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Biomedical subjects

M Hummel

Publications and source records attributed to M Hummel.

At least 145 records · Page 8Linked to original sources
PubMed1998

A randomized active-controlled trial of mycophenolate mofetil in heart transplant recipients. Mycophenolate Mofetil Investigators.

BACKGROUND: After heart transplantation, 1-year and 5-year survival rates are 79% and 63%, respectively, with rejection, infection, and allograft coronary artery disease accounting for the majority of deaths. Mycophenolate mofetil (MMF), an inhibitor of the de novo pathway for purine biosynthesis, decreases rejection in animals and in human renal transplantation. METHODS: In a double-blind, active-controlled trial, 28 centers randomized 650 patients undergoing their first heart transplant to receive MMF (3000 mg/day) or azathioprine (1.5-3 mg/kg/day), in addition to cyclosporine and corticosteroids. Rejection and survival data were obtained for 6 and 12 months, respectively. Because 11% of the patients withdrew before receiving study drug, data were analyzed on all randomized patients (enrolled patients) and on patients who received study medications (treated patients). RESULTS: Survival and rejection were similar in enrolled patients (MMF, n=327; azathioprine, n=323). In treated patients (MMF, n=289; azathioprine, n=289), the MMF group compared with the azathioprine group was associated with significant reduction in mortality at 1 year (18 [6.2%] versus 33 deaths [11.4%]; P=0.031) and a significant reduction in the requirement for rejection treatment (65.7% versus 73.7%; P=0.026). There was a trend for fewer MMF patients to have > or = grade 3A rejection (45.0% versus 52.9%; P=0.055) or require the murine monoclonal anti-CD3 antibody or antithymocyte globulin (15.2% versus 21.1%; P=0.061). Opportunistic infections, mostly herpes simplex, were more common in the MMF group (53.3% versus 43.6%; P=0.025). CONCLUSIONS: Substitution of MMF for azathioprine may reduce mortality and rejection in the first year after cardiac transplantation.

Aged↗
PubMed1998

Non-radioactive measurement of telomerase activity in human bladder cancer, bladder washings, and in urine.

Early diagnosis is still the most important prerequisite for successful cancer treatment and this holds true for bladder cancer. Urine cytology is commonly used as a non-invasive screening procedure for the detection of bladder carcinoma, but this method is labour-intensive and often generates false-negative results. The ribonucleoprotein telomerase appears to be promising new cancer marker, since its activity has been reported to correlate with indefinite growth. The aim of this study was to investigate whether telomerase activity can be detected in bladder cancer and in corresponding bladder washings. For this purpose, a sensitive non-radioactive TRAP (telomeric repeat amplification protocol) detection system was developed. With this technique, telomerase activity was found in 95 per cent of the carcinomas (n = 20), in 70 per cent of the corresponding bladder washings, but in none of the urine samples obtained from patients with bladder carcinoma. No telomerase activity was detectable in normal urothelium or in samples from dysplastic urothelium. The data obtained from bladder washings show that superficial carcinoma cells released into the bladder still harbour telomerase activity. The absence of telomerase activity in voided urine is thus most likely due to degradation or inactivation under these conditions. The high rate of telomerase activity in bladder carcinoma indicates that the activation of telomerase in a common step in the tumourigenesis of bladder cancer.

Aged↗
PubMed1998

Demonstration of constant upregulation of the telomerase RNA component in human gastric carcinomas using in situ hybridization.

