Biomedical subjects

R D Davis

Publications and source records attributed to R D Davis.

At least 91 records · Page 5Linked to original sources

PubMed1997

Radiologic issues in lung transplantation for end-stage pulmonary disease.

Lung transplantation has evolved into an effective therapy for end-stage pulmonary disease. The radiologist has an important role in the management of these patients before and after transplantation. Unfortunately, the radiologic findings of the major complications (i.e., reperfusion edema, infection, rejection) that occur after transplantation overlap and are often nonspecific. Clinical correlation, bronchoalveolar lavage, and transbronchial biopsy are usually required for accurate differentiation. The following rules of thumb may be helpful: Radiographic opacities seen during the first week are usually due to reperfusion edema: persistent or progressive opacities beyond the first week suggest infection or acute rejection: infection in the first month is usually bacterial, and opportunistic pneumonia is more common thereafter, nodular opacities are usually due to infection or posttransplantation lymphoproliferative disorders but can also be due to transbronchial lung biopsy; and progressive bronchial dilatation and air trapping seen on expiratory CT are useful signs of BOS.

Humans↗

PubMed1997

Endotoxin concentration in contact lens storage cases.

BACKGROUND: The contamination of contact lens storage cases by gram-negative bacteria has been associated with ulcerative keratitis. This study investigated the concentration of endotoxin, a substance produced by gram-negative bacteria, in contact lens cases. METHODS: The limulus amebocyte lysate (LAL) test was used to measure the concentration of endotoxin in the storage cases of 27 contact lens wearers. The units of concentration used were endotoxin units per ml (EU/ml). The type of storage solution used by each patient, as well as other aspects of lens care and use, were recorded. RESULTS: Twenty-one storage cases--78% of those tested--contained measurable amounts of toxin. Two cases contained extremely high concentrations of endotoxin: 60 EU/ml and 300 EU/ml. Both cases were from persons using Opti-Free. Cases from six persons using Opti-Free accounted for five of the top seven endotoxin concentrations when cases were ranked on that basis. Fewer hours of daily lens wear and lower lens age were also possibly associated with higher concentrations of endotoxin, although those associations may have resulted by chance (p = 0.057 and p = 0.095, respectively). CONCLUSIONS: The LAL test was useful in estimating the degree of contamination of cases by gram-negative bacteria. Most cases contained measurable amounts of endotoxin, indicating at least some contamination by gram-negative bacteria. The effectivity of Opti-Free in inhibition of bacterial growth in contact lens cases should be investigated further.

Biofilms↗

PubMed1997

An adult canine model of chronic pulmonary hypertension for cardiopulmonary transplantation.

BACKGROUND: This study establishes a chemically-induced canine model of chronic pulmonary hypertension (CPH) using monocrotaline pyrrole (MCTP) and then characterizes this model in terms of hemodynamic, morphologic, and cardiac functional changes. METHODS: Thirty-three adult mongrel dogs (22 to 25 kg) were used. All animals underwent pulmonary artery catheterization to measure central venous pressure, mean right ventricular pressure (mRVP), mean pulmonary artery pressure (mPAP), and pulmonary capillary wedge pressure before and 6 weeks after a right atrial injection of either 60 mg/kg monocrotaline (group A, n = 8), 5 mg/kg MCTP (group B, n = 4), 3 mg/kg MCTP (group C, n = 13) or placebo (control, n = 8). Six weeks after injection, hearts in control and group C dogs were instrumented with flow probes, dimension transducers, and micromanometers to measure dynamic ventricular pressures and volumes. RESULTS: No significant differences in baseline hemodynamic indexes were observed between groups. All animals in group B and five in group C died after MCTP injection as a result of pulmonary edema. No significant increase in any hemodynamic parameters occurred in group A or in control dogs 6 weeks after injection. In group C, significant increases in central venous pressure, mRVP, and mPAP were observed 6 weeks after injection. Significant increases in right ventricular (RV) function and the weight ratio of the RV to left ventricle were observed in group C when compared with controls. CONCLUSIONS: A chemically-induced canine model of CPH has been created. Significant increases in mRVP, mPAP, and pulmonary capillary wedge pressure were observed 6 weeks after MCTP injection. RV function adapts to the increased afterload in the short term without evidence of failure. A stable model of pulmonary hypertension is provided as a potential means to evaluate posttransplantation RV dysfunction in the setting of CPH.

