Characterization of antiendothelial cell and antiheart antibodies following heart transplantation.
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Aorta↗
Biomedical subjects
P Barath
Publications and source records attributed to P Barath.
Growth factors in pathogenesis of coronary arterial restenosis.
Restenosis occurs in 25% to 55% of patients within 6 months of successful angioplasty. The major histologic component of the restenotic lesion is intimal hyperplasia, which is almost certainly driven by growth factors. After vascular injury, smooth muscle cells proliferate, reaching a maximum rate at day 2. Smooth muscle cell proliferation diminishes as the vessel surface is re-endothelialized at about day 7, and by week 4 the smooth muscle cell mitotic rate returns to baseline of less than 1% per day. The events of the histologic evolution of arterial injury can be used to create a hypothetical paradigm for the role of growth factors in restenosis. Restenosis might logically be prevented by an inhibitory intervention at any of the various steps in the healing process.
Animals↗
Cutting balloon: a novel approach to percutaneous angioplasty.
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Angioplasty, Balloon, Coronary↗
Low density lipoprotein activates monocytes to express tumor necrosis factor.
We analyzed the effect of acetylated low density lipoprotein (aLDL) incubation on tumor necrosis factor (TNF) mRNA and protein expression in isolated resting human monocytes in serum free DMEM. TNF mRNA expression was about one third that of PMA and was dose dependent. The maximum stimulatory effect on TNF mRNA was at 250 micrograms/ml, while 500 micrograms/ml induced downregulation. The maximum stimulatory effect occurred at 6 hours, and by 24 hours TNF mRNA expression returned to the resting state. Acetyl LDL also induced the expression of immunoreactive TNF, reaching a sevenfold maximum above control at 12 hours following a 6 hour exposure period. The results suggest that aLDL is a potent stimulator of TNF expression in resting monocytes. This mechanism may be operational in atheroma evolution.
Blotting, Northern↗
Detection and localization of tumor necrosis factor in human atheroma.
Tumor necrosis factor (TNF) is a secretory product of normal macrophages that can cause cell necrosis, new blood vessel formation and thrombosis. These are also 3 characteristic features of the progression of stable atheroma to endothelial disruption. Accordingly, an immunohistochemical method was developed to detect TNF in human tissue. Using this method TNF positivity was demonstrated in 57 of 65 (88%) of tissue sections classified as atherosclerotic and in 5 of 11 (45%) sections classified as minimally atherosclerotic. TNF was absent in 6 sections classified as normal. TNF positivity was found not only in the cytoplasm of macrophages, but also in the cytoplasm and attached to the cell membrane of smooth muscle cells and endothelial cells of the human atheroma. Because TNF is known to cause new vessel formation, hemorrhagic necrosis and increased thrombogenicity, it may play a role in the evolution of uncomplicated to complex atheroma.
Antibodies, Monoclonal↗
Tumor necrosis factor gene expression in human vascular intimal smooth muscle cells detected by in situ hybridization.
We used immunohistochemistry to detect tumor necrosis factor (TNF) and in situ hybridization to detect TNF messenger RNA (mRNA) in the intimal mesenchymal-appearing cells and in the medial smooth muscle cells of human atherosclerotic arteries. Medial smooth muscle cells showed localization of immunoreactive TNF on the cell surface and did not express TNF mRNA. Conversely, in intimal mesenchymal-appearing cells, TNF was localized in the cytoplasm and TNF mRNA was expressed by in situ hybridization. Thus 89% of intimal cells were immunohistochemically positive for TNF, 96% of them were positive by in situ hybridization, and 76% were positive for the smooth muscle cell marker, HHF35. Our results suggest that intimal mesenchymal-appearing cells are mostly, but not exclusively, derived from smooth muscle cells. These cells express TNF, whereas the medial smooth muscle cells in the atherosclerotic human arteries do not. The expression of TNF by these mesenchymal-appearing cells may have implications regarding the evolution of the atherosclerotic plaque.
Arteries↗
NIH3T3 transforming gene not a general feature of atherosclerotic plaque DNA (atherosclerosis/oncogene/NIH3T3 transfection assay).
A recent study indicated that the DNA isolated from human coronary atherosclerotic lesions is capable of transforming NIH3T3 cells in culture. Using DNA isolated from rabbit aortic and human carotid atherosclerotic lesions, we failed to observe such transforming activity. Thus, NIH3T3 transforming activity does not appear to be a general feature of atherosclerotic lesions.
Animals↗
An update on transplantation in the geriatric heart transplant patient.
Discussions of the ethics involved in allocating scarce resources often proceed without a grounding in factual experience. This study explored whether there was statistical evidence to support the use of set age limits in patient selection criteria for heart transplantation. Many transplant teams have selection criteria that include age limits, excluding patients more than 60 or 65 years of age from being considered as transplant candidates. The hypothesis was made that patients in the age bracket of 60-69 should have a comparable success rate with transplantation to that of younger recipients when selected by using the same medical and psychiatric criteria. Based on their clinical observations, the authors postulated that the elderly would report better quality of life postoperatively than younger control subjects.
Adolescent↗
Bradyarrhythmias requiring pacemaker implantation after orthotopic heart transplantation: association with rejection.
