PubMed Health⌕ Search

Biomedical subjects

B P Griffith

Publications and source records attributed to B P Griffith.

At least 91 records · Page 5Linked to original sources

Extracorporeal membrane oxygenation for lung transplant recipients with primary severe donor lung dysfunction.

Primary severe donor lung dysfunction (DLD) is a significant complication after lung transplantation (LTx), and a high mortality is reported with conventional therapy. The purpose of this report is to review the experience of the University of Pittsburgh with extracorporeal membrane oxygenation (ECMO) for primary severe DLD after LTx. From September 1991 to May 1995, 220 LTx were performed at our center. Eight patients (8/220 = 3.6%) with severe DLD after LTx required ECMO support. The age of LTx recipients was 44 +/- 5 years (mean +/- SD); seven patients were female and one was male. Indications for LTx were: chronic obstructive pulmonary disease in four patients, bronchiectasis in two, and pulmonary hypertension in two. There were three single LTx and five bilateral LTx. The interval from LTx to institution of ECMO was 5.6 +/- 3.2 h (range 0-10 h). Three patients were supported with veno-venous (v-v) ECMO and five had veno-arterial (v-a) ECMO. The duration of ECMO support was 7.3 +/- 4.8 days (range 3-15 days). activated glotting time (ACT) was maintained between 110 and 180 s with intermittent use of heparin. Seven patients (7/8 = 87%) were successfully weaned from ECMO and six patients (6/8 = 75%) were discharged home; they are currently alive after a follow-up of 17 +/- 10.1 months. One patient died on ECMO support for refractory DLD and another died 2 months after ECMO wean from multisystem organ failure. At 6 months follow-up, forced expiratory volume in 1 s (FEV1) is 2.35 +/- 0.91 (75% +/- 17.4% predicted) and mean forced vital capacity (FVC) is 2.53 +/- 0.81 (64% +/- 14% predicted). We conclude that ECMO can be lifesaving when instituted early after primary severe DLD. The v-v ECMO support is preferred when the patient is hemodynamically stable and adequate long-term function of the allograft is anticipated.

Adult↗

Minimally invasive coronary artery bypass grafting.

BACKGROUND: Standard options for the invasive management of proximal disease of the left anterior descending coronary artery include coronary artery bypass grafting with a left internal mammary artery and percutaneous transluminal coronary angioplasty. METHODS: We describe a surgical technique for bypass of the left anterior descending coronary artery with a left internal mammary artery without median sternotomy and without cardiopulmonary bypass. Thoracoscopy is used to harvest the internal mammary artery, whereas the mammary-coronary artery anastomosis is performed under direct vision through a limited anterior thoracotomy. RESULTS: We have performed this procedure successfully in 3 patients with minimal morbidity and shortened hospital stay. Average operative time was 3 hours and postoperative hospital stay averaged less than 48 hours. CONCLUSION: Although experience is limited and follow-up is very short, with further experience, this less invasive surgical technique may become a viable option for the management of proximal left anterior descending disease.

Adult↗

Discharging patients who are undergoing mechanical circulatory support.

Six patients supported by the Baxter Novacor left ventricular assist system have been discharged during the period of mechanical circulatory support at the University of Pittsburgh Medical Center. Benefits of discharge couple quality of life improvements and economic advantages for mechanical circulatory support patients. Limitations caused by regulations within current protocols have been shown to detract from patient and caregiver quality of life. Eliminating the unnecessary regulations will improve discharge capabilities without increasing the risk for clinical complications.

Adult↗

Results of extended bridge to transplantation: window into the future of permanent ventricular assist devices.