Age Factors↗

PubMed1997

Effects of nitric oxide after cardiac transplantation in the setting of recipient pulmonary hypertension.

BACKGROUND: Recipient pulmonary hypertension secondary to chronic congestive heart failure is a significant risk factor for right ventricular failure after cardiac transplantation. In this study, the hemodynamic and inotropic effects of nitric oxide (NO) were examined after bicaval cardiac transplantation in the setting of monocrotaline pyrrole-induced recipient chronic pulmonary hypertension. METHODS: Twenty dogs underwent 10 successfully completed transplantation experiments. Recipients underwent pulmonary artery injection of 3 mg/kg monocrotaline pyrrole 4 months before transplantation. Measurements were taken 1 hour after cessation of cardiopulmonary bypass and after NO inhalation. Pulmonary vascular impedance was calculated using Fourier analysis, and cardiac function was assessed with load-insensitive means (preload recruitable stroke work). RESULTS: At the time of transplantation, the precardiopulmonary bypass levels of pulmonary vascular resistance in recipient animals were significantly greater when compared with donor levels, and were further significantly increased after cardiopulmonary bypass. Three recipients died after transplantation secondary to acute right ventricular failure. In the surviving animals, NO led to significant improvements in pulmonary vascular resistance and vascular impedance, which occurred in association with significant increases in transpulmonary efficiency. No significant changes were observed in right and left ventricular preload recruitable stroke work after NO inhalation. CONCLUSIONS: These data suggest that NO may be an effective means to improve vascular impedance and pulmonary vascular efficiency after cardiac transplantation in the setting of recipient chronic pulmonary hypertension.

Animals↗

PubMed1996

Effect of perfusion pressure on cerebral blood flow during normothermic cardiopulmonary bypass.

BACKGROUND: We have recently shown that during hypothermic cardiopulmonary bypass (CPB), cerebral autoregulation has a positive slope such that for every 10 mm Hg change in pressure, a 0.86 mL.100 g-1.min-1 change in cerebral blood flow (CBF) is predicted. The purpose of this study was to define the influence of mean arterial blood pressure (MAP) on CBF during normothermic CPB. METHODS AND RESULTS: CBF was measured by use of 133Xe washout and alpha-stat blood gas management during nonpulsatile CPB. CBF measurements were made at a pump flow of 2.4 L.min-1.m-2 at stable normothermia and approximately 15 minutes later after the MAP was increased or decreased > or = 20%. A third data set was recorded after the pressure was returned to the initial value. Forty-five patients were entered into the study. Temperature was held constant. We found a significant effect (P = .016) of change in MAP on change in CBF during normothermic CPB. For a 10 mm Hg increase in MAP, an increase in CBF of 1.78 mL.100 g-1.min-1 is predicted. Along with change in CBF, significant increases in both cerebral metabolic rate and cerebral oxygen delivery were observed. CONCLUSIONS: This information, along with our previous data shows that autoregulation during CPB has a positive slope that is greater with normothermia than hypothermia. Although it is unlikely that these small changes in flow are an important primary effect in the development of hypoperfusion, increased metabolic rate with increased CBF may indicate pressure-dependent collateral flow potentially in regions embolized during CPB.

Adult↗

PubMed1996

Extracellular superoxide dismutase transgene overexpression preserves postischemic myocardial function in isolated murine hearts.

