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Biomedical subjects

M I Hertz

Publications and source records attributed to M I Hertz.

At least 19 recordsLinked to original sources
PubMed1999

Adjuvant treatment of refractory lung transplant rejection with extracorporeal photopheresis.

BACKGROUND: Extracorporeal photopheresis is an immunomodulatory technique in which a patient's leukocytes are exposed to ultraviolet-A light after pretreatment with 8-methoxypsoralen (methoxsalen). There have been few reports describing the use of extracorporeal photopheresis in lung transplant recipients. METHODS: We reviewed our experience using extracorporeal photopheresis in 8 lung transplant recipients since 1992. All 8 patients had progressively decreasing graft function and 7 were in bronchiolitis obliterans syndrome grade 3 before the initiation of photopheresis. One patient had undergone a second transplant operation for obliterative bronchiolitis. Two patients had a pretransplantation diagnosis of chronic obstructive pulmonary disease, 1 alpha1-antitrypsin deficiency, 1 cystic fibrosis, 1 bronchiectasis, 1 idiopathic pulmonary fibrosis, and 2 primary pulmonary hypertension. Before refractory rejection developed, all patients had been treated with 3-drug immunosuppression and anti-T-cell therapy. The median time from transplantation to the start of extracorporeal photopheresis was 16.5 months and the median number of treatments was 6. RESULTS: The condition of 5 of 8 patients subjectively improved after extracorporeal photopheresis therapy. In these 5 patients photopheresis was associated with stabilization of the forced expiratory volume in 1 second. In 2 patients there was histologic reversal of rejection after photopheresis. With a median follow-up of 36 months, 7 patients are alive and well. Three patients required retransplantation at a median of 21 months after completion of the treatments. Four patients have remained in stable condition after photopheresis. There were no complications related to extracorporeal photopheresis. CONCLUSION: We believe that this treatment is a safe option for patients with refractory lung allograft rejection when increased immunosuppression is contraindicated or ineffective.

Adolescent↗
PubMed1999

Staging of bronchiolitis obliterans syndrome using home spirometry.

OBJECTIVES: To compare the detection of bronchiolitis obliterans syndrome (BOS) in lung transplant recipients by clinic pulmonary function laboratory measurement and home spirometry. DESIGN: The subjects served as their own control group. SETTING: A university-based thoracic transplant center. SUBJECTS: Forty-five lung transplant recipients (26 women and 19 men; average +/- SD age, 47.7+/-11.4 years old at the time of transplantation). Lung function declined to at least BOS stage 1 in 17 of the 45 subjects. MEASUREMENTS: All subjects were participants in a home monitoring program utilizing home spirometry measurements. Clinic spirometry and home spirometry measurements were collected concurrently. The determinations of BOS staging were based on home and clinic FEV1 values using retrospective analysis and development of the home-based BOS staging algorithm. RESULTS: BOS stage 1 was detected an average of 341 to 276 days earlier with home spirometry than with clinic pulmonary function testing in the 17 subjects who had a pulmonary decline to BOS stage 1, depending on the persistence of the decline (1 day or 3 days, respectively). The difference in BOS detection time was statistically significant for both persistence requirements (p < 0.001). CONCLUSIONS: Home spirometry detects pulmonary decline earlier than clinic spirometry; home spirometry can be a reliable and safe alternative to frequent pulmonary function testing in lung recipients.

Algorithms↗
PubMed1998

T-cell and major histocompatibility complex requirements for obliterative airway disease in heterotopically transplanted murine tracheas.

