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Biomedical subjects

B A Reitz

Publications and source records attributed to B A Reitz.

At least 91 records · Page 5Linked to original sources

Successful twenty-four-hour lung preservation with donor core cooling and leukocyte depletion in an orthotopic double lung transplantation model.

Donor core cooling with cardiopulmonary bypass is a valid method of clinical lung preservation. However, organ ischemia with this method is still limited to short-term intervals. Since circulating leukocytes participate in postischemic injury through the release of oxygen-derived free radicals, we examined whether leukocyte depletion by mechanical filtration could extend ischemic tolerance of the lung during preservation and subsequent double lung transplantation. Bovine donor lungs were preserved by donor core cooling (10 degrees to 15 degrees C) with cardiopulmonary bypass. Donor lungs were removed, stored in 4 degrees C donor blood for 24 hours, and transplanted. Graft function was studied for 6 hours after transplantation. Group 1 animals (n = 6) underwent standard cardiopulmonary bypass with whole blood for donor and recipient procedures. In group 2 (n = 6), leukocyte filters were incorporated into the cardiopulmonary bypass circuit in both donor and recipient operations. In group 2 recipient animals leukocyte counts decreased to 3% of mean baseline values and remained low during the experiment. Postischemic lung function (assessed by systemic arterial oxygenation, pulmonary artery pressure, pulmonary vascular resistance, airway pressure, lung water content, and end-point histologic characteristics) was significantly better preserved in the animals with leukocyte depletion. Leukocyte depletion by mechanical filtration in both donor and recipient improves the ischemic tolerance of the lung beyond that provided by donor core cooling alone, resulting in excellent lung function after 24 hours of ischemia.

Animals↗

Indium-111 myosin-specific antibodies and technetium-99m pyrophosphate in the detection of acute cardiac rejection of transplanted hearts: studies in a heterotopic rat heart model.

111In-labelled myosin-specific antibodies were evaluated as an indicator of early changes in acute rejection in a rat heart heterotopic transplant model. Uptake of antibodies was measured in allograft and isograft hearts of animals undergoing different regimens of cyclosporine treatment and compared with the uptake of technetium-99m pyrophosphate. The data were correlated with histological estimation of the severity of myocyte necrosis and signs of early rejection (venous cuffing and endocardial inflammation, indicators of perivascular infiltrate and intermyocyte extension, respectively). Myocyte necrosis in transplanted hearts was reflected by increases in technetium-99m pyrophosphate accumulation (r = 0.88) but was poorly correlated with labelled antibody uptake (r = 0.58). There was no positive correlation between the degree of early cardiac rejection and uptake of either of the radiopharmaceuticals: accumulation of the labelled antibodies paradoxically declined with increased histological severity scores, whereas that of technetium-99m pyrophosphate remained unchanged. Cyclosporine treatment augmented the uptake of labelled antibodies in transplanted hearts. This may be due to alterations in plasma membrane permeability brought about by the drug, resulting in a rise in antibody binding to intracellular myosin.

Animals↗

Current indications, risks, and outcome after pericardiectomy.

A retrospective analysis of the records of 60 patients who underwent pericardiectomy over a 10-year period (1980 to 1990) at The Johns Hopkins Hospital was performed. Indications for operation were effusive disease in 24 patients and constriction in 36 patients. Six patients (10%) with pericardial effusion had pain as the primary symptom necessitating intervention. The operative approach for pericardiectomy was median sternotomy in 52 patients (4 patients required cardiopulmonary bypass) and left anterior thoracotomy in 8 patients. Nine patients (5 with constriction and 4 with effusion) with a prior limited pericardial procedure required formal pericardiectomy. The operative mortality rate for pericardial effusion and constriction was 4.2% and 5.6%, respectively. Follow-up (median follow-up, 56.9 +/- 38.2 months) was obtained on 56 patients (93.3%). Actuarial survival at 1 year, 5 years, and 10 years for all patients was 82.1% +/- 5.1%, 71.7% +/- 6.7%, and 59.8% +/- 12.2%, respectively. A Cox proportional hazards regression analysis was performed using 20 clinical variables. A history of malignancy, previous pericardial procedure, and preoperative New York Heart Association class IV were found to be predictors of poor survival. All patients who underwent operation primarily for effusion with associated pain are alive and have improved functional capacity without steroid use. We conclude that pericardiectomy can be performed with low mortality and can result in good long-term survival and improved functional capacity. Patients who are seen primarily with pain refractory to steroid therapy can be relieved of symptoms with operation.

