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Biomedical subjects

R R Lower

Publications and source records attributed to R R Lower.

At least 37 records · Page 2Linked to original sources
PubMed1985

Cyclosporine in cardiac transplantation.

Cyclosporine is a new immunosuppressive drug that acts early in the exposure of a host to allogeneic stimulation. It is a peptide of fungal origin. It has selective action on T cells, leaving the other cells of the immune system intact. It acts by preventing the function of the early activation signals of T cells, such as the acquisition of receptors for Il 2 and Il 1. It is lipophilic, moderately well absorbed by the gut, and metabolized by the liver. Factors affecting absorption or hepatic metabolism alter the amount of cyclosporine available in the circulation. Circulating levels can be measured by radioimmunoassay or HPLC. Doses should be tailored to trough levels taken approximately 12 hours after an oral or intravenous dose or to individual pharmacokinetic curves. The drug is nephrotoxic, hepatotoxic, and neurotoxic. In addition, cyclosporine has been associated with hypertension, hemolytic-uremic syndrome, increased incidence of intravascular thrombotic events, hypertrichosis, gum hyperplasia, pericardial effusion, and lymphoproliferative disorders. Despite these complications, cyclosporine usage seems to have improved short-term cardiac allograft survival and to have reduced the complications associated with side effects of steroids. As a result, cyclosporine has spawned a resurgence of interest in cardiac transplantation, which will be of great benefit in prolonging the lives of patients with end-stage cardiac disease.

Animals↗
PubMed1985

Serial coronary angioplasty for atherosclerosis following heart transplantation.

A 51-year-old man underwent orthotopic heart transplantation for end-stage ischemic cardiomyopathy. Forty-six months after the operation significant coronary artery disease was demonstrated in the allografted heart, with severe (90% to 95%) proximal stenosis of the left anterior descending artery as well as diffuse distal and smaller branch lesions. Percutaneous transluminal coronary angioplasty of the proximal left anterior descending artery lesion was successfully performed, reducing the stenosis to a 20% to 30% narrowing. Sixteen months later, repeated angiography showed sustained improvement of the proximal left anterior descending artery lesion and development of new significant lesions in the mid-left anterior descending and left circumflex coronary arteries. Coronary angioplasty of the mid-left anterior descending and proximal circumflex artery lesions was successfully performed and an angiogram four months later showed continued angiographic improvement at each of the distal sites. This case represents the first reported coronary artery angioplasty in a heart transplant recipient. It demonstrates the successful application of a non-operative myocardial revascularization procedure using percutaneous transluminal coronary angioplasty to achieve sustained palliation of significant coronary artery disease following heart transplantation.

Angioplasty, Balloon↗
PubMed1985

A prospective randomized trial of pretransfusion/azathioprine/prednisone versus cyclosporine/prednisone immunosuppression in cardiac transplant recipients: preliminary results.

Cyclosporine has gained acceptance as the immunosuppressive agent of choice in cardiac transplantation, but the validity of this assumption has yet to be established. Since January 1983, 25 patients have been randomly assigned to receive either conventional immunosuppression (azathioprine/antithymocyte globulin/prednisone) and pretransplant transfusion (PAAP, n = 11) or cyclosporine immunosuppression (cyclosporine and prednisone [CyA], n = 14). There was no difference in the age distribution (41 +/- 9 vs 38 +/- 11 years), indications for transplantation, preoperative serum creatinine level (1.2 +/- 0.2 vs 1.4 +/- 0.3 mg/dl), or postoperative follow-up time (13.5 +/- 5.4 vs 13.5 +/- 5.2 months). Mortality was not different (PAAP = 2, CyA = 3) and there was no difference in rejection episodes per patient (PAAP = 1.8, CyA = 1.9). Patients in the PAAP group had more serious infections (PAAP = 8, CyA = 3; P less than .02), but those in the CyA group developed a greater incidence of systemic hypertension (PAAP = 1, CyA = 10; p less than .02), pericardial effusion (PAAP = 0, CyA = 6; p = .05), and impaired renal function (creatinine 1.5 mg/dl, PAAP = 2, CyA = 11; p less than .02). Thus it appears that in this small series, cyclosporine is not associated with a significant increase in early survival. It does appear that patients on PAAP immunosuppression develop a greater number of serious infections, but the incidence of rejection episodes appears to be the same. Renal dysfunction and hypertension in patients receiving cyclosporine continue to be long-term concerns and may add to the morbidity and mortality of patients treated with this immunosuppressive regimen.

