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Dental Equipment↗
Biomedical subjects
F Keith
Publications and source records attributed to F Keith.
Effects of dobutamine on hemodynamics and left ventricular performance after cardiopulmonary bypass in cardiac surgical patients.
BACKGROUND: Dobutamine is commonly used to improve ventricular performance after cardiopulmonary bypass. The authors determined the effect of dobutamine on hemodynamics and left ventricular performance immediately after cardiopulmonary bypass in patients undergoing coronary artery bypass graft surgery. METHODS: One hundred patients received sequential 3-min infusions of dobutamine at 0-40 microg x kg(-1) x min(-1) immediately after cardiopulmonary bypass. Ten additional patients who received no dobutamine served as controls. Hemodynamics and left ventricular performance (fractional area change by transesophageal echocardiography, stroke volume index, and thermodilution cardiac index) were measured. Mixed-effects modeling accounted for repeated-measures data and interindividual differences and allowed for potential effects of covariates. RESULTS: Heart rate increased in a dose-dependent manner. The slope of HR versus dobutamine dose was steeper in individuals in whom peak dobutamine dose was not reached compared with that in the remaining individuals; slope decreased 2.71 +/- 0.68% per year of age. Dobutamine affected blood pressure minimally, but slightly decreased pulmonary capillary wedge pressure and central venous pressure. Systemic vascular resistance initially increased with dobutamine 10 microg x kg(-1) x min(-1) and remained constant with larger doses. Dobutamine produced a dose-dependent increase in left ventricular performance, primarily by increasing heart rate, because stroke volume index decreased with dobutamine dose. CONCLUSION: Our results suggest that the response to graded dobutamine infusion in the post-cardiopulmonary bypass period differs from that previously reported. After cardiopulmonary bypass, the dominant mechanism by which dobutamine improves left ventricular performance is by increasing heart rate. Dobutamine affects blood pressure minimally.
Aged↗
Successful immunomodulation with intravenous gamma globulin and cyclophosphamide in an alloimmunized heart transplant recipient.
A highly human leukocyte antigen-sensitized heart transplant candidate underwent immunomodulation with intravenous gamma globulin and cyclophosphamide. His panel reactive antibody screen fell from 64% to 14%. He underwent successful orthotopic heart transplantation with a histoincompatible, T-cell cross-match-negative heart without the development of hyperacute rejection. The combination of intravenous gamma globulin and cyclophosphamide may be a simple and effective means to overcome the human leukocyte antigen-barrier in sensitized heart transplant candidates.
Combined Modality Therapy↗
Assessment of early left ventricular remodeling in orthotopic heart transplant recipients with cine magnetic resonance imaging: potential mechanisms.
We performed short axis cine magnetic resonance imaging studies in 11 patients 2 months after they underwent orthotopic heart transplantation (OHT), and in 10 control subjects, to measure left ventricular (LV) volumes, mass, and end-systolic wall stress to assess ventricular remodeling after OHT. Although there were no significant differences in ventricular volumes and ejection fractions between heart transplant recipients and control subjects, heart transplant recipients had significantly higher LV mass (198 +/- 61 vs 132 +/- 27 gm, p = 0.001). As a consequence of myocardial hypertrophy, end-systolic wall stress was significantly reduced in heart transplant recipients compared with control subjects (34 +/- 16 vs 57 +/- 10 kdyne/cm2, p = 0.001). Moreover, heart transplant recipients had significantly reduced end-systolic wall stress/volume ratio when compared with control subjects (0.89 +/- 0.3 vs 1.26 +/- 0.3 kdyne/cm2/ml, p < 0.01), indicating an already reduced LV contractility 2 months after heart transplantation. Univariate regression analysis revealed a significant correlation between LV mass and averaged cyclosporine levels, but no correlation between LV mass and blood pressure, cold ischemic time, acute rejection, age, body mass, blood pressure, plasma catecholamine levels, or plasma renin activity. Magnetic resonance imaging demonstrates early LV remodeling after OHT with reduced myocardial contractility. Cyclosporine may be contributing to these changes.
Adult↗
Iodine-123 metaiodobenzylguanidine scintigraphic assessment of the transplanted human heart: evidence for late reinnervation.