Actuarial Analysis↗

The two forms of bronchiolitis obliterans in heart-lung transplant recipients.

Bronchiolitis obliterans has emerged as the major long-term complication of heart-lung transplantation. We reviewed the histologic findings in lungs obtained from 11 patients who had received a combined heart-lung transplant at The Johns Hopkins Hospital. Ten lungs were obtained at autopsy, and one was obtained from a patient who was retransplanted because of severe bronchiolitis obliterans. Bronchiolitis obliterans was identified in seven of these 11 lungs. Three of the seven lungs with bronchiolitis obliterans were from patients who had received their transplants more than 6 months previously; the bronchiolitis obliterans in these patients was characterized by a relatively acellular concentric fibrosing process that was limited to the terminal bronchioles. The bronchiolitis obliterans in these three patients was felt to be secondary to chronic lung allograft rejection. Four of the seven patients with bronchiolitis obliterans had received their transplants less than 6 months previously; the bronchiolitis obliterans in these patients was focal and cellular. It extended into the distal alveolar spaces and, in several cases, was associated with aspirated material and foreign body-type giant cells. All four of these patients had concurrent infections, aspiration, or large airway obstruction, which were felt to be responsible for the development of bronchiolitis obliterans. Bronchiolitis obliterans in lung allograft recipients may have a variety of etiologies, and the etiology of this process in a particular case can often be deduced by the morphologic appearance of this lesion.

Adult↗

Transesophageal echocardiography in renal cell carcinoma: an accurate diagnostic technique for intracaval neoplastic extension.

Between 4 and 10% of patients with renal cell carcinoma have tumor involving the inferior vena cava and many of these patients have suprahepatic extension. In patients with intracaval neoplastic extension precise definition of the superior aspect of the tumor thrombus is critical. Transabdominal ultrasonography, computerized tomography (CT), magnetic resonance imaging (MRI) and inferior venacavography are all currently used to evaluate the inferior vena cava in these patients. Intraoperative transesophageal echocardiography was used to image the inferior vena cava in 5 patients with renal cell carcinoma and intracaval neoplastic extension. In each patient transesophageal echocardiography correctly revealed the superior extent of tumor thrombus. In 3 patients tumor thrombus was found at a higher level by transesophageal echocardiography than by CT, MRI and inferior venacavography. In all patients tumor imaging by transesophageal echocardiography correlated well with the gross appearance and extent of tumor found at operation. Echocardiography also documented the absence of residual gross tumor after resection. Transesophageal echocardiography was also useful to assess left ventricular function. Although each of these patients had a pulmonary artery catheter as well transesophageal echocardiography can be useful in situations when right atrial tumor thrombus prevents right heart catheterization. This small series demonstrates that intraoperative transesophageal echocardiography can accurately evaluate the extent of tumor thrombus and provides a means to assess myocardial function complementary to the pulmonary artery catheter.

Carcinoma, Renal Cell↗

Angiographic localization of spinal cord blood supply and its relationship to postoperative paraplegia.

Forty-seven patients underwent selective catheterization of middle and lower thoracic intercostal and upper lumbar arteries to define the origin of the artery of Adamkiewicz. One patient had significant atheroembolism, and a second had transient lower extremity paresthesias. No other complications occurred. The origin was found in 26 (55%), and 21 patients underwent thoracoabdominal aneurysm repair with this knowledge. When the critical lumbar or intercostal artery could be included as part of a long proximal or distal anastomosis, all 12 patients could be included as part of a long proximal or distal anastomosis, all 12 patients survived, and one was paralyzed. However, if the aneurysm repair mandated a midgraft anastomosis to intercostal arteries critical to spinal cord perfusion, seven of nine patients either died or were paralyzed (p less than 0.05). In the group of 19 patients operated on in whom spinal cord blood supply was not identified three patients had a technically unsuccessful operation; two died, and one was paralyzed. Twelve of 16 patients who had an adequate, but unsuccessful attempt at localization were treated by intercostal "neglect" and survived. Late paresis developed in two patients, but they are walking now. One of the patients who died had multiple systems failure and awakened paraplegic. She had a patent, enlarged, thoracic radicular artery at T-5 which probably supplied to spinal cord and which was missed angiographically. Paralysis was associated with aneurysm extent (group 2 and III B, dissections vs group 1 & 3, p less than 0.05). Selective intercostal angiography requires further refinement, but it is safe and offers the promise of understanding the mechanisms and risks of spinal cord complications after repair of extensive thoracoabdominal aneurysms.

