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J D Cooper

Publications and source records attributed to J D Cooper.

At least 55 records · Page 3Linked to original sources
PubMed1999

Cytotoxic T lymphocytes directed against donor HLA class I antigens on airway epithelial cells are present in bronchoalveolar lavage fluid from lung transplant recipients during acute rejection.

BACKGROUND: The lung epithelium is among the first donor tissues encountered by the lung allograft recipient's immune system. The purpose of this study was to determine whether lung epithelium was recognized by T lymphocytes that are isolated from bronchoalveolar lavage fluid of lung allograft recipients during periods of acute rejection. METHODS: Lymphocytes isolated from 45 bronchoalveolar lavage samples (from 41 lung transplant recipients) served as effector cells in standard cell-mediated cytolytic assays with several cell lines as targets: BEAS-2B (an immortalized airway epithelial cell line); B-lymphoblastoid cell lines; and K562 (a natural killer-sensitive cell line). Cytotoxic T-lymphocyte activity of bronchoalveolar lavage lymphocytes was correlated with pathologic status. RESULTS: During acute rejection alone (ie, without concomitant cytomegalovirus infection), mean lysis of the airway epithelial target was significantly greater, compared with during no rejection, when these targets expressed donor-specific HLA class I antigens (P =.007). Lysis of donor class I-matched B-lymphoblastoid cell line targets during rejection was not significantly different from lysis during no-rejection periods (P =.18). Mean lysis of K562, a natural killer cell target, did not differ between acute rejection (without concomitant cytomegalovirus infection) and no rejection (P =.30). During cytomegalovirus infection (without concomitant acute rejection), there was no difference in mean lysis of airway epithelial cells, B-lymphoblastoid cell lines, or K562 targets compared with during no cytomegalovirus infection, whereas during acute rejection, compared with cytomegalovirus infection without rejection, there was a significant increase in mean lysis of the airway epithelial target when it expressed donor-specific HLA antigens (P =.01). CONCLUSIONS: Donor HLA class I-specific cytotoxic T-lymphocyte activity directed at airway epithelial cells was demonstrated in bronchoalveolar lavage lymphocytes from lung transplant recipients. Lysis of these targets was significantly higher during episodes of acute rejection.

Acute Disease↗
PubMed1999

Bilateral sequential lung transplantation without sternal division eliminates posttransplantation sternal complications.

OBJECTIVE: The objective of this study was to assess the efficacy and safety of an alternative surgical incision for bilateral sequential lung transplantation. The vast majority of these operations worldwide have been performed through an anterolateral thoracosternotomy known as the "clamshell" incision. Recently, we have undertaken most of these operations through bilateral anterolateral thoracotomies without sternal division. METHODS: Our medical center performed 262 bilateral sequential single lung transplantations from 1989 to April 1998. Between July 1996 and April 1998 we performed 69 bilateral sequential single lung transplantations on 68 recipients with 52 transplantations being conducted without initial sternal division. We retrospectively reviewed the results of these operations to assess the safety of the altered exposure and the efficacy in avoiding sternal wound complications such as malunion, dehiscence, osteomyelitis, and migrating hardware. Comparison was made to a historical control group composed of the last 50 patients in whom the full clamshell incision was used. RESULTS: Of the 68 patients who underwent transplantations, 52 patients underwent the initial exploratory procedure without sternal division. Two patients required emergency sternal division for institution of cardiopulmonary bypass to control life-threatening bleeding. Eleven of 68 patients were placed on bypass electively to permit transplantation, and the lack of a sternotomy in 8 patients did not present an obstacle to ascending aortic and right atrial cannulation. There were no wound healing complications in the 50 patients for whom the sternum was left intact. In a historical control group of 50 patients who underwent transplantation with sternal division, 34% experienced morbidity or mild disability as a direct result of poor sternal healing. CONCLUSIONS: We conclude that bilateral anterolateral thoracotomy without sternal division is a safe approach that allows adequate exposure without the risk of commonly observed problems with sternal healing.

