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Biomedical subjects

J K Kirklin

Publications and source records attributed to J K Kirklin.

At least 37 records · Page 2Linked to original sources
PubMed2000

Enhanced allograft survival induced by posttransplant donor spleen cell infusion occurs via a mechanism that is distinct from the mechanism of enhancement by donor bone marrow.

BACKGROUND: Our previous studies have shown that the ability of donor bone marrow to augment skin graft survival in antithymocyte serum (ATS)-treated recipients is dependent on the presence of functional CD95-ligand (Fas-ligand) molecules on donor cells. Because donor spleen cells can augment graft survival to a similar degree in the same model, we investigated whether the donor spleen cell effect was also dependent on the presence of CD95-ligand on donor cells and CD95 on recipient cells. METHODS: Mutant mice bearing defects in the expression of CD95 (lpr mutation) and CD95-ligand (gld mutation) were used as recipients and cell donors, respectively. Recipients were injected with rabbit ATS on days -1 and +2, and then were injected with 5x10(7) spleen cells on day +7. Skin graft survival was compared and correlated with the use of mutant mice as recipients and cell donors. RESULTS: The combination of ATS and infusions of wild-type [median survival (MST)=44 days, P=0.0004] and gld (mutant CD95-ligand, MST=37 days, P=0.02) donor spleen cells enhanced C3H graft survival, compared with (C57BL/6 x A)F1 recipients treated with ATS alone (MST=27 days). Furthermore, C57BL/6 lpr (CD95-deficient) strain recipients treated with ATS and donor spleen cells demonstrated enhanced B10.D2(R107) strain skin graft survival (MST=44 days, P=0.003), compared with C57BL/6 lpr recipients treated with ATS alone (MST=31 days). Wild-type C57BL/6 recipients treated in the same manner also exhibited an extension of graft survival (MST=64 days) versus controls treated with ATS alone (MST=31 days). CONCLUSION: The data demonstrate that the ability of donor spleen cells to augment allograft survival is not dependent on the CD95/CD95-ligand pathway; therefore the deletion of allospecific cells by donor spleen cells may be induced via a pathway other than deletion by donor bone marrow cells.

Animals↗
PubMed2000

Right thoracotomy for mitral reoperation: analysis of technique and outcome.

BACKGROUND: This report describes technical details of the right thoracotomy approach for mitral surgery, and analyzes our experience with this procedure for patients with a prior sternotomy. Three methods for myocardial management (hypothermic cardioplegic arrest, beating heart, and fibrillating heart) are compared. METHODS: Records were abstracted of patients who had a right thoracotomy between January 1, 1992 and July 1, 1999 for mitral surgery after at least one prior sternotomy. Demographic, operative, and outcome data were collected for analysis. Telephone follow-up was used to measure postoperative New York Heart Association functional status. RESULTS: Eighty-four patients (mean age 60 +/- 15 years) had reoperative mitral surgery via a right thoracotomy. Myocardial management included ventricular fibrillation in 10 patients, operation on the beating heart in 58 patients, and hypothermic blood cardioplegia arrest in 16 patients. The mean time in the operating room was 185 +/- 73 minutes, and the mean duration of cardiopulmonary bypass was 63 +/- 56 minutes. There were no perioperative strokes and the prevalence of death for patients who received cardioplegic arrest was significantly higher than the prevalence of death for patients who had mitral surgery with perfused fibrillating or beating heart techniques (p = 0.007; Fisher's exact test comparing risk-unadjusted mortality). CONCLUSIONS: Right thoracotomy provides efficient exposure for reoperative mitral surgery. Mitral valve procedures on the fibrillating or beating heart are feasible in most patients and are at least as safe as surgery using cardioplegic arrest.

Adult↗
PubMed2000

The utility of open lung biopsy following lung transplantation.