BACKGROUND: One third of human lung allografts develop chronic rejection manifested as obliterative bronchiolitis. Heterotopically transplanted allogeneic murine tracheas develop obliterative airway disease (OAD) leading to a lesion resembling human obliterative bronchiolitis. The purpose of this study was to determine the T-cell and major histocompatibility complex (MHC) molecule requirements of murine OAD. METHODS: BALB/c allografts and C57BL/6 (B6) isografts were transplanted into B6 severe combined immunodeficient (SCID) and B6 wild-type (WT) recipients. MHC class I-discrepant bm1 grafts, class II-discrepant bm12 grafts, and F1(bm1 x bm12) (F1) grafts also were transplanted into B6 WT recipients. Grafts were harvested between days 5 and 56 following transplantation and evaluated histologically. RESULTS: Complete MHC-disparate allografts placed in WT recipients had significantly more disease than similar allografts in SCID recipients, and the latter were indistinguishable from isografts in either WT or SCID recipients, indicating a lymphocyte dependence on the disease development. Pathology was significantly more severe in bm1 and F1 allografts than in isografts recovered from B6 recipients, but bm12 allografts appeared no different than isografts. T-cell infiltrates in these bm12 allografts contained only CD4+ cells, whereas infiltrates in the BALB/c, bm1, and F1 allografts manifesting OAD contained both CD4+ and CD8+ cells. No grafts had significant B-cell infiltration. CONCLUSIONS: These findings suggest that OAD relies on a host T-cell response that includes CD8+ cells, directed against allo-class I-bearing donor cells within the graft.

Animals↗
PubMed1998

Donor-derived antibodies and hemolysis after ABO-compatible but nonidentical heart-lung and lung transplantation.

BACKGROUND: Organ donors and transplant recipients are routinely tested for ABO compatibility. ABO-identical organs are preferred, but occasionally the use of an ABO-compatible but nonidentical donor is clinically warranted. In heart-lung transplantation, the incidence of hemolysis from donor-derived anti-ABO antibodies is as high as 70%. The incidence of hemolysis for lung-only transplantation is not known. Our current posttransplantation transfusion policy for ABO-compatible but nonidentical lung-only transplant recipients is, when indicated, to use donor ABO group red blood cells. METHODS: To evaluate the efficacy of our transfusion policy, we reviewed our experience from 1986-96. One heart-lung transplant, four single lung transplant, and three bilateral single lung transplant recipients received ABO-compatible but nonidentical organs. RESULTS: The heart-lung transplant recipient developed a positive direct antiglobulin test (DAT), with anti-A eluted, and severe hemolysis on postoperative day 8 requiring plasma and whole blood exchange. Four of six lung-only transplant patients tested developed a positive DAT with anti-A eluted. Two early lung-only patients, who did not receive donor ABO group red blood cells, demonstrated clinical and laboratory evidence of hemolysis. Three bilateral lung transplant recipients were followed prospectively. The first patient had a negative DAT. The next two patients developed positive DATs on postoperative day 8 and 10, respectively. No evidence of hemolysis was detected in any of these cases. CONCLUSIONS: These results confirm that donor-derived anti-ABO antibodies develop with lung-only transplants. Our current transfusion policy is justified for both heart-lung and lung recipients of ABO-compatible but nonidentical organs. A high index of suspicion for donor-derived antibody causing hemolysis and communication with blood bank personnel are mandatory in this setting.

ABO Blood-Group System↗
PubMed1998

Randomized trial of daily versus three-times-weekly prophylactic ganciclovir after lung and heart-lung transplantation.

BACKGROUND: Cytomegalovirus is an important cause of morbidity and mortality risk after lung transplantation. Ganciclovir, when given for a period of up to 3 months after lung transplantation, has been shown to reduce the incidence and severity of cytomegalovirus. However, daily prophylaxis is associated with considerable expense, inconvenience, and morbidity risk. The goal of this study was to determine whether 3-times-weekly dosage is as effective as daily prophylaxis with ganciclovir in preventing cytomegalovirus disease. METHODS: Seventy-two consecutive subjects who had either donor or recipient cytomegalovirus seropositivity were randomized to the daily group (n = 35) or the 3-times-weekly group (n = 37). All subjects received twice-daily ganciclovir treatment for 2 weeks. Thereafter, subjects received either daily or 3-times-weekly ganciclovir dosing until 90 days after transplantation. Subjects were then monitored for 28 +/- 13 months to identify outcomes and complications. RESULTS: There were no significant differences between the daily and 3-times-weekly groups with respect to survival free from cytomegalovirus infection or survival free from cytomegalovirus disease. In both groups, cytomegalovirus infection and disease frequently emerged after the termination of prophylaxis. However, in most cases the cytomegalovirus syndromes observed were mild and in many cases could be treated on an outpatient basis. There was no significant difference between the groups in the incidence of obliterative bronchiolitis or time to onset of grade 2 bronchiolitis obliterans syndrome. Overall patient survival was better in the daily group, but the survival advantage did not appear to be related to a reduction in cytomegalovirus-related disease. Complications of ganciclovir prophylaxis included leukopenia in 2 subjects in the 3-times-weekly group and catheter-related sepsis in 6 subjects from each group. CONCLUSIONS: We conclude that intravenous ganciclovir given 3 times weekly for 3 months after transplantation is as effective as daily ganciclovir given for a similar time period. The 3-times-weekly dosing regimen did not result in increased infection, disease, or sequelae of cytomegalovirus infection when compared with the daily regimen.