Upregulation of the ribonucleoprotein telomerase seems to be a prerequisite for immortality, a feature of malignant cells. Using a polymerase chain reaction (PCR)-based assay, it is possible to demonstrate telomerase activity (TA) in specimens of most human malignancies, whereas it is absent from most normal tissues. It remains unclear, however, why between 5 and 50 per cent of various malignant tumour samples give negative results when TA is measured by the telomeric repeat amplification protocol (TRAP). The expectation that reverse transcription (RT)-PCR for detection of the telomerase RNA component (hTR) would be able to complement or to replace the TRAP assay failed, since malignant as well as non-malignant tissue samples gave positive results in most instances. In the present study, in situ hybridization (ISH) was developed to demonstrate the RNA component of human telomerase at the single cell level. With this method, 13 specimens of fresh frozen gastric carcinoma and four of normal, dysplastic, or inflamed gastric mucosa were investigated and the results were compared with those obtained by RT-PCR and the TRAP assay. In addition, ISH was performed on formalin-fixed sections of the same cases. The TRAP assay revealed positive results in 8 out of 13 gastric carcinomas and was negative in all non-malignant tissues. RT-PCR led to amplification of the telomerase RNA component in all specimens tested, irrespective of the presence or absence of malignant cells. By ISH, all gastric carcinomas showed strong telomerase RNA component-specific signals over malignant cells, whereas only a few grains were detectable over some types of normal somatic cells, including activated lymphocytes. In conclusion, high expression of the telomerase RNA component was restricted to the malignant cells of all the gastric carcinomas investigated, as shown by ISH. This indicates that the absence of TA in a proportion of carcinomas is due to methodological problems of the TRAP assay and is not caused by biological factors. The detection of high levels of the telomerase RNA component by ISH is thus a useful technique for demonstrating malignant cells in frozen and formalin-fixed pathological specimens.

Adult↗
PubMed1998

[Electron-beam computed tomography in heart surgery].

PURPOSE: Electron beam CT (EBCT) has been devised to improve the imaging of the heart and the great vessels. Therefore, this method is expected to facilitate the imaging workup of patients referred for cardiothoracic surgery. We set out to review the most important surgical issues that can be addressed with this method. METHODS: From June, 1997 until July, 1998, more than 300 patients were referred from cardiothoracic surgery. In a retrospective analysis, diagnostic results were reviewed and compared with surgical findings and the clinical course. RESULTS: Aortocoronary bypass graft occlusions were detected with a sensitivity of 100% and a specificity of 95%. Calcifications of the aorta, pericardium and intracardiac tumors were surgically confirmed in all instances. There was a significant association of the degree of coronary artery calcification and the progression of cardiac allograft vasculopathy in 50 heart transplant recipients. In EBCT of the aorta, a high degree of diagnostic confidence was found for aortic dissection, aortic wall hematoma or aortic perforation. CONCLUSIONS: We conclude that EBCT represents an important diagnostic tool both for surgical planning and postoperative surveillance in cardiothoracic surgery.

Adult↗
PubMed1998

Daily noninvasive rejection monitoring improves long-term survival in pediatric heart transplantation.

BACKGROUND: Acute rejection episodes and transplant vasculopathy (TVP) account for most of the late deaths after heart transplantation in both adults and children. Accumulating evidence indicates that fatal acute rejection and TVP are related to unrecognized and untreated early and ongoing acute rejection. Day-by-day surveillance of the heart and prompt treatment of any rejection may yield improved long-term survival. METHODS: In almost all patients having transplantation at our institution (978 patients since 1986), the intramyocardial electrogram (IMEG) was recorded routinely every day through a telemetry pacemaker and transmitted to our center by telephone modem. Earlier studies showed a substantial voltage drop in the IMEG QRS complex is highly indicative of acute rejection, including humoral rejection. In this study, we reviewed the data from 69 pediatric patients up to 16 years old for the incidence of acute rejection, TVP, and long-term outcome. Diagnostic endomyocardial biopsies were performed in only 10 patients, and recent coronary angiograms from 29 children were reviewed. RESULTS: In 50 children discharged after heart transplantation, IMEG surveillance data for a mean of 2.9 years indicated 72 acute rejection episodes. During follow-up of 1 month to 10.5 years (mean follow-up, 4.4 years), 2 patients died late of causes unrelated to either rejection or TVP. Another patient died of rejection during unrecognized underimmunosuppression nearly 8 years after transplantation and nearly 31/2 years after discontinuing IMEG recordings. Two patients without IMEG recording died of acute rejection or late TVP. In 1 patient, moderate TVP was seen on an angiogram after 41/2 years (incidence, 2.0%; 5-year incidence, 5.6%). CONCLUSIONS: Daily recording of the IMEG can reliably detect early stages of acute rejection episodes, and immediate rejection treatment seems to keep the incidence of TVP low. The IMEG appears better than all the other rejection monitoring protocols currently in use.

Acute Disease↗
PubMed1998

Lymphoproliferative lesions of the ocular adnexa. Analysis of 112 cases.