BACKGROUND: Most pulmonary complications associated with lung transplantation have non-specific clinical characteristics. Furthermore, common diagnostic modalities, including bronchoscopy with transbronchial biopsy (TBB), often do not render a definitive diagnosis. In this study, we reviewed our experience with open lung biopsy (OLB) following lung transplantation, specifically regarding its ability to safely provide clinically relevant information that affects therapeutic decisions. METHODS: From October 1989 to March 2000, 202 patients underwent lung transplantation at our institution. We reviewed the clinical course of the 42 patients who received 48 OLBs. Of these patients, we determined the pre-operative clinical condition, preceding TBB histologic information, OLB histology, treatment changes, and procedural complications as a result of the OLB. RESULTS: A new, clinically unsuspected diagnosis was made in 14 biopsies (29% of all OLB), and all of these resulted in therapy changes. Thirty-two biopsies (67% of all OLB) confirmed our clinical suspicions, and new therapy was initiated in 30 of these patients. Two patients (4% of all OLB) had non-diagnostic OLB. Four biopsies (8% of all OLB), including the 2 non-diagnostic OLBs, did not result in any therapy changes or initiation of new therapy. Complications occurred in 3 patients, all of whom had an air leak for >7 days. CONCLUSION: Open lung biopsy in lung transplant patients renders a new, unsuspected diagnosis in nearly one third of patients and leads to specific, directed therapy in the vast majority of patients. Open-lung biopsy can be performed safely and should be considered when diagnosis is uncertain in clinically deteriorating patients.

Biopsy↗
PubMed2000

Neuropsychological functioning among heart transplant candidates: a case control study.

Neuropsychological performance was examined among a group of patients with end-stage heart disease undergoing routine evaluation for transplantation using a matched case-control design. Heart transplant candidates and controls were matched case by case for gender, race, education and age range. In order to match all 44 controls, a clinical series of 303 heart transplant candidates evaluated between October 1995 through March 1998 were considered. Although not specifically matched on variables of estimated IQ and socioeconomic status, statistical analysis showed no group differences on these variables. A separate analysis of variance on each neuropsychological test indicated that the heart transplant candidates performed significantly worse than controls on tasks of fine motor speed and dexterity (i.e., Grooved Peg Board), psychomotor speed and mental flexibility (i.e., Trail Making Test, Part B), and abstract reasoning and problem solving ability (i.e., Shipley Institute of Living Scale-Abstraction subtest). Implications of the results and future directions are discussed.

Adult↗
PubMed2000

31P-magnetic resonance spectroscopy studies of cardiac transplant patients at rest.

Studies in animal models and patients have suggested that 31P-magnetic resonance spectroscopy (MRS) may be useful in diagnosing transplant rejection, but such studies often are confounded by the late inclusion of patients after transplantation. The present study examined the utility of 31P-MRS in the diagnosis of acute allograft rejection during the first posttransplant month. Thirteen recent heart transplant recipients underwent 57 resting 31P-MRS studies within 24 hr of a biopsy. Subjects lay supine with a 10-cm surface coil placed over the heart. A 1-dimensionsal chemical shift imaging protocol was used to collect spectral information. Spectra from the heart were weighted for distance from the coil and summed before analysis. ANOVA and Duncan's multiple range test were used to analyze the data comparing phosphocreatine (PCr)/ATP ratios with biopsy scores. Transplant patients had significantly lower myocardial PCr/ATP ratios when compared with a normal control group (1.27 +/- 0.27 versus 1.61 +/- 0.22, p < 0.001). However, when the patient group was classified by biopsy score, the expected order of score, 0 > 1 > 2 > 3, was not obtained. Rather, the order was 2 > 0 > 1 > 3. Although the difference between scores 2 and 3 was significant (1.46 versus 1.14, alpha = 0.05 level), the lower three groups were statistically indistinguishable. In addition, the PCr/ ATP ratios were not predictive of future biopsies. Although significantly lower than normal control subjects, resting myocardial PCr/ATP ratios of transplant subjects are not useful in assessing thelevel of rejection. It is suggested that the measurement may be more predictive in mildly exercised myocardium.