BACKGROUND: There is interest in expanding ventricular assist device use from short-term bridging to transplantation to long-term and permanent support. METHODS: We have reviewed the outcome of 162 patients who had as mechanical bridge to transplantation that lasted at least 60 days. Eighty-five patients received the HeartMate, 40 the Novacor, and 37 the Thoratec device. RESULTS: Of the 162 patients, 125 received transplants, and 115 survived after transplantation (93%). Within the group there were 174 complications including 54 infections of the driveline, 73 other infections, and thromboembolic strokes in 47. Infections of the driveline were considered major in 24 of 54 cases, and other infections were major in 36 of 73 cases. Twenty-seven of those who sustained thromboembolic events had residual effects. Of 11 patients with a major stroke and infection, only 1 survived transplantation. Eighty-two patients were supported between 60 and 100 days, 63 patients between 101 and 200 days, 12 patients between 201 and 300 days, and only 5 patients in excess of 300 days. A greater percentage of candidates died waiting between 101 and 200 days than between 60 and 100 days (25% versus 10%). The incidence of complications also rose in those patients bridged more than 100 days. CONCLUSIONS: The data reinforce the excellent results obtained in the bridge to transplantation trials that reported a shorter duration of support. For those interested in extended bridge to transplantation or permanent use of the currently available devices, the results suggest reasonable success can be anticipated, but the serious infections and strokes tend to be more common with longer duration of support.

Heart Transplantation↗

Development and initial testing of a pediatric centrifugal blood pump.

BACKGROUND: We are developing a miniaturized centrifugal blood pump for use as a temporary cardiac assist device in neonatal and pediatric sized patients. This pump has a very low priming volume of 13 mL. A small motor stator has also been designed, which resulted in a device that can be placed very close to the patient, thereby minimizing overall circuit volume. METHODS: Testing to date has included in vitro hemodynamic performance, in vitro hemolysis generation, and in vivo evaluation in 5 lambs weighing 5.5 to 21 kg. Two lambs underwent peripheral cannulation from external jugular vein to carotid artery, whereas 3 others were cannulated from left atrium to carotid artery. RESULTS: In vitro data demonstrated pump capacity spanning 0.3 to 3.0 L/min and very low hemolysis generation at these conditions. In vivo, the pump functioned satisfactorily for periods up to 148 hours, and the bypass appeared to be well tolerated by the animals. Plasma free hemoglobin levels remained less than 25 mg/dL during all animal experiments. All devices were thrombus-free at explantation. CONCLUSIONS: We conclude that this device has merit as an alternative to current oversized systems used for neonatal and pediatric cardiac assistance. In addition, a chronic neonatal lamb model in which to evaluate pediatric circulatory assist devices has been developed successfully.

Animals↗

Effect of aminoguanidine and cyclosporine on lung allograft rejection.

BACKGROUND: Aminoguanidine, a nitric oxide synthase inhibitor, has been shown to reduce the inflammatory allogeneic response. Here we used it in combination with cyclosporine to evaluate its effect on a clinically relevant immunosuppressive protocol. METHODS: Orthotopic left lung transplantation was performed in 120 rats, of which 24 were syngeneic Lewis to Lewis controls, and allogeneic transplantations were performed across major histoincompatibility barriers (ACI to Lewis). We studied synchronous histologic changes accompanying cytokines and nitric oxide synthase messenger RNA by reverse transcriptase polymerase chain reaction in the grafted lungs. Nitrate/nitrite, oxidized degradation products of nitric oxide, were measured in the whole blood, as were concentrations of cyclosporine. Lung tissue was immunohistochemically stained for nitric oxide synthase protein. Rats receiving allografts were either untreated (24) or received low-dose cyclosporine (232 +/- 105 ng/mL blood by high-performance liquid chromatography), high-dose cyclosporine (2,046 +/- 664 ng/mL), aminoguanidine alone (800 mg. kg-1. day-1 intraperitoneally), or aminoguanidine plus low-dose cyclosporine. RESULTS: The results suggest that aminoguanidine combined with low doses of cyclosporine can reduce the allogeneic response across major histoincompatibilities in rodent lung transplantation. Its biologic effect may not exclusively depend on the inhibition of nitric oxide synthase and may, by other means, reduce proinflammatory cytokines. CONCLUSIONS: Aminoguanidine may be an effective adjuvant to conventional immunosuppression.

Animals↗

Role of lung reduction in lung transplant candidates with pulmonary emphysema.