BACKGROUND: Myocardial injury after ischemia and reperfusion may be mediated, at least in part, by oxygen-derived free radicals; this supposition is supported by the observation that significant quantities of these radicals are generated during reperfusion. To directly assess the protective effect of extracellular superoxide dismutase (EC-SOD), this study was designed to investigate the ability of EC-SOD overexpression in the hearts of transgenic mice to protect myocardial tissue against ischemiareperfusion injury by use of an isolated work performing murine heart preparation and functional analysis. METHODS AND RESULTS: Ten transgenic mice (EC.SOD, 28 to 31 g) were studied and compared with 10 control mice (Ctl, 28 to 31 g) in terms of preischemic and postischemic myocardial function. All hearts underwent cardiac harvest and arrest, followed by instrumentation and subsequent reperfusion with warm Krebs-Henseleit solution. Preload-dependent functional analysis was then performed to evaluate cardiac output, contractility (dP/dt), heart rate, stroke work, and stroke volume before and after a 7-minute period of warm ischemia. Results are expressed as mean +/- SEM (ANOVA, paired unpaired t tests). There was no significant difference in preischemic myocardial performance for Ctl and EC-SOD mice. After warm ischemia, cardiac output in EC-SOD was significantly improved compared with Ctl (EC-SOD, 4.55 +/- 0.37 mL/min; Ctl, 2.55 +/- 0.28 mL/min; P < .05). Postischemic dP/dt, stroke work, and stroke volume were also significantly improved in EC-SOD compared with Ctl mice (EC-SOD, 1808 +/- 39 mm Hg/s, 745 +/- 67 dyne.cm, and 13.1 +/- 1.2 microL, respectively; Ctl, 1497 +/- 87 mm Hg/s, 472 +/- 83 dyne.cm, and 8.2 +/- 1.5 microL; P < .05). CONCLUSIONS: EC-SOD overexpressed mice showed significant improvement in postischemic cardiac function compared with Ctl mice. Thus, EC-SOD overexpressed hearts are less susceptible to mild degrees of ischemia-reperfusion injury than normal hearts.

Animals↗

PubMed1996

Brain death further promotes ischemic reperfusion injury of the rabbit myocardium.

BACKGROUND: Little is known about preload-dependent cardiac function after brain death (BD) and subsequent graft preservation. METHODS: A validated model of BD in rabbits was developed and myocardial performance was studied after BD induction and 1 hour of subsequent global hypothermic ischemia using a validated rabbit model and an isolated work-performing heart preparation. RESULTS: Significant decreases in stroke work, left ventricular contractility, and left ventricular relaxation were observed 2 hours after BD. After global hypothermic ischemia, significant decreases in stroke work, left ventricular contractility, and left ventricular relaxation were observed in the BD group compared with controls. Cardiac output and coronary flow were also significantly decreased in BD hearts compared with controls. Creatine kinase release was increased by 32.5% in BD hearts compared with controls. CONCLUSIONS: In a rabbit model, BD combined with global hypothermic ischemia causes a significant decrease in left ventricular function compared with global hypothermic ischemia. This dysfunction may be attributed to a significant decrease in coronary flows in BD hearts.

Animals↗

PubMed1996

Survival benefits of heart and lung transplantation.

OBJECTIVE: Heart and lung transplantation has gained acceptance as therapy for end-stage cardiac and pulmonary failure. The early and intermediate survival benefits of one center's 10-year experience with 177 patients undergoing thoracic transplantation were examined. SUMMARY BACKGROUND DATA: As experience in cardiac and pulmonary transplantation has increased, improvements in patient selection, organ preservation, preoperative support, and perioperative care have significantly reduced the early threats to patient survival. Graft dysfunction due to chronic rejection appears to be the main risk for longer-term survival, and data compiled by the United Network for Organ Sharing (UNOS) indicate a 70% 5-year survival for heart transplants and a 50% 5-year survival for lung transplant recipients. METHODS: The medical records of 120 heart recipients, 52 lung transplant recipients, and 5 heart-lung recipients were reviewed. Cumulative survival estimates were made using Kaplan-Meier analysis. The etiologies of operative and long-term mortality in each transplant population were identified. A comparison of long-term survival after heart transplantation versus coronary revascularization in a group of patients with ischemic cardiomyopathy was performed. RESULTS: Operative mortality in both the cardiac and pulmonary transplant recipients was 8%. From 1990 to 1995, 70 consecutive adult cardiac transplant procedures were performed without an operative mortality. Three of five patients survived heart-lung transplantation. The extended actuarial survival rate at 5 years was 80% for the cardiac transplant recipients. The 2-year actuarial survival rate for the lung transplant recipients was 88%. Graft dysfunction was the most common cause of operative mortality in the heart transplant group whereas infection was responsible for most of the operative mortality after lung transplantation. CONCLUSIONS: Cardiac and pulmonary transplantation can be applied to morbidly ill patients with excellent operative and intermediate-term survival.

Adolescent↗

PubMed1996

Fungal infections in lung and heart-lung transplant recipients. Report of 9 cases and review of the literature.

