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Biomedical subjects

W Weimar

Publications and source records attributed to W Weimar.

At least 91 records · Page 5Linked to original sources
PubMed2000

Circulating donor-specific cytotoxic T lymphocytes with high avidity for donor human leukocyte antigens in pediatric and adult cardiac allograft valved conduit recipients.

OBJECTIVE: Specific immunological responses may be involved in the process of cryopreserved allograft valved conduit (AVC) degeneration, which is more frequently seen in young recipients. Rejection of heart and corneal allografts is preceded by an increase in the fraction of cytotoxic T lymphocytes (CTL) with high avidity for donor human leukocyte antigens (HLA) circulating in both peripheral blood and the affected graft. These donor-specific high-avidity CTLs are regarded as the destructive cells capable of causing graft damage. To monitor the precursors of these cells (CTLp) in young and adult AVC recipients, in vitro quantitative tests were performed on sequentially taken blood samples to quantitate CTLp frequencies and their avidity for donor antigens. METHOD: Six children and nine adults who received a cryopreserved AVC in the period between 1994 and 1997 were included in the study. From these patients, two to six blood samples were obtained up to 3 years after valve implantation. The number of circulating CTLp present within the peripheral blood mononuclear cell (PBMC) population was determined by limiting dilution analysis (LDA). The fraction of CTLp with high avidity for donor HLA class I was determined by addition of CD8 monoclonal antibodies (mAb) during the cytotoxic phase of the assay. Third-party stimulator cells were used to verify the donor-specificity of the response. RESULTS: The number of donor-specific CTLp increased significantly in the period 6-12 months after AVC implantation, while third-party-specific CTLp frequencies were not affected. Additionally, we found a significant increase of the high-avidity fraction of CTLp directed against donor antigens as early as during the first 6 months after AVC implantation. The fraction of high-avidity CTLp remained significantly higher post- compared with pre-implantation, even after 12 months. We observed no significant difference in the kinetics of CTLp frequencies between pediatric and adult AVC recipients. CONCLUSION: Implantation of cryopreserved human AVC induces an increase in the total number of circulating CTLp directed against donor HLA class I in both adults and children. The shift towards more destructive high-avidity CTLp in the peripheral blood indicates their potential damaging effect towards the heart valve allograft.

Adolescent↗
PubMed2000

Renal failure after clinical heart transplantation is associated with the TGF-beta 1 codon 10 gene polymorphism.

BACKGROUND: To determine whether genetic factors are involved in the development of renal dysfunction due to cyclosporine nephrotoxicity, we analyzed 2 polymorphisms in the signal sequence of the transforming growth factor (TGF)-beta 1 gene; codon 10 (Leu(10) --> Pro) and codon 25 (Arg(25) --> Pro). METHOD: Using sequence specific oligonucleotide probing, we analyzed both TGF-beta1 gene polymorphisms in cardiac allograft recipients (n = 168) who survived at least 1 year with minimal follow-up of 7 years. Patients received cyclosporine and steroids as maintenance immunosuppressive therapy. Renal dysfunction was defined as a serum creatinine > or = 250 micromol/liter. RESULTS: Renal dysfunction was observed in 2% (3/168) of the patients at 1 year, in 7% (11/160) at 3 years, in 12% (18/152) at 5 years, and in 20% (26/131) at 7 years post-transplantation. The genotypic distributions for TGF-beta1 codon 10 were 7% Pro/Pro, 61% Pro/Leu, and 32% Leu/Leu, and for codon 25 these percentages were 1% Pro/Pro, 12% Pro/Arg, and 87% Arg/Arg. We found an association between the TGF-beta 1 genotype encoding proline at codon 10 and renal dysfunction. At 7 years post-transplantation, 26% (23/89) of the patients with the heterozygous Pro/Leu or homozygous Pro/Pro genotype had renal dysfunction vs only 7% (3/42) of the patients with the homozygous Leu/Leu genotype (p = 0.017). For the TGF-beta1 codon 25 genotypes, we found no association between TGF-beta 1 genotypes and renal dysfunction. CONCLUSION: Our data support the hypothesis that TGF-beta 1 is involved in the process leading to renal insufficiency in cyclosporine-treated cardiac allograft recipients. In these patients the presence of TGF-beta 1 Pro(10) might be a risk factor.