Cardiopulmonary Bypass↗
PubMed1999

Determination of eletriptan in plasma and saliva using automated sequential trace enrichment of dialysate and high-performance liquid chromatography.

The use of the system, automated sequential trace enrichment of dialysates (ASTED), to prepare plasma and saliva prior to high pressure liquid chromatography of eletriptan (HPLC) is described. Chromatographic identification of one metabolite, UK-135,800 was also established. Using this technique the procedure was observed to be specific and linear over the range 0.50-250 ng/ml. The intra-batch imprecision (C.V.) of the method ranged from 0.56 to 5.70% at plasma eletriptan concentrations from 5.00 to 200 ng/ml, and the corresponding inter-batch imprecision ranged from 1.44 to 6.36%. At these plasma analyte concentrations, the overall inaccuracy (% bias) of the procedure ranged from -5.00 to 1.50%. Similar performances were observed for the estimation of eletriptan in saliva using near identical assay conditions. The application of the assay to a pharmacokinetic investigation during a clinical study is presented.

Chromatography, High Pressure Liquid↗
PubMed1999

Lung transplantation: a decade of experience.

OBJECTIVE: To review the 10-year clinical experience of a single institution's adult lung transplant program. METHODS: Since July 1988, 450 lung transplants have been performed in 443 patients. Recipient diagnoses included emphysema in 229 patients, cystic fibrosis in 70 patients, pulmonary fibrosis in 48 patients, pulmonary hypertension in 49 patients, and miscellaneous end-stage lung diseases in 47 patients. Single-lung transplant was performed in 157 cases, bilateral sequential lung transplant in 283 cases, en bloc double-lung transplant in 8 cases, and heart-lung transplant in 2 cases. Graft lungs were obtained from local donors in 24% of cases and from distant donors in 76% of cases. Ideal donors were used in 74% of cases; in 26%, the donor was classified as marginal based on objective criteria. RESULTS: Four hundred six (91.6%) lung transplant recipients survived to hospital discharge. There were 37 hospital deaths from cardiac events (n = 8), primary graft failure (n = 8), sepsis (n = 6), anastomotic dehiscence (n = 6), and other causes (n = 9). A diagnosis of chronic rejection (bronchiolitis obliterans syndrome [BOS]) was made in 191 patients (42.5%). BOS has not been improved by any specific therapy. Rates of freedom from BOS at 1, 3, and 5 years after the transplant are 82%, 42%, and 25%. One-, 3-, and 5-year actuarial survival rate for the entire group are 83%, 70%, and 54%. There is no statistical difference in survival according to diagnosis or type of lung transplant. Recipient waiting time was 116 days in the first 90 patients and 634 days in the most recent 90 patients. CONCLUSIONS: Lung transplantation offers patients with end-stage lung disease acceptable prospects for 5-year survival. Chronic rejection and long waiting lists for donor lungs continue to be major problems facing lung transplant programs. The use of marginal and distant donors is a successful strategy in improving donor availability.

Adult↗
PubMed1999

Results of transcervical thymectomy for myasthenia gravis in 100 consecutive patients.

