.005). Graft and patient survival were similar; 12% and 5% vs. 91% and 9% in high-risk vs. control groups, respectively (P = NS). Donor renal pathology was scored 0-3 (none to severe disease) in four areas: glomerulosclerosis, interstitial fibrosis, tubular atrophy, and vascular disease. A donor vessel score of 3/3 was associated with a 100% incidence of delayed graft function and a mean 1-year Cr level of 275+106 micromol/L (compared with 43% and 192+54 micromol/L in those with lower vessel scores, P<.05). Calculated donor CrCl <100 ml/min was associated with higher recipient Cr levels at 1 year, 240+/-95 micromol/L vs. 180+/-54 micromol/L in recipients of kidneys from donors with CrCl levels >100 ml/min (P<.05). The mean 1-year Cr level was 320+/-102 micromol/L in recipients with both a vascular score of 3/3 and a donor CrCl <100 ml/min and 184+/-63 micromol/L in those with neither factor (P = .001). CONCLUSION: Calculated donor CrCl and donor vascular pathology predict recipient graft function and may be helpful in selecting high-risk donors for single kidney transplantation.

Aged↗
PubMed1997

A randomized controlled trial of verapamil on cyclosporine nephrotoxicity in heart and lung transplant recipients.

BACKGROUND: Cyclosporine (CsA) is a potent immunosuppressive drug widely used in organ transplantation and in the treatment of autoimmune diseases (1, 2). However, its common nephrotoxic effect is a major limiting factor. Short-term CsA treatment has been shown to cause reversible renal vasoconstriction, whereas long-term treatment can lead to an afferent arteriolopathy and chronic renal failure. METHODS: We performed a randomized controlled trial to examine the short-term renal effects of verapamil in 32 CsA-treated heart or lung transplant recipients. Sixteen patients each were randomized to receive a 6-week course of verapamil or control treatment (atenolol in hypertensive patients and placebo in normotensive patients) 1-2 months after transplantation. An 8-hr sequential clearance study of inulin and p-aminohippuric acid for estimating glomerular filtration rate and renal plasma flow, respectively, was performed at baseline and at completion of study. The integral area under the curve of the clearance parameter over 8 hr was then calculated to generate a clearance-time index. RESULTS: There was no difference in the clearance-time indices for inulin and p-aminohippuric acid between the two groups at baseline. However, at the completion of study, the within-group change in the glomerular filtration rate clearance-time index was different between the verapamil and control groups (48+/-20 vs. -35+/-17 ml/min/1.73 m2 x hr, respectively; P=0.0038). A similar trend was seen for renal plasma flow, but did not reach statistical significance. Mean arterial blood pressure and whole-blood CsA levels did not differ between the two groups during the study. Verapamil treatment was also associated with a decrease in CsA dose requirement (7.6+/-0.58 mg/kg/day at baseline vs. 4.6+/-0.40 mg/kg/day at completion; P<0.001) without any significant change in trough whole blood CsA levels. Rejection episodes did not differ between the two groups. CONCLUSIONS: The use of verapamil in the heart or lung transplant recipients may therefore provide both renal protective effects and cost savings.

Adult↗
PubMed1997

Treatment of Kaposi's sarcoma after solid organ transplantation.

PURPOSE: This retrospective review of all patients who developed Kaposi's sarcoma (KS) after solid organ transplantation at a single institution was undertaken to define the clinical presentation of this malignancy in the setting of iatrogenic immunodeficiency, and to determine the most appropriate treatment for patients in this clinical setting. MATERIALS AND METHODS: The records of 2,099 patients who underwent heart, lung, liver, or kidney transplantation at The Toronto Hospital between January 1, 1981 and June 30, 1995, were reviewed. Twelve patients were identified who developed biopsy-proven KS in the posttransplantation period. Five patients who had disseminated KS who had not responded to either reduction or withdrawal of immunosuppression or to local radiotherapy were treated with combination chemotherapy consisting of doxorubicin 20 to 30 mg/m2, bleomycin 10 mg/m2, and vincristine 2 mg (ABV) administered intravenously every 3 weeks. RESULTS: Eight of 12 patients were male and nine were of Italian origin. KS was limited to a localized area of the skin for only six patients, all after kidney transplantation. Visceral KS was present in three patients. Four of five patients responded to ABV chemotherapy (two complete and two partial remissions). The fifth patient responded to second-line etoposide and cisplatin. The median duration of response was in excess of 13 months (range, 8+ to 45+ months). Toxicity was limited to grade 1 neurotoxicity and grade 1 skin toxicity. CONCLUSION: KS is an uncommon but recognized complication of solid organ transplantation. Combination chemotherapy is a safe and effective treatment for patients with disseminated or visceral KS that fails to respond to changes in immunosuppression.