Adult↗

Monitoring of spinal cord stimulation evoked potentials during thoracoabdominal aneurysm surgery.

Repair of a thoracoabdominal aneurysm involves a significant risk of ischemic injury to the spinal cord. Standard monitoring of somatosensory evoked potentials, which relies upon peripheral nerve stimulation, becomes nonspecific and insensitive during this surgery when aortic cross-clamping produces lower extremity ischemia causing a peripheral conduction block. Techniques for the insertion of percutaneous epidural electrodes, developed originally for pain management, have been adapted to this setting to permit direct stimulation of the spinal cord for intraoperative monitoring of evoked potentials. The clinical outcome in patients monitored by this technique has been consistent with evoked potential findings.

Aorta, Abdominal↗

Routine use of the left internal mammary artery graft in the elderly.

Left internal mammary artery (LIMA) grafts have better long-term patency rates than do saphenous vein grafts and result in improved late survival. The present study was undertaken to assess the results of LIMA grafting in the elderly. From 1980 through 1988, 723 patients 70 years of age or older had isolated coronary artery bypass grafting performed. During the first 5 years, only 11% of the elderly patients received LIMA grafts, whereas 86% having coronary artery bypass grafting since 1985 had LIMA grafts. Since 1986, LIMA use in the elderly has become routine, with 92% of patients receiving internal mammary artery grafts. During the first 5 years, elderly patients had a hospital mortality rate of 9.3%. Since 1985, the hospital mortality rate fell to 5.5%. In addition, the occurrence of major surgical complications was either unchanged or reduced in patients receiving LIMA grafts. Furthermore, late follow-up indicates a significantly improved 4-year survival rate in patients with internal mammary artery grafts compared with those without: 86 +/- 0.02% versus 77 +/- 0.03% (p less than 0.01). Analysis of multiple potential risk factors for early mortality was performed using multiple logistic regression and late survival using the Cox proportional hazards model. Although unmeasured predictor variables may confound retrospective analyses, LIMA grafting appears to be an independent predictor both of improved early and late survival.

Aged↗

Long-term results of total repair of tetralogy of Fallot in childhood.

Between 1958 and 1977, 170 children aged 10 years or less underwent total repair of tetralogy of Fallot at The Johns Hopkins Hospital. Follow-up data were obtained on 128 (90%) of the 143 who survived the operation at 10 to 28 years postoperatively (mean follow-up, 18 years). All patients completed an extensive questionnaire, and 59 returned for a thorough evaluation consisting of a history and physical examination, electrocardiogram, 24-hour Holter monitoring, exercise stress testing, pulmonary function testing, and two-dimensional and Doppler echocardiography. Late survival was excellent with only two of four known late deaths due to cardiac-related causes and with all 59 patients in New York Heart Association class I or II. None had cyanosis or clubbing. Normal sinus rhythm was present in 90%. One patient had complete heart block, and 75% had right bundle-branch block on the electrocardiogram. Right ventricular function was normal by echocardiography in 78%. Residual mild to moderate pulmonary stenosis was noted by Doppler study in 8 patients. Pulmonary regurgitation was present in 78%, but in only 11 patients was it graded as moderate and in none was it severe. Stress testing documented the excellent functional status of most patients, with 92% of predicted exercise time and 94% of maximum heart rate being attained. In the few who had impaired cardiac performance, this correlated best with moderate pulmonary regurgitation. Although the overall late functional status of patients undergoing repair in the first decade of life was very good, these patients need continued follow-up to assess the severity of pulmonary regurgitation and the need of possible intervention.

Adult↗

Leukocyte depletion results in excellent heart-lung function after 12 hours of storage.