OBJECTIVE: To review the results of the authors' most recent 100 consecutive cases of transcervical thymectomy for myasthenia gravis (MG) in terms of complications and outcome in comparison with other reported techniques. SUMMARY BACKGROUND DATA: Myasthenia gravis is believed to be an autoimmune disorder characterized by increasing fatigue with exertion. The role of thymectomy in the management of the disease remains unproven, but there is widespread acceptance of the notion that complete thymectomy improves the course of the disease. Complete excision of the thymus is the goal in all cases; however, the best technique to achieve complete thymectomy remains controversial. The authors favor a transcervical approach through a small collar incision aided by a specially designed sternal retractor. Others prefer a transsternal, a combined transcervical and transsternal ("maximal"), or a video-assisted thoracoscopic surgical approach. METHODS: A retrospective review of the authors' most recent 100 consecutive transcervical thymectomies for nonthymoma-associated MG was performed using medical records and telephone interviews. Patients' symptoms were graded before surgery and at the most recent (within the last 6 months) postoperative time point, using the modified Osserman classification: 0 = asymptomatic, 1 = ocular signs and symptoms, 2 = mild generalized weakness, 3 = moderate generalized weakness, bulbar dysfunction, or both, and 4 = severe generalized weakness, respiratory dysfunction, or both. RESULTS: There were 61 female patients and 39 male patients with a mean age of 38 years (range, 14 to 84). The median hospital stay was 1 day. There were no deaths and no significant complications. Seventy-eight patients who had undergone surgery >12 months ago were available for analysis. In these patients, with a mean follow-up time of 5 years (median 5.3; range, 12 months to 10 years), the median preoperative Osserman grade improved from 3.0 (mean 2.73) before surgery to 1.0 after surgery (mean 0.94). CONCLUSIONS: The transcervical approach for thymectomy for the treatment of MG produces results similar to those of other surgical approaches, with the added benefits of shortened hospital stay, decreased complications, reduced cost, and broader physician and patient acceptance of surgical treatment.

Adolescent↗
PubMed1998

Ganglioside GM1 potentiates NGF action on axotomised medial septal cholinergic neurons.

Transection of the fimbria fornix leads to retrograde degeneration of axotomised septal cholinergic neurons as manifested by loss of choline acetyltransferase and p75NGFR immunoreactivity. Intracerebroventricularly administered nerve growth factor initiated at the time of axotomy can prevent these changes. We have shown that concurrent intraperitoneal administration of GM1 with a low and otherwise unprotective intracerebroventricular dose of nerve growth factor, can also prevent the loss of these fimbria fornix axotomised cholinergic neurons, where GM1 alone does not have this effect. This study further confirms the neuroprotective actions of GM1 and suggests that it may interact to potentiate the effect of nerve growth factor on these axotomised septal cholinergic neurons.

Acetylcholine↗
PubMed1998

HLA-A locus mismatches and development of antibodies to HLA after lung transplantation correlate with the development of bronchiolitis obliterans syndrome.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is the most common cause of morbidity and mortality after lung transplantation (LT). A retrospective analysis of clinical and immunologic variables were done to identify those that might predict the development of BOS. METHODS: Of 112 LT performed over a 42-month interval, 94 survived at least 3 months and form the basis of this analysis. There was a minimum of 21 months follow-up. BOS was defined on the basis of declining spirometry (FEV1 <80% of baseline) and/or the presence of histologic obliterative bronchiolitis. All variables analyzed were subjected first to a univariate analysis; those variables appearing to carry significance were then subjected to a multivariate logistic regression analysis. RESULTS: Univariate analysis revealed the following to be predictors of the development of BOS: age (the probability of developing BOS declined with advancing age); donor/recipient HLA-A locus mismatch, with actuarial freedom from BOS being significantly greater with no A-locus mismatches versus cases with one or two mismatches (P=0.031); and development of anti-HLA antibodies after transplantation (P=0.006 vs. recipients without detectable antibodies). In multivariate analysis, only HLA locus mismatch and development of anti-HLA antibodies were significant independent predictors of the development of BOS. The remaining clinical variables (gender, type of LT, indication for LT, graft ischemic time, use of cardiopulmonary bypass, cytomegalovirus) and immunologic variables (crossmatch, frequent early acute rejection) did not correlate with the development of BOS. CONCLUSIONS: These data suggest that BOS is the result of an immune process, that differences at the HLA-A locus may play an important role in this process, and antibody-mediated injury may play a role in BOS.

Adult↗
PubMed1998

Lung transplantation.

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Bronchiolitis Obliterans↗
PubMed1998

Long-term clinical outcome after transcervical thymectomy for myasthenia gravis.

