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Biomedical subjects

M L Barr

Publications and source records attributed to M L Barr.

At least 19 recordsLinked to original sources
PubMed2006

Report of a National Conference on Donation after cardiac death.

A national conference on organ donation after cardiac death (DCD) was convened to expand the practice of DCD in the continuum of quality end-of-life care. This national conference affirmed the ethical propriety of DCD as not violating the dead donor rule. Further, by new developments not previously reported, the conference resolved controversy regarding the period of circulatory cessation that determines death and allows administration of pre-recovery pharmacologic agents, it established conditions of DCD eligibility, it presented current data regarding the successful transplantation of organs from DCD, it proposed a new framework of data reporting regarding ischemic events, it made specific recommendations to agencies and organizations to remove barriers to DCD, it brought guidance regarding organ allocation and the process of informed consent and it set an action plan to address media issues. When a consensual decision is made to withdraw life support by the attending physician and patient or by the attending physician and a family member or surrogate (particularly in an intensive care unit), a routine opportunity for DCD should be available to honor the deceased donor's wishes in every donor service area (DSA) of the United States.

Adolescent↗
PubMed2006

Immunosuppression: evolution in practice and trends, 1994-2004.

Over the last 10 years, there have been important changes in immunosuppression management and strategies for solid-organ transplantation, characterized by the use of new immunosuppressive agents and regimens. An organ-by-organ review of OPTN/SRTR data showed several important trends in immunosuppression practice. There is an increasing trend toward the use of induction therapy with antibodies, which was used for most kidney, pancreas after kidney (PAK), simultaneous pancreas-kidney (SPK) and pancreas transplant alone (PTA) recipients in 2004 (72-81%) and for approximately half of all intestine, heart and lung recipients. The highest usage of the tacrolimus/mycophenolate mofetil combination as discharge regimen was reported for SPK (72%) and PAK (64%) recipients. Maintenance of the original discharge regimen through the first 3 years following transplantation varied significantly by organ and drug. The usage of calcineurin inhibitors for maintenance therapy was characterized by a clear transition from cyclosporine to tacrolimus. Corticosteroids were administered to the majority of patients; however, steroid-avoidance and steroid-withdrawal protocols have become increasingly common. The percentage of patients treated for acute rejection during the first year following transplantation has continued to decline, reaching 13% for those who received a kidney in 2003, 48% of which cases were treated with antibodies.

Evolution, Molecular↗
PubMed2005

Living donor lobar lung transplantation: current status and future directions.

Living lobar lung transplantation was developed as a procedure for adult and pediatric patients considered too ill to await cadaveric transplantation. One hundred thirty-eight living lobar transplants have been performed in 133 patients at our institution between January 1993 and September 2004. Actuarial 1-, 3-, and 5-year survival are similar to ISHLT registry data. There has been no donor mortality, and morbidity has been relatively low. Long-term postoperative pulmonary function studies demonstrate the relatively smaller-sized lobes can provide similar pulmonary function and exercise capacity to bilateral cadaveric lung transplants. Living lobar lung transplantation should be considered a viable option in patients with end-stage lung disease deemed unable to await a cadaveric organ and in those patients in which further deterioration would make cadaveric transplantation inappropriate.

Adult↗
PubMed2001

A novel paracorporeal method for isolated rodent lung reperfusion.