BACKGROUND: The average waiting time for candidates for lung transplantation (LTx) with end-stage emphysema is 21 months with a 15% mortality. We hypothesized that lung reduction might offer an alternative to LTx. METHODS: Of 95 patients with end-stage emphysema evaluated by our LTx program, 45 were accepted for both lung reduction and LTx and 35 underwent lung reduction. RESULTS: All 35 patients survived lung reduction. Thirty patients had a follow-up of 3 months. There was a significant improvement (p < 0.05) of forced expiratory volume in 1 second (0.64 to 0.97 L), forced vital capacity (2.12 to 2.76 L), residual volume (5.62 to 4.26 L), maximum voluntary ventilation (28.1 to 38.5 L/min), 6-minute walk (904 to 1,012 feet), Borg dyspnea index (3.7 to 2.4), and arterial carbon dioxide tension (44.9 to 41.6 mm Hg). Twenty patients (66%) were removed from the LTx list due to their significant improvement (group A). Compared with the remaining 10 patients with 3 months of follow-up (group B), percent increase in forced expiratory volume in 1 second (70% in group A versus 27% in group B) and in forced vital capacity (41% group A versus 18% group B) and percent decrease in residual volume (26% group A versus 1.5% group B) were significantly better in group A (p < 0.01). Seven patients in group B were bridged to LTx; 6 of these patients (86%) had hypercarbia before lung reduction compared with 8 (40%) in group A (p < 0.05). All are alive after LTx: the forced expiratory volume in 1 second is 53% and the forced vital capacity is 64% of predicted. CONCLUSIONS: Lung reduction is safe and effective in selected LTx candidates with end-stage emphysema and has the potential to provide an alternative to LTx. Long-term follow-up is warranted to confirm these results.

Adult↗

Immediate effects of lung transplantation on right ventricular morphology and function in patients with variable degrees of pulmonary hypertension.

OBJECTIVES: This study sought to determine the immediate effects of lung transplantation on right ventricular morphology and function in patients with variable degrees of pulmonary hypertension and to evaluate these features as potential markers of immediate outcome. BACKGROUND: Selected lung transplant recipients with severe preoperative pulmonary hypertension have previously been shown to have a reduction in right ventricular size and improved function at follow-up evaluation. METHODS: Thirty-two consecutive patients (mean [+/- SD] age 44 +/- 11 years) were prospectively classified into three groups according to their pretransplantation pulmonary artery systolic pressure: severe pulmonary hypertensive group > or = 75 mm Hg, intermediate pulmonary hypertensive group 40 to 74 mm Hg and non-pulmonary hypertensive group < 40 mm Hg. Hemodynamic and transesophageal echocardiographic variables were measured immediately before and after lung transplantation. RESULTS: Pulmonary artery systolic and mean pressures markedly decreased after transplantation in the severe pulmonary hypertensive group (from 115 +/- 26 to 45 +/- 19 mm Hg and from 76 +/- 14 to 31 +/- 11 mm Hg, respectively, both p < 0.05). Mean pulmonary artery pressure decreased in the intermediate group (from 34 +/- 7 to 26 +/- 7 mm Hg, p < 0.05). Right ventricular end-diastolic area, end-systolic area and eccentricity index decreased in the severe pulmonary hypertensive group after transplantation. End-diastolic area also decreased in the intermediate pulmonary hypertensive group. Right ventricular fractional area change was not significantly different between groups and did not change consistently after transplantation. Three patients with severe pulmonary hypertension who had continued depression of right ventricular function after transplantation died in the immediate postoperative period. CONCLUSIONS: Lung transplantation is associated with an immediate decrease in pulmonary artery pressures and right ventricular size and normalization of septal geometry but variable changes in right ventricular function. Continued depression of right ventricular fractional area change may be a potential marker of poor outcome.

Adult↗

Early lung allograft function in twin recipients from the same donor: risk factor analysis.