Antiviral Agents↗
PubMed1997

Aspergillus airway colonization and invasive disease after lung transplantation.

BACKGROUND: Invasive Aspergillus is an important cause of morbidity and mortality among lung transplant recipients. The diagnosis can be difficult and treatment is often unsuccessful so many centers preemptively treat all Aspergillus airway isolates to prevent invasive disease. This approach is untested as little is known about the relationship between Aspergillus airway colonization and invasive disease. This study was undertaken to evaluate the incidence of Aspergillus airway colonization after lung transplantation and the risk of invasive disease after colonization. DESIGN: All cultures and histologic specimens obtained from a consecutive series of 151 lung transplant cases were reviewed for the presence of Aspergillus and compared with clinical data. RESULTS: Aspergillus was isolated from the airway in 69 (46%) of 151 transplant recipients. Invasive disease occurred in five cases and was uniformly fatal, accounting for 13% of all posttransplant deaths. Results of cytologic examination of BAL fluid were normal in all cases of invasive disease and cultures were positive in only one of five patients prior to invasion. Invasive disease occurred exclusively in patients who died or were colonized with Aspergillus fumigatus within the first 6 months posttransplant. Patients growing A. fumigatus from the airway during the first 6 months were 11 times more likely to develop invasive disease relative to those not colonized. CONCLUSION: Aspergillus airway colonization after lung transplantation is common and in most cases, transient. In contrast, invasive Aspergillus disease is less common, but fatal. Bronchoscopy with cytologic examination and fungal culture are not sensitive or timely predictors of invasive disease. Invasive Aspergillus occurred only in patients initially colonized with A. fumigatus within the first 6 months posttransplant. A trial of empiric anti-Aspergillus therapy limited to the first 6 months posttransplant may be warranted.

Adolescent↗
PubMed1997

Cyclosporine reduces development of obliterative bronchiolitis in a murine heterotopic airway model.

Obliterative bronchiolitis (OB), an important threat to the long-term survival of lung transplant recipients, is characterized histologically by fibroproliferation within small airways. The pathogenesis of OB is thought to involve chronic allograft rejection, and therapy frequently includes augmentation of immunosuppression. We have developed a model that reproduces the pathologic lesion of OB and allows study of interventions designed to limit airway fibrosis. In this model, heterotopic transplantation of murine airways into immune-mismatched recipients results in epithelial abnormalities and fibroproliferation in the airway lumen, changes not seen in heterotopic isografts. Cyclosporine (CsA) inhibits activation and proliferation of T lymphocytes and is commonly administered after lung transplantation. We hypothesized that use of CsA in our model system would reduce fibroproliferation in tracheal allografts. To test this hypothesis, murine tracheas were transplanted heterotopically into allo matched and allomismatched recipients, and then treated with varying doses (5, 10, 15, or 25 mg/kg i.p. q.d.) of CsA. Controls included allografts and isografts not treated with CsA. After 30 days, tracheas were harvested and examined histologically. CsA markedly reduced the development of fibroproliferation in allografts (19% in treated allografts versus 90% in untreated allografts, P<0.0001), but did not reduce inflammation or airway epithelial cell injury. High-dose (25 mg/kg/day) CsA was more effective than lower doses in reducing fibroproliferation (0% in high dose versus 29% in low dose, P=0.04). These findings demonstrate that CsA significantly reduces development of the pathologic lesion of OB, and supports the role of alloimmunity in the pathogenesis of this disease.