BACKGROUND: The isolated perfused lung model is commonly used in small animals to study lung function after preservation and cold storage. Measurements of oxygenation, compliance, and capillary filtration coefficient (Kf) permit analysis of preservation solutions or modifications of these solutions. However, inter-investigator variability using different perfusates makes comparisons difficult. Whole blood perfusion more closely mimics the in vivo situation, but extracorporeal circulation may alter the physiologic integrity of the model. Paracorporeal support has been used, but this technique required mechanical ventilation of the support rodent and did not incorporate a method for determining Kf. We evaluated a less-invasive technique, of providing cross-circulatory syngeneic support, maintaining the ability to compute Kf. METHODS: Angiocatheters were inserted into both femoral arteries and one femoral vein of the support rat. The venous cannula was connected to the pulmonary artery of the ex vivo lung block to provide inflow. Pulmonary effluent blood from the lung block was collected via a left atrial cannula and returned to the support rat via the femoral artery. A separate, height-adjustable column was included in the circuit for measurement of Kf. RESULTS: Each support rat was used to sequentially perfuse three double-lung blocks. The inflow sample to each lung block was analyzed for pH, pO2, pCO2, and hematocrit to follow alterations in support rat physiology. There were no statistical differences in the pH, PO2, or hematocrit. No significant differences were noted in the pO2 of the pulmonary effluent blood or the Kf; analyzed to determine whether the sequence of reperfusion affected the pulmonary function assessment. CONCLUSIONS: The syngeneic support rat delivers constant pressure systemic venous blood at stable physiologic parameters to the ex vivo lung block. Recirculation of the perfusate through the support rat diminishes the need to pool blood from donors, detoxifies and deoxygenates pulmonary effluent blood, and permits examination of sequential lung blocks. This technique represents a hybrid model between isolated perfused and orthotopic transplant models, maintaining Kf determination, a sensitive indicator of reperfusion injury. This technique could be applicable to reperfusion injury models of other organs (using arterial inflow instead) and may permit increased standardization among investigators.

Animals↗
PubMed2001

Regional topical hypothermia of the beating heart: preservation of function and tissue.

BACKGROUND: Protection of the myocardium during beating heart operations is paramount. The goal of this study is to determine if regional topical hypothermia (RTH) preserves myocardial viability and function during periods of temporary coronary artery occlusion. METHODS: Sixteen pigs were divided into two groups (RTH and control). Each group received 40 minutes of midleft anterior descending coronary occlusion followed by 3 hours of reperfusion. The RTH group (n = 10) received RTH and the control group (n = 6) received no cooling. Myocardial and core temperatures were measured with thermistors. Sonomicrometers and micromonameters were used to determine load independent indices of myocardial function. These indices were measured at base line, during coronary occlusion, and at 3 hours of reperfusion. The myocardium at risk and the infarct area were determined with monastral blue dye and triphenyl tetrazolium chloride staining. RESULTS: The mean myocardial temperature in the risk zone during coronary occlusion was significantly less in the RTH group (29.4 degrees C +/- 5.6 degrees C versus 35.7 degrees C +/- 1.1 degrees C, p < 0.05). After 40 minutes of coronary occlusion, both the RTH group and control had a significant reduction in regional elastance (9.38 +/- 3.54 and 11.05 +/- 1.67 mm Hg/mm) compared with base line measurements (14.70 +/- 2.42 and 16.80 +/- 4.79 mm Hg/mm), p < 0.05. However, after 3 hours of reperfusion, the elastance returned to base line levels in the RTH group (15.83 +/- 3.06 mm Hg/mm) but remained significantly depressed in the control group (9.97 +/- 3.63 mm Hg/mm, p < 0.04). Myocardial necrosis as a percentage of the risk zone was significantly less in the hypothermia group (25% +/- 2% versus 62% +/- 5%, p < 0.001). CONCLUSIONS: Regional topical hypothermia during isolated temporary coronary occlusion provides regional myocardial protection expressed as a return of function and decreased necrosis. Regional topical hypothermia may be clinically applicable to myocardial preservation during beating heart operations.

Animals↗
PubMed2001

Bronchiolitis obliterans is not the primary cause of death in pediatric living donor lobar lung transplant recipients.