Adenosine Triphosphate↗
PubMed1999

Infection during circulatory support with ventricular assist devices.

BACKGROUND: This study is a retrospective analysis of infections in patients supported by ventricular assist devices (VADs) as a bridge to cardiac transplantation. METHODS: Infections were assigned to four classes. Class I were patient-related nonblood infections, class II were blood-borne infections, class III were percutaneous site infections, and class IV were infections of intracorporeal VAD components. RESULTS: The cumulative number and incidence of infections were higher during the early VAD experience than in more recent patients (p < 0.05), although the cumulative number and incidence of class II and IV infections were similar in earlier and later patients. There were 28 serious (ie, class II and IV) infections in 9 patients who died, and 35 serious infections in 11 patients who survived until transplantation. Three of 4 patients with class IV infections died. A larger cumulative number of infections (ie, total class I-IV) was associated with more fungal isolates (p < 0.001) and more class II and IV infections (p < 0.02). Positive fungal cultures were obtained in 16 patients, but there were only 3 class III and 1 class IV fungal isolates. CONCLUSIONS: Infection remains an important problem for patients with VADs. Bloodstream infections (class II) can often be controlled by appropriate therapy. However, intracorporeal device infections (class IV) are associated with substantial morbidity and mortality. Optimal implant techniques together with optimal wound care, appropriate use of prophylactic antibiotics, and avoidance of infection in indwelling catheters remain the most practical means for minimizing the risk of VAD infection.

Adult↗
PubMed1999

Management of wound and left ventricular assist device pocket infection.

Our patient developed a wound infection that involved an implanted left ventricular assist device. At surgery, the pump was washed with a detergent-containing bacteriocidal solution, then antibiotic-impregnated polymethylmethacrylate beads were placed around the pump. The wound was revised using rectus muscle to cover the pump. The incisions have healed and the patient is now at home. She is on no systemic antibiotics and has no evidence of infection 11 months postoperatively.

Adult↗
PubMed1999

Control of the inflammatory response in extended myocardial preservation of the donor heart.

The damaging effects of inflammation after prolonged myocardial ischemia are typically manifest during the period of reperfusion. The imbalance between free radical generation and availability of natural free radical scavengers during postischemic reperfusion set the stage for free radical injury. Calcium overload may convert reversible ischemic damage to fatal myocyte contracture. Complement activation and neutrophil activation, adhesion, and diapedesis are central components of the damaging inflammatory response. Cytokines such as tumor necrosis factor and IL1 simulate IL8 synthesis which is also a potent chemoattractant for neutrophils. The endothelial contribution to ischemic-reperfusion injury results from an imbalance between the production of naturally occurring vasodilators, such as prostacycline and nitric oxide, and vasoconstrictor products, such as endothelin, thromboxane A2, and angiotensin 2. Knowledge of these basic mechanisms has stimulated the formulation of preservation solutions and strategies to ameliorate the inflammatory response during reperfusion.

Animals↗
PubMed1999

Determinants of waiting time for heart transplants in the United States.

BACKGROUND: Reports have been published on factors affecting the variations in waiting times for kidney and liver transplant candidates who have been registered on the United Network for Organ Sharing's waiting list. This study reports on determinants of waiting time differences that occur in the eleven UNOS regions for heart transplant candidates. METHODS: Retrospective analysis of 11,345 primary heart waiting-list registrations and 15,868 cadaveric donors, from whom 7,043 hearts were recovered and transplanted for the years 1994-96. Because estimated populations in the eleven UNOS regions vary from 10.8 to 43.2 million, analyses utilized Registrations/million population and Transplants/million population to obtain an R/T ratio. The relationship of the R/T ratio to the median waiting time was then examined for different demographic variables. RESULTS: The numbers of new heart candidate registrations, heart transplants performed, and waiting list deaths have undergone little change from 1991 through 1996. National median waiting times varied by basic demographic variables such as ABO blood type, race, age group, and UNOS medical urgency status. In the eleven UNOS regions, registrations per million ranged from 11.5 to 33.0 and transplants per million from 5.3 to 10.7. Registration/Transplant ratios correlated with median waiting times for urgency Status 1 and 2 as well as for blood group O recipients. Correlation with blood type AB recipients was less consistent, in part, due to the small number of AB recipients. CONCLUSIONS: There are wide variations in the number of heart transplant candidate registrations and in the number of heart transplants performed in the eleven UNOS regions. The registration to transplantation ratio correlated with median waiting times in these regions. Factors possibly contributing to the observed variations were examined.