Animals↗
PubMed1997

Determination of reliability and validity in home monitoring data of pulmonary function tests following lung transplantation.

Electronic spirometry units were used to monitor lung transplantation recipients upon their return home. The data from 77 participants were used to develop methods to verify that the pulmonary function measurements, forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1), were reliable and valid. The standard deviation was calculated for the best daily effort on consecutive days of home spirometry. An acceptable upper limit for the standard deviation, as the measure of day-to-day reliability, was 0.20 for FVC and 0.15 for FEV1. Validity was determined by examining the mean difference (bias) between the spirometry done in the pulmonary function laboratory and the home monitoring results. The clinic values were slightly higher, with an average difference of 0.15 for FVC and 0.12 for FEV1. Therefore, the home spirometry measurements have a high degree of reliability and validity and can now be used for early detection of serious complications.

Adolescent↗
PubMed1997

Early and late airway complications after lung transplantation: incidence and management.

BACKGROUND: Airway anastomosis complications continue to be a source of morbidity for lung transplant recipients. METHODS: This study analyzes incidence, treatment, and follow-up of airway anastomotic complications occurring in 127 consecutive lung transplant airway anastomoses (77 single lung and 25 bilateral sequential lung). Complications were categorized as stenosis (11), granulation tissue (8), infection (7), bronchomalacia (5), or dehiscence (3). Follow-up after treatment ranged from 6 months to 4 years. RESULTS: Nineteen airway anastomosis complications (15.0%) occurred in 18 patients. Telescoping the airway anastomosis reduced the complication rate to 12 of 97 (12.4%), compared with 7 of 30 (23.3%) for omental wrapping, (p = 0.15). Complications developed in 13 of 77 single-lung airway anastomoses (16.9%) versus 6 of 50 bilateral sequential lung recipients (12.0%). Treatment consisted of stenting (9 airway anastomoses), bronchodilation (8), laser debridement (4), rigid bronchoscopic debridement (2), operative revision (2), and growth factor application (2). There was no difference in actuarial survival between patients with or without airway anastomosis complications (p = 1.0). CONCLUSIONS: Airway anastomosis complications can be successfully managed in the immediate or late postoperative period with good outcome up to 4 years after intervention.

Adult↗
PubMed1997

Risk factors for the development of bronchiolitis obliterans syndrome after lung transplantation.

OBJECTIVE: This study identifies specific clinical and immunologic factors in lung transplant recipients that influence the subsequent development of chronic allograft dysfunction. METHODS: The study group consisted of 132 consecutive patients who received lung allografts (76 single, 25 bilateral single, and 31 heart-lung) and survived at least 90 days. One hundred twenty-one patients were used in the analysis that modeled time to development of histologic obliterative bronchiolitis or bronchiolitis obliterans syndrome. RESULTS: Variables noted to have an effect on the time to development of bronchiolitis obliterans syndrome included cytomegalovirus pneumonitis (RR = 3.2, p = 0.001), late acute rejection (RR = 1.3, p = 0.02), human leukocyte antigen mismatches at the A loci (RR = 1.8, p = 0.02), total human leukocyte antigen mismatches (RR = 1.4, p = 0.04), and absence of donor antigen-specific hyporeactivity (52% vs 100% survival free from bronchiolitis obliterans syndrome at 2 years; p = 0.005). Cytomegalovirus pneumonitis had a significant effect on time to obliterative bronchiolitis (RR = 3.6, p = 0.0005), as did donor antigen-specific hyporeactivity (52% vs 100% survival free from obliterative bronchiolitis at 2 years; p = 0.01). In multivariate analysis, cytomegalovirus pneumonitis (RR = 3.2, p = 0.02), human leukocyte antigen mismatches at the A loci (RR = 2.4, p = 0.006), and late acute rejection (RR = 1.3, p = 0.02) were identified as predictors of bronchiolitis obliterans syndrome. Cytomegalovirus pneumonitis was associated with time to development of histologic obliterative bronchiolitis (RR = 2.3, p = 0.02). CONCLUSIONS: Several risk factors were associated with the development of chronic allograft dysfunction, which, in turn, had a significant impact on long-term survival. Early identification of lung allograft recipients with risk factors for the development of bronchiolitis obliterans syndrome may allow modification in immunosuppression and antiviral therapy to potentially decrease the prevalence of this disorder.