BACKGROUND: Obliterative bronchiolitis (OB) is the chief cause of mortality in cadaveric lung transplant patients (CL). But, is OB the primary cause of mortality for living donor lobar recipients? To answer this question, we reviewed the causes of mortality in our pediatric patients who underwent living donor lobar lung transplantation (LD) and compared them with our pediatric patients who received whole cadaveric lungs (CL). METHODS: Data collected included demographics, transplant type, hospital days, immunosuppression regimen, and cause of death. Statistical analysis was done using Fisher's Exact test and Student's t-test (mean +/- SD). RESULTS: From May 1993 to December 1999, 53 patients underwent lung transplantation (21 males, 32 females; mean age 12.4 +/- 5.4 years). Twenty-nine patients had LD procedures (12 males, 17 females; mean age 14.4 +/- 3.6 years) and 24 patients had CL surgery (9 males, 15 females; p = .78 [not significant]; mean age 9.8 +/- 6.3 years; p =.001). All patients received triple immunosuppression without induction. During the study period, 9 LD (6 males, 3 females; mean age 15.7 +/- 5.0 years) and 14 CL (3 males, 11 females; mean age 11.3 +/- 6.9 years) patients died. There was no significant difference between patients in the LD and CL groups who died with regard to gender (p = .08), age at the time of death (p = .12), mortality rate (p = .06), number of hospital days (p = .09), immunosuppressive medications (p > .08), incidence of non-specific graft failure (p = .26), or incidence of infection (p = .18). However, there was a significant difference in the incidence of OB between LD and CL recipients (p = .002). CONCLUSIONS: OB was not found to be the chief cause of mortality in pediatric LD recipients. We speculate that prevention of infections, possibly by a modest reduction in immunosuppressive therapy and aggressive antimicrobial therapy, may improve long-term survival in pediatric living donor lobar lung transplant recipients.

Adolescent↗
PubMed2001

Life satisfaction in renal transplant recipients: preliminary results from the transplant learning center.

The Transplant Learning Center (TLC) was designed to improve quality of life (QOL) and preserve graft function in solid-organ transplant recipients. To meet the specific goals of the program, the Life Satisfaction Index and Transplant Care Index were designed to serve as composite measures for measuring transplant-specific QOL and the ability to care for a transplant, respectively. In this study, we analyzed self-reported health information to examine relationships between comorbidities and individual posttransplantation side effects, life satisfaction, and transplant care, defined by renal transplant recipients. Patients entered the TLC through self-referral or referral by a health professional. Included in the analysis were 3,676 TLC enrollees with a mean time since transplantation of 4.8 years. Comorbidities and adverse effects were common, with high blood pressure reported by 89% of respondents and unusual hair growth reported by 70%. Sexual dysfunction and headache had a greater impact on QOL than more common adverse effects, such as changes in body and facial shape, hirsutism, and tremor. Regression modeling was used to identify the most significant associations between QOL indices and structural (nonmedical), medical, and psychosocial factors. Greater life satisfaction was most strongly associated with being in control of one's health and living a normally active life with satisfying emotional relationships. Management of such clinical problems as adverse effects of medication and nonadherence should be informed by the patient's perspective. Clinicians should actively solicit information about physical activity, appearance concerns, side effects of medications, nonadherence, and sexual and relationship issues when evaluating renal transplant recipients.

Adult↗
PubMed2001

Building a clinical cardiothoracic surgical program: a multi-institutional model.

Building a multi-institutional cardiothoracic surgical program has the same guiding principles and values as a traditional single institutional program: ensuring high-quality patient care, training and fostering residents, recruiting and retaining quality faculty, and contributing to basic and clinical research. With a well-designed infrastructure and support system, this more complicated type of organization may permit academic cardiothoracic surgical programs to compete effectively and grow in a constantly changing economic and political environment.

Education, Medical, Graduate↗
PubMed2000

Consensus statement on the live organ donor.

