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Biomedical subjects

Jan F Gummert

Publications and source records attributed to Jan F Gummert.

At least 37 records · Page 2Linked to original sources

Synergistic effects of sirolimus with cyclosporine and tacrolimus: analysis of immunosuppression on lymphocyte proliferation and activation in rat whole blood.

BACKGROUND: Whole-blood analysis of lymphocyte function was used to investigate the pharmacodynamic (PD) interaction of sirolimus (SRL) with cyclosporine (CsA) or tacrolimus (TRL) in vitro and to determine the relation between PD and pharmacokinetics (PK) of SRL in an in vivo rat model. METHODS: In vitro, experiments involved incubation of increasing concentrations (0.25-25 [corrected] nM) of SRL with either CsA or TRL in rat whole blood. For the in vivo study, rats were orally treated with different doses of SRL alone (1, 3, 5, or 8 mg/kg) or with a combination of 3 mg/kg SRL plus 2.5 or 5 mg/kg CsA. Blood was obtained before and at different times after dosing. Inhibition of lymphocyte proliferation (proliferating cell nuclear antigen [PCNA]) and activation (CD25, CD71, CD11a, CD134) in mitogen-stimulated blood was determined using fluorescence-activated cell sorter analysis. SRL and CsA blood concentrations were determined at the same time points by light chromatography tandem mass spectrometry (LC-MS). RESULTS: In vitro, concentrations of SRL between 0.25-25 [corrected] nM acted synergistically in combination with CsA or TRL at concentrations between 0.25-1.0 [corrected] nM. Higher SRL concentrations did not further increase inhibition of lymphocyte function in these combinations. In vivo, good correlations (r=0.68-0.94) were observed between PD parameters of lymphocyte function and SRL-PK and dose. Increasing SRL doses produced higher blood concentrations, but SRL doses of 8 mg/kg did not further increase inhibition of lymphocyte function. PD effects on lymphocyte function were prolonged, but maximal inhibition was not increased when SRL was applied in combination with CsA as compared to SRL mono therapy. CONCLUSIONS: The results suggest that analysis of lymphocyte function in whole blood may be useful to optimize dosing of SRL in combination with CsA or TRL and that PD monitoring of immunosuppressive drugs will enhance the value of PK monitoring.

Animals↗

On-pump versus off-pump coronary artery bypass grafting: impact on postoperative renal failure requiring renal replacement therapy.

BACKGROUND: Despite refinements in perioperative patient management postoperative renal failure requiring hemofiltration or dialysis is still a common complication after coronary artery bypass grafting associated with impaired patient outcome. METHODS: Prospective data on 9,631 patients receiving myocardial revascularization with (coronary artery bypass grafting [n = 8,870]) or without cardiopulmonary bypass (off-pump coronary artery bypass grafting [n = 761]) between April 1996 and August 2001 were evaluated by univariate and multivariate logistic regression analysis. RESULTS: Overall prevalence of postoperative continuous renal replacement therapy was 4.1% (coronary artery bypass grafting, 4.3%; off-pump coronary artery bypass grafting, 1.8%; p = 0.001). Thirty of 40 selected preoperative and intraoperative patient and treatment related variables had a high association with the requirement for postoperative renal replacement therapy; fifteen of these variables were independent predictors in the whole study population. Off-pump coronary artery bypass surgery was identified as having a significantly lower predictive value for postoperative continuous renal placement therapy. In the subgroup of patients undergoing off-pump coronary artery bypass grafting surgery, a second multivariate logistic regression model revealed preoperative cardiogenic shock, urgent operation, intraoperative low cardiac output, and high transfusion requirement as independent predictors for postoperative renal replacement therapy. CONCLUSIONS: Patients with preoperative nondialysis dependent renal insufficiency are at a high risk for further decline in renal function requiring postoperative continuous renal replacement therapy. Off-pump coronary artery bypass surgery is associated with a lower prevalence of postoperative renal replacement therapy after coronary artery bypass grafting.

Aged↗

Predictors of delirium after cardiac surgery delirium: effect of beating-heart (off-pump) surgery.