We reviewed the pattern and incidence of fungal infections in patients undergoing lung and heart-lung transplantation at Duke University Medical Center from September 1992 until August 1995, and present here 9 illustrative cases. Of the 73 lung and heart-lung transplant recipients studied, 59 (81%) had positive fungal cultures at some point after transplantation. The cases presented here illustrate that lung transplant recipients are predisposed to a wide variety of fungal infections. The clinical pattern of these infections ranges from asymptomatic to rapidly progressive fatal disease. In addition to the reactivation of previous fungal infections and recent exposure to new environmental sources, the donor lung itself can be the source of fungal infection, as we showed by using molecular epidemiology techniques. Because of the associated morbidity and mortality, efforts should be directed at investigating prophylactic antifungal regimens in lung transplant recipients. Preliminary reports on the use of itraconazole and aerosolized amphotericin B have been encouraging. Prospective randomized studies are needed to assess the safety and cost effectiveness of different regimens. Fungal infections in patients after lung transplantation can significantly impede recovery and lead to substantial mortality.

Adult↗

PubMed1996

Delayed right heart failure following lung transplantation.

Dynamic right ventricular outflow tract obstruction (RVOTO) has been reported following lung transplantation for pulmonary hypertension, usually in association with the use of inotropic agents. This report describes delayed severe right-sided heart failure associated with right ventricular outflow tract obstruction following sequential bilateral lung transplantation and closure of a ventricular septal defect. The patient had no evidence of outflow tract obstruction in the early posttransplant period but developed progressive right heart failure more than 2 months later. Catheterization revealed dynamic RVOTO and an elevated right ventricular end-diastolic pressure. The patient was treated with metoprolol tartrate and diltiazem hydrochloride with resolution of the outflow tract obstruction and heart failure. This case demonstrates that RVOTO can occur in the late posttransplant period and must be included in the differential diagnosis for patients who develop right-sided heart failure.

Adrenergic beta-Antagonists↗

PubMed1996

Diagnostic yield of bronchoscopies after isolated lung transplantation.

Lung transplantation has become an acceptable therapeutic option for end-stage pulmonary diseases. The most common causes of long-term mortality after transplantation are infections and obliterative bronchiolitis (OB). While acute rejection has been shown to be associated with an increased risk of development of OB, cytomegalovirus (CMV) pneumonitis is more controversial as a risk factor for OB. Surveillance bronchoscopies are therefore advocated as a method of detecting silent episodes of CMV pneumonitis or acute rejection. We performed 226 bronchoscopies in 43 lung transplant recipients over 34 months. One hundred fifty-seven of the 226 bronchoscopies were performed according to a surveillance protocol. Acute rejection was diagnosed if lung histologic study revealed grade 2 to 4 rejection or if prompt reversal of clinical deterioration occurred after initiation of pulse steroid therapy. CMV pneumonitis was diagnosed when transbronchial biopsy histologic specimens revealed evidence of CMV inclusion bodies, or when CMV was recovered on BAL fluid in the presence of allograft deterioration. The proportion of patients who were free from any episode of acute rejection or CMV pneumonitis after transplantation was determined by Kaplan-Meier analysis. Twenty-one percent of our transplant recipients were free from acute rejection or CMV pneumonitis after a mean follow-up of 13 months. All patients who had acute rejection or CMV pneumonitis had the initial episode in the first 4 months after transplantation. Patients free of acute rejection or CMV pneumonitis 4 months after transplantation continued to be event free for the duration of follow-up. Our data suggest that surveillance bronchoscopy can be aborted in patients who are free from acute rejection or CMV pneumonitis by 4 months after transplantation. The role of surveillance bronchoscopy in decreasing the incidence of OB or improving survival can be determined only by future randomized prospective trials.

Acute Disease↗

PubMed1996

Total pulmonary artery occlusion immediately after lung transplantation: successful revascularization with intravascular stents.

Occlusion of the pulmonary artery anastomosis is an uncommon early complication of lung transplantation which necessitates emergency surgical revision. Percutaneous correction of such a complication has not been previously reported. We report a patient who had total pulmonary artery occlusion less than 24 hours after right single lung transplantation with successful revascularization achieved by means of percutaneously delivered endovascular stents.