OBJECTIVE: To recommend practice guidelines for transplant physicians, primary care providers, health care planners, and all those who are concerned about the well-being of the live organ donor. PARTICIPANTS: An executive group representing the National Kidney Foundation, and the American Societies of Transplantation, Transplant Surgeons, and Nephrology formed a steering committee of 12 members to evaluate current practices of living donor transplantation of the kidney, pancreas, liver, intestine, and lung. The steering committee subsequently assembled more than 100 representatives of the transplant community (physicians, nurses, ethicists, psychologists, lawyers, scientists, social workers, transplant recipients, and living donors) at a national conference held June 1-2, 2000, in Kansas City, Mo. CONSENSUS PROCESS: Attendees participated in 7 assigned work groups. Three were organ specific (lung, liver, and kidney) and 4 were focused on social and ethical concerns (informed consent, donor source, psychosocial issues, and live organ donor registry). Work groups' deliberations were structured by a series of questions developed by the steering committee. Each work group presented its deliberations to an open plenary session of all attendees. This information was stored and shaped into a statement circulated electronically to all attendees for their comments, and finally approved by the steering committee for publication. The term consensus is not meant to convey universal agreement of the participants. The statement identifies issues of controversy; however, the wording of the entire statement is a consensus by approval of all attendees. CONCLUSION: The person who gives consent to be a live organ donor should be competent, willing to donate, free from coercion, medically and psychosocially suitable, fully informed of the risks and benefits as a donor, and fully informed of the risks, benefits, and alternative treatment available to the recipient. The benefits to both donor and recipient must outweigh the risks associated with the donation and transplantation of the living donor organ.

Health Status↗
PubMed2000

Modulation of pulmonary NA+ pump gene expression during cold storage and reperfusion.

BACKGROUND: Reperfusion injury with pulmonary edema continues to be a major complication after lung transplantation. Alveolar fluid homeostasis is regulated by Na+/K+-ATPase activity on the basolateral surface of alveolar epithelial cells. Intact Na+/K+-ATPase is essential to the resolution of pulmonary edema. We characterized the effects of cold ischemia and reperfusion on expression of Na+/K+-ATPase mRNA and protein. METHODS: Baseline values for Na+/K+-ATPase mRNA and protein were determined from freshly harvested lungs with no cold storage time or reperfusion (group I). Group II lungs were analyzed after cold storage times of 12 or 24 hr without subsequent reperfusion. Group III lungs were analyzed after cold storage times of 12 or 24 hr with subsequent reperfusion. Lungs were flushed with either Euro-Collins (EC) or University of Wisconsin (UW) solution in each group. All samples were quantified for Na+/K+-ATPase mRNA and Na+/K+-ATPase protein. Physiological parameters including oxygenation and compliance were also measured. RESULTS: There were no significant differences in the level of mRNA and protein for samples that were cold stored without reperfusion (group II). With reperfusion (group III) there was a significant increase in the level of the Na+/K+-ATPase mRNA after 12 hr of storage for both EC and UW. After 24 hr of storage and subsequent reperfusion, lungs flushed with EC had significantly decreased Na+/K+-ATPase protein and mRNA, although lungs preserved with UW maintained their increased levels of Na+/K+-ATPase protein and mRNA. CONCLUSIONS: Our data suggest that ischemia-reperfusion injury results in an initial up-regulation of Na+/K+-ATPase mRNA. With prolonged injury in lungs preserved with EC, the level of the mRNA decreased with a corresponding decrease in the Na+/K+-ATPase protein. The different response seen in EC versus UW may be explained by better preservation of pump function with UW than EC and correlates with improved physiological function in lungs preserved with UW solution.

Adenosine↗
PubMed2000

Platelet activating factor acetylhydrolase decreases lung reperfusion injury.