BACKGROUND: Despite improved outcomes after cardiac operations, postoperative delirium remains a common complication that is associated with increased morbidity and prolonged hospital stay. METHODS: Univariate and multivariate predictors of postoperative delirium were determined from prospectively gathered data on 16,184 patients undergoing cardiac operations with cardiopulmonary bypass (conventional, n = 14,342) and without cardiopulmonary bypass (beating-heart surgery, n = 1847) between April 1996 and August 2001. Delirium was defined as a transient mental syndrome of acute onset characterized by global impairment of cognitive functions, a reduced level of consciousness, attentional abnormalities, increased or decreased psychomotor activity, and a disordered sleep-wake cycle. RESULTS: The overall prevalence of postoperative delirium was 8.4%. Of 49 selected patient-related risk factors and treatment variables, 35 were highly associated with postoperative delirium by univariate analysis. Stepwise logistic regression revealed the following variables as independent predictors of delirium: history of cerebrovascular disease, peripheral vascular disease, atrial fibrillation, diabetes mellitus, left ventricular ejection fraction of 30% or less, preoperative cardiogenic shock, urgent operation, intraoperative hemofiltration, operation time of 3 hours or more, and a high perioperative transfusion requirement. Two variables were identified as having a significant protective effect against postoperative delirium: beating-heart surgery and younger patient age. CONCLUSIONS: Postoperative delirium is a common complication in cardiac operations. The increased use of beating-heart surgery without cardiopulmonary bypass may lead to a lower prevalence of this complication and thus improve patient outcomes.

Age Distribution↗

Predictors of prolonged ICU stay after on-pump versus off-pump coronary artery bypass grafting.

OBJECTIVE: To define predictors for prolonged ICU stay in order to improve patient outcome and reduce costs. PATIENTS AND METHODS: Prospective data on 10,759 patients undergoing coronary artery bypass grafting with and without use of cardiopulmonary bypass (coronary artery bypass grafting, CABG; n =8,917; off-pump coronary artery bypass grafting, OPCAB; n =765; minimally invasive direct coronary artery bypass grafting, MIDCAB; n =1,077) between April 1996 and August 2001 were subjected to univariate and, consecutively, to multivariate logistic regression analysis. Prolonged ICU stay was defined as intensive care treatment for three postoperative days and longer. MEASUREMENTS AND RESULTS: Mean duration of ICU stay was 3.8+/-6.9 days; overall prevalence of prolonged ICU stay was 37.1%. The hospital mortality was 3.5% (ICU > or =3 days: 5.9%; ICU <3 days: 2.0%). Out of 39 selected pre- and intraoperative patient- and treatment-related variables, by univariate analysis, 32 variables having a high association with prolonged ICU stay were identified. Using a stepwise logistic regression model, 20 variables were shown to be independent predictors for prolonged ICU stay. Both OPCAB and MIDCAB surgery were identified as having a significantly lower association with prolonged ICU stay. CONCLUSION: As prolonged ICU stay is associated with poor patient outcome and increased costs it is of utmost importance to identify patients at a high risk for prolonged ICU stay. More frequent off-pump CABG may optimize patient outcome.

Aged↗

Assessment of immunosuppressive drug interactions: inhibition of lymphocyte function in peripheral human blood.

Cyclosporin (CsA) or tacrolimus (TRL) is routinely combined with either sirolimus (SRL) or mycophenolate mofetil (MMF) in immunosuppressive regimes in organ transplantation. The aim of our study was to establish a specific human blood assay of lymphocyte function in order to assess interactions of these drug combinations. Different concentrations (10(6)-10(9) nM) of CsA, TRL, SRL or mycophenolic acid (MPA, the active metabolite of MMF) was added to whole blood of five human volunteers. Drug combinations were studied by adding 250, 500 or 1000 nM of MPA to different concentrations of CsA, TRL, or SRL or by adding 1, 10 or 25 nM of SRL to different concentrations of CsA or TRL. After concanavalin-A stimulation, whole blood cultures were analyzed by flow cytometry detecting lymphocyte proliferation and activation by bivariate expression of proliferating cell nuclear antigen (PCNA)/DNA content and T cell-surface activation antigens (e.g. CD25, CD95, and CD154). We found an order of potency inhibiting lymphocyte function with SRL>TRL>CsA>MPA. In addition, we observed enhanced inhibition of PCNA, CD25, CD95 or CD154, if either CsA or TRL was combined with low concentrations of MPA, or SRL alone or if SRL was combined with low concentrations of MPA. Data analysis revealed an independent functional synergism or partial agonism in most combinations. This human blood assay is able to assess lymphocyte function and to monitor immunosuppressive therapy. The assay also permits pharmacological analysis of drug interactions, which will lead to improved safety and therapeutic efficacy in transplanted patients.