Adolescent↗
PubMed1999

Nonpharmacologic validation of the intrinsic heart rate in cardiac transplant recipients.

BACKGROUND: The maximum sinus rate during exertion in humans is inversely related to age. However, the sinus rate at rest is quite variable. The intrinsic heart (IHR) following pharmacologic blockade of autonomic tone with propranolol and atropine has been proposed as a test of sinus node function and is related to age by the linear regression equation: IHR = 118.1 - (0.57 x age). Whether this relationship exists for transplanted hearts for which the donor sinus node is denervated has not been determined. METHODS: The relationship between the resting heart rate and the age of the donor heart was examined in 103 patients 1 year following orthotopic cardiac transplantation in the absence of rejection or intercurrent illness. Patients receiving beta-blockers, calcium blockers, antiarrhythmic drugs, digitalis, theophylline, or with biopsy evidence of rejection or abnormal coronary arteriograms were excluded from analysis. RESULTS: The recipient age, left ventricular ejection fraction, pulmonary capillary pressure, cardiac index, donor heart ischemic time and cardiopulmonary bypass time did not correlate with the rate of the resting donor sinus node. The resting heart rate was inversely related to age of the donor heart by the linear regression equation: HR = 112.0 - (046 x age). CONCLUSION: The resting rate of the denervated sinus node is related to donor age with a regression equation that is similar, though slightly slower, than that predicted after pharmacologic autonomic blockade.

Adolescent↗
PubMed1998

Gene polymorphisms for plasminogen activator inhibitor-1/tissue plasminogen activator and development of allograft coronary artery disease.

BACKGROUND: Impaired fibrinolytic activity has been linked to the presence and severity of allograft vasculopathy (Tx CAD). This impairment may be associated with the presence of certain fibrinolytic protein gene polymorphisms. METHODS AND RESULTS: To investigate the relation between donor-specific fibrinolytic protein genotypes and Tx CAD, we identified donor plasminogen activator inhibitor-1 (PAI-1) HindIII and tissue plasminogen activator (TPA) EcoRI restriction fragment length polymorphisms-based genotypes by Southern blot analysis in 48 recipients of cardiac allografts and correlated these genotypes with the development of CAD. No association was found between donor TPA genotypes and the presence of Tx CAD. Among the 48 patients, 17% were homozygous for the 1/1 PAI-1 genotype, 51% for the 2/2 PAI-1 genotype, and 32% for the 1/2 PAI-1 genotype. The actuarial freedom from any CAD for the recipients with each respective donor PAI-1 genotype at 12 and 24 months was 100% and 100% for the 1/1 PAI-1 genotype, 92% and 92% for the 1/2 PAI-1 genotype, and 75% and 45% for the 2/2 PAI-1 genotype (P=0.03). Recipients with a diseased 2/2 PAI-1 genotyped allograft had longer ischemic times (P=0.02) than those recipients with a Tx CAD-free allograft. CONCLUSIONS: These data suggest that recipients with a 2/2 PAI-1 genotype are at a significant risk of developing Tx CAD. This genotype may serve as a useful screening tool for predicting the future development of Tx CAD.

Adult↗
PubMed1998

A prospective algorithm for the management of air leaks after pulmonary resection.