Adult↗
PubMed2000

Immunologic monitoring of the beneficial effect of one HLA-DR-shared blood transfusion in heart transplant patients.

BACKGROUND: Pre-transplant blood transfusion (BT) results in better graft survival in organ transplant recipients, especially when BT donor and allograft recipient share an HLA-DR antigen. Although the immunologic mechanisms involved are still poorly understood, we wanted to know whether down regulation of donor-reactive T cells play a role. METHODS: In a retrospective study, we analyzed the clinical effects of BT for 45 heart transplant (HTx) patients who had each received 1 BT that shared an HLA-DR-antigen with the recipient, and 55 who had a DR-mismatched BT before heart transplantation. From 30 patients, 15 with DR-shared BT and 15 with DR-mismatched BT, peripheral blood lymphocytes (PBL) were available. From each patient, we analyzed PBL samples taken at the day of transplantation (pre-transplant), and 1 to 2 months, 5 to 7 months, 9 to 14 months, 2 years, and 6 to 7 years after transplantation. Cytotoxic T-lymphocyte precursors (CTLp) and helper T-lymphocyte precursors (HTLp) were measured in a combined limiting dilution assay. RESULTS: Analysis of survival during the first 10 years revealed a significantly (p = 0.016) better survival rate in the group of patients who had received HLA-DR-shared BT compared with the group who had received HLA-DR-mismatched BT. Patients of the DR-shared group experienced significantly (p = 0.042) less acute rejections compared with the patients who received DR-mismatched BT. We found no differences in the development of graft vascular disease. Frequencies of CTLp specific for the organ donor did not change with time after transplantation in the individual patients, nor did we detect any differences between the two BT groups. We found the same for organ donor-specific HTLp frequencies. CONCLUSIONS: These data suggest again that transfusion effect depends on HLA-DR compatibility between the heart transplant recipient and the pre-transplant BT donor. The mechanism that caused better survival rate was not down regulation of the donor-reactive T-cell frequency.

Adult↗
PubMed2000

A longitudinal study of TGF-beta1 protein levels in renal allograft recipients converted from CsA to MMF or AZA.

Cyclosporine (CsA) is thought to enhance transforming growth factor (TGF)-beta1 production in vitro and in vivo and this may have a negative effect on long-term graft survival. Therefore, we studied TGF-beta1, plasma levels in 30 patients before kidney transplantation, after transplantation during CsA treatment and after conversion from CsA to azathioprine (AZA) or mycophenolate mofetil (MMF). We questioned whether TGF-beta1 plasma levels would decrease after the discontinuation of CsA and whether the TGF-beta1 plasma levels did correlate with CsA trough levels and kidney function, measured by serum creatinine levels. TGF-beta1 plasma levels measured 1 yr after transplantation were lower compared to levels measured before transplantation, however not significantly (p = 0.08). After conversion from CsA to MMF or AZA, a slight increase was observed in some patients, but in the total group TGF-beta1 levels remained unaffected. No correlation was found between the TGF-beta1 levels and CsA trough levels nor with creatinine levels. In conclusion, we did not observe higher TGF-beta1 plasma levels in plasma levels of patients receiving CsA treatment compared to blood from the same patients while on AZA or MMF.

Azathioprine↗
PubMed2000

Variability of relative blood volume during haemodialysis.