OBJECTIVE: Lymphoproliferative lesions of the ocular adnexa were analyzed to examine (1) the suitability of the Revised European-American Lymphoma (REAL) classification for the subtyping of the lymphomas in these sites; (2) the predictive value of the REAL classification for the evolution of these tumors; and (3) the frequency and prognostic impact of tumor type, location, proliferation rate (Ki-67 index), p53, CD5 positivity and the presence of monoclonality within these tumors. DESIGN: Retrospective review. METHODS: The clinical, histomorphologic, immunohistochemical, and molecular biologic (polymerase chain reaction [PCR]) features of lymphoid proliferations of the ocular adnexa were studied. STUDY MATERIALS: The ocular adnexal lymphoproliferative lesions were located as follows: orbit in 52 patients (46%), conjunctiva in 32 patients (29%), eyelid in 23 patients (21%), and caruncle in 5 patients (4%). RESULTS: Reactive lymphoid hyperplasia was diagnosed in 12 cases and lymphoma in 99 cases; 1 case remained indeterminate. The five main subtypes of lymphoma according to the REAL classification were extranodal marginal-zone B-cell lymphoma (64%), follicle center lymphoma (10%), diffuse large cell B-cell lymphoma (9%), plasmacytoma (6%), and lymphoplasmocytic lymphoma (5%). Age, gender, and anatomic localization of the lymphomas did not have prognostic significance during a follow-up period of 6 months to 16.5 years (mean, 3.3 years). Extent of disease at time of presentation was the most important clinical prognostic factor: advanced disease correlated with increased risk ratios of having persistent disease at the final follow-up and with lymphoma-related death (P < 0.001). Histomorphologic features and immunohistochemical markers positively correlating with disseminated disease at presentation, stage at final follow-up, and occurrence of lymphoma-related death included cytologic atypia (P < 0.001), MIB-1 proliferation rate (P < 0.001), and tumor cell p53 positivity (P < 0.001). The MIB-1 proliferation rates greater than 20% in extranodal marginal-zone B-cell lymphoma corresponded to at least stage II lymphoma (P < 0.05). CONCLUSION: The REAL classification is suitable for the subdivision of the ocular adnexal lymphomas. The MIB-1 proliferation rate and p53 positivity may aid the prediction of disease stage and disease progression, whereas PCR can support the diagnosis and reduce the number of histologically indeterminate lesions.

Adolescent↗
PubMed1998

Integrin alpha5beta1: a potent inhibitor of experimental lung metastasis.

The integrin alpha5beta1 seems to be the most relevant receptor of tumor cells for binding to fibronectin. Although numerous studies suggest a role of tumor cell fibronectin interaction in tumor metastasis, differential integrin expression on tumor cells has, however, not been correlated with metastatic capabilities. We addressed this question by transfection of the integrin alpha5beta1 cDNA into HT-29 human colon carcinoma cells which led to de novo expression of functional integrin alpha5beta1. Similar to other reports, expression of the integrin alpha5beta1 in HT-29 tumor cells exerted an inhibitory action on cell proliferation as indicated in our study by formation of fewer colonies in soft agar. The tumor growth inhibitory property of the integrin alpha5beta1 was also shown by reduction of subcutaneous xenograft growth in nude mice to approximately 50% of that of control transfectants. For the first time, we found that several clones of integrin alpha5 subunit transfectants displayed dramatically reduced formation of lung colonies and cutaneous metastasis after intravenous injection into nude mice. While most animals inoculated with control transfectant cells formed macroscopically visible lung colonies ranging from 12.6 +/- 2.6 to 22.0 +/- 6.6 (mean colony number +/- SEM), mice inoculated with HT-29 cell clones expressing the integrin alpha5beta1 were almost completely free of lung colonies (ranging from 0.0 +/- 0 to 0.2 +/- 0.1). Our results imply that integrin alpha5beta1 expression inhibits circulating tumor cells in pursuing late steps of the metastatic process as represented by the artificial metastasis (lung colonisation) model.

Animals↗
PubMed1998

Systemic inflammation in patients with heart failure.