Extended preservation of the heart-lung block for 12 hours in a bovine model of heart-lung transplantation was achieved using donor core cooling, static hypothermic storage, and reperfusion on cardiopulmonary bypass with leukocyte-depleted (LD) blood. Orthotopic heart-lung transplantation was performed with (n = 4, LD group) or without (n = 4, control group) LD blood during cardiopulmonary bypass. Postoperative measurements of cardiopulmonary function were made at 2, 4, and 6 hours after reperfusion. Only 2 animals (50%) of the control group survived more than 2 hours, whereas all animals in the LD group survived the study period. Arterial oxygen tension on 100% oxygen was 535.63 +/- 64.96 mm Hg and 146.45 +/- 90.9 mm Hg in the LD and control groups, respectively, at 2 hours (p less than 0.5) and 524.3 +/- 73.32 and 147.9 +/- 255.67 mm Hg at 6 hours. Pulmonary artery systolic pressure-to-systemic pressure ratio was 0.49 +/- 0.08 and 0.62 +/- 0.35 at 2 and 6 hours in the LD group. Extravascular lung water was 17.81 +/- 0.02 mL/kg (control group) and 11.28 +/- 9.15 mL/kg (LD group) at 2 hours. At reperfusion, the mean neutrophil count was 27 +/- 27 and 764 +/- 635 x 10(9)/L in the LD and control groups, respectively. This novel approach of leukocyte depletion during reperfusion after heart-lung preservation resulted in excellent cardiac and pulmonary protection.

Animals↗

Combination thalidomide and cyclosporine for cardiac allograft rejection. Comparison with combination methylprednisolone and cyclosporine.

Combination CsA with corticosteroids is the most commonly used maintenance immunosuppressive regimen after cardiac transplantation, although their high-toxicity profiles frequently limit their clinical benefit. Immunosuppressive agents that would act synergistically with CsA but without the toxicity profile of corticosteroids would be clinically useful. Thalidomide was removed from the market due to its teratogenic effects, although it has known immunomodulatory activity. The purpose of this study was (1) to determine whether maintenance immunosuppression with thalidomide and subtherapeutic doses of CsA can help prevent rat cardiac allograft rejection; and (2) to compare its synergism with CsA to the commonly used corticosteroid, methylprednisolone. ACI-LEW allografts were all treated with subtherapeutic doses of CsA (10 mg/g/day, s.c.) for 4 days. When CsA was then discontinued, severe rejection developed by posttransplant day 14. Group 1 received CsA alone. Group 2 received in addition oral thalidomide 100 mg/day for 14 days. Groups 3, 4, and 5 received CsA and methylprednisolone (low dose: 0.2 mg/kg/day s.c.; moderate dose: 2.0 mg/kg/day s.c.; and high dose: 20 mg/kg/day s.c. Twelve histologic parameters of rejection were semiquantitatively graded 0-4, and total pathology scores were determined. The combination of thalidomide and subtherapeutic CsA significantly reduced the severity of myocardial necrosis, interstitial inflammation, interstitial edema, and the total pathology score. Thalidomide was found to be equally as effective as low-, moderate-, and high-dose methylprednisolone. The results of this study suggest the potential clinical role of CsA and thalidomide in maintenance immunosuppressive regimens, thereby avoiding the use of corticosteroids.

Animals↗

Accelerated arteriosclerosis in heart transplant recipients is associated with a T-lymphocyte-mediated endothelialitis.

Accelerated arteriosclerosis has emerged as a major life-threatening complication in long-term survivors of heart transplantation. It has been proposed that accelerated arteriosclerosis is an immune-mediated complication of rejection. We observed a striking endothelialitis in the coronary arteries of two explanted hearts obtained from patients with severe transplant-related accelerated arteriosclerosis. This finding prompted us to review the pathologic changes in the coronary arteries of 23 autopsied patients who had received heart transplants. The infiltrate in these vessels was characterized using immunohistochemical stains for lymphocytes (CD45), macrophages (MAC-387), T lymphocytes (CD45RO), B lymphocytes (L-26), and smooth muscle cells (actin). In addition, a full panel of monoclonal antibodies was used on the fresh-frozen tissue available from one of the two explanted hearts. Ten of the eleven recipients with accelerated arteriosclerosis had a moderate to marked lymphocytic endothelialitis compared to 3 of 14 without transplant-related arteriosclerosis (P less than 0.005). Immunohistochemical staining of the paraffin-embedded material demonstrated that most of the lymphocytes in the subendothelial space of these vessels were T lymphocytes and that this infiltrate was associated with an accumulation of macrophages and a proliferation of smooth muscle cells in the intima. In the explanted heart from which fresh-frozen tissue was available for more detailed cell typing, the T cells marked predominantly as cytotoxic T lymphocytes (CD8+, CD2+). These results suggest that accelerated arteriosclerosis may be mediated, in part, by a cytotoxic T-lymphocyte-directed endothelialitis.

Adult↗