BACKGROUND: Air leaks (ALs) are a common complication after pulmonary resection, yet there is no consensus on their management. METHODS: An algorithm for the management of chest tubes (CT) and ALs was applied prospectively to 101 consecutive patients who underwent elective pulmonary resection. Air leaks were graded daily as forced expiratory only, expiratory only, inspiratory only, or continuous. All CTs were kept on 20 cm of suction until postoperative day 2 and were then converted to water seal. On postoperative day 3, if both a pneumothorax and AL were present, the CT was placed to 10 cm H2O of suction. If a pneumothorax was present without an AL, the CT was returned to 20 cm H2O of suction. Air leaks that persisted after postoperative day 7 were treated with talc slurry. RESULTS: There were 101 patients (67 men); on postoperative day 1, 26 had ALs and all were expiratory only. Univariable analysis showed a low ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) (p = 0.005), increased age (p = 0.007), increased ratio of residual volume to total lung capacity (RV/TLC) (p = 0.04), increased RV (p = 0.02), and an increased functional residual capacity (FRC) (p = 0.02) to predict the presence of an AL on postoperative day 1. By postoperative day 2, 22 patients had expiratory ALs. After 12 hours of water seal, 13 of the 22 patients' ALs had stopped, and 3 more sealed by the morning of postoperative day 3. However, 2 of the 6 patients whose ALs continued experienced a pneumothorax. Five of the 6 patients with ALs on postoperative day 4 still had ALs on postoperative day 7, and all were treated by talc slurry through the CT. All ALs resolved within 24 hours after talc slurry. CONCLUSIONS: Most ALs after pulmonary resection are expiratory only. A low FEV1/FVC ratio, increased age, increased RV/TLC ratio, increased RV, and an increased FRC were predictors of having an ALs on postoperative day 1. Conversion from suction to water seal is an effective way of sealing expiratory AL, and pneumothorax is rare. If an expiratory AL does not stop by postoperative day 4 it will probably persist until postoperative day 7, and talc slurry may be an effective treatment.

Adult↗
PubMed1998

The relationship between cardiac function and neuropsychological status among heart transplant candidates.

BACKGROUND: Cognitive deficits among heart transplant candidates have been well documented. This study was designed to examine the hypothesis that impaired cognitive test performance among heart transplant candidates may be attributed, in part, to decreased cerebral perfusion secondary to poor cardiac function. METHODS AND RESULTS: Sixty-two patients participated in the study who underwent heart catheterization within 1 day of completing a battery of cognitive tests. Multiple demographic and patient characteristics were examined for their potential moderating role in the relationship between measures of cardiac function and cognitive performance including age, education, race, gender, psychiatric history, medication usage, cardiac surgical history, and self-reported symptoms of depression and anxiety. Only age and education were significantly related to cognitive performance (P < .01). Thus, partial correlation analyses controlling for age and education were used to examine the relationship between cardiac function and cognitive performance. In general, increasing hemodynamic pressure variables (ie, pulmonary artery pressure and right atrial pressure), and to a lesser extent cardiac output and cardiac index, were related (r = - .32 to - .43; P < .01) to decreased performance on cognitive tasks that assessed simple attention, speed of mental processing, and mental flexibility (Digit Span-Forward, Trail Making Test-Part B, Symbol Digits Modalities Test, and Stroop Neuropsychological Screening Test). Left ventricular ejection fraction, systemic and pulmonary vascular resistance, and mean arterial pressure were largely unrelated to cognitive performance in this sample of patients with end stage cardiac disease. CONCLUSIONS: Hemodynamic pressure variables seem to be most consistently related (ie, inversely) to cognitive functioning among heart transplant candidates.

Cognition Disorders↗
PubMed1998

An essential role for Fas ligand in transplantation tolerance induced by donor bone marrow.