BACKGROUND: A decrease in blood volume is thought to play a role in dialysis-related hypotension. Changes in relative blood volume (RBV) can be assessed by means of continuous haematocrit measurement. We studied the variability of RBV changes, and the relation between RBV and ultrafiltration volume (UV), blood pressure, heart rate, and inferior caval vein (ICV) diameter. METHODS: In 10 patients on chronic haemodialysis, RBV measurement was performed during a total of one hundred 4-h haemodialysis sessions. Blood pressure and heart rate were measured at 5-min intervals. ICV diameter was assessed at the start and at the end of dialysis using ultrasonography. RESULTS: The changes in RBV showed considerable inter-individual variability. The average change in RBV ranged from -0.5 to -8.2% at 60 min and from -3.7 to -14.5% at 240 min (coefficient of variation (CV) 0.66 and 0.35 respectively). Intra-individual variability was also high (CV at 60 min 0.93; CV at 240 min 0.33). Inter-individual as well as intra-individual variability showed only minor improvement when RBV was corrected for UV. We found a significant correlation between RBV and UV at 60 (r= -0.69; P<0.001) and at 240 min (r= -0.63; P<0.001). There was a significant correlation between RBV and heart rate (r= -0.39; P<0.001), but not between RBV or UV and blood pressure. The level of RBV reduction at which hypotension occurred was also highly variable. ICV diameter decreased from 10.3+/-1.7 mm/m(2) to 7.3+/-1. 5 mm/m(2). There was only a slight, although significant, correlation between ICV diameter and RBV (r= -0.23; P<0.05). The change in ICV-diameter showed a wide variation. CONCLUSIONS: RBV changes during haemodialysis showed a considerable intra- and inter-individual variability that could not be explained by differences in UV. No correlation was observed between UV or changes in RBV and either blood pressure or the incidence of hypotension. Heart rate, however, was significantly correlated with RBV. Moreover, IVC diameter was only poorly correlated with RBV, suggesting a redistribution of blood towards the central venous compartment. These data indicate that RBV monitoring is of limited use in the prevention of dialysis-related hypotension, and that the critical level of reduction in RBV at which hypotension occurs depends on cardiovascular defence mechanisms such as sympathetic drive.

Aged↗
PubMed2000

TNF-alpha: mRNA, plasma protein levels and soluble receptors in patients on chronic hemodialysis, on CAPD and with end-stage renal failure.

BACKGROUND: Patients on hemodialysis suffer from an impaired immunity against infectious agents, hyporesponsiveness to vaccination and are prone to develop malignancies. This clinical state of immunoincompetence may be due to a disbalance in their defense mechanisms in which TNF-alpha and its soluble receptors 1 and 2 play a central role. PATIENTS AND METHODS: We measured, with double-sandwich ELISA, the levels of TNF-alpha and the soluble TNF-receptors in peripheral blood of patients on chronic intermittent hemodialysis (CIHD), on peritoneal dialysis (CAPD) and pre-dialysis end-stage renal failure (ESRF). Using reverse transcriptase polymerase chain reaction (RT-PCR) analysis, we quantified the amount of TNF-alpha mRNA in peripheral blood mononuclear cells (PBMC) obtained from these patient groups. RESULTS: In none of the patient groups, elevated levels of TNF-alpha were detected with ELISA, while high levels of soluble TNF receptors were present in ESRF, CAPD and CIHD patients. This may be the result of an activated TNF-alpha system or due to their impaired renal clearance. TNF-alpha mRNA level was elevated in CIHD patients compared to ESRF and CAPD patients or healthy controls. CONCLUSION: This suggests that only during chronic HD is the TNF-alpha system activated. High levels of sTNFR, found in ESRF or CAPD patients do not reflect activation of TNF-alpha system, but are the result of impaired renal clearance of the receptors. Indeed, we found a strong linear correlation between the levels of sTNF receptors and renal function. Nevertheless, these high levels of sTNF receptors are biological active, as they were able to bind active TNF-alpha up to 75% (range 46 - 83%) and thus inhibit the bioactivity and bioavailability of produced TNF-alpha. This may play a role in the immunoincompetence of these patients.

Adult↗
PubMed2000

Induction of cytotoxic T lymphocytes with destructive potential after cardiac valve homograft implantation.

BACKGROUND AND AIM OF THE STUDY: Clinical and experimental studies have shown that a specific immunological response may play a role in the degeneration of human cardiac valve homografts. In heart and corneal transplantation, cytotoxic T lymphocytes (CTL) with high avidity for donor antigens are presumed to be the major effector cells causing graft destruction. We studied the kinetics of these donor-specific CTL precursors (CTLp) and their high-avidity fraction in peripheral blood of patients receiving a cryopreserved valve homograft. METHODS: Limiting dilution analysis (LDA) was used to enumerate donor-specific CTLp in peripheral blood samples of 15 patients, obtained up to 12 months after valve implantation. Donor-specificity was proven by using donor-HLA mismatched third-party stimulation cells as controls. CD8 monoclonal antibodies were used to distinguish high- and low-avidity CTLp. RESULTS: A significant increase in total donor-specific CTLp among the peripheral blood mononuclear cell population occurred in 14/15 patients (93%) at 3-6 months (p = 0.045) after implantation and remained so for up to 12 months (p = 0.015). In addition, a significant increase was seen in the fraction of circulating CTLp with high avidity for donor antigens (p<0.026) within the first 3 months after implantation. CONCLUSION: Implantation of cryopreserved valve homografts increases the number of donor-specific CTLp and their high-avidity fraction, in the peripheral blood. These cells have the capacity to destroy organ and tissue grafts.