AIMS: We hypothesized that chronic heart failure as a model of systemic hypoxia may result in systemic inflammation. The signs of a systemic inflammatory response should disappear after successful mechanical circulatory support using biventricular assist device systems. METHODS AND RESULTS: Plasma levels of cytokines (IL-6, IL-8, TNF-alpha) and soluble adhesion molecules (sVCAM, sE-, sL-, sP-Selectin) were determined in samples obtained from patients with chronic heart failure NYHA classes II-III, patients with overt cardiogenic shock before and after implantation of a mechanical assist-device system ('Berlin Heart') and in patients with coronary artery disease as a control. Elevated levels of cytokines and soluble adhesion molecules could be observed in patients with cardiogenic shock, although slightly decreased levels of soluble adhesion molecules were also detectable in patients with chronic heart failure NYHA classes II-III. The signs of systemic inflammation disappeared following successful mechanical circulatory support, but persisted in patients who developed infectious complications. CONCLUSIONS: Our data suggest that a systemic hypoxic and inflammatory syndrome is manifested during end-stage heart failure, such as in patients with sepsis or who have suffered non-infectious insults. During mechanical circulatory support, elevated levels of inflammatory mediators may be indicative of persistent peripheral hypoxia associated with a high risk for infection or sepsis. Therefore, the monitoring of inflammatory mediators should be evaluated as markers of the effectiveness of this therapy.

Adult↗
PubMed1998

Coronary angioplasty, bypass surgery, and retransplantation in cardiac transplant patients with graft coronary disease.

BACKGROUND: Graft coronary disease (GCD) remains the single greatest limitation to long-term survival of heart transplant recipients. Therapeutic strategies for the prevention or retardation of GCD in the cardiac allograft are limited; palliative coronary revascularization has been attempted. Because of the high mortality rate associated with advanced forms of GCD our institution offers the option of retransplantation in selected cases. The aim of this study was by analyzing retrospectively the outcomes of angioplasty, coronary bypass grafting, and retransplantation in cardiac transplant patients to attempt to identify subgroups of transplant recipients with graft coronary disease who may profit from myocardial revascularization. METHODS: Of the 989 patients undergoing 1016 heart transplantations (HTx) at our institution between 10/86 and 12/97, all were screened for the development of GCD. Analyzing routinely annual angiography, intracoronary ultrasound in defined study patients, and autopsy findings, GCD was diagnosed in 124 patients (110 male, 14 female) 2 to 107 months after HTx (mean 30 months). RESULTS: PTCA: Fourty-six out of 124 patients underwent 76 angioplasties at a mean of 50 +/- 30 months (range 4-91 mo) following cardiac transplantation. The primary success rate was 96% (73/76). The reason for the unsuccessful angioplasty attempts (n = 3) was failure to completely penetrate a stenosis of LAD in 2 patients and severe dissection of RCA, which required emergency surgery, in one. Angiographic restenosis occurred in 42% (31 of 76 lesions) and was diagnosed 11 +/- 11 months after the first angioplasty. There was no procedure-related death. CABG: Seven patients underwent bypass surgery at a mean of 67 months (range 6-128 months) after HTx. Elective surgery was performed in 2 patients with proximal severe triple-vessel disease (Type A lesion) and in 1 patient with severe tricuspid regurgitation who received a tricuspid valve replacement and concomitant single-vessel bypass surgery for proximal GCD (Type A lesion). One patient with combined Type A and B/C lesions required emergency surgery for dissection of RCA after an angioplasty procedure. Three patients with post-infarction unstable angina developed worsening congestive heart failure which required emergency surgery. Angiographically all these patients showed diffuse, distal arteriopathy (combined Type B/C lesions). The electively operated patients and the patient with dissection of RCA were successfully treated and survived beyond hospital discharge (overall survival for CABG in GCD patients 4/7 = 57%). After a mean follow-up of 10 months (range 2-32 months) all are in good clinical condition. All 3 patients with distal arteriopathy and emergency surgery died in hospital of left-ventricular failure (43%). Retransplantation: Eight patients underwent retransplantation at a mean of 54 months (range 6-96 months) after HTx. Six of 8 patients had successful operations and survived beyond hospital discharge with a one-year-survival rate of 75%. In a mean follow-up of 31 months (5-68 months) 3 of 6 retransplant recipients developed a recurrence of GCD. CONCLUSION: The presence of angiographic distal arteriopathy should be considered a significant factor in patient selection for coronary revascularization procedure. Coronary angioplasty is to be considered as a method of treatment for severe, local stenoses (Type A lesion). PTCA may be applied in these selected cardiac transplant recipients with primary success and complication rates comparable to routine angioplasty but with an increased rate of restenosis especially in small vessels (diameter < 2.5 mm). The distinction between Type A lesions in large (diameter > or = 2.5 mm) and small vessels may be important not only with respect to restenosis but also with respect to long-term benefit. The overall survival did not differ between GCD patients with and without PTCA, suggesting this treatment to be largely palliative. (ABSTR

Angioplasty, Balloon, Coronary↗
PubMed1998

Improved polymerase chain reaction detection of clonally rearranged T-cell receptor beta chain genes.

