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Biomedical subjects

B P Griffith

Publications and source records attributed to B P Griffith.

At least 19 recordsLinked to original sources
PubMed1995

Automated echocardiographic measures of right ventricular area as an index of volume and end-systolic pressure-area relations to assess right ventricular function.

BACKGROUND: On-line determination of right ventricular (RV) volume to assess its function is clinically difficult. Echocardiographic automated border detection measures of left ventricular (LV) cavity area have been shown to reflect changes in volume, and pressure-area relations have been used to estimate LV contractility. The potential for RV cavity area to estimate changes in volume and to assess RV function, however, has not been evaluated. Accordingly, the objective of this study was to determine the relation between echocardiographic automated border-detected RV cross-sectional area and true volume and to assess the potential for end-systolic pressure-area relations to estimate RV function in an isovolumically contracting isolated canine heart preparation. METHODS AND RESULTS: Eight excised dog hearts with both right and left intraventricular balloons were perfused in an ex vivo apparatus in which both ventricular volumes were controlled independently. RV area data from the level of the left midventricular short-axis plane and pressure data were recorded on a computer through a customized hardware and software interface with the ultrasound system. RV volumes were varied from 9.4 +/- 3.9 to 43.8 +/- 6.9 mL at each of three different LV volume ranges (low range, 12.5 +/- 3.8 mL; medium range, 23.9 +/- 5.6 mL; and high range, 37.5 +/- 5.4 mL). The variation of RV area during isovolumic contraction, which we called deformational area change, was considerable (1.49 +/- 0.68 cm2 mean +/- SD) but did not change significantly with changing RV and LV volumes. Linear regression analysis correlated the maximum, minimum, and mean automated border-detected RV area during isovolumic contraction with absolute volume. A predominantly linear relation was observed, with the group mean r = .98 (y = 0.16x + 0.97; SEE = 0.21 cm2). The effect of LV volume on RV area-volume relation was a significant parallel downward shift (P < .05) by increases in LV volume. End-systolic pressure-area and pressure-volume relations using simultaneously RV pressure were both highly linear and covaried with changing LV volume. CONCLUSIONS: Echocardiographic automated border-detected RV area reflects changes in RV volume under a constant LV volume, and the derived end-systolic pressure-area relation has potential for on-line assessment of RV function.

Animals↗
PubMed1995

Left atrial thrombus after lung transplantation.

We report on a 16-year-old boy who developed a thrombus at the left atrial suture line after undergoing a bilateral sequential single lung transplantation. The diagnosis was made by transesophageal echocardiogram.

Adolescent↗
PubMed1995

Transesophageal echocardiography to evaluate patients with severe pulmonary hypertension for lung transplantation.

The surgical approach to lung transplantation for patients with severe pulmonary hypertension will be dependent on the primary disease and specific cardiac anatomy. To determine the safety and utility of transesophageal echocardiography in the management of patients with severe pulmonary hypertension who are being evaluated for lung transplantation, we studied 48 consecutive patients, aged 38 +/- 11 years, with pulmonary artery systolic pressure of 70 mm Hg or greater. All patients previously underwent left and right heart catheterization, transthoracic echocardiography, and radionuclide ventriculography. Transesophageal echocardiography was tolerated well by all patients. Additional data that significantly altered surgical therapy was found in 12 of 48 patients (25%): proximal pulmonary artery thrombi (3), patent foramen ovale with significant right to left shunting (2), atrial septal defect (2), double-outlet right ventricle (2), ventricular septal defect (2), and exclusion of atrial septal defect (1). These findings were confirmed surgically in all patients except 3, who died awaiting transplantation. Transesophageal echocardiography is useful in the evaluation of patients with severe pulmonary hypertension.

Adult↗
PubMed1995

Endobronchial management of benign, malignant, and lung transplantation airway stenoses.