BACKGROUND: Transplantation of lung allografts from the same donor into 2 recipients ("twinning") provides an opportunity to study recipient and donor factors that influence early allograft function. METHODS: Twenty-seven pairs of recipients were identified and evaluated using multivariate logistic regression analysis (p < 0.05). Four measures of early graft function were analyzed: alveolar-arterial gradient in the operating room, first alveolar-arterial gradient in the intensive care unit, alveolar-arterial gradient at 24 hours, and days of mechanical ventilation. RESULTS: Analysis of the pooled data without regard to pairing showed that alveolar-arterial gradient in the operating room was influenced by donor age, length of donor hospitalization, recipient mean pulmonary artery (PA) pressure at unclamping, and transplantation of a left lung. The alveolar-arterial gradient in the intensive care unit was correlated with donor age, donor cause of death, and mean PA pressure on arrival in that unit. Only mean PA pressure remained significant at 24 hours. Days of mechanical ventilation was determined by mean PA pressure on arrival in the intensive care unit, drop in mean PA pressure during operation, and diagnosis of the recipient. In the paired analysis, receiving a left lung, recipient diagnosis (pulmonary hypertension worse than others), and need of cardiopulmonary bypass were significantly associated with immediate graft dysfunction, although these influences did not persist beyond the immediate postoperative period. Donor arterial oxygen tension and time of ischemia were not significant predictors in any analysis. CONCLUSIONS: Immediate allograft function was associated with donor-related characteristics initially, but these lost importance over the ensuing 24 hours. Recipient PA pressure was an immediate and persisting influence. In the analysis of differences in function between the members of each pair, transplantation of the left lung, recipient diagnosis, and cardiopulmonary bypass were identified, but their influence did not persist beyond the first 6 hours.

Adult↗

Successful management of secondary aortoesophageal fistula.

Aortoesophageal fistula is a rare complication after thoracic aortic aneurysm repair. Six previously reported cases of aortoesophageal fistula management have been uniformly fatal. We present our successful management and review the literature of this topic.

Aged↗

A prospective trial of tacrolimus (FK 506) in clinical heart transplantation: intermediate-term results.

Between January 1, 1989, and December 31, 1994, we have treated 122 primary heart recipients with FK 506 (group I) and 121 with cyclosporine (group II). Fifty patients in the cyclosporine (CyA) group received no lympholytic induction (CyA alone) and 71 others received lympholytic induction with either rabbit antithymocyte globulin or OKT3 (CyA+LI). The mean follow-up was longer in the FK 506 group than in the CyA groups (3.2 +/- 1.3 vs 2.3 +/- 1.8 years; p< 0.01). Patient survival did not differ on the basis of the type of immunosuppression used. At 3 months after transplantation, the freedom from rejection in the FK 506 group was higher than that of the CyA-alone group (47% vs 22%, p < 0.01) but similar to that of the CyA+LI group (47% vs 53%). The linearized rejection rate (episodes/100 patient-days) of the FK 506 group (0.09 episodes) was lower (p < 0.05) than that of the CyA-alone group (0.26) and the CyA+LI group (0.13). The requirement for pulsed steroids to treat rejection was less in common in the FK 506 group than in either CyA group. Eighteen patients in the CyA group had refractory rejections; all resolved with FK 506 rescue. Two patients in the FK 506 group had refractory rejection that resolved with total lymphoid irradiation (n=1) and methotrexate therapy (n=1). Patients receiving FK 506 had a lower risk of hypertension and required a lower dose of steroids. Although the mean serum creatinine concentration at 1 year was higher in the FK 506 group, this difference disappeared after 2 years. No patients required discontinuation of FK 506 because of its side effects. Our intermediate-term results indicate that FK 506 compares favorably with CyA as a primary immunosuppressant in heart transplantation.

Adult↗

Transplant candidate's clinical status rather than right ventricular function defines need for univentricular versus biventricular support.

We have studied our experience since 1988 with 31 patients who required a mechanical circulatory bridge to transplantation and also had biventricular failure (mean right ventricular ejection fraction 11.8%) to better define the need for biventricular or total artificial heart support versus univentricular support. Clinical factors including preoperative inotropic need, fever without detectable infection, diffuse radiographic pulmonary edema, postoperative blood transfusion, and right ventricular wall thickness were compared with hemodynamic parameters including cardiac index, right ventricular ejection fraction, central venous pressure, mean pulmonary arterial pressure, and total pulmonary resistance for ability to predict need for mechanical or high-dose inotropic support for the right ventricle. Patients were grouped according to need for right ventricular support after left ventricular-assist device implantation: none (group A, 14) inotropic drugs (group B1, 7), and right ventricle mechanical support (group B2, 10). There were no differences in preimplantation hemodynamic variables. Groups B1 and B2 had significantly lower mixed venous oxygen saturation (39.2% vs 52.5% in group A; p < 0.001), greater level of inotropic need (p < 0.02), greater impairment of mental status, and lower ratio of right ventricular ejection fraction to inotropic need (0.37 vs 0.56 for group A; p < 0.02) before left ventricular-assist device implantation. A significant discriminator between groups B1 and B2 was the presence of a fever without infection within 10 days of left ventricular-assist device implantation (43% in group B1 vs 70% in group B2). Group B2 had more patients with preimplantation pulmonary edema seen on chest radiography and a greater requirement for postoperative blood transfusion (5 units of cells in group B1 vs 14.8 units in group B2. Right ventricular wall thickness at left ventricular-assist device explantation was 0.83 cm in group B2 vs 0.44 cm in group B1 (p < 0.05). Transplantation rates after bridging were 100% in group A, 71% in group B1, and 40% in group B2. Clinical factors that reflect preimplantation degree of illness and perioperative factors that result in impairment of pulmonary blood flow or reduced perfusion of the right ventricle after left ventricular-assist device implantation are now considered to be more predictive of the need for additional right ventricular support than preimplantation measures of right ventricular function or hemodynamic variables.