OBJECTIVES: This study attempted to determine whether cardiac sympathetic reinnervation occurs late after orthotopic heart transplantation. BACKGROUND: Metaiodobenzylguanidine (MIBG) is taken up by myocardial sympathetic nerves. Iodine-123 (I-123) MIBG cardiac uptake reflects intact myocardial sympathetic innervation of the heart. Cardiac transplant recipients do not demonstrate I-123 MIBG cardiac uptake when studied < 6 months from transplantation. However, physiologic and biochemical studies suggest that sympathetic reinnervation of the heart can occur > 1 year after transplantation. METHODS: We performed serial cardiac I-123 MIBG imaging in 23 cardiac transplant recipients early (< or = 1 year) and late (> 1 year) after operation. In 16 subjects transmyocardial norepinephrine release was measured late after transplantation. RESULTS: No subject had visible I-123 MIBG uptake on imaging < 1 year after transplantation. However, 11 (48%) of 23 subjects developed visible cardiac I-123 MIBG uptake 1 to 2 years after transplantation. Only 3 (25%) of 12 subjects with a pretransplantation diagnosis of idiopathic cardiomyopathy demonstrated I-123 MIBG uptake compared with 8 (73%) of 11 with a pretransplantation diagnosis of ischemic or rheumatic heart disease (p = 0.04). All 10 subjects with a net myocardial release of norepinephrine had cardiac I-123 MIBG uptake; all 6 subjects without a net release of norepinephrine had no cardiac I-123 MIBG uptake. CONCLUSIONS: Sympathetic reinnervation of the transplanted human heart can occur > 1 year after operation, as assessed by I-123 MIBG imaging and the transmyocardial release of norepinephrine. Reinnervation is less likely to occur in patients with a pretransplantation diagnosis of idiopathic cardiomyopathy than in those with other etiologies of congestive heart failure.
3-Iodobenzylguanidine↗
Biological features of leukaemic cells associated with autonomous growth and reduced survival in acute myeloblastic leukaemia.
The blast cells from up to 70% of patients with acute myeloblastic leukaemia exhibit a variable degree of autonomous growth in vitro, which is related to the production of autocrine growth factors. It has recently been established that patients with autonomous blast cell growth have both a lower remission rate and a higher relapse rate, compared to otherwise comparable patients whose blasts exhibit non-autonomous in vitro growth. In a group of 50 patients the actuarial disease-free survival for the autonomous growth group was 11% at 5 years compared to greater than 50% for the non-autonomous growth group. This data suggests that AML blasts with autocrine growth characteristics may be resistant to cytotoxic drug therapy. Here we present further data demonstrating that AML blasts with autonomous growth are relatively resistant to the induction of programmed cell death (apoptosis) and that this is related to the autocrine production of GM-CSF. Also AML blasts with autonomous growths have aberrant expression of genes associated with resistance to apoptosis induced by cytotoxic drugs. These include high expression of the bcl-2 oncoprotein and abnormalities of expression of the p53 tumour suppressor gene. Furthermore bcl-2 expression was found to be unregulated by both exogenous and autocrine GM-CSF suggesting that the documented negative prognostic effect of autonomous growth on treatment outcome in AML, is in part due to the regulatory effect of autocrine GM-CSF on bcl-2 expression, thus protecting cells from apoptosis induced by cytotoxic drug therapy.
Cell Division↗
Effect of orthotopic cardiac transplantation on peripheral vascular function in congestive heart failure: influence of cyclosporine therapy.
The objective of this study was to examine peripheral vascular function before and after cardiac transplantation and to assess the effect of immunosuppressive therapy on peripheral vascular reactivity. Peripheral vascular function abnormalities present in congestive heart failure may be reversed with cardiac transplantation, but immunosuppressive therapy may alter these changes in the peripheral vasculature. Venous occlusion plethysmography was used to study peripheral vascular function in nine patients with severe congestive heart failure who underwent cardiac transplantation. Forearm blood flow and forearm vascular resistance were measured in patients with congestive heart failure in response to cold stimulation, maximal hyperemia, and hand grip exercise (1) before transplantation; (2) 24 to 36 hours posttransplantation before the commencement of cyclosporine; (3) 6 to 8 days posttransplantation in the presence of therapeutic cyclosporine levels; and (4) 6 weeks posttransplantation. Venous capacitance was also measured. After cardiac transplantation, mean arterial pressure increased and remained elevated. Forearm blood flow initially increased after transplantation but subsequently decreased with cyclosporine. Cold-induced reflex sympathetic activation decreased immediately after transplantation but was significantly enhanced with cyclosporine. The maximal vasodilatory response following ischemic cuff occlusion and with 5 minutes of isometric hand grip exercise increased significantly after transplantation and remained improved at 6 weeks. Thus after cardiac transplantation, peripheral vasodilator function improves and is not altered by cyclosporine. However, with cyclosporine therapy resting forearm vascular resistance increases and reflex sympathetic vasoconstriction is enhanced, suggesting that cyclosporine may potentiate adrenergic-mediated peripheral vasoconstriction and thus may contribute to posttransplant hypertension.