Medawar and co-workers originally demonstrated that injection of donor bone marrow (DBM) into immuno-incompetent neonatal rodents could induce tolerance to grafts from animals of the same strain as the bone marrow donor. Induction of tolerance in this manner can also be accomplished in mature mice, dogs and monkeys if the resident T-cell populations in the recipient are depleted by a polyclonal antithymocyte globulin or an anti-T cell immunotoxin. The molecular mechanisms by which bone marrow cells mediate the induction of tolerance remain uncertain. Here we examined a well-established adult mouse model of antithymocyte globulin and DBM treatment and show that expression of functional Fas ligand (FasL, also CD95L) on the injected bone marrow cells is required for tolerance induction. The results indicate that a state of microchimerism per se is insufficient for the induction of tolerance in T cell-depleted transplant recipients. Moreover, the results are consistent with the hypothesis that tolerance induced by DBM involves an apoptotic process leading to deletion of graft-reactive cells.

Animals↗
PubMed1998

Risk of death or incapacitation after heart transplantation, with particular reference to pilots.

Pilots who have received a heart transplant may subsequently want to resume flying. This study was undertaken to determine whether a group of heart transplant recipients who had a particularly low risk of sudden unexpected death could be identified from clinical data. An event, "rapid-onset death," was defined incorporating a number of possible causes of death that could result in a heart transplant recipient-pilot losing control of an airplane. The survival of 3676 patients undergoing a first heart transplantation was 85% and 73% at 1 and 5 years, respectively, the hazard function having a high early phase of risk. When time zero was moved to the beginning of the second year after transplantation, the freedom from "rapid-onset death" at posttransplantation year 2 and posttransplantation year 5 was 96.8% and 88%, respectively. For patients who had both a "normal" coronary angiogram and no episodes of acute heart rejection during the first year transplantation, the probability of "rapid onset death" during the second posttransplantation year was 1.4%, and given the same circumstances, during the third posttransplantation year the risk of "rapid-onset death" was 1.6%. This information is potentially useful to the Federal Aviation Administration for policy decisions regarding this issue.

Adolescent↗
PubMed1998

Heart transplant coronary artery disease detected by coronary angiography: a multiinstitutional study of preoperative donor and recipient risk factors. Cardiac Transplant Research Database.

BACKGROUND: Controversy exists regarding donor and recipient factors that promote the development and progression of coronary artery disease after heart transplantation and the likelihood of coronary artery disease causing death or retransplantation. METHODS: To investigate this issue in a large cohort of patients, we analyzed 5963 postoperative angiograms performed in 2609 of the 3837 patients undergoing heart transplantation at 39 institutions between January 1990 and December 1994. Coronary artery disease was classified as mild, moderate, or severe on the basis of left main involvement, primary vessel stenoses, and branch stenoses. Coronary artery disease was considered severe if left main stenosis was > 70% or 2 or more primary vessels stenoses were > 70% or branch stenoses were > 70% in all 3 systems. RESULTS: By the end of 5 years after heart transplantation, coronary artery disease was present in 42% of the patients, mild in 27%, moderate in 8%, and severe in 7%. Coronary artery disease-related events (death or retransplantation) had an actuarial incidence of 7% at 5 years and occurred in 2 of 3 of the patients with development of angiographically severe coronary artery disease. By multivariable logistic analysis, risk factors for donor coronary artery disease included older donor age (P < .0001) and donor hypertension (P=.0002). By multivariable analysis in the hazard function domain, risk factors identified for the earlier onset of allograft coronary artery disease included older donor age (P < .0001 ), donor male sex (P=.0006), donor hypertension (P=.07), recipient male sex (P=.02), and recipient black race (P=.01). The actuarial incidence of severe coronary artery disease was 9% at 5 years. CONCLUSIONS: Angiographic coronary artery disease is very common after heart transplantation, occurring in approximately 42% of the patients by 5 years. Older donor age, donor hypertension, and male donor or recipient predict earlier onset of angiographic allograft coronary artery disease. Although severe angiographic allograft coronary artery disease occurs in only 7% of the patients at 5 years, its presence is highly predictive of subsequent coronary artery disease-related events or retransplantation.

Adolescent↗