Adolescent↗

Prevalence and predictors of depression and anxiety-related disorders during the year after heart transplantation.

This study longitudinally evaluates prevalence, clinical characteristics, and risk factors for DSM-III-R Major Depression, Generalized Anxiety Disorder (GAD), associated Adjustment Disorders, and Post-Traumatic Stress Disorder related to the transplant (PTSD-T) in a large, representative sample of heart recipients followed during the first year after transplantation. Lifetime pretransplant prevalence as well as 1-year posttransplant rates were determined for the 154 recipients via standardized clinical interview schedules. Major Depression was the most prevalent disorder posttransplant (1- year rate of 17.3%), followed by PTSD-T (13.7%), and Adjustment Disorders (10.0%). There were no cases of GAD. Specific pretransplant and perioperative factors increased recipients' risk for any psychiatric disorder (vs none) posttransplant, including pretransplant psychiatric history; poor social supports from primary family caregiver, other relatives, and friends; the use of avoidance coping strategies for managing health problems; and low self-esteem early posttransplant. Within diagnostic groups, additional risk factors distinguished recipients with anxiety-related vs depressive disorders posttransplant: those at highest relative risk for anxiety had waited more briefly for a donor heart, were more likely to have a family psychiatric history, had the poorest family and friend support of all recipients, utilized the poorest coping skills, and had a poor sense of mastery. The findings have implications for the development of primary and secondary prevention strategies for psychiatric disorder in heart recipient populations.

Adaptation, Psychological↗

Effect of stavudine on human immunodeficiency virus type 1 virus load as measured by quantitative mononuclear cell culture, plasma RNA, and immune complex-dissociated antigenemia.

The antiviral effect of stavudine (2', 3'-didehydro-3'-deoxythymidine) against human immunodeficiency virus (HIV) type 1 was measured in 15 HIV-infected patients at baseline and at weeks 4, 10, 22, 34, and 52 of therapy. Patients received 0.1, 0.5, 1.0, or 2.0 mg/kg/day of stavudine. At all time points examined during the 52 weeks of therapy, the median virus titers in peripheral blood mononuclear cells were decreased 1-2 logs, and median immune complex-dissociated antigen levels were reduced 37%-67% compared with baseline values. Plasma RNA content measured by polymerase chain reaction was reduced approximately 0.5 log from baseline median values at both time points examined (weeks 10 and 52). These data demonstrate that stavudine has a substantial and durable antiviral effect.

Antigen-Antibody Complex↗

"Keyhole" coronary artery bypass surgery.