Cyclosporine↗

Stroke after cardiac surgery: a risk factor analysis of 16,184 consecutive adult patients.

BACKGROUND: Stroke remains a devastating complication after cardiac surgical procedures despite advances in perioperative monitoring and management. The purpose of this study was to determine the predictors of stroke in a large, contemporary cardiac surgery population. METHODS: Prospective data on 16,184 consecutive patients undergoing cardiac surgery (coronary artery bypass grafting [CABG], n = 8,917; beating heart CABG, n = 1,842; aortic valve surgery, n = 1,830; mitral valve surgery, n = 708; double or triple valve surgery, n = 381; CABG and valve surgery, n = 2,506) between April 1996 and August 2001 were subjected to univariate and multivariate analysis. Stroke was defined as any new permanent (manifest stroke) or temporary neurologic deficit or deterioration (transient ischemic attack or prolonged reversible ischemic neurologic deficit) and was confirmed by computed tomography or magnetic resonance imaging whenever possible. RESULTS: Overall incidence of stroke was 4.6% and varied between surgical procedures (CABG 3.8%; beating-heart CABG 1.9%; aortic valve surgery 4.8%; mitral valve surgery 8.8%; double or triple valve surgery 9.7%; CABG and valve surgery 7.4%). Of 63 patient-specific and treatment variables, 54 were found to have a significant univariate association with postoperative stroke. Multivariable analysis revealed 10 variables that were independent predictors of stroke: history of cerebrovascular disease, peripheral vascular disease, diabetes, hypertension, previous cardiac surgery, preoperative infection, urgent operation, CPB time more than 2 hours, need for intraoperative hemofiltration, and high transfusion requirement. Beating heart CABG was associated with a lower incidence of stroke in this multivariable analysis. CONCLUSIONS: Identification of predictors for stroke is important for understanding the pathogenesis of this devastating complication as well as for developing preventative strategies. Although retrospective analyses can be subject to selection bias we believe beating heart CABG is associated with a lower incidence of stroke and may therefore improve patient outcomes.

Adult↗

Secundum ASD closure using a right lateral minithoracotomy: five-year experience in 122 patients.

BACKGROUND: Surgical closure of secundum atrial septal defect (ASD) is a standard procedure associated with very low mortality and morbidity. We evaluated outcomes in the era of catheter-based interventional closure and minimally invasive techniques. METHODS: From May 1996, February 2002, 177 patients with a body weight of more than 30 kg underwent surgical ASD closure. A right lateral minithoracotomy (LMT) was used in 122 patients and a conventional approach, in 55. Diagnoses included secundum ASD in 106 patients in the LMT group and 40 in the conventional group, sinus venosus ASD in 13 patients in each group, and status post interventional closure in 3 and 2 patients, respectively. Mean age was 37 +/- 17 years in the LMT group and 43 +/- 20 years, in the conventional group and mean body weight was 66 +/- 17 kg and 70 +/- 16 kg, respectively. In the LMT group, femoral cannulation was performed for cardiopulmonary bypass. RESULTS: Direct ASD closure was carried out in 67.2% of patients in the LMT group and 58.2% of those in the conventional group. The remaining patients had pericardial patch closure. There was one death: A patient in the conventional group who required explantation of an Amplatzer device because of infection died postoperatively. Average stay in the intensive care unit was 1.2 +/- 0.5 days. Two patients required reoperation for residual ASD after direct closure; 1 sustained a temporary neurological deficit that resolved completely. On postoperative echocardiography, a minimal residual shunt was seen in only 3 patients. All patients were in good clinical condition with improved functional status at discharge from the hospital. CONCLUSIONS: Secundum ASD closure by LMT has become as standard and safe an operation as the conventional technique and achieves good perioperative results and satisfactory long-term outcomes. Thus LMT is an attractive option for patients who are not suitable for closure using catheter-based devices.

Adolescent↗

Intraoperative left atrial ablation (for atrial fibrillation) using a new argon cryocatheter: early clinical experience.