Adolescent↗
PubMed1999

Effect of cyclosporine on mycophenolic acid trough levels in kidney transplant recipients.

BACKGROUND: Triple drug treatment consisting of mycophenolate mofetil (MMF), in a standard dose of 2 g daily, combined with cyclosporine (CsA) and prednisone, has become the standard immunosuppressive regimen after kidney transplantation in many centers. The need for therapeutic drug monitoring of mycophenolic acid (MPA) has not yet been established. Several drug interactions with MMF are known. We investigated the influence of CsA withdrawal on MPA trough levels in renal transplant patients. METHODS: Fifty-two patients were treated with 1 g of MMF twice daily, and prednisone and CsA targeted between 125 and 175 ng/ml for 6 months after transplantation. At 6 months after transplantation, 19 patients were randomized for continuation of triple therapy (group A), 19 patients discontinued CsA (group B), and 14 patients discontinued prednisone (group C). We compared 12-hr fasted MPA trough levels at 6 and 9 months after transplantation within and between these groups. RESULTS: MPA trough levels during treatment with CsA, MMF, and prednisone were significantly lower than those during treatment with MMF and prednisone only (group B); median levels were 1.87 mg/L (range: 0.56-5.27) vs. 3.16 mg/L (range: 0.32-7.78), respectively (P=0.002). MPA trough levels in groups A and C did not change between 6 and 9 months after transplantation; group A median levels were 1.87 (range: 0.31-4.32) vs. 1.53 mg/L (range: 0.36-3.70), and group C median levels were 1.62 (range: 0.69-10.34) vs. 1.79 mg/L (range: 0.54-6.00), respectively. At 9 months after transplantation, patients in whom CsA was discontinued had higher MPA trough levels as compared with patients who continued the use of triple therapy (P=0.001) or patients in whom steroids were withdrawn (P=0.014). CONCLUSION: A significant increase of MPA trough levels was found after discontinuation of CsA (6 months after transplantation), resulting in almost a doubling of MPA trough levels at 9 months after transplantation. This resulted in increased MPA levels in patients without CsA as compared to MPA levels in patients continuing triple therapy or discontinuing prednisone.

Cyclosporine↗
PubMed1999

[Heart transplants in infants: an estimate of need and restrictions].

The need for cardiac transplantation in children in the Netherlands can be estimated at 5-14 per year, including 1-3 in newborns. This treatment can only be successful in close cooperation with an existing programme for adult cardiac transplantation and in a centre where the surgery for congenital heart disease is performed to its complete extent. Heart transplantation should not be the primary treatment for hypoplastic left heart syndrome as the Norwood operation constitutes a good alternative. Donor shortage is a problem for children also. In the treatment of endstage heart disease in newborns, owing to ethical dilemmas, surgical treatment is not a matter of course.

Contraindications↗
PubMed1999

A randomized double-blind, multicenter plasma concentration controlled study of the safety and efficacy of oral mycophenolate mofetil for the prevention of acute rejection after kidney transplantation.