Since 1991, we have managed 57 patients with benign (10), malignant (23), or lung transplantation (24) airway obstructions using silicone stenting and debridement (manual/neodymium:yttrium-aluminum garnet laser). Ten patients with benign lesions (4 intubation, 4 inflammatory, 1 malacia, 1 bronchial fistula) had 4 T tubes, 3 Y stents, 3 bronchial stents, and 1 straight tracheal stent placed. Eight of 10 patients (80%) received symptomatic relief with the stents in place for up to 43 months. Twenty-three patients with malignant strictures (18 lung, 5 metastatic) had 26 stents inserted (13 Y stents, 12 bronchial, 1 T tube) of which 16 required combined debridement and stenting. Four stents required repositioning. three hospital deaths were due to unrelated causes. Of 20 discharged patients, 6 remain alive at 2 to 10 months, whereas 14 patients who died of progressive disease obtained effective palliation for 10.5 +/- 5.6 months. Significant bronchial anastomotic complications developed in 24 of 212 lung transplants (11.3%). Thirty-one stents were placed in 19 of the patients; 5 patients were managed with laser debridement alone. Of the 19 patients receiving stents, 3 required only temporary stents (6 to 15 days), 11 patients needed long-term stents (40 to 507 days), and 5 patients died with their stents in place functioning well. All patients received symptomatic relief with stenting. There were no procedure-related deaths and one bronchial laceration during attempted stent placement. Early, aggressive treatment of benign and malignant tracheobronchial strictures with endoscopic debridement and stenting is safe and well tolerated, and effectively palliates airway obstruction. Repositioning of stents frequently may be required in the transplant population.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Clinical trial of tacrolimus versus cyclosporine in lung transplantation.

BACKGROUND: A prospective clinical trial was undertaken to compare the efficacy of tacrolimus (FK 506) versus cyclosporine as the primary immunosuppressive agent after lung transplantation. METHODS: Between October 1991 and May 1994, 133 single-lung and bilateral-lung recipients were randomized to receive either cyclosporine (n = 67) or tacrolimus (n = 66). The two groups were similar in age, sex, and underlying disease. RESULTS: One-year and 2-year survival rates were similar in the two groups, although the trend was toward increased survival with tacrolimus. Acute rejection episodes per 100 patient-days were fewer (p = 0.07) in the tacrolimus group (0.85) than in the cyclosporine group (1.09). Obliterative bronchiolitis developed in significantly fewer patients in the tacrolimus group (21.7%) compared with the cyclosporine group (38%) (p = 0.025), and there was greater freedom from obliterative bronchiolitis over time for patients receiving tacrolimus (p < 0.03). Significantly more cyclosporine-treated patients (n = 13) required crossover to tacrolimus than tacrolimus-treated patients to cyclosporine (n = 2) (p = 0.02). The switch to tacrolimus controlled persistent acute rejection in 6 of 9 patients. The overall incidence of infections was similar in the two groups, although bacterial infections were more common with cyclosporine (p = 0.0375), whereas the risk of fungal infection was higher with tacrolimus (p < 0.05). CONCLUSIONS: This trial demonstrates the advantage of tacrolimus in reducing the risk of obliterative bronchiolitis, the most important cause of long-term morbidity and mortality after lung transplantation.

Acute Disease↗
PubMed1995

Extracorporeal membrane oxygenation as an adjunct treatment for primary graft failure in adult lung transplant recipients.

Primary graft failure is a catastrophic event in lung transplantation. Failure is characterized by profound abnormalities of gas exchange that are frequently unresponsive to alterations in mechanical ventilation. This condition can be fatal and, if less severe, is usually associated with significant permanent damage to the allograft. We report the use of extracorporeal membrane oxygenation as a means to support lung transplant recipients with severe graft failure. Since 1991, extracorporeal membrane oxygenation has been used on 17 occasions for the temporary support of 16 adult lung transplant recipients. All patients met or exceeded standard National Institutes of Health guidelines for institution of extracorporeal membrane oxygenation. Nine double lung, six single lung, and one heart-lung recipients were supported for 1 to 12 days (mean 4.6 +/- 2.2 days). Extracorporeal membrane oxygenation was instituted early, within 7 days of transplantation, in ten patients. Eight early patients (80%) were successfully weaned from extracorporeal membrane oxygenation. Seven of ten (70%) patients were long-term survivors, and five of the seven had normal lung function. In comparison, there were no survivors among six recipients placed on extracorporeal membrane oxygenation for late (> or = 7 days) graft dysfunction. Extracorporeal membrane oxygenation is a lifesaving adjunct in recipients with acute graft failure after lung transplantation. Ischemia-reperfusion injury and acute graft dysfunction after lung transplantation can be successfully reversed with early aggressive intervention.