PURPOSE: Recently surgical treatment of atrial fibrillation has gained more popularity and presently is being performed in large numbers of patients. This report describes our early experience in treatment of patients with chronic or paroxysmal atrial fibrillation with a new tool for left atrial cryoablation. DESCRIPTION: From July 2002 through January 2003, 28 patients underwent left atrial cryoablation with the Surgifrost CryoCath. Patients underwent cryotherapy as an isolated procedure (n = 1), in combination with mitral valve surgery (n = 13), or with other surgical procedures (n = 14). In all patients contiguous lesion lines to the orifices of the pulmonary veins connected to the mitral annulus and the atriotomy were created. Surgery was performed through a conventional sternotomy in 8 patients (29%) and a right lateral minithoracotomy using video-assistance in 20 patients (71%). EVALUATION: Postoperatively sinus rhythm was restored in 27 patients (96%). At discharge 82% (23/28) of patients were in sinus rhythm and 18% (5/28) were in atrial fibrillation. Four patients (14%) required pacemaker implantation. There was no in-hospital mortality. At 6-months follow-up (19/28 patients) all were alive and 74% were in stable sinus rhythm, New York Heart Association functional class was 1.2 +/- 0.4. CONCLUSIONS: As indicated by our small and early patient cohort left atrial cryoablation with the Surgifrost argon cryocatheter is effective for the treatment of atrial fibrillation. This new device is technically easy to handle, it can be applied through a median sternotomy or lateral minithoracotomy. Long-term follow-up is necessary to evaluate further rhythm outcome.

Adult↗

Global surgical experience with the Acorn cardiac support device.

OBJECTIVE: Surgical intervention is an option for treating the remodeled and dilated left ventricles of patients with heart failure. Providing end-diastolic support with an innovative mesh-like cardiac support device reduces mechanical stress, improves function, and reverses cardiac remodeling in animal models without safety issues. The objective of this study was to review the global clinical safety and feasibility experience of this device. METHODS: The Acorn CorCap cardiac support device (Acorn Cardiovascular, Inc, St Paul, Minn) has been implanted worldwide in more than 130 patients with dilated cardiomyopathy with or without concomitant cardiac surgery. The device is positioned around the ventricles and given a custom fit. A series of 48 patients were implanted with the device in initial safety and feasibility studies, of whom 33 also received concomitant cardiac surgery. RESULTS: At implantation, 11 patients were in New York Heart Association class II, 33 were in class III, and 4 were in class IV. The average CorCap implantation time was 27 minutes. The mean intraoperative reduction in left ventricular end-diastolic dimension was 4.6% +/- 1%. There were no device-related intraoperative complications. Eight early and 9 late deaths occurred during follow-up extending to 24 months. Actuarial survival was 73% at 12 months and 68% at 24 months. There were no device-related adverse events or evidence of constrictive disease, and coronary artery flow reserve was maintained. Ventricular chamber dimensions decreased, whereas ejection fraction and New York Heart Association class were improved in patients overall and in those patients implanted with the CorCap device without concomitant operations. CONCLUSIONS: The CorCap device appears safe for patients with dilated cardiomyopathy. Randomized clinical trials are underway in Europe, Australia, and North America.

Adolescent↗

Mitral valve repair in patients with end stage cardiomyopathy: who benefits?

OBJECTIVE: Patients with end stage cardiomyopathy frequently present with additional severe mitral regurgitation. We analyzed the outcome of mitral valve reconstruction in this high risk patient group. METHODS: Sixty-six patients with significant mitral regurgitation and an ejection fraction (EF) below 30% (dilated cardiomyopathy=53, ischemic cardiomyopathy (ICM)=13) were retrospectively evaluated from 07/96 and 02/02. All received annuloplasty ring implantation and additional repair (n=4) if required. Mean follow-up was 28+/-18 months. RESULTS: Mitral valve repair (MVR) was technically feasible in all patients. Intraoperative transesophageal echocardiography (TEE) revealed none (n=60) or only trivial (n=6) residual mitral regurgitation. Thirty day mortality was 6.1%. Actuarial survival after 1 and 5 years was 86+/-4 and 66+/-8%, respectively. During follow-up seven patients were transplanted due to lack of clinical improvement after 10+/-7 months (range 1-23). Echocardiography revealed a significant improvement in EF (25+/-10.5% pre-op, 34+/-15% post-op) and a slight decrease in left ventricular end-diastolic diameter (69+/-10 mm pre-op, 67+/-13 mm follow up). Patients were in NYHA functional -class 3 (median) preoperatively and in class 2 at long term-follow-up. Gender, left ventricular enddiastolic diameter, preoperative ejection fraction or type of surgical approach (sternotomy, right lateral minithoracotomy) had no significant influence on patient outcome. Patients with ICM or patients older than 60 years showed an increased risk for clinical events both early post-operatively and at long-term follow-up. CONCLUSION: MVR can be performed with low perioperative morbidity and mortality even in patients with advanced heart failure, modifying selection criteria for potential candidates may further improve long term outcome.