BACKGROUND: We reviewed the long-term clinical outcome after transcervical thymectomy for generalized myasthenia gravis without thymoma in 52 patients who had this procedure at The Toronto Hospital between 1977 and 1986, and compared the results with those reported after more radical surgical approaches. METHODS: Preoperative and postoperative patient evaluations were based on a modified Osserman classification. We defined complete remission as asymptomatic with normal strength and without medications for myasthenia gravis. The complete remission rate was selected as the best measure for comparison between different surgical approaches. RESULTS: The 52 patients were followed up for a mean of 8.4 years (+/-6.1 years [standard deviation]). The preoperative mean Osserman grade was 2.7 compared with 0.4 at final follow-up. Complete remission occurred in 44.2% of patients. Similar results are reported after transsternal thymectomy. CONCLUSIONS: Comparable results after transcervical and transsternal thymectomy favor the use of the less radical approach.

Adolescent↗
PubMed1998

Outcome of Medicare patients with emphysema selected for, but denied, a lung volume reduction operation.

BACKGROUND: Lung volume reduction operation shows promise in relieving symptoms and improving function in highly selected patients with emphysema. Withdrawal of Medicare funding for patients selected for operation by standard criteria created a matched control group with which to compare lung volume reduction recipients. METHODS: A retrospective study was done comparing 22 volume reduction candidates denied operation with 65 contemporaneous and comparable volume reduction recipients. Baseline physiologic characteristics were compared and longitudinal measures of pulmonary function were followed up for 24 months. RESULTS: Patients denied operation were similar to volume reduction recipients in all baseline measurements. Patients denied operation experienced a progressive worsening of their function, whereas volume reduction patients experienced sustained improvements. Absolute survival to date is 82% for the surgical group and 64% for the medical group. CONCLUSIONS: The improvement seen in volume reduction patients cannot be attributed to the effects of patient selection or preoperative and postoperative rehabilitation.

Aged↗
PubMed1998

Recombinant Kunitz protease inhibitor ameliorates reperfusion injury in rat lung transplantation.

BACKGROUND: Recombinant Kunitz protease inhibitor (rKPI-BG022) is more homologous to human Kunitz protease inhibitor than is aprotinin. Because aprotinin has been reported to inhibit free radicals, we hypothesized that rKPI would ameliorate reperfusion injury caused by free radicals. We examined its effect and the timing of administration in an in vivo rat lung transplantation model. METHODS: All lungs were flushed with low-potassium dextran-1% glucose solution and stored for 24 hours at 4 degrees C, then orthotopic left lung transplantations were performed. Rats were divided into 4 groups (n=6) as follows: group 1 served as control; in Group 2, rKPI was added to the flush solution (10 micromol/L); in group 3, rKPI (5 mg/kg) was administered intravenously to the recipient just after reperfusion; and in group 4, rKPI was added to the flush solution (10 micromol/L) and rKPI (5 mg/kg) was administered intravenously to the recipient just after reperfusion. Twenty-four hours after transplantation, the right main pulmonary artery and right main bronchus were ligated, and the rats were ventilated with 100% O2 for 5 minutes. Peak airway pressure, blood gas analysis, serum lipid peroxide level, tissue myeloperoxidase activity, and wet-dry weight ratio were measured. RESULTS: The partial oxygen tension values of group 2 were higher than those of groups 1 and 4 (groups 1, 2, and 4: 104.8+/-15.8, 245.1+/-49.0, 101.4+/-4.5 mm Hg, respectively; p < 0.01). The partial carbon dioxide tension values of groups 3 and 4 were lower than those of group 1 (groups 1, 3, and 4: 74.5+/-5.7, 42.0+/-11.0, 46.0+/-8.4 mm Hg, respectively; p < 0.05). Peak airway pressures were lower in groups 2 and 3 than in groups 1 and 4 (groups 1, 2, 3, and 4: 22.5+/-0.5, 18.2+/-0.5, 19.2+/-0.8, 22.5+/-1.1 mm Hg; p < 0.01). Serum lipid peroxide levels in groups 2 and 3 were lower than those of groups 1 and 4 (groups 1, 2, 3, and 4: 0.793+/-0.037, 0.577+/-0.069, 0.560+/-0.029, and 0.785+/-0.053 nmol/mL, respectively; groups 2 and 3 vs group 1, and group 3 vs group 4: p < 0.01; group 2 vs group 4: p < 0.05). There were no differences in wet-dry weight ratio and tissue myeloperoxidase activity between the groups. CONCLUSION: Recombinant Kunitz protease inhibitor ameliorates reperfusion injury caused by free radicals in an in vivo rat lung transplantation model. Administration of rKPI through the flush solution and intravenous injection after reperfusion were effective separately, but the combination of the two administrations was not effective.