OBJECTIVE: The objective of this study was to identify the utility of "keyhole" thoracotomy approaches to single vessel coronary artery bypass surgery. SUMMARY BACKGROUND DATA: Although minimally invasive surgery is efficacious in a wide variety of surgical disciplines, it has been slow to emerge in cardiac surgery. Among 49 selected patients, the authors have used a left anterior keyhole thoracotomy (6 cm in length) combined with complete dissection of the eternal mammary artery (IMA) pedicle under thoracoscopic guidance or directly through the keyhole incision to accomplish IMA coronary artery bypass grafting (CABG) to the left anterior descending (LAD) coronary artery circulation or to the right coronary artery (RCA). METHODS: Keyhole CABG was accomplished in 46 of 49 patients in which this approach was attempted. All patients had significant (> 70%) obstruction of a dominant coronary artery that had failed or that was inappropriate for endovascular catheter treatment (percutaneous transluminal coronary angioplasty or stenting). Forty-four of the 49 patients had proximal LAD and 5 had proximal RCA stenoses. The mean age of the patients (35 men and 14 women) was 61 years, and their median New York Heart Association anginal class was III. The mean left ventricular ejection fraction was 42%. Femoral cardiopulmonary bypass support was used in 9 (19%) of 46 patients successfully managed with the keyhole procedure. Short-acting beta-blockade was used in the majority of patients (38 of 46) to reduce heart rate and the vigor of cardiac contraction. RESULTS: As 49 patients have survived operation, which averaged 248 minutes in duration. Median, postoperative endotracheal intubation time for keyhole patients was 6 hours with 25 of 46 patients being extubated before leaving the operating room. The median hospital stay was 4.3 days. Conversion to sternotomy was required in three patients to accomplish bypass because of inadequate internal mammary conduits or acute cardiovascular decompensation during an attempted off-bypass keyhole procedure Postoperative complications were limited to respiratory difficulty in three patients and the development of a deep wound infection in one patient. Nine (19%) of 46 patients received postoperative transfusion. There have been no intraoperative or postoperative infarctions, and angina has been controlled in all but one patient who subsequently had an IMA-RCA anastomotic stenosis managed successfully with percutaneous transluminal coronary angioplasty. CONCLUSIONS: These early results with keyhole CABG are encouraging. As experience broadens, keyhole CABG may become a reasonable alternative to repeated endovascular interventions or sternotomy approaches to recalcitrant single-vessel coronary arterial disease involving the proximal LAD or RCA.

Coronary Artery Bypass↗

Aerosolized cyclosporine in lung recipients with refractory chronic rejection.

This study evaluated aerosolized cyclosporine as rescue therapy for lung transplant recipients with unremitting chronic rejection. Nine patients with histologic active obliterative bronchiolitis and progressively worsening airway obstruction refractory to conventional immune suppression received aerosolized cyclosporine. Improvement in rejection histology was seen in seven of nine patients. We compared the changes in the FVC and FEV1 over time using linear regression analysis in these seven histologic responders and nine historical control patients. During the pretreatment period for both the experimental and control groups, the FVC and FEV1 declined at comparable rates. After aerosolized cyclosporine there was stabilization of pulmonary function, whereas in the controls there was continued decline. Cyclosporine blood levels were less than 50 ng/ml 24 h after an aerosolized dose of 300 mg in five patients receiving oral tacrolimus. Nephrotoxicity, hepatotoxicity, and a greater than expected rate of infection was not observed. This study suggests that aerosolized cyclosporine is safe and may be effective therapy for refractory chronic rejection in lung transplant recipients.

Adult↗

Predicting ICU length of stay following single lung transplantation.

STUDY OBJECTIVE: The aim was to identify potential predictors of ICU length of stay (LOS) for single lung transplant patients. DESIGN: Retrospective chart review. SETTING: University medical center. PATIENTS: All single lung transplant recipients for 1992 and 1993 at our institution. RESULTS: Data were collected from 69 patients. The median ICU LOS was 5 days, and this was highly correlated with the duration of mechanical ventilation. The mean acute physiology and chronic health evaluation (APACHE II) score was 10. Patients with pulmonary hypertension had the longest ICU LOS. Similarly, patients with a measured transpulmonary gradient of 20 mm Hg or less had a significantly shorter ICU LOS. Patients with an immediate postoperative PaO2/fraction of inspired oxygen (FIo2) ratio greater than 200 mm Hg and a flow mismatch between the two lungs of 30% or less also had a significantly shorter ICU LOS. Positive and negative predictive values for the immediate postoperative PaO2/FIo2 ratio of 200 mm Hg or less were 77% for an ICU LOS greater than 5 days, and the calculated receiver operating characteristic (ROC) curve area was 0.74. CONCLUSION: Overall, the immediate postoperative PaO2/FIo2 ratio of 200 mm Hg or less had the best positive and negative predictive values as well as the highest ROC curve area for predicting an ICU LOS greater than 5 days.

Critical Care↗