Adult↗

PubMed1995

Generation of tumor-specific T lymphocytes for the treatment of posttransplant lymphoma.

BACKGROUND: The incidence of lymphoproliferative disease, including B-cell lymphomas (BCL) in patients who have undergone heart or combined heart-lung transplants, has been reported to be as high as 15%. The majority of these tumors contain Epstein-Barr virus (EBV) DNA and regress when immunosuppressive agents are discontinued. This tumor regression is thought to be secondary to cytotoxic T lymphocytes (CTL) reactive to EBV-infected cells whose function is impaired in patients receiving immunosuppressive agents. We hypothesize that EBV-CTL expanded in the absence of these agents may demonstrate an antitumor effect against an EBV-expressing human BCL in vitro and in vivo. METHODS AND RESULTS: An EBV-expressing BCL from a heart transplant recipient was isolated and expanded in culture. EBV-CTL were generated by stimulation of peripheral blood leukocytes with irradiated autologous tumor cells in low-dose interleukin-2. Autologous BCL, HLA-mismatched BCL, lymphokine-activated killer target cell line (Daudi), and the natural killer target cell line (K562) were used in a standard 4-hour cytotoxicity assay using 51CrO4 after 7, 14, and 28 days of stimulation. There was significant percent specific lysis of autologous BCL targets (78%) at an effector-to-target ratio as low as 20:1 as compared with control cells. EBV-CTL were then adoptively transferred into SCID mice (provided by Duke University Vivarium) that had been engrafted with autologous BCL 7 days before. There was a significant survival advantage to those mice engrafted with EBV-CTL as compared with control cells. CONCLUSIONS: The results indicate that ex vivo expansion of EBV-CTL in the absence of immunosuppressive agents results in a population that has significant antitumor activity. This strategy may be useful in the generation of EBV-CTL that might be effective antitumor agents in transplant recipients with EBV-associated lymphomas.

Animals↗

PubMed1995

Isothiocyanate-substituted benzyl ether opioid receptor ligands derived from 6 beta-naltrexol.

A series of regioisomeric substituted 6-O-benzyl ethers of 6 beta-naltrexol (12) in which isothiocyanate groups were attached directly to or one carbon removed from the aromatic ring of the benzyl group were prepared. These agents were prepared to obtain electrophilic opioid ligands potentially useful in the characterization of opioid receptors and drug-receptor interactions. Preparation of these ligands was accomplished from 3-O-trityl-6 beta-naltrexol (13) via phase transfer-catalyzed alkylation of the regioisomeric o-, m-, and p-nitrobenzyl halides and the o-, m-, and p-cyanobenzyl halides. The intermediates were deprotected and reduced, and formation of the isothiocyanates from the corresponding amines completed the synthesis. The ligands (6-11) were tested in radioligand displacement assays in guinea pig brain homogenate for opioid receptor binding affinity and irreversibility. All six of the isothiocyanates demonstrated significant affinity in the displacement assays for all three opioid receptors. They also appeared to be irreversibly bound at each of the receptor types. Compound 6, the o-isothiocyanatobenzyl ether analog, had the highest affinity, and it demonstrated significant irreversibility at very low concentration. It appears to be suitable for further investigation.

Animals↗

PubMed1995

Predictors of cognitive decline after cardiac operation.

Despite major advances in cardiopulmonary bypass technology, surgical techniques, and anesthesia management, central nervous system complications remain a common problem after cardiopulmonary bypass. The etiology of neuropsychologic dysfunction after cardiopulmonary bypass remains unresolved and is probably multifactorial. Demographic predictors of cognitive decline include age and years of education; perioperative factors including number of cerebral emboli, temperature, mean arterial pressure, and jugular bulb oxygen saturation have varying predictive power. Recent data suggest a genetic predisposition for cognitive decline after cardiac surgery in patients possessing the apolipoprotein E epsilon-4 allele, known to be associated with late-onset and sporadic forms of Alzheimer's disease. Predicting patients at risk for cognitive decline allows the possibility of many important interventions. Predictive power and weapons to reduce cellular injury associated with neurologic insults lend hope of a future ability to markedly decrease the impact of cardiopulmonary bypass on short-term and long-term neurologic, cognitive, and quality-of-life outcomes.