Adult↗
PubMed1995

Analysis of time-dependent risks for infection, rejection, and death after pulmonary transplantation.

Infection and rejection remain the greatest threats to the survival of pulmonary allograft recipients. Furthermore, a relationship may exist between these events, because the occurrence of one may predispose to the other. By using multivariate analysis for repeated events, we analyzed the risk factors for bacterial, fungal, and viral infection, grade II or greater acute rejection, and death among 239 lung transplant recipients who received 250 allografts between January 1988 and September 1993. A total of 90 deaths, 491 episodes of acute rejection, and 542 infectious episodes occurred during a follow-up of 6 to 71 months. The hazard or risk patterns of death, infection, and rejection each followed an extremely high risk during the first 100 days after transplantation, a second modest risk period at 800 to 1200 days, and a lower constant risk. Infection and graft failure manifested by diffuse alveolar damage were the major causes of early death (< 100 days), whereas infection and chronic rejection were primary causes of later death after pulmonary transplantation. By multivariate analysis, cytomegalovirus mismatching risk for primary infection was the most significant risk factor for death, rejection, and infection. Absence of cytomegalovirus prophylaxis was also a risk factor for early and late death and late infection. Survival of recipients who received cytomegalovirus prophylaxis was significantly improved. Immunosuppression based on cyclosporine versus FK 506 was a risk factor for late death and late infection. Graft failure manifested by diffuse alveolar damage/adult respiratory distress syndrome was a significant risk for death late after transplantation. These data suggest the following: (1) The hazard for death, infection, and rejection after pulmonary transplantation appears biphasic; (2) lower survival is associated with ischemia-reperfusion lung injury represented by diffuse alveolar damage/adult respiratory distress syndrome; (3) cytomegalovirus mismatch, absence of cytomegalovirus prophylaxis, and development of cytomegalovirus disease are significant threats for death, rejection, and infection after pulmonary transplantation; (4) prevention of cytomegalovirus disease should improve survival by decreasing the prevalence of infection and rejection.

Adolescent↗
PubMed1995

Critical issues in pediatric lung transplantation.

Forty children (aged 1 to 18 years, 27 female and 13 male) have undergone heart-lung (21), double lung (17), and single lung (2) transplant procedures at our center from 1985 through April 1994. The indications for transplantation have been diverse, primary pulmonary hypertension (10), cystic fibrosis (11), congenital heart disease (10), arteriovenous malformation (3), emphysema (1), graft-versus-host disease (1), rheumatoid lung (1), cardiomyopathy (1), desquamative interstitial pneumonitis (1), and Proteus syndrome (1). The actuarial 1-year survival was 73% (mean follow-up 2 years). One-year actuarial survival for disease groups ranged from 60% for cystic fibrosis to 90% for congenital heart disease. We have identified six issues critical to the patient and programatic survival of pediatric lung transplantation. Our experience and management strategies in these areas are reviewed. Cytomegalovirus: Cytomegalovirus disease developed in six of eight patients with cytomegalovirus mismatching (donor +/recipient-) and in seven of 32 patients who survived more than 30 days (23%). All but cytomegalovirus donor -/recipient- patients were treated with ganciclovir for 4 weeks after transplantation. Obliterative bronchiolitis: Obliterative bronchiolitis developed in seven of 32 (25%) patients who survived more than 30 days. Obliterative bronchiolitis was manifest within the first posttransplantation year as a rapid decline in small airway function. Aggressive augmentation of immunosuppression has been used with little success. Posttransplantation lymphoproliferative disease: Posttransplantation lymphoproliferative disease developed in five of 32 (15%) patients who survived more than 30 days developed. One patient died (17% mortality) despite retransplantation. In four patients the disease resolved with reduction in immunosuppression alone, and one required the addition of interferon alfa. Cystic fibrosis: We have changed our management strategies to avoid triple drug immunosuppression, perioperative blood and bronchial cultures, aggressive antimicrobial therapy, and exclusion of patients with panresistant organisms; this has resulted in elimination of infectious mortalities thus far in the pediatric cystic fibrosis group. Airways: In 21 heart-lung recipients with tracheal anastomoses we have had no airway complications. The double and single lung transplant recipients accounted for 34 bronchial and one tracheal anastomoses. Three (9%) bronchial stenoses developed. Two were treated with silicone stents and one with balloon dilation.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1995

