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Biomedical subjects

W A Baumgartner

Publications and source records attributed to W A Baumgartner.

At least 19 recordsLinked to original sources
PubMed1992

Anatomic and clinical considerations of an internal mammary artery harvest.

In an effort to understand the perceived correlation of internal mammary artery harvesting and wound healing difficulties in the inferior margins of the sternotomy incision, we showed the cutaneous vascular perfusion in the sternal and xiphoid areas by India ink injection studies in cadavers. With these studies, we demonstrated an inherent paucity of nutrient supply to the inferior sternum and xiphoid area. The classic internal mammary artery harvest further compromises the blood supply to these areas. We believe that limiting the most inferior dissection of the internal mammary artery and not including the distal bifurcation leaves intact the lateral musculophrenic nutrient supply to the inferior sternum and xiphoid area and to the ipsilateral abdominal rectus muscle. These guidelines will help to prevent ischemic complications of this area and may aid in reconstruction. If the bifurcation is harvested, we believe that the removal of the avascular xiphoid cartilage at the time of the initial bypass procedure may eliminate this as a potential septic focus.

Abdominal Muscles↗
PubMed1992

Effects of cyclosporine on cerebral blood flow and metabolism in dogs.

Neurological side effects associated with cyclosporine immunosuppressive therapy are generally believed to occur with CsA blood concentrations above the therapeutic range. The effects of high blood CsA levels on cerebral hemodynamics, metabolism, and electrophysiologic activity were studied in acute (no CsA prior treatment) and chronic (with CsA prior treatment) dogs. In acute animals, when parenteral CsA (10 mg/kg or 25 mg/kg) was administered intravenously (CsA blood level 2000-22,000 ng/ml), slight but significant time-dependent decreases in cerebral blood flow (CBF), prolongation of absolute latencies of somatosensory-evoked potential (SSEP), and brainstem auditory-evoked responses (BAER) were noted. In the CsA chronically administered animals (oral CsA 25 mg/kg/24 hr for 14 days, CsA blood level 1077 ng/ml), baseline cerebral physiologic parameters were normal, and the cerebral responses to further administration of CsA (25 mg/kg, CSA blood level 56,000 ng/ml) intravenously were similar to those of the acute animals. Animals given Cremophor EL, the solvent for parenteral CsA preparation, showed similar cerebral responses to those observed in animals given CsA. Thus this study showed that CsA, regardless of the dose given, whether chronically or acutely administered, or the solvent for CsA all induced similar cerebral physiologic responses. We suggest that the cerebral physiologic and functional changes associated with parenteral CsA administration were small and were likely caused by its solvent, Cremophor EL, rather than CsA itself. Furthermore on the basis of our results, it is unlikely that high blood CsA per se can account for neurological side effects that occur in immunosuppressed patients.

Animals↗
PubMed1992

Detection of benzodiazepines in human hair by radioimmunoassay.

OBJECTIVE: In this preliminary investigation, we sought to determine whether a standard benzodiazepine radioimmunoassay (RIA) could detect three benzodiazepines in human hair. DESIGN: Hair samples of 20-50 strands (minimum 10 mg) were cut from eight patients receiving diazepam, two patients receiving alprazolam, three patients receiving lorazepam, and two negative controls. Samples were treated with ethanol and phosphate buffer washes at 37 degrees C to remove external contamination. The protein hair matrix was destroyed using proprietary procedures, then analyzed with Abuscreen RIA designed to detect various benzodiazepines and their metabolites, using oxazepam as a reference standard. SETTING: Patients were hospitalized in a locked psychiatric facility. PATIENTS: Twelve patients with chronic psychiatric conditions who had received therapeutic dosages of benzodiazepines for 1-11 months were included in the sample. One outpatient who reported heavy prior diazepam use was also included. MAIN OUTCOME MEASURE: Detection of benzodiazepines was well above a 1.5 ng/10 mg cutoff level with the Abuscreen assay. RESULTS: Diazepam was readily detected, but alprazolam and lorazepam were not detected. CONCLUSIONS: There is no test that can currently determine duration and extent of prior benzodiazepine use. Hair analysis for diazepam offers a potential, new clinical and research tool for characterizing prior level and extent of usage.