BACKGROUND: Adding a fixed dose of 1 g b.i.d. of mycophenolate mofetil (MMF) to an immunosuppressive regimen consisting of cyclosporine and prednisone results in a 50% reduction in the incidence of acute rejection after kidney transplantation. This study was designed to investigate the relationship between pharmacokinetic data (mycophenolic acid area under the curve; MPA AUC) and the prevention of rejection after kidney transplantation. METHODS: A total of 154 adult recipients of a primary or secondary cadaveric kidney graft were randomly allocated, in this double-blind trial, to receive MMF treatment aimed at three predefined target MPA AUC values (16.1, 32.2, and 60.6 microg x hr/ml). During the first 6 months after transplantation, plasma samples for nine AUCs were collected. After analysis of the samples, a coded dose adjustment advice was generated using a Bayesian algorithm, maintaining the double blinding. Immunosuppressive therapy further consisted of cyclosporine and prednisone. The primary end point of this study was the occurrence of biopsy-proven acute rejection within the 6-month study period. RESULTS: A total of 150 patients were eligible for analysis. Although after day 21, the mean MMF dose was reduced, the mean MPA AUC gradually increased and target MPA AUC values were exceeded in all three groups. The incidences of biopsy-proven acute rejection in the low, intermediate, and high target MPA AUC groups were 14 of 51 (27.5%), 7 of 47 (14.9%), and 6 of 52 (11.5%), respectively. The incidences of premature withdrawal from the study due to adverse events in the three groups were 4 of 51 (7.8%), 11 of 47 (23.4%), and 23 of 52 (44.2%), respectively. Logistic regression analysis showed a highly statistically significant relationship between median ln(MPA AUC) and the occurrence of a biopsy-proven rejection (P<0.001). The logistic regression using median ln(Cpredose) was also statistically significant for this relationship (P=0.01), whereas it was not when using mean MMF dose (P=0.082). In contrast, the logistic regression using mean MMF dose for comparison of patients who successfully completed the study versus patients experiencing premature withdrawal due to adverse events was highly significant (P<0.001), whereas this was not significant when using median ln(Cpredose) (P=0.512) or median ln(MPA AUC) (P=0.434). CONCLUSION: MPA Cpredose and MPA AUC are significantly related to the incidence of biopsy-proven rejection after kidney transplantation, whereas MMF dose is significantly related to the occurrence of adverse events.

Acute Disease↗
PubMed1999

[Laparoscopic donor nephrectomy for kidney transplants from living family members: good preliminary results].

OBJECTIVE: Evaluation of safety and technical feasibility of laparoscopic live donor nephrectomy. DESIGN: Descriptive. METHOD: The per- and postoperative results were analysed of 15 patients subjected to laparoscopic live donor nephrectomy in the Erasmus Medical Centre Rotterdam, Dept. of General Surgery, the Netherlands. Both left and right nephrectomy were performed via the transperitoneal route. The kidney was removed via a subumbilical incision. RESULTS: Laparoscopic donor nephrectomy was attempted in 15 patients and completed successfully in 14. Conversion to flank incision was resorted to one patient because of a venous bleeding. Median operating time was 290 min (SD: 57). Mean warm ischaemia time was 7 min (range: 4-17), including laparoscopic harvest. All kidneys were functioning well after transplantation. The mean duration of postoperative hospitalization of the donors was 4 days. CONCLUSION: Laparoscopic live donor nephrectomy is a safe and technically feasible procedure in a kidney transplant programme involving a living relative.

Adult↗
PubMed1999

Anti-CD25 therapy reveals the redundancy of the intragraft cytokine network after clinical heart transplantation.

BACKGROUND: Despite blockade of the interleukin-2/interleukin 2 receptor (IL-2/IL-2R) pathway by the murine anti-CD25 (i.e., IL-2R alpha chain) monoclonal antibody BT563, cardiac rejection can still occur. In these cases, growth factors other than IL-2 may contribute to allograft rejection. We studied the expression of IL-15, a macrophage-derived cytokine associated with T-cell activation, which interacts with the beta and gamma chains of the IL-2R during rejection episodes under anti-CD25 therapy. METHODS: We measured intragraft IL-15 mRNA expression and the number of IL-15- and CD68-positive cells in posttransplantation endomyocardial biopsies (EMBs; n=45) and in nontransplanted, donor-heart specimens (n=11) by competitive template reverse transcription-polymerase chain reaction and immunohistochemistry, respectively. RESULTS: IL-15 mRNA expression was present in the majority of posttransplantation EMB specimens (91%, 41/45) and in nontransplanted donor-heart specimens (91%, 10/11). Relative IL-15 mRNA levels were neither associated with transplantation nor with rejection status. After transplantation, the number of IL-15- and CD68-positive cells significantly increased (P<0.001), but IL-15-positive cell counts did not reflect the histological rejection grade. Anti-CD25 treatment, in contrast to its effects on the IL-2/IL-2R complex, had no influence on intragraft IL-15 mRNA and protein production. In rejection EMB specimens, during (n=5) and after (n=8) anti-CD25 therapy, no differences in relative IL-15 mRNA levels, or in IL-15- and CD68-positive cell counts, were measured. CONCLUSIONS: After heart transplantation, high numbers of IL-15- and CD68-positive cells infiltrate the graft. This phenomenon is independent of the rejection status. IL-15 remains present during blockade of the IL-2/IL-2R pathway by anti-CD25 monoclonal antibodies, and it may participate in T cell-dependent donor-directed immune responses, thereby explaining the occurrence of rejection in the absence of IL-2.