A new method for the detection of all known possible rearrangements at the variable (V), diversity (D), and joining (J) segments of the T-cell receptor beta chain (TcR beta) gene in tissue DNA extracts is described that involves two polymerase chain reactions (PCRs). The first PCR round (screening PCR) allowed the identification of the J beta segment involved in a clonal rearrangement. A J beta-primer was used for the second PCR (J beta-specific PCR), recognizing the J beta segment identified in the screening PCR in combination with a consensus V beta primer. This PCR generated prominent and short amplificates suitable for direct sequence analysis because of their low background. Using this approach, clonal TcR beta gene rearrangements were able to be demonstrated in all T-cell lines (n = 7) and in all peripheral T-cell lymphomas (n = 33) analyzed. No clonal TcR beta gene rearrangements were found in any of the normal tissues studied nor in any B-cell non-Hodgkin lymphomas. This method is applicable to DNA from fresh frozen tissues, and, after the TcR beta rearrangement of a patient's malignant T-cell clone has been identified by the screening PCR, DNA can also be detected in follow-up formalin-fixed paraffin-embedded samples by the J beta-specific PCR with high sensitivity and specificity.

Clone Cells↗
PubMed1998

Cellular localization of latent murine cytomegalovirus.

Herpesviruses typically establish latent infection in their hosts. The cell(s) responsible for harboring latent virus, in most cases, is not known. Using immunofluorescence and PCR-in situ hybridization (PISH), a technique which combines the sensitivity of PCR with the localization and specificity of in situ hybridization, we provide the first direct evidence that endothelial cells are a major site of murine cytomegalovirus (MCMV) DNA in latently infected animals. These findings are consistent with existing knowledge of the biological behavior of CMV, in particular the transmission of latent CMV by solid organ and bone marrow transplantation, in both human and animal models. In addition, we have localized MCMV DNA in the lung alveolar macrophage and in bone marrow cells. Our findings confirm that bone marrow-derived hematopoietic cells are a site of CMV latency and further suggest that bone marrow may be a reservoir of infected progeny capable of migrating into the circulation and establishing latency in various tissues. These findings provide clearly needed insight into the site of latent infection which is central to an understanding of the mechanisms of reactivation.

Animals↗
PubMed1998

Expression patterns of cyclin D1 and related proteins regulating G1-S phase transition in uveal melanoma and retinoblastoma.

BACKGROUND/AIMS: A checkpoint mechanism in late G1, whose regulation via loss of retinoblastoma protein (pRB) or p16, or overexpression of cyclin D1 or cyclin dependent kinase 4 (CDK4), has been proposed to constitute a common pathway to malignancy. The aims of this study were (a) to compare markers of cell cycle G1-S phase transition in an intraocular tumour with known pRB deficiency (retinoblastoma) and compare it with one with an apparently functional pRB (uveal melanoma); (b) to determine if one of these markers may have a role in the pathogenesis of uveal melanoma; and (c) to determine if there is a difference in cell cycle marker expression following treatment of uveal melanoma and retinoblastoma. METHODS: 90 eyes were enucleated from 89 patients for retinoblastoma (n = 24) or for choroidal or ciliary body melanoma (n = 66). Conventional paraffin sections were assessed for cell type and degree of differentiation. Additional slides were investigated applying standard immunohistochemical methods with antibodies specific for cyclin D1 protein, pRB, p53, p21, p16, BCL-2, and MIB-1. RESULTS: Cyclin D1 protein and pRB were negative in retinoblastoma using the applied antibodies. In contrast, cyclin D1 protein expression was observed in 65% of uveal melanomas; a positive correlation between cyclin D1 cell positivity and tumour cell type, location, growth fraction, as well as with pRB positivity was observed. p53, p21, and p16 could be demonstrated in both tumours. An inverse relation between p53 and p21 expression was demonstrated in most choroidal melanomas and in some retinoblastomas. Apart from a decrease in the growth fractions of the tumours as determined by MIB-1, a significant difference in the expression of G1-S phase transition markers in vital areas of uveal melanoma and retinoblastoma following treatment with radiotherapy and/or chemotherapy was not observed. CONCLUSION: Retinoblastomas and uveal melanomas, two tumours of differing pRB status, differ also in their immunohistochemical pattern for markers of the G1-S phase transition of the cell cycle. The results of the present study support the concept of (a) an autoregulatory loop between pRB and cyclin D1 in tumours with a functional pRB and the disruption of this loop in the presence of pRB mutation, as well as (b) a checkpoint mechanism in late G1, whose regulation via loss of p16 or pRB, or overexpression of cyclin D1 constitutes a common pathway to malignancy. Further, the results raise the possibility of cyclin D1 overexpression having a role in the pathogenesis of uveal melanoma.