Adult↗
PubMed1997

Thrombotic microangiopathy in renal transplant recipients treated with cyclosporin A.

Thrombotic microangiopathy is an uncommon but well described complication of renal transplantation. This study is a review of the case records of 18 patients with biopsy proven post transplant thrombotic microangiopathy, without cellular rejection. There was no single characteristic underlying cause of renal failure in native kidneys. Although only two (11%) patients had undergone previous transplantation, 16 (89%) had panel reactive antibodies (PRA). All patients received prophylactic antilymphocyte globulin, a single patient had cyclosporin A (CSA) at the time of transplant and in 16 patients CSA was introduced when graft function was established. On this protocol 16 (89%) patients had early graft function. All patients developed acute renal failure and 16 (89%) required dialysis. Nine (50%) patients developed hematological abnormalities. All patients were treated aggressively with anti-rejection therapy, CSA was temporarily withdrawn, and 2 (11%) patients received plasmapheresis. Seven (39%) patients lost their grafts. Renal function in the remaining patients recovered to serum creatinine levels ranging from 104 mumol/l to 430 mumol/l (1.2 mg% to 4.8 mg%). All patients with surviving grafts had CSA successfully reintroduced. This study indicates that there is an association between patients who develop posttransplant thrombotic microangiopathy after CSA administration and high PRA levels. The condition appears to respond to anti-rejection therapy and stopping CSA in the majority of cases. The safe reintroduction of CSA suggests that endothelial cell damage in the posttransplant period may be multifactorial and not solely due to CSA therapy.

Adolescent↗
PubMed1996

Quality of life following transplantation of the heart, liver, and lungs.

The purpose of this study was to describe the quality of life of patients who have received a transplant of the heart, liver, and lungs. We wished to document how the different patient groups fared in relation to each other with respect to physical, psychological, and social functioning, as well as in relation to published normative data. We also wished to identify factors that contribute to better functioning. We sent out a questionnaire by mail and received responses from 55 heart, 149 liver, and 59 lung transplant recipients (82% response rate). Measures included the SF-36, Mental Health Inventory, the State Anxiety Inventory, the UCLA Loneliness Scale-Revised, a quality of life measure that rated degree of improvement since transplantation, a measure of degree of difficulty in following medical and lifestyle regimens, sleep disturbance, and the Illness Intrusiveness Rating Scale. Results indicated that lung transplant patients reported better functioning than heart or liver transplant patients in all three domains of physical, psychological, and social functioning. Lung patients' level of functioning was equivalent to or better than published norms for the SF-36. Heart and liver recipients reported equivalent functioning to published norms in some domains, but reported impairment in the areas of physical and social functioning. Heart patients especially reported greater intrusiveness of their illness on their daily lives and indicated more difficulty complying with their lifestyle regimen. In all three groups, a large majority of patients reported feeling that life had improved since transplant with respect to health, energy level, activity level, and overall quality of life. Fewer patients reported improvements in the areas of sex life, marriage, family relationships, and social relationships. Where there were differences among the three patient groups, again it was the lung patients who reported more improvement in life since transplantation. Patients with better physical functioning tended to have more energy and pep, to be younger, to see themselves as being in better health, to feel less intrusion on their lives of their illness, and to be employed. Those with better psychological functioning tended to report less sleep disturbance, less loneliness, better social functioning, more vitality, and to be older. Better social functioning was associated with better mental health, less illness intrusiveness, and less role impairment as a result of physical or emotional factors. Relatively few patients-roughly a quarter of the total sample-reported that they were working either full or part time. We conclude that transplantation results in improved quality of life overall, but that problems persist for some patients in their physical and social functioning. Interventions aimed at improving rehabilitation in specific targeted areas may enable patients to resume a more fulfilling lifestyle posttransplant.

Activities of Daily Living↗
PubMed1995

Sustained vasoconstriction associated with daily cyclosporine dose in heart and lung transplant recipients: potential pathophysiologic role of endothelin.