Adult↗
PubMed1984

Clinical significance of in situ detection of T lymphocyte subsets and monocyte/macrophage lineages in heart allografts.

Seventy fresh frozen biopsies of 22 human heart allografts were stained with mouse antihuman monoclonal antibodies (OKT-4, OKT-8, and OKM-1) using the immunoperoxidase method. The numbers of infiltrating cell phenotypes were correlated with patients' clinical status and histopathological diagnoses of the biopsies. At the clinically stable stage the number of OKT-4-positive cells (T-4 cells, helper/inducer), OKT-8-positive cells (T-8 cells, suppressor/cytotoxic), OKM-1-positive cells (M-1 cells, monocyte/macrophage) and T4/T8 ratio were lowest. During the early stage of rejection T-4 cells increased to the highest values. T-8 cells also increased significantly and T4/T8 ratio increased to the peak level as well. During the later stage of rejection, T-8 and M-1 cells increased to the highest values and T-4 cells and T4/T8 ratio decreased. After the treatment of rejection T-4 cells continued to decrease and T-8 cells and M-1 cells decreased to intermediate levels, but T4/T8 ratio still remained level. The numbers of T-4 cells, T-8, cells and M-1 cells were closely associated with the histopathologic severity of rejection. These results were also correlated with the allografts' prognoses. Interestingly, high T4/8 ratios with high number of T-4 cells in biopsies during the quiescent period were often followed by rejection episodes within 7 days, even though the pathological diagnoses were mild rejection. Another important finding was that after the treatment of rejection, persistent M-1 cells and low T4/T8 ratios in situ were frequently accompanied by recurrent rejections. Thus, monitoring of infiltrating cell phenotypes may be beneficial in the management of clinical cardiac transplantations.

Antibodies, Monoclonal↗
PubMed1983

Radiographic findings in the chest of patients following cardiac transplantation.

The postoperative chest radiographic findings in 38 patients undergoing orthotopic (37 patients) and heterotopic (1 patient) cardiac transplantation were evaluated. Findings were correlated with those of echocardiograms, sputum and blood cultures, and lung and heart biopsies. The radiographic manifestations in the chest of these patients are classified in the following three main categories: (1) Newly formed cardiac silhouette findings due to the transplanted heart itself, i.e., changes in size and shape of the new heart and pericardial effusion resulting from the placement of a smaller heart in a larger pericardial sac. (2) Infectious complications due to bacteria, fungal, and other opportunistic agents secondary to immunosuppressive therapy, and (3) Usual postoperative complications following thoracotomy and open-heart surgery.

Adolescent↗
PubMed1983

Long-term myocardial preservation: thromboxane production and coronary resistance.

In a series of 18 experiments on long-term myocardial preservation we evaluated whether vasoactive substances like thromboxane and prostacyclin are associated with the secondary increase in coronary resistance during preservation perfusion of the canine heart. In a control group (n = 12) and in a group treated with a specific thromboxane synthetase inhibitor (OKY 1581) coronary resistance was measured at 10 and 30 min, and at 1, 4, and 24 hr. At the same time intervals thromboxane A2 and prostacyclin (PGI2) production were determined as TXB2 and 6-keto PGF1 alpha, respectively. After OKY 1581 treatment no increase in TXB2 occurred and no secondary increase in coronary resistance was observed, while in the control group both TXB2 levels and resistance increased (P less than 0.01); 6-keto PGF1 alpha levels showed the same increase in control and in treated hearts. From this study it is concluded that during 24-hr myocardial preservation the characteristic secondary increase in coronary resistance is related to thromboxane production in the heart and is prevented by inhibition of thromboxane synthetase.

6-Ketoprostaglandin F1 alpha↗