Analysis of Variance↗
Oxygen free radicals in cardiac transplantation.
After prolonged ischemia, reperfusion of the myocardium with oxygenated blood results in high levels of superoxide anions. Several mechanisms for superoxide anion generation have been proposed, including increased xanthine oxidase activity, neutrophil activation, and arachidonate cascade activation. Superoxide anion accumulation may cause enzyme inactivation and lipid peroxidation in the sarcolemma with resultant intracellular calcium accumulation and excitation-contraction uncoupling. A review of a number of animal studies has shown that free radical scavengers such as superoxide dismutase and catalase can preserve myocardial function and metabolism during transplantation. In addition, other data indicate a role for inhibitors of free radical generation (i.e., allopurinol or oxypurinol), iron chelators (i.e., deferoxamine), or metabolic substrates such as L-glutamate in the inhibition of free radical myocardial injury. In addition, glutathione has been demonstrated to produce faster recovery of ventricular function in hypothermia preserved and reperfused rat hearts, presumably by inhibiting free radical production. Confirmatory data for human cardiac transplantation is not yet available.
Animals↗
Infection surveillance in cardiac transplantation.
Infections are a major cause of morbidity and mortality in cardiac transplantation. There is little information describing screening and prospective surveillance of heart recipients. We describe a surveillance program that was used for 35 patients, which screens and follows recipients through serologic, virologic, and immunologic parameters. Pretransplantation surveillance identified four (11.4%) patients whose skin tests with purified protein derivative (PPD) were positive, one patient with giardiasis, and seven (20%) recipients who were susceptible to cytomegalovirus (CMV). Twelve (34.3%) patients had CMV infections, only one of which was primary and involved a seropositive donor. The low rate of primary infection (14%) may result from our use of CMV-negative blood products. Seven (20%) recipients who were seronegative for toxoplasmosis received seropositive hearts, and disseminated toxoplasmosis developed in one of them. Eight (22.8%) patients had asymptomatic significant increases in Epstein-Barr virus antibody titers, without evidence of lymphoma. Fifteen (42.8%) recipients had at least one herpes simplex virus reactivation. Preventive, diagnostic, and early therapeutic interventions should occur as a result of infection surveillance, thus leading to a reduced risk of infection during the period after cardiac transplantation.
Cross Infection↗
Systemic embolization from thrombus in normal left ventricles.
It is extremely rare for a thrombus to form in a normal functioning left ventricle. We present two patients in whom this occurred without any plausable explanation. In both instances the patients presented with systemic emboli and had no heart disease or hypercoagulable state. The diagnosis was made by two-dimensional echocardiography and subsequently confirmed during surgery.
Adult↗
Intimo-intimal intussusception: an unusual presentation of aortic dissection.
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Adult↗
Distribution of lung vascular resistance after chronic systemic-to-pulmonary shunts.
Congenital cardiac shunts produce pathological lesions on the arterial side of the lung vasculature. We examined the effects of chronic shunts (14.2 +/- 1.2 mo) in 10 young dogs, between the left subclavian and the left lower lobe (LLL) artery, on pulmonary vascular pressure and flow (P-Q) relationships, segmental resistance with arterial and venous occlusion (AVO), and sensitivity to drugs. At final thoracotomy, mean LLL pulmonary arterial pressure (Ppa) was 23.2 +/- 4.3 mmHg compared with 11.9 +/- 0.9 in the right lung (P less than 0.05); two animals had LLL Ppa of 41 and 48 mmHg. The LLL artery and vein were cannulated, and pressure-flow (P-Q) and AVO measurements were made and compared with previous control LLL (n = 11) and contralateral right lower lobe (RLL, n = 5). Responses to serotonin, histamine, and vasodilators (diltiazem and isoproterenol) were evaluated. Comparisons of morphometric measurements were made between LLL and RLL. We found a significant increase in arterial resistance as measured with AVO and a hypersensitivity to serotonin in the shunt LLL, without changes in total pulmonary vascular resistance or P-Q measurements; vasodilators had a small effect only in the hypertensive lobes. Our data suggest that chronic shunts to the pulmonary circulation increase arterial resistance and sensitivity to serotonin, even in the absence of discernible morphometric changes, and that vasoconstriction may be an important precursor to the development of morphological lesions.