Adult↗

[Surgical strategies for the treatment of heart failure].

Currently, heart transplantation is the gold standard of treatment for patients with end-stage heart failure. With the number of donor organs steadily decreasing, new surgical strategies have evolved. Selected patients with ischaemic cardiomyopathy or mitral valve insufficiency may be suitable candidates for conventional surgical procedures. New developments regarding assist devices such as LVAD and TAH increase our chances of employing these systems as a definite treatment option (destination therapy). New innovative concepts like external ventricular reshaping (Myosplints, CorCap) or left ventricular reconstruction are currently undergoing clinical evaluation. The clinical results of cardiac resynchronisation therapy offer a new treatment option for patients with LBB. The value of different treatment options and their role in modern surgical heart failure management is discussed.

Cardiac Surgical Procedures↗

Computer-enhanced endoscopic coronary artery bypass grafting: the da Vinci experience.

Anatomical and technical limitations as well as human factors render endoscopic coronary artery bypass surgery difficult. The da Vinci telemanipulator overcomes some of these shortcomings by restoring the dexterity and precision of a distant operator within the confined space in a closed-chest environment. Using the da Vinci system, total endoscopic coronary artery bypass grafting has evolved from a merely experimental surgical approach to a clinically applicable treatment option. Initially exclusively performed on the arrested heart, adjunct technologies such as endoscopic vacuum-assisted stabilizers now allow a single-vessel closed-chest beating heart procedure in selected patients. Despite the technical progress, endoscopic multivessel bypass grafting has yet to be achieved. The development of endoscopically applicable anastomotic devices and heart-positioning devices along with further refinements in telemanipulator technology, better optical systems, and image guided augmented reality scenarios may facilitate endoscopic bypass grafting in the future.

Cardiac Surgical Procedures↗

[Arterial revascularization of coronary vessels].

UNLABELLED: ARTERIAL GRAFTS: Atherosclerosis is the major cause of late vein graft failure and has led to the use of arterial grafts. The use of the left internal thoracic artery (ITA) is associated with improved survival which has been proven in numerous studies. Recent studies have also demonstrated a survival benefit of double over single ITA graft use. Especially in younger patients bilateral ITA grafting is recommended. SURGICAL TECHNIQUE: In terms of dissection of the graft, the technique of skeletizing the artery seems beneficial especially in diabetics to decrease the likelihood of mediastinitis. The radial artery is mainly used as a T graft in order to achieve complete arterial revascularization. RESULTS: While patency rates seem superior as compared to vein grafts, a survival benefit has yet to be proven. Irrespective of graft type, in-situ-grafts have a superior patency as opposed to free grafts. As has long been demonstrated with vein grafts, patency of arterial grafts also depends on the size of the recipient vessel. Grafts to the distal circumflex and distal right coronary artery have worse patency rates than grafts to the LAD. Conflicting results exist concerning the gastroepiploic artery; its use can only be recommended if the vessel is of good caliber. All other arterial conduits are used infrequently and there are no data to draw any meaningful conclusion for routine use. Arterial revascularization on the beating heart is feasible and short and midterm follow-up data are encouraging. CONCLUSION: Our current policy is to perform complete arterial revascularization in all patients under the age of 70 using bilateral ITAs and radial arteries.

Arteries↗

Minimal access aortic valve replacement: effects on morbidity and resource utilization.