Efficacy of inhaled cyclosporine in lung transplant recipients with refractory rejection: correlation of intragraft cytokine gene expression with pulmonary function and histologic characteristics.

BACKGROUND: Refractory rejection is a major cause of morbidity and death among lung transplant recipients. Traditional rescue therapies have proved only modestly successful. We recently demonstrated the safety of inhaled cyclosporine for patients with end-stage chronic rejection; this trial was extended to patients with refractory acute rejection. The present study was to determine whether effective inhaled cyclosporine therapy was correlated with suppression of cytokine gene expression. METHODS: Twelve lung transplant recipients were studied. Maintenance therapy, cyclosporine or FK 506, azathioprine, and prednisone, was continued, and inhaled cyclosporine at a dose of 300 mg/day was added. Pulmonary function testing and histologic characteristics from transbronchial biopsy specimens were used to assess efficacy of therapy. Bronchoalveolar lavage (BAL) and peripheral blood cells were analyzed for the presence of messenger RNA by using 32P-labeled primers of cytokines interleukin-2 (IL-2), IL-6, IL-10, and interferon-gamma (gamma) via reverse transcriptase-polymerase chain reaction. RESULTS: Nine of 12 patients (five with acute rejection, four with chronic rejection) exhibited histologic resolution of rejection within 3 months of inhaled cyclosporine therapy. Pulmonary function (forced expiratory volume in 1 second) improved from pretherapy levels in the patients with acute rejection (p < 0.05). All of the nine histologic responders exhibited 4- to 150-fold decreases (p < 0.05) in IL-6 and interferon-gamma messenger RNA levels in the BAL, whereas the three patients who failed exhibited persistent or increased cytokine profiles. IL-2 and IL-10 in BAL and peripheral blood lymphocyte cytokines were not informative. CONCLUSIONS: These results indicate that inhaled cyclosporine is effective therapy for refractory pulmonary rejection and that its mechanism of action is associated with suppression of proinflammatory cytokines IL-6 and interferon-gamma within the allograft.

Administration, Inhalation↗
PubMed1995

The need for accurate risk-adjusted measures of outcome in surgery. Lessons learned through coronary artery bypass.

OBJECTIVE: The authors review the Pennsylvania Health Care Cost Containment Council reports on coronary artery surgery and compare this reporting structure to others, including the Society for Thoracic Surgeons database, currently used by their own program. The authors review the growing likelihood of a need for outcome measures for all of the surgical subspecialties. SUMMARY AND BACKGROUND DATA: Pressure from consumers and insurers will require surgical specialties to be graded by objective outcome measures. Practitioners must be prepared and become involved in the process. METHODS: The authors reviewed the data, which grades all of Pennsylvania's hospitals at which coronary artery bypass is performed. Apparently, the major risk factors commonly employed in most other risk adjustment schemes for cardiac surgery have been deleted, and the practitioners might be judged unfairly. The Pennsylvania system appears to be insurance driven to reward low-cost providers who operate on patients with the lowest risk. RESULTS: Review of data suggests that the Pennsylvania Health Care Cost Containment Council's annual publication, A Consumer's Guide for Coronary Artery Bypass Surgery, misrepresents fair risk adjustment in favor of lower-risk patients, thereby encouraging better score cards for those institutions with patients who are less ill. Data regarding charges for the procedure have not been risk adjusted or related to a regional economic index. CONCLUSIONS: Surgeons must prepare to better understand relevant models that evaluate outcome. Cardiothoracic surgery is one of the first specialties to feel the pressures of mandated evaluations, and the lessons learned in Pennsylvania should be applicable to other states and their practitioners.