Adult↗
PubMed1997

Obliterative bronchiolitis.

Obliterative bronchiolitis following lung transplantation is common and potentially devastating. Its exact cause is undefined, but multiple immune and nonimmune processes contribute to its pathogenesis. Severe acute rejection and recurrent acute rejection have been shown to confer the greatest risk for obliterative bronchiolitis, signifying the central importance of alloimmunity in the disease process. Treatment of established disease with intensification of immune suppression has been of limited benefit, so current clinical strategies include early detection and minimization of risk. As our understanding of the disease evolves, it is hoped that effective interventions targeted at specific pathogenetic steps will emerge. In the meantime, obliterative bronchiolitis remains the most important and sinister long-term complication of lung transplantation.

Acute Disease↗
PubMed1996

Sequential measurement of peripheral blood allogeneic microchimerism levels and association with pulmonary function.

We have shown in lung recipients that high levels of peripheral blood allogeneic microchimerism at 12 to 18 months posttransplant correlated with donor antigen-specific hyporeactivity (i.e., decreased proliferative response to donor antigen in MLC while response to 3rd-party cells remains unchanged); both parameters correlated with an obliterative bronchiolitis (OB)-free state. We have expanded these studies to determine any association of sequential microchimerism levels with concomitant clinical events. In this preliminary study of 7 lung recipients, we used limiting-dilution PCR to quantify peripheral blood microchimerism at serial timepoints ranging from 3 to >48 months posttransplant. These levels were compared with a variety of immunologic and clinical parameters: acute rejection, CMV infection, OB, donor antigen-specific hyporeactivity, and pulmonary function. Pulmonary function was measured per the International Society of Heart and Lung Transplantation: "current FEV1/ baseline FEV1" (FEV1: forced expiratory volume in 1 second). Of the clinical parameters, the association between microchimerism and pulmonary function was the most striking. We observed dynamic patterns of peripheral microchimerism, which reflected the general rise and fall of FEV1. In all 7 recipients, chimerism and FEV1 were high very early posttransplant, then dropped at various rates and to various degrees. After its initial decline, microchimerism increased with FEV1 for the 1 hyporesponsive recipient; for the other 6 recipients, both values declined. These results illustrate, for the first time, that the fluctuation of peripheral blood microchimerism levels is associated with the recipient's clinical condition.

Blood Grouping and Crossmatching↗
PubMed1996

An expert system for diagnosis and therapy in lung transplantation.

An expert system for diagnosis and therapy after lung transplantation has been developed and evaluated by domain experts. The system captures a total of 21 diagnoses encompassing rejection, pulmonary infection, and some diseases of gastrointestinal origin. The disease hypotheses are scored and ranked by their ability to explain the patient findings. A hypothesis is accepted as a candidate disease if it is ranked high on the list and is able to account for the cardinal findings of the disease. The therapy knowledge is captured in the form of rules. The results demonstrate the feasibility of an expert system for diagnosis and therapy after lung transplantation.

Evaluation Studies as Topic↗
PubMed1996

Quantitation of cytomegalovirus DNA and characterization of viral gene expression in bronchoalveolar cells of infected patients with and without pneumonitis.

Cytomegalovirus (CMV) is often present in bronchoalveolar lavage (BAL) fluid of immunosuppressed patients without CMV pneumonitis. The amount of viral DNA within BAL cells of patients with definite CMV pneumonitis and of viral shedders was quantitated by polymerase chain reaction (PCR) and the extent of CMV gene expression within BAL cells was defined by reverse transcription - PCR. No viral DNA was detected in 6 viral shedders, and 12 had low copy numbers (mean, 72 copies/10(5) BAL cells; median, 20) compared with numbers in pneumonitis patients (267,580 and 57,000, respectively). When CMV intranuclear inclusions were absent within BAL cells of patients with pneumonitis, copy numbers (mean, 9362; median, 7110) were still significantly higher than among shedders. Expression of viral glycoprotein H mRNA was detected in BAL cells of all 11 pneumonitis patients tested but in 0 of 18 viral shedders. Thus, high-grade infection and viral replication within BAL cells are integral features of CMV pneumonitis but not viral shedding.