Animals↗
PubMed1998

Isolated lung liposome-mediated gene transfer produces organ-specific transgenic expression.

BACKGROUND: Gene therapy is a promising strategy for the treatment of inoperable pulmonary tumors and rejection after lung transplantation. However, unlike ex vivo administration, intravenous in vivo transfection lacks organ specificity and has a limited duration of expression. The objectives of this study were to limit transfection to a single lung and to increase the duration of gene expression in vivo. METHODS: Sixteen male Fisher rats were anesthetized and divided into two groups. Animals in group I (n = 7) received an intrajugular administration of 1,320 microg of chloramphenicol acetyl transferase (CAT) complementary DNA complexed with cationic liposomes. Animals in group II (n = 9) received 660 microg of CAT complementary DNA complexed with cationic liposomes into the pulmonary artery of an isolated left lung over 10 minutes. After 40 minutes of incubation, the lung was flushed with 10 mL of normal saline solution, and the perfusate was suctioned through a left pulmonary venotomy. The circulation to the left lung was then restored. After 48 hours, the animals were divided into subgroups (a and b) and CAT activity was assessed in the lungs, hearts, livers, and kidneys of groups Ia (n = 3) and IIa (n = 5). After 21 days, CAT activity was assessed in the left lungs of groups Ib (n = 4) and IIb (n = 4). RESULTS: After 48 hours, animals that had received intravenous administration of CAT cDNA showed strong expression in the lungs and hearts and negligible expression in the livers and kidneys. In contrast, animals in group IIa, which had received isolated left lung perfusion of CAT cDNA showed expression only in the left lung. After 21 days, the left lungs of animals in group Ib, which had received intravenous administration of CAT complementary DNA, showed no CAT expression, but the left lungs of animals in group IIb, which had received isolated left lung perfusion of CAT complementary DNA, exhibited strong CAT expression. CONCLUSIONS: Compared with intravenous administration, isolated lung liposome-mediated gene transfer provides prolonged organ-specific gene expression. This provides a useful model to study the effects of gene therapy on pulmonary tumors, which may have further application when gene therapy is used in clinical practice.

Animals↗
PubMed1998

Effect of development of antibodies to HLA and cytomegalovirus mismatch on lung transplantation survival and development of bronchiolitis obliterans syndrome.

OBJECTIVE: A retrospective analysis was performed to examine the role of HLA antibodies and cytomegalovirus mismatch on the development of bronchiolitis obliterans syndrome and survival after lung transplantation. METHODS: Of 339 consecutive lung transplantations performed over a 102-month interval, 301 patients survived at least 3 months. There was a minimum follow-up period of 13 months. Bronchiolitis obliterans syndrome was defined as a decline in forced expiratory volume in 1 second less than 80% of posttransplantation baseline and/or histologic presence of obliterative bronchiolitis and was defined as occurring "early" if documented within 3 years of transplantation. Variables analyzed included preoperative donor and recipient cytomegalovirus status and the development of antibodies to human leukocyte antigens after transplantation. Microcytotoxicity was used to determine the presence of antibodies to human leukocyte antigens. Variables were subjected to Kaplan-Meier analysis to determine their impact on freedom from bronchiolitis obliterans syndrome and survival. RESULTS: The development of antibodies to human leukocyte antigens after transplantation correlated significantly with bronchiolitis obliterans syndrome (P = .02). The development of antibodies to human leukocyte antigens did not affect survival (P = .33) unless they were detected within 2 years of transplantation (P = .04). There was greater frequency of early bronchiolitis obliterans syndrome in cytomegalovirus seronegative patients who received allografts from seropositive donors compared with all other combinations (P = .02). There was also a trend toward worse survival of cytomegalovirus seronegative patients who received allografts from seropositive donors (P = .13). CONCLUSION: These data suggest that bronchiolitis obliterans syndrome is the result of an immune-mediated process in which HLA antibodies and cytomegalovirus may play a significant role.