Coronary Artery Bypass↗
PubMed1995

Stability of free and complexed human immunodeficiency virus type 1 antigen at 4 degrees C and at room temperature.

Free and immune-complex-dissociated (ICD) human immunodeficiency virus type 1 (HIV-1) antigenemias in serum specimens stored at room temperature (RT) and 4 degrees C for 1 to 35 days were evaluated. At all time points examined, there was no significant loss in detectable levels of ICD HIV-1 antigen at either RT or 4 degrees C. Free HIV-1 antigen was not stable in serum samples stored at RT for more than 2 days but was stable in samples stored at 4 degrees C for up to 4 days. Loss of free antigen occurred more rapidly in samples with high antigen content at baseline. Use of the ICD antigen assay allowed accurate quantitation of antigen in samples stored at RT or 4 degrees C for as long as 1 month.

Antigen-Antibody Complex↗
PubMed1995

Delivery and distribution of aerosolized cyclosporine in lung allograft recipients.

The aim of the present study was to identify factors determining the delivery to and distribution of aerosolized cyclosporine A (CSA) in the lungs of patients with severe pulmonary allograft rejection. Five such patients inhaled a previously characterized radioaerosol consisting of 4 to 6 cc of CSA (50 mg/ml) in ethanol mixed with technetium-99m (99mTc) bound to human serum albumin, generated by an AeroTech II nebulizer. The total dose of CSA depositing in the lungs was determined with a previously described inspiratory/expiratory mass-balance filter technique. Regional distribution of drug within the lungs was measured using a gamma camera. In addition, the following physiologic parameters were measured: regional volume and ventilation using xenon-133 (133Xe) equilibrium and 133Xe washout, respectively, and regional perfusion using intravenous 99mTc macroaggregates. The relationships between these parameters and regional drug deposition were assessed using linear regression analysis. The lung dose ranged from 20 to 53 mg (0.097 to 0.175 mg CSA deposited per milligram placed in nebulizer). In recipients of single-lung allografts, preferential drug deposition occurred either in the allograft (two patients) or in the native lung (one patient). Marked nonuniformities in regional distribution were also apparent in two double-lung allograft recipients. There was a weak but statistically significant correlation between regional drug deposition and regional ventilation, as measured by 133Xe washout (r = -0.542, p = 0.014), suggesting that although regional ventilation is important, it is not the only factor determining regional deposition in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Neurohormonal activation and exercise function in patients with severe heart failure and patients with left ventricular assist system. A comparative study.

OBJECTIVES: The aim of this study was to evaluate the effects of implantation of a left ventricular assist system (LVAS) on the neurohormonal status, exercise capacity and symptomatic state in patients with severe congestive heart failure (CHF). BACKGROUND: Severe CHF is characterized by decreased exercise tolerance and activation of several neurohormonal systems. METHODS: Parameters of neurohormonal activation and exercise capacity in patients with LVAS (n = 7) were compared with those in groups of New York Heart Association (NYHA) class 3 (n = 121) and class 4 (n = 81) patients. Plasma levels of norepinephrine (NE), plasma renin activity (PRA), and atrial natriuretic peptide (ANP) and maximal and submaximal exercise capacities were measured monthly in LVAS patients and compared with results in CHF patients. RESULTS: Plasma NE and PRA levels were significantly lower in LVAS patients than in NYHA class 4 patients, and plasma ANP levels in LVAS patients were significantly lower than those in NYHA class 3 and 4 patients. The distance walked during submaximal exercise testing and peak oxygen consumption during maximal exercise testing were similar for the LVAS and NYHA class 3 patients. The class 4 patients were unable to exercise. CONCLUSIONS: We conclude that the LVAS lessens the neurohormonal activation and exercise intolerance characteristic of the CHF state and that the exercise capacity early after LVAS (< 4 months) is similar to that observed in NYHA class 3 patients.