Transient decreases in glomerular filtration rate (GFR) and renal plasma flow (RPF) have been associated with each daily dose of cyclosporine (CYA) in patients with renal allografts. We examined the differential dose effects of CYA on native renal function in 24 recipients of heart or lung transplants (treated with 7.3 +/- 0.5 mg/kg/day [mean +/- SEM]) and in seven patients with psoriasis (treated with 4.2 +/- 0.7 mg/kg/day). GFR and RPF were measured by urinary inulin and para-aminohippuric acid clearances 2 hours before the morning CYA dose and for 6 hours after. The age of heart and lung transplant recipients at renal study (2 months after transplantation) was 47 +/- 2.0 years. Their serum creatinine levels rose from 80 +/- 4.0 mumol/L during the first week after transplantation to 120 +/- 4.0 mumol/L at renal study (p < 0.0001). Their GFR and RPF were decreased before the CYA dose at 64 +/- 2.4 and 340 +/- 16 ml/min per 1.73 m2 and did not vary during the study. In comparison, the age of patients with psoriasis was 51 +/- 4.6 years at renal study (24 +/- 4.0 months after CYA treatment). Their serum creatinine levels rose from 80 +/- 4.0 mumol/L before treatment to 100 +/- 10 mumol/L at renal study (p = 0.07). Transient decreases of their baseline GFR and RPF (85 +/- 7.4 and 380 ml/min per 1.73 m2) with a nadir occurring during the first 2 hours of CYA ingestion were observed together with the recovery of these parameters toward baseline by the end of the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Cyclosporine↗
PubMed1993

Coronary sinus sampling of cytokines after heart transplantation: evidence for macrophage activation and interleukin-4 production within the graft.

OBJECTIVES: This study was undertaken to evaluate the organ-specific release of cytokines after heart transplantation and to assess any correlation with transplant rejection. This cytokine profile should document the relative activation of mononuclear cell subsets within the graft. BACKGROUND: Up to 60% of mononuclear cells infiltrating the cardiac allograft during rejection are macrophages, but their role is undetermined. The T lymphocytes are activated, but the activity of specific T cell subsets is not known. We sought to assess for the first time in humans the in vivo activation of mononuclear cell subsets by measuring coronary sinus cytokine levels after heart transplantation. METHODS: Paired superior vena cava and coronary sinus serum samples were assayed for interleukin (IL)-2, IL-4 and IL-6, soluble IL-2 receptors, tumor necrosis factor-alpha and neopterin in 10 patients at the time of 40 routine endomyocardial biopsy procedures. All cytokine measurements were made by using enzyme-linked immunosorbent assay; neopterin was measured by using radioimmunoassay. RESULTS: Interleukin-2 levels were not detectable (< 0.8 U/ml) in either the superior vena cava or the coronary sinus in the presence or absence of rejection. Interleukin-2 receptor levels were uniformly elevated to 1,283 U/ml in the superior vena cava and to 1,232 U/ml in the coronary sinus, with no correlation with rejection severity. Interleukin-4 levels were consistently higher in coronary sinus serum than in peripheral blood (229 vs. 61 pg/ml, p < 0.0005), but there was no relation with rejection. Interleukin-6 levels were higher in the coronary sinus than in the superior vena cava (200 vs. 120 pg/ml, p < 0.05). Tumor necrosis factor-alpha showed consistently elevated levels in coronary sinus serum (68 vs. 17 pg/ml, p < 0.0005), with no relation with rejection. Neopterin, which is produced only by activated macrophages, was also consistently elevated in the coronary sinus (2.5 vs. 2.2 nmol, p = 0.08). CONCLUSIONS: The cardiac allograft is a major source of cytokines after heart transplantation. The cytokine profile allows the activity of subsets of the mononuclear cell infiltrate to be investigated. Elevated coronary sinus activity of the macrophage-specific metabolite neopterin suggests macrophage activation within the allograft. This possibility is supported by elevated coronary sinus levels of tumor necrosis factor-alpha and IL-6. The T lymphocytes are activated, as evidenced by high soluble IL-2 receptor levels, but IL-2 production was suppressed by conventional immunosuppressive therapy. Coronary sinus IL-4 levels represent T helper-2 cell activation within the graft despite immunosuppression. We could find no temporal relation between the coronary sinus or superior vena cava cytokine concentration or profile and severity of rejection on concurrent biopsy studies.