BACKGROUND: Ischemia-reperfusion injury involves free radical production, polymorphonuclear neutrophil chemotaxis/degranulation, and production of proteolytic enzymes, complement components, coagulation factors, and cytokines. Activated polymorphonuclear neutrophils, endothelial cells, and macrophages produce platelet activating factor, which further promotes these inflammatory reactions. The recently cloned plasma form of platelet activating factor-acetylhydrolase (PAF-AH) demonstrates antiinflammatory effects by degrading platelet activating factor. We evaluated the effects of PAF-AH in an isolated perfused rat lung model by adding it to the flush solutions or to the reperfusion blood. METHODS: Rat lungs were isolated, flushed with EuroCollins (EC) or University of Wisconsin (UW) solution, stored at 4 degrees C for 6 or 12 hours, and reperfused using a cross-circulating syngeneic support rat. During reperfusion, oxygenation, compliance, and capillary filtration coefficient were calculated. There were four groups in the study; group I (control) had no PAF-AH added, group II had PAF-AH added to the flush solution, group III had PAF-AH added to reperfusion blood, and group IV had PAF-AH added to both flush solution and reperfusion blood. RESULTS: After 6 hours of storage, oxygenation, compliance, and capillary filtration coefficient significantly improved for EC in group IV. For UW, oxygenation improved in group IV whereas compliance improved in groups II, III, and IV. After 12 hours of storage, compliance improved for EC in group IV and capillary filtration coefficient improved in groups III and IV. For UW, oxygenation and compliance improved in groups II and IV, whereas capillary filtration coefficient improved in group IV. CONCLUSIONS: Addition of PAF-AH to intracellular organ preservation solutions and to the blood reperfusate significantly improves postreperfusion oxygenation and compliance, and reduces lung capillary permeability.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2000

Prophylactic photopheresis and chronic rejection: effects on graft intimal hyperplasia in cardiac transplantation.

BACKGROUND: Despite the decreased incidence of acute rejection episodes and improvements in short and intermediate term graft survival with current immunosuppressive agents, there has been little progress in decreasing the morbidity and mortality from chronic rejection. This phenomenon may, in part, be related to the development of a humoral immune response with increases in anti-HLA antibodies, which presents as accelerated graft arteriopathy with intimal hyperplasia. METHODS: Based on prior experimental work, a pilot, prospective, randomized study was performed in 23 primary cardiac transplant recipients to determine whether the addition of prophylactic photopheresis to a cyclosporine, azathioprine and prednisone regimen was safe and resulted in decreased levels of panel reactive antibodies (PRA) and transplant arteriopathy. RESULTS: There was no difference between the two groups in regard to infection or acute rejection incidence. The photopheresis group had a significant reduction in PRA levels at two time points within the first 6 postoperative months. Coronary artery intimal thickness was significantly reduced in the photopheresis group at 1-yr (0.23 vs. 0.49 mm, p < 0.04) and 2-yr (0.28 vs. 0.46 mm, p < 0.02) follow-up compared with the control group. CONCLUSION: In this small pilot study, photopheresis is a safe, well-tolerated immunomodulatory technique that is capable of decreasing the severity of chronic rejection manifesting as post-transplant graft intimal hyperplasia.

Adolescent↗
PubMed1999

A comparison of the new preservation solution Celsior to Euro-Collins and University of Wisconsin solutions in lung reperfusion injury.

BACKGROUND: The lung is particularly susceptible to reperfusion injury, both experimentally and clinically after transplantation. The extracellular-type preservation solution Celsior, which has been predominantly studied in cardiac preservation, has components designed to prevent cell swelling, free radical injury, energy depletion, and calcium overload. Using an isolated blood-perfused rat lung model, we investigated whether Celsior would decrease preservation injury and improve lung function after cold ischemic storage and reperfusion compared to Euro-Collins (EC) and University of Wisconsin (UW) solutions. METHODS: Lewis rat lungs were isolated, flushed with the respective cold preservation solution, and then stored at 4 degrees C for 6 or 12 hr. After ischemic storage, the lung block was suspended from a force transducer, ventilated with 100% O2, and reperfused for 90 min with fresh blood via a cannula in the pulmonary artery. Lung compliance, alveolar-arterial oxygen difference, and outflow oxygen tension were all measured. The capillary filtration coefficient (Kf), a sensitive measure of changes in microvascular permeability, was determined. RESULTS: For 6 hr of cold storage, lungs stored in Celsior had lower Kf values than those stored in EC, indicating decreased microvascular permeability. No other significant differences were noted between Celsior and EC or UW. For 12 hr of cold storage, Celsior provided increased oxygenation, decreased alveolar-arterial O2 differences, increased compliance, and decreased Kf values as compared to both EC and UW. CONCLUSIONS: Celsior provides better lung preservation than EC or UW as demonstrated by increased oxygenation, decreased capillary permeability, and improved lung compliance, particularly at 12-hr storage times. These results are highly relevant, inasmuch as EC and UW are the most common clinically used lung preservation solutions. Further studies of Celsior in experimental and clinical lung transplantation, as well as in other solid organs, are indicated.