Actuarial Analysis↗
PubMed1998

Pediatric and adult lung transplantation for cystic fibrosis.

OBJECTIVE: This paper was undertaken to review the experience at our institution with bilateral sequential lung transplantation for cystic fibrosis. METHODS: Since 1989, 103 bilateral sequential lung transplants for cystic fibrosis have been performed (46 pediatric, 48 adult, 9 redo); the mean age was 21 +/- 10 years. Cardiopulmonary bypass was used in all but one pediatric (age <18) transplant, and in 15% of adults. RESULTS: Hospital mortality was 4.9%, with 80% of early deaths related to infection. Bronchial anastomotic complications occurred with equal frequency in the pediatric and the adult populations (7.3%). One- and 3-year actuarial survival are 84% and 61%, respectively (no significant difference between pediatric and adult age groups; average follow-up 2.1 +/- 1.6 years). Mean forced expiratory volume in 1 second increased from 25% +/- 9% before transplantation to 79% +/- 35% 1 year after transplantation. Acute rejection occurred 1.7 times per patient-year, with most episodes taking place within the first 6 months after transplantation. The need for treatment of lower respiratory tract infections occurred 1.2 times per patient in the first year after transplantation. Actuarial freedom from bronchiolitis obliterans was 63% at 2 years and 43% at 3 years. Redo transplantation was performed only in the pediatric population and was associated with an early mortality of 33%. Eight living donor transplants (four primary transplants, four redo transplants) were performed with an early survival of 87.5%. CONCLUSION: Patients with end-stage cystic fibrosis can undergo bilateral lung transplantation with morbidity and mortality comparable to that seen in pulmonary transplantation for other disease entities.

Actuarial Analysis↗
PubMed1998

Lobectomy combined with volume reduction for patients with lung cancer and advanced emphysema.

OBJECTIVE: Early-stage lung cancer is best treated by anatomic pulmonary resection. Patients with lung cancer and severe emphysema are often denied resection or are offered only limited, nonanatomic resections when established pulmonary function criteria for lobectomy are not met. Recently, with the introduction of the volume reduction operation, selected patients with disabling emphysema have undergone excision of approximately 30% of the most destroyed lung tissue and have subsequently demonstrated subjective and objective improvement in pulmonary function. Using these principles, we elected to combine anatomic lobectomy with volume reduction in a select group of patients with both emphysema and lung cancer who would not otherwise be candidates for pulmonary resection. METHODS: Five patients with severe emphysema and suspected or proven lung cancers, who were poor candidates for anatomic lobectomy by traditional criteria but were good candidates for volume reduction, underwent lobectomy combined with volume reduction of one or more additional lobes. RESULTS: All five patients having lung volume reduction and anatomic lobectomy for early-stage primary lung cancer did well postoperatively. Furthermore, each patient has demonstrated subjective and objective improvement in respiratory function on serial postoperative studies. CONCLUSIONS: Selected patients with disabling emphysema and suitable anatomy for volume reduction, who have a lung cancer situated in destroyed lung tissue, may benefit from combined lobectomy and volume reduction. The introduction of the volume reduction operation has added a new factor in the algorithm for the evaluation and treatment of lung cancer in selected patients with advanced emphysema.

Aged↗