Analysis of Variance↗
PubMed1989

A randomized controlled trial of prednisone in patients with idiopathic membranous nephropathy.

We conducted a prospective randomized study in which patients with biopsy-confirmed idiopathic membranous nephropathy were assigned to receive either a six-month course of prednisone given on alternate days (45 mg per square meter of body-surface area; n = 81) or no specific treatment (n = 77). The mean duration of follow-up was 48 months. Patients in the prednisone group (median age, 46 years) entered with a mean disease duration of 15 months, a median creatinine clearance of 1.2 ml per second per 1.73 m2 (range, 0.25 to 2.6), and a median rate of urinary protein excretion of 6.8 g per day (0.3 to 26). The annual change in the corrected creatinine clearance at six months did not differ between the prednisone group and the control group (0.10 vs. 0.06 ml per second; P = 0.8), or at the last follow-up evaluation (-0.07 vs. -0.02 ml per second; P = 0.2; 95 percent confidence interval on the difference, -0.03 to 0.13). The proportion of patients with complete remission of proteinuria was also similar in the groups at 6 and 12 months and after a mean of 48 months. Outcomes were similar in the two groups with respect to progression to renal failure (3 vs. 4 patients), death (3 vs. 1 patient), complete remission of proteinuria at 36 months (16 vs. 19 patients), and a decline of 25 percent or more in the creatinine clearance at 60 months (32 vs. 25 percent of patients). A multivariate analysis, which adjusted for differences at entry in sex distribution, urinary protein excretion, and creatinine concentration, as well as other prognostic variables, failed to provide an explanation for the lack of effect of prednisone. We conclude that a six-month course of therapy in which prednisone is given on alternate days is of no benefit to patients with idiopathic membranous nephropathy.

Adolescent↗
PubMed1989

Short-term effects of calcium antagonists on hemodynamics and cyclosporine pharmacokinetics in heart-transplant and kidney-transplant patients.

Effects of two calcium antagonists on hemodynamics and on cyclosporine pharmacokinetics were studied in eight transplant patients (four heart-transplant and four kidney-transplant patients) by use of a single-blind, randomized, crossover, and placebo-controlled design. Patients received, at least 1 week apart, either 90 mg diltiazem, 20 mg nifedipine (in tablet form), or placebo, given 1 hour before cyclosporine. Cyclosporine and its main metabolite (metabolite 17) were measured in plasma (separated at 25 degrees C) by use of HPLC. Both calcium antagonists tended to increase absorption rate and elimination rate, but none of the pharmacokinetic parameters of cyclosporine were significantly altered. Moreover, the area under the curve of plasma concentrations of metabolite 17 did not change. On the other hand, both nifedipine and diltiazem significantly altered the hemodynamics, but to a different extent in the two groups of patients. The heart-transplant patients showed larger decreases in systolic and diastolic blood pressure than the kidney-transplant patients after administration of both nifedipine and diltiazem, but they showed smaller increases in cardiac index and heart rate with nifedipine. In contrast, diltiazem caused small decreases in heart rate and cardiac index in heart-transplant patients and small increases in heart rate and cardiac index in kidney-transplant patients. We conclude that a single dose of either nifedipine or diltiazem does not affect, to a clinically significant extent, the pharmacokinetics of cyclosporine. In addition, heart-transplant patients show different hemodynamic responses to these two calcium antagonists than the responses shown by kidney-transplant patients, probably because of cardiac denervation.

Absorption↗
PubMed1988

Digoxin-cyclosporine interaction: severe digitalis toxicity after cyclosporine treatment.

Digoxin toxicity developed in two patients awaiting cardiac transplantation upon the initiation of cyclosporine. Toxicity was associated with elevated digoxin concentrations (10.6 and 5.7 nmoles/L), gastrointestinal symptoms, and arrhythmias classic for digoxin toxicity (bidirectional ventricular tachycardia and AV nodal block with accelerated junctional rhythm respectively). A previously unreported drug interaction between cyclosporine and digoxin was suspected and digoxin pharmacokinetics were studied in two additional patients both before and after cyclosporine therapy prior to cardiac transplantation. The study confirmed a significant interaction between cyclosporine and digoxin; the apparent volume of distribution of digoxin decreased by 71% and its plasma clearance decreased by 53%. Until further information regarding the cyclosporine-digoxin interaction is available, this combination should be used with great caution.

Coronary Disease↗