Animals↗
Effects of cyclosporine on renal function following orthotopic heart transplantation.
The early and late nephrotoxicity of cyclosporine was examined in 23 orthotopic heart transplant recipients and two heart-lung transplant recipients up to four years after the operation. Cyclosporine was given orally pre-operatively and intravenously for the first two to five days after the operation. Subsequent daily oral therapy, in two divided doses, was adjusted to maintain serum trough levels in the range of 150 vg/ml to 200 vg/ml. By six months after the transplantation, the trough level was reduced to approximately 100 vg/ml. The mean pre-operative creatinine was 119 +/- 27 microM/L. After the operation there was transient oliguria in all patients, the mean peak creatinine (251 +/- 104 microM/L) occurring on days two to five. By day eight, creatinine (138 +/- 68 microM/L) was not significantly different from the pre-operative value. The maximal cyclosporine trough level (479 +/- 216 vg/ml) was also seen on days two to five and declined (195 +/- 53 vg/ml) on day ten. Despite the temporal association, linear regression analysis demonstrated no correlation between the early increase in creatinine and the cyclosporine level. There was, however, a correlation between the pre-operative creatinine and the peak post-operative creatinine. Two patients required dialysis but no death could be attributed to renal failure. By six months after the operation, serum creatinine had increased to 145 +/- 53 microM/ml and thereafter, with gradual reduction in cyclosporine dosage serum creatinine levels stabilized at 197 +/- 97 mu/mL at two years.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Transcoronary and pulmonary vascular dynamics of endothelin-1 in heart transplant recipients.
BACKGROUND: Endothelin-1, a potent endothelium-derived vasoconstrictor peptide, has recently been shown to be elevated in heart transplant recipients and may be a participant in posttransplantation vasculopathy. METHODS: We measured peripheral venous endothelin-1 concentrations in eight heart transplant recipients and eight age- and gender-matched healthy controls. Subsequently, in 21 transplant recipients, right atrial, aortic, and coronary sinus plasma was obtained and endothelin-1 levels were measured. Potential correlations to donor and recipient age, cyclosporine levels, hemodynamic parameters, donor heart ischemic time, time from transplantation, and serum creatinine were examined. In eight more patients, right atrial levels of endothelin-1 were measured before and after endomyocardial biopsy to examine the effect of this procedure on endothelin-1 concentrations. RESULTS: Peripheral endothelin-1 concentrations were significantly higher in heart transplant recipients (45.6 +/- 1.8 versus 25.8 +/- 2.3, p < 0.001). Multiple regression analysis showed a significant correlation between right atrial endothelin-1 and pulmonary artery systolic pressure (r = 0.48), as well as serum creatinine (r = 0.52). No relation to blood pressure, right atrial pressure, pulmonary vascular resistance, recipient age, cyclosporine levels, or donor heart ischemic time was observed. In 11 patients, a 38% +/- 7% fall in endothelin-1 levels across the pulmonary bed was observed, suggesting extraction across the lung in these subjects. Nine patients had net release of endothelin-1 (95% +/- 26% rise) across the coronary vascular bed, whereas 12 patients showed net extraction (24% +/- 4% fall). Endomyocardial biopsy had no influence on endothelin-1 levels (prebiopsy: 48.3 +/- 1.7; postbiopsy: 42.3 +/- 2.34; p = Not significant). CONCLUSION: These findings suggest that endothelin-1 levels in transplant recipients may be influenced by renal function and may contribute to pulmonary hypertension. The significance of transcardiac release of endothelin in some patients is unclear: further studies are needed to determine the pathophysiologic significance of endothelin-1 in heart transplant recipients.
Adult↗
Cyclosporine-induced hemolytic uremic syndrome in a heart transplant recipient.
We report a case of hemolytic uremic syndrome associated with the use of cyclosporine in a heart transplant recipient. The patient manifested many classic signs and symptoms of hemolytic uremic syndrome, and a diagnosis was confirmed by kidney biopsy. Treatment with plasma exchange was effective in halting the hemolysis, but renal function failed to improve. Rechallenge with cyclosporine caused recurrence of microangiopathic hemolysis. Because of concerns regarding allograft rejection, an experimental immunosuppressive agent, RS-61443, was used that was effective in controlling rejection and was not associated with recurrence of hemolytic uremic syndrome.
Cyclosporine↗