Adenosine↗
PubMed1999

Addition of a water-soluble alpha-tocopherol analogue to University of Wisconsin solution improves endothelial viability and decreases lung reperfusion injury.

BACKGROUND: Reperfusion injury following lung preservation has been associated with free radical formation and subsequent endothelial cell damage. Trolox is a water-soluble analogue of the free radical scavenger alpha-tocopherol. We hypothesized that addition of this form of vitamin E to University of Wisconsin (UW) solution would decrease reperfusion injury and improve lung function after cold ischemic preservation. MATERIALS AND METHODS: Bovine aortic endothelial cells were cultured and stored at 4 degrees C for 12, 24, and 48 h in UW or UW + Trolox (UWT). Endothelial cell viability after storage was assessed by dimethylthiazole tetrazolium cytotoxicity assay. An isolated rat perfused lung (IPL) model was used and lungs were flushed with the respective solutions with cold storage times of 6 and 12 h. Following storage, the lungs were reperfused with fresh blood and lung function was assessed by blood gas analysis, alveolar-arterial gradient, and compliance. RESULTS: There was no difference in endothelial cell viability between UW and UWT after 12 or 24 h; however, UWT had higher endothelial cell viability than UW with 48 h of cold ischemic storage. Using the IPL model, the pO2 was higher with UWT than UW after 6 and 12 h of cold ischemia. The alveolar-arterial oxygen difference was significantly lower for UWT versus UW at 6 h. UWT provided increased compliance at 6 and 12 h of ischemia. CONCLUSIONS: The addition of a water-soluble vitamin E analogue to UW solution resulted in increased endothelial cell viability after prolonged storage and improved whole lung preservation in the postreperfusion period as evidenced by higher oxygenation and increased compliance. These results are clinically relevant as the lung is extremely sensitive to reperfusion injury and UW solution is being increasingly used in lung transplantation and remains the predominant solution in abdominal organ transplantation.

Adenosine↗
PubMed1999

Comparison of outcomes between living donor and cadaveric lung transplantation in children.

BACKGROUND: Long-term survival in lung transplant is limited by bronchiolitis obliterans (BOS). We compared outcomes in pediatric living donor bilateral lobar (LL) vs cadaveric lung transplant (CL). METHODS: Children were studied who had LL or CL with at least 1 year follow-up. Data collected included acute rejection episodes, pulmonary function tests (PFT), BOS, and survival. Mean age was 13.36+/-3.16 years in LL and 12.00+/-4.19 years in CL patients (p = 0.37, ns). RESULTS: There was no difference in rejection (p = 0.41, ns). CL had rejection earlier (2.48+/-3.84 months) than LL (13.60+/-10.74 months; p = 0.02). There was no difference in 12 month PFT. But at 24 months, LL had greater forced expiratory volume in 1 second (FEV1) (p = 0.001) and FEF25-71% (p = 0.01) than CL. BOS was found in 0/14 LL vs 9/11 (82%) CL after 1 year (p = 0.04). After 2 years, 0/8 LL and 6/7 (86%) CL had BOS (p < 0.05). LL had 85% survival vs 79% for CL at 12 months. At 24 months, LL survival was 77% vs 67% for CL. CONCLUSIONS: Pediatric LL had less BOS and better pulmonary function than CL. As BOS is a determinant of long-term outcome, we believe LL is the preferred lung transplant method for children.

Adolescent↗