Adult↗
PubMed1992

Demonstration of cytomegalovirus nucleic acids in the coronary arteries of transplanted hearts.

Cytomegalovirus (CMV) infection has been associated with the development of accelerated arteriosclerosis in heart transplant recipients. This association prompted the authors to examine, using in situ hybridization techniques, the coronary arteries of 19 patients who had received heart transplants for the presence of CMV nucleic acids. Two probes were employed on formalin-fixed paraffin-embedded tissues. The first was an S35-labeled nick translated probe derived from CMV DNA. CMV nucleic acids were identified in the arterial intima of 5 (45%) of 11 transplanted hearts examined with this probe. Hybridization to cells morphologically consistent with endothelial cells, lymphocytes, and smooth muscle cells was identified. Hybridization was not detected in any of the hearts when a control probe, a vector without CMV DNA, was employed. The second probe that was used was a tritium-labeled strand-specific ribo-probe derived from the immediate early (IE1) gene of CMV. Using this second probe, hybridization was detected in the coronary arteries of three of five hearts that were positive with the DNA probe, in one of the hearts that was negative with the DNA probe, and in three (38%) of eight additional transplanted hearts. The pattern of hybridization was the same as that seen with the DNA probe, and no hybridization was detected when a control sense probe for the IE1 gene of CMV was employed. These results suggest that CMV nucleic acids are present in the coronary arteries of heart transplant recipients.

Adolescent↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

Myocardial high-energy phosphate metabolism and allograft rejection in patients with heart transplants.

To determine whether myocardial high-energy phosphate metabolism is altered in cardiac allograft patients undergoing rejection, 14 patients with heart transplants were examined with image-guided, one-dimensional, phase-encoded surface-coil phosphorus-31 nuclear magnetic resonance (NMR) spectroscopy on 19 occasions 39-2,021 days after transplantation. On average, patients underwent mild rejection (detected with endomyocardial biopsy) and had a reduced ratio of anterior myocardial phosphocreatine (PCr) to adenosine triphosphate (ATP) (1.57 +/- 0.50 [standard deviation] vs 1.93 +/- 0.2; P less than .01) compared with that of 17 healthy control subjects. Ratios of PCr to inorganic phosphate also appeared lower whenever detectable. However, P-31 NMR spectroscopy did not permit reliable identification of patients who required augmented therapy for rejection detected with biopsy either on the day of the P-31 NMR spectroscopic study or at the next scheduled biopsy 10-140 days thereafter (sensitivity, 50%, and specificity, 73% with use of cardiac-averaged PCr/ATP values for each heart; sensitivity, 88%, and specificity, 55% with use of the lowest myocardial PCr/ATP ratios measured in each heart).

Adenosine Triphosphate↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

Heart and heart-lung transplantation at the Johns Hopkins Hospital.

Since 1983, 120 patients have undergone heart transplantation and 18 patients have had heart-lung transplants at our institution. Transplantation is limited only by donor referrals but relaxation of donor criteria has increased donor availability. Immunosuppression currently consists of a 3-drug protocol of CsA, Aza, and P. Our current 1- and 5-year survival rates for heart transplants are 85% and 66%, respectively. The 1-year survival for heart-lung transplantation is 53%. Research continues in many areas of transplantation. The development of coronary artery disease in grafted hearts remains a problem. We have found that older donor age and Cmv infection are significant predictors of developing coronary disease. Routine successful extended heart-lung preservation has been difficult to achieve. A successful technique of prolonged preservation would allow for better matching, reduced logistics, and, potentially, increased numbers of donor organs.

Age Factors↗