Adolescent↗
PubMed1994

A prospective randomized trial of FK506 versus cyclosporine after human pulmonary transplantation.

We have conducted a unique prospective randomized study to compare the effect of FK506 and cyclosporine (CsA) as the principal immunosuppressive agents after pulmonary transplantation. Between October 1991 and March 1993, 74 lung transplants (35 single lung transplants [SLT], 39 bilateral lung transplant [BLT]) were performed on 74 recipients who were randomly assigned to receive either FK or CsA. Thirty-eight recipients (19 SLT, 19 BLT) received FK and 36 recipients (16 SLT, 20 BLT) received CsA. Recipients receiving FK or CsA were similar in age, gender, preoperative New York Heart Association functional class, and underlying disease. Acute rejection (ACR) was assessed by clinical, radiographic, and histologic criteria. ACR was treated with methylprednisolone, 1 g i.v./day, for three days or rabbit antithymocyte globulin if steroid-resistant. During the first 30 days after transplant, one patient in the FK group died of cerebral edema, while two recipients treated with CsA died of bacterial pneumonia (1) and cardiac arrest (1) (P = NS). Although one-year survival was similar between the groups, the number of recipients free from ACR in the FK group was significantly higher as compared with the CsA group (P < 0.05). Bacterial and viral pneumonias were the major causes of late graft failure in both groups. The mean number of episodes of ACR/100 patient days was significantly fewer in the FK group (1.2) as compared with the CsA group (2.0) (P < 0.05). While only one recipient (1/36 = 3%) in the group treated with CsA remained free from ACR within 120 days of transplantation, 13% (5/38) of the group treated with FK remained free from ACR during this interval (P < 0.05). The prevalence of bacterial infection in the CsA group was 1.5 episodes/100 patient days and 0.6 episodes/100 patient days in the FK group. The prevalence of cytomegaloviral and fungal infection was similar in both groups. Although the presence of bacterial, fungal, and viral infections was similar in the two groups, ACR occurred less frequently in the FK-treated group as compared with the CsA-treated group in the early postoperative period (< 90 days). Early graft survival at 30 days was similar in the two groups, but intermediate graft survival at 6 months was better in the FK group as compared with the CsA group.

Adult↗
PubMed1994

Estimation of left ventricular compliance using on-line echocardiographic automated border detection and pressure data.

The end-diastolic pressure-volume relationship can be used to describe left ventricular (LV) compliance. The objective of this study was to utilize measurements of LV cavity area by echocardiographic automated border detection and pressure data to estimate the end-diastolic pressure-volume curve in an isolated heart preparation where true volume could be measured by an intraventricular balloon. Six dog hearts were excised for placement of an intraventricular balloon and a micromanometer catheter and perfused in an ex vivo circuit. Mid-ventricular short-axis images were used to measure cross-sectional area by automated border detection while LV volumes were increased from 5 ml to maximal volume (30-40 ml) in each preparation. Simultaneous area and pressure data were recorded on a computer workstation through a customized interface with the ultrasound system. Three runs of varying LV volumes at 1 ml increments were performed on each of 6 hearts for a total of 1,080 simultaneous measurements. Pressure-volume and pressure-area curves were analyzed by linear regression analyses, the slope of which was used to estimate compliance. End-diastolic pressure-area and pressure-volume relationships were significantly correlated with mean r = 0.97 +/- 0.02 (p < 0.001) from individual hearts. The slopes which served to estimate compliance of the individual pressure-area and pressure-volume curves were similar and differed by only 7 +/- 4%. A similar correlation was observed by second order regression analyses with r = 0.97 +/- 0.01 (p < 0.001) for pressure-area and r = 0.98 +/- 0.01 (p < 0.001) for pressure-volume relationships.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