Base Sequence↗
PubMed1996

Primary pulmonary hypertension as a risk factor for the development of obliterative bronchiolitis in lung allograft recipients.

STUDY OBJECTIVES: Obliterative bronchiolitis (OB) is a major factor limiting long-term survival after lung transplantation. The etiology of this disease process remains incompletely understood. Several risk factors have been identified previously, including acute rejection and cytomegalovirus pneumonitis. The purpose of this study was to evaluate primary pulmonary hypertension (PPH) as a potential risk factor for the development of OB after lung transplantation. DESIGN AND PATIENTS: We retrospectively analyzed 107 lung allograft recipients (28 heart-lung, 18 bilateral sequential single-lung, 61 single-lung) who underwent transplantation between May 1, 1986, and April 30, 1994, and survived at least 3 months posttransplant. Mean follow-up posttransplant was 28.6 months (range, 3.5 to 99 months). Actuarial survival was estimated for patients with or without PPH and for those who did or did not develop OB. RESULTS: In all, 25 patients (23.4%) developed OB, diagnosed by strict histologic criteria. Of 23 patients with PPH, 9 (39.1%) developed OB, compared with 16 (19.0%) of 84 patients without PPH (p = 0.044). Actuarial survival, sex, time on waiting list, and follow-up posttransplant were not significantly different between groups. PPH was the major determinant for the development of OB (p = 0.0468) when evaluating PPH and cytomegalovirus pneumonitis together as risk factors. Patients with PPH also developed OB significantly earlier posttransplant, compared with patients with other primary disease (p = 0.05). CONCLUSIONS: Patients with PPH who undergo lung transplantation are at increased risk for the development of OB, which also occurs at a shorter time interval posttransplant. This subgroup needs aggressive monitoring for diagnosis and treatment of OB.

Adolescent↗
PubMed1996

Methotrexate for lung transplant recipients with steroid-resistant acute rejection.

BACKGROUND: Steroid-resistant or recurrent acute rejection is a risk factor for the development of chronic graft failure in lung transplant recipients. The best treatment for these patients is not known. Methotrexate has been used successfully in heart transplant recipients with persistent or recurrent acute rejection. This study was performed to evaluate the efficacy of methotrexate in lung transplant recipients with steroid-resistant acute rejection. METHODS: From January 1991 to December 1995, 12 patients with steroid-resistant acute rejection were treated with methotrexate given weekly for 6 weeks and dose-adjusted according to laboratory data and clinical side effects. After completion of therapy, all patients underwent transbronchial biopsy to evaluate the efficacy of methotrexate treatment. RESULTS: Twelve patients underwent treatment with methotrexate for steroid-resistant acute rejection. Acute rejection resolved in all patients completing at least 4 weeks of therapy; 10 of 12 patients (83%) had no further episodes of acute rejection during a mean follow-up period of 12.5 months (range 1 to 42 months). Acute rejection recurred in two patients 6 and 16 months after methotrexate therapy. Both resolved with high-dose corticosteroid therapy. One patient had asymptomatic cytomegalovirus shedding 8 weeks after completion of methotrexate therapy. One patient had aseptic meningitis after her fourth dose of methotrexate. Neither infectious complication was associated with neutropenia. One patient had bone marrow suppression and neutropenic fevers after augmentation of her methotrexate dose. Two patients received shortened methotrexate courses because of gastrointestinal side effects. CONCLUSIONS: Methotrexate is efficacious in the treatment of lung transplant recipients with steroid-resistant acute rejection. Patients must be monitored for side effects during therapy and dosing must be individualized based on laboratory and clinical parameters.

Acute Disease↗