Antibodies, Monoclonal↗
PubMed1999

The vanishing importance of age in renal transplantation.

BACKGROUND: The growing number of patients awaiting a kidney transplant raises questions about allocation of kidneys to the elderly and about the use of elderly donors. In all reported studies analyzing the influence of age on the outcome after renal transplantation, age is investigated as a categorical variable. METHODS: We studied age both as a categorical (Kaplan-Meier) and as a continuous (Cox) variable in a total of 509 cyclosporine-treated recipients of a primary cadaveric kidney graft who underwent transplantation between July 1983 and July 1997. For the Kaplan-Meier analysis, the population was divided into three comparably sized age groups: 17-43 years (n=171), 44-55 years (n=169), and 56-75 years (n=169). RESULTS: Patient survival was better and graft survival censored for death was worse in the younger patients. Overall graft survival (end point was death or graft failure) was not significantly influenced by age. In the Cox proportional hazards analysis, transplantation year turned out to be an important, independent variable influencing all end points. Because the influence was not linear, three periods were defined in which the relative risk remained stable: 1983-1990, 1991-1993, and 1994-1997. In the second period, the relative risk for transplant failure or death was 49% of that in the first period. In the third period, the relative risk had decreased to 22% of that in the first period. Recipient age and donor age were significant predictors of overall transplant failure. There was no interaction between these variables and transplantation year. Within each transplantation period, an increase in recipient age by 1 year increased the relative risk for overall graft failure by only 1.44%. The influence of donor age followed a J-shaped curve with a minimum at 30 years. The influence of increasing either recipient or donor age was counteracted by the improving results over time. CONCLUSION: Considering the improving results over time, there are, at this moment, no arguments for an age restriction for kidney transplant recipients or donors.

Adolescent↗
PubMed1999

A size-matching heterotopic aortic valve implantation model in the rat.

BACKGROUND: Structural failure of cardiac valve allografts may be related to technical factors such as size mismatch, resulting in early intimal proliferation and fibrosis or immunological reactions against the transplanted valves, featuring lymphocytic infiltration. OBJECTIVE: To develop a heterotopic aortic valve implantation model in the rat to study the immunological factors leading to graft failure in the setting of a technical adaptation for size mismatch. METHODS: Syngeneic (WAG-WAG or DA-DA) and allogeneic (WAG-BN or WAG-DA) rat strain combinations were used to study the effect of the allogeneic response on valve properties. An end-to-side anastomosis was made between the U-shaped aortic root graft and the recipient's abdominal aorta to resolve the problems of size matching. RESULTS: No animals suffered from ischemic or neurological complications during the study period. One hundred percent survival and patency of the aortic grafts were achieved at the end of a 21-day observation period. In the syngeneic group 9 of 10 valves were still competent when assessed during retrograde injection. In contrast, 2 of 10 allogeneic valve grafts were competent on postoperative Day 21. Microscopic evaluation revealed no fibrosis or intimal thickening in the syngeneic valve grafts while the allogeneic valve grafts demonstrated rejection-like morphology. CONCLUSION: The absence of fibrosis and intimal thickening in the syngeneic transplanted valve grafts indicates that this implantation model is not influenced by nonimmunological-based structural changes. Therefore, this new model enables us to study the association between donor-directed immune responses and allograft degeneration in a technically unbiased manner.

Animals↗
PubMed1999

Atypical mycobacterium infection with dermatological manifestation in a renal transplant recipient.

In April 1997, a 58-year-old renal transplant recipient presented with abscess-like nodules in his left calf and on his right foot. Furuncular disease was suspected and the patient was treated with flucloxacillin. However, the lesions increased in size and became ulcerative. In the following 3 months, cultures of punctuated material, blood, and urine remained negative and gram stains did not reveal micro-organisms. In June 1997, acid-fast stains were positive. A diagnosis of a nontuberculous mycobacterium (NTM) infection was made and empirical antimycobacterial therapy was started. The combination of relatively minor symptoms with enlarged purulent lesions, causing severe morbidity, raises the possibility of NTM infection in the immunocompromised patient.

Clarithromycin↗