Age Factors↗

PubMed1995

Complete atrioventricular cardiac transplantation: improved performance compared with the standard technique.

BACKGROUND: There has been renewed clinical interest in an alternative technique to orthotopic cardiac transplantation involving six anastomoses: left pulmonary veins, right pulmonary veins, inferior vena cava, pulmonary artery, aorta, and superior vena cava (complete technique). In this study, the results of the complete technique are compared with those of the standard operation (ventricular transplantation with atrioplasty). METHODS: Dogs were used for ten acute standard and ten acute complete atrioventricular transplantations. There were no significant differences in the baseline cardiac function (preload-independent right and left ventricular recruitable stroke work), bypass times, and cardiac ischemic times between the two groups. RESULTS: After transplantation, sinus rhythm was preserved after all ten complete and after only one standard transplantation but no significant hemodynamic differences were observed. The right and left ventricular preload-independent recruitable stroke work in the complete group and the left ventricular preload-independent recruitable stroke work in the standard group were conserved after transplantation, but the right ventricular preload-independent recruitable stroke work decreased by 39% +/- 8% (p < 0.05) in the standard group. There was also a significant decrease in the rate of biventricular filling in the standard group after transplantation. CONCLUSIONS: Complete atrioventricular transplantation is a feasible alternative technique and conserves normal sinus rhythm. The ischemic and bypass times are comparable for both methods. The insignificant change in the rate of biventricular filling in the dogs undergoing the complete technique indicates right and left ventricular diastolic function may be conserved after transplantation.

Animals↗

PubMed1995

Pulmonary transplantation.

OBJECTIVE: More than 2700 lung transplants have been performed since the initial clinical success in 1983. The evolution in the techniques of lung transplantation and patient management and the effects on results are reviewed. SUMMARY BACKGROUND DATA: Improvements in donor management, lung preservation, operative techniques, immunosuppression management, infection prophylaxis and treatment, rejection surveillance, and long-term follow-up have occurred in the decade following the first clinically successful lung transplant. A wider spectrum of diseases and patients treated with lung transplant have accentuated the shortage of suitable lung donors. The organ shortage has led to the use of marginal donors and a limited experience using living, related donors. METHODS: Changes in techniques and patient selection and management are reviewed and controversial issues and problems are highlighted. RESULTS: One-year survival of greater than 90% for single-lung transplant recipients and greater than 85% for bilateral lung transplant recipients have been achieved. Complications caused by airway complications has been reduced greatly. Obliterative bronchiolitis develops in 20% to 50% of long-term survivors and is the leading cause of morbidity and mortality after the first year after transplant. CONCLUSIONS: Lung transplantation has evolved into an effective therapy for a wide variety of causes of end-stage lung disease. Wider applicability requires solutions to the problems of donor shortage and development of obliterative bronchiolitis.

Humans↗

PubMed1995

Jugular bulb saturation and mixed venous saturation during cardiopulmonary bypass.

Systemic venous oxygen saturation is clinically used as an indicator of a satisfactory oxygen supply demand balance on cardiopulmonary bypass (CBP). Cerebral desaturation has been associated with postoperative cognitive dysfunction and has an incidence of 17% to 23% on bypass. We tested the hypothesis that systemic venous saturation did not correlate with jugular bulb venous saturation. Blood was drawn from the radial artery, jugular bulb catheter, and venous return line for determination of pH, oxygen tension and saturation, and carbon dioxide tension at four times during bypass: warm 1 (following initiation of CPB); cold 1 (stable hypothermia); cold 2 (hypothermia prior to rewarm); and warm 2 (nasopharyngeal temperature 36 degrees C to 37 degrees C). Correlations of jugular bulb and systemic venous saturation at cold 1 were r = 0.29, r2 = 0.08, and p = 0.0005, and at warm 2 were r = 0.22, r2 = 0.05, and p = 0.007. We conclude that systemic saturation is a poor indicator of cerebral saturation. The poor association of jugular and systemic pump venous saturations underscores our inability to evaluate adequacy of cerebral perfusion. Jugular saturation is lower than pump venous return blood, especially at times of lower oxygen delivery, thus either continuous invasive or noninvasive evaluation of cerebral oxygenation is required to evaluate the adequacy of cerebral perfusion.

Aged↗