Adolescent↗
PubMed1998

Humoral and cellular immune parameters before and during immunosuppressive therapy of a patient with stiff-man syndrome and insulin dependent diabetes mellitus.

OBJECTIVES: Humoral and cellular immune reactivity are reported for two neuroendocrine autoantigens-glutamic acid decarboxylase (GAD) and the protein tyrosine phosphatase IA-2-in a patient with the autoimmune type of stiff-man syndrome and insulin dependent diabetes (IDDM). METHODS: Antibodies and T cell proliferation against GAD and IA-2 and cytokine release of antigen stimulated T cells (IFN-gamma) were determined before and several times during immunosuppressive therapy with prednisolone. RESULTS: Raised GAD antibodies against full length GAD65 or chimeric constructs were detected before therapy and they remained at a high concentration despite a marked clinical improvement during cortisone treatment. Antibodies to IA-2 were undetectable, but weak T cell responses to both GAD and IA-2 were seen before therapy and once on reduction of high cortisone dosages when the patient showed signs of clinical deterioration. Cytokine profiles showed increased IFN-gamma production after stimulation with GAD or IA-2 suggesting increased activation of TH1 cells. CONCLUSION: Immunosuppressive therapy --even with extremely high doses of 500 mg a day--does not lead to the reduction of antibody concentrations in the periphery nor to a switch in epitope recognition of such antibodies despite clinical improvement. The amount of T cell reactivity to various antigens, however, may be a useful marker to monitor the effectiveness of immunotherapy.

Autoantibodies↗
PubMed1998

European Multicenter Tacrolimus (FK506) Heart Pilot Study: one-year results--European Tacrolimus Multicenter Heart Study Group.

BACKGROUND: Tacrolimus (FK506) may represent a major advance in the management of allograft rejection after solid organ transplantation. In August 1994 a European heart transplantation pilot study was initiated to assess the efficacy and safety of tacrolimus when administered exclusively through an oral route. METHODS: Eighty-two heart transplant recipients were randomized to treatment (2:1 ratio) with either tacrolimus- (n=54) or cyclosporine-based therapy (n=28). RESULTS: No significant differences were evident between the two treatment groups in either rejection or survival rates at 1 year. Kaplan-Meier estimates of the freedom from rejection were 26.3% and 18.5%, respectively, for the tacrolimus and cyclosporine treatment groups (p=.444). Survival rates were 79.6% and 92.9% (p=.125). At 3 of the 5 centers, patients received antithymocyte globulin during the immediate postoperative period and fared better than those who did not (with acute rejection-free rates of 49.2% and 26.7% for tacrolimus and cyclosporine, respectively [p=.080], as opposed to 7.1% and 8.3% [p=.965]; patient survival rates of 84.6% and 93.3% [p=.382] vs 75.0% and 92.3% [p=.243]). The overall rates of infection, impaired renal function (31.5% vs 21.4%), and glucose intolerance (7.0% vs 4.3%) did not differ significantly between the tacrolimus and cyclosporine treatment groups. Tacrolimus seemed to possess an advantage with regard to a reduced requirement for antihypertensive therapy (59.5% vs 87.5%, p=.025). CONCLUSIONS: Immunosuppression with oral tacrolimus provides a viable alternative to treatment with cyclosporine, particularly when administered in conjunction with antibody therapy. Further studies are warranted to optimize the administration of tacrolimus in this indication.

Administration, Oral↗