BACKGROUND: The aim of this study was to compare outcomes in patients undergoing minimal access versus conventional aortic valve replacement (AVR). METHODS: We reviewed prospectively gathered data on all patients who were undergoing first-time AVR, with or without replacement of the ascending aorta, over a 1-year period at our institution. RESULTS: A total of 176 patients underwent minimal access and 258 underwent conventional AVR. The conventional group was older, had more incidence of diabetes, and more aortic stenosis (all p < 0.05). Eight minimal access AVR patients (2%) required conversion to a complete sternotomy. Minimal access AVR patients had longer aortic crossclamp times than conventional AVR patients (60 +/- 22 vs 55 +/- 23 minutes, p = 0.03) but similar CPB times (93 +/- 38 vs 88 +/- 42 minutes, p = 0.20). Postoperative creatine kinase-MB levels were similar for the two groups. Total postoperative blood loss was significantly lower in the minimal access group, and these patients received less red blood cell and fresh frozen plasma transfusions. Minimal access AVR patients were less likely to have postoperative respiratory failure (3% vs 10%); they had shorter intensive care unit stays (3.7 +/- 5.4 vs 4.5 +/- 5.6 days) and shorter hospital stays (10 +/- 6 vs 12 +/- 7 days, all p < 0.05). Mortality was lower in patients undergoing minimal access surgery (3% vs 9%, p = 0.008) by univariate analysis. Multivariate predictors of mortality were age, hypertension, and CPB time. CONCLUSIONS: Although patient selection may have influenced some of the observed differences between our patient groups, minimal access surgery appears to be associated with decreased morbidity and resource use when compared to conventional AVR.

Aortic Valve↗

Novel assays of multiple lymphocyte functions in whole blood measure: new mechanisms of action of mycophenolate mofetil in vivo.

The antiproliferative effects of MMF are believed to be the mechanism of its immunosuppressive action. We further investigated the mechanisms of action by assessing the pharmacodynamics (PD) of MMF in treated animals using whole blood assays not only of lymphocyte proliferation but also of activation. In vitro, different MPA concentrations were added to rat whole blood. In vivo, Lewis rats were treated with single doses of 5, 10 or 20 mg/kg MMF (n = 6 rats/dose group). Blood was obtained before and at different times after drug administration. For both in vitro and in vivo studies, different mitogens with calcium-dependent (TCR) or -independent (co-stimulatory) pathways of lymphocyte activation were added to the blood for stimulation. Proliferation was measured by [3H]TdR incorporation and by flow cytometric detection of DNA content. Activation was measured by changes in T cell surface expression of CD25, CD134, CD71, CD11a and CD54. In vitro and in vivo studies showed a dose-dependent inhibition by MPA and MMF, respectively, of lymphocyte proliferation and surface antigen expression. We observed high correlations between MMF PD effects over time with both MMF dose and MPA plasma concentrations in vivo. We show that MMF, apart from its antiproliferative effect, induced a dose-dependent suppression of calcium-dependent and -independent stimulated expression of important lymphocyte cell surface antigens. These data suggest that the ex vivo assessment of immune function in whole blood can uncover new mechanisms of MMF action. Our results demonstrated that the measurement of the PD is a means to assess the functional effects of MMF after its administration in vivo.

Animals↗

Pharmacodynamics of mycophenolate mofetil after heart transplantation: new mechanisms of action and correlations with histologic severity of graft rejection.

The primary mechanism of action in vivo of mycophenolate mofetil (MMF) is believed to be inhibition of lymphocyte proliferation. We used novel assays of lymphocyte functions (pharmacodynamics, PD) in whole blood collected from rat heart allograft recipients treated with MMF to investigate the mechanisms of action of the active metabolite of MMF, mycophenolate acid (MPA) in vivo. Allograft recipients were treated orally once daily with 3 different doses of MMF. Seven days after transplantation, blood was collected 24h after the penultimate dose and several timepoints after the last dose, after which grafts were removed for microscopic grading of rejection. Lymphocytes in whole blood samples were mitogen stimulated through calcium-dependent and -independent signaling pathways. Inhibition of PD was measured by lymphocyte proliferation and expression of several surface antigens on T cells, and was calculated as area under the time-inhibition of immune function effect curve (AUE0-24h). We found that inhibition of lymphocyte proliferation and antigen expression by MPA correlated highly with MMF-dose, MPA level and with the histologic severities of graft rejection (p <0.05). In summary, MPA suppressed lymphocyte proliferation and expression of T-cell surface antigens in whole blood collected from MMF-treated allograft recipients, thus demonstrating the multiple mechanisms of suppression of rejection on peripheral blood T cells after MMF treatment.

Animals↗