Patients with severe sinus-node dysfunction that required pacemaker implantation after orthotopic heart transplantation were reviewed. During a 21-month period, 42 transplantations were performed in 41 patients. Five patients (12.2%) required a permanent pacemaker because of severe dysrhythmias. Three patients had moderate-to-severe cellular and/or humoral (vascular) rejection, and two of the five patients (40%) died. In the remaining two patients, bradyarrhythmias were due most likely to trauma to the sinus node during harvesting of the donor heart, and these patients have shown no evidence of significant rejection on repeated biopsies. A strong relationship was found between moderate or severe rejection and the development of significant bradyarrhythmias that required the placement of a permanent pacemaker. The development of severe dysrhythmias during the early or late posttransplantation period should be considered a manifestation of an ongoing rejection episode until proven otherwise. In our experience this evidence of rejection may imply a poor prognostic sign because it is associated with high mortality rates.
Adult↗
When does relaxation actually begin? The early phases of relaxation.
Exact timing of relaxation within the cardiac cycle was carried out by aid of polygrams consisting of epicardial segmental length curves, contractile force, left ventricular, left atrial and aortic pressures, indirect carotid curves, apex cardiogram, their derivatives and ECG reference tracings in the open-chest dog heart. The relaxation starts in late systole before aortic valve closure, at the nadir of the epicardial segmental length curve and at the climax of the contractile force curve. Onset of relaxation is indicated by the late systolic knee of the left ventricular pressure curve and, by the apex cardiogram as well as by the start of the downstroke of the negative phase on their first derivatives. The earliest phase of relaxation, from its beginning to the isovolumic relaxation period (IVRP), is proposed to be named "auxobaric relaxation period" (ABRP). Considerable lengthening was found during both ABRP and IVRP. This lengthening may provide an explanation for pre-inflow volume increments. The higher the frequency the longer the ABRP and the shorter the IVRP. In the more severe form of ischemia there is a sudden lengthening during ABRP and IVRP (late systolic bulging) whereas in the less severe form only onset of the relaxation is postponed within the cardiac cycle. The data suggest that ischemia leads to alterations in the early phase of relaxation even before involvement of the contraction phase (hypokinesis, akinesis, dyskinesis).
Animals↗
Combined antiviral and immunoglobulin therapy as prophylaxis against cytomegalovirus infection after heart transplantation.
BACKGROUND: Cytomegalovirus is a frequent cause of infection and morbidity after heart transplantation, especially in patients treated with antilymphocytic drugs where the incidence may be as high as 50%. METHODS: To determine the efficacy of combined antiviral and intravenous immune globulin therapy for prevention of cytomegalovirus disease in transplant recipients receiving OKT3 and to compare two different antiviral drug regimens, we reviewed 115 transplant recipients from December 1988 to December 1993 who survived for more than 30 days. Of these, 29 received oral acyclovir for 3 months (group A) and 86 received intravenous ganciclovir for 2 weeks followed by oral acyclovir up to 3 months (group G); all received six infusions of 5% intravenous immune globulin over 2 months. All patients had OKT3 for 10 to 14 days and triple-drug immunosuppression. RESULTS: Cytomegalovirus disease (pneumonitis, gastroenteritis, or leukopenia with fever) occurred in 10% of patients (12 of 115 patients) and was confirmed by positive culture, typical microscopic inclusions, or polymerase chain reaction. In 91 seropositive recipients, there was a trend to less cytomegalovirus disease in group G (3.0%, 2 of 67 patients) than in group A (12.5%, 3 of 24 patients) (p = 0.11), which was more apparent in recipients with seropositive donors where the incidence was reduced from 16.7% (group A) to 2.4% (group G; p = 0.08). In 24 seronegative recipients, cytomegalovirus disease incidence was higher overall and not significantly less in group G (26%, 5 of 19 patients) than in group A (40%, two of five patients) (p = Not significant). CONCLUSIONS: Prophylaxis with combined antiviral and immune globulin therapy produces a low (10%) incidence of cytomegalovirus disease in OKT3-treated heart transplant recipients. In seropositive recipients treated with combined therapy, ganciclovir may be more effective than acyclovir. Larger trials and more aggressive prophylactic strategies are needed in seronegative patients who receive hearts from seropositive donors.
Acyclovir↗
Donors with a history of cocaine use: effect on survival and rejection frequency after heart transplantation.
The frequency of cocaine use among donors is currently unknown. Cocaine has cardiotoxic effects and could affect the outcome of heart transplantation. To examine the frequency of nonintravenous cocaine use in organ donors and the outcome of heart transplantation with such donors, we retrospectively analyzed the clinical, biopsy, and donor information on 112 consecutive patients who underwent transplantation between December 1988 and August 1993. Ten patients were excluded because of incomplete information regarding the donor's cocaine status. Of the remaining 102 patients, 16 (16%) had a positive donor history for nonintravenous cocaine use (cocaine group) and 86 patients (84%) had a negative history (noncocaine group). Survival, frequency of cellular rejection (grade > or = 1B), and humoral rejection were compared between the two groups. Survival rates at 30 days (100% versus 97% +/- 2%) and at 1 year (93 +/- 7% versus 89 +/- 3%) were similar (p = not significant, cocaine versus noncocaine group). Freedom from rejection was similar at 30 days (81% +/- 10% versus 79% +/- 4% cellular rejection-free, 33% +/- 14% versus 60% +/- 6% humoral-free) and 6 months (34% +/- 12% versus 55% +/- 5% cellular-free, 16% +/- 11% versus 36% +/- 6% humoral-free) (p = not significant). No significant difference was found in donor inotropic support before procurement, ischemic time, length of stay in intensive care unit, or total stay in the hospital. In conclusion, a high incidence of nonintravenous cocaine use exists among donors. The outcome of patients who receive transplanted hearts obtained from nonintravenous cocaine users is favorable, suggesting that the use of such hearts is safe.
Adult↗