Biomedical subjects

J K Harrison

Publications and source records attributed to J K Harrison.

At least 55 records · Page 3Linked to original sources

PubMed1998

Excitotoxic brain injury stimulates expression of the chemokine receptor CCR5 in neonatal rats.

Chemokines interact with specific G-protein-coupled receptors to activate and direct recruitment of immune cells. Some chemokines are up-regulated in pathological conditions of the central nervous system, and recently several chemokine receptors, including CCR5, were identified in the brain. However, little is known about the regulation of expression of chemokine receptors in the brain. Direct intracerebral injection of N-methyl-D-aspartate (NMDA), an excitatory amino acid agonist, elicits reproducible focal excitotoxic brain injury; in neonatal rats, intrahippocampal NMDA injection stimulates expression of pro-inflammatory cytokines and elicits a robust microglia/monocyte response. We hypothesized that NMDA-induced neurotoxicity would also stimulate expression of CCR5 in the neonatal rat brain. We evaluated the impact of intrahippocampal injections of NMDA on CCR5 expression in postnatal day 7 rats. Reverse transcription polymerase chain reaction revealed an increase in hippocampal CCR5 mRNA expression 24 hours after lesioning, and in situ hybridization analysis demonstrated that CCR5 mRNA was expressed in the lesioned hippocampus and adjacent regions. Western blot analysis demonstrated increased CCR5 protein in hippocampal tissue extracts 32 hours after lesioning. Complementary immunocytochemistry studies identified both infiltrating microglia/monocytes and injured neurons as the principal CCR5-immunoreactive cells. These results provide the first evidence that acute excitotoxic injury regulates CCR5 expression in the developing rat brain.

Animals↗

PubMed1998

The Ross procedure: shorter hospital stay, decreased morbidity, and cost effective.

BACKGROUND: The Ross procedure has become an accepted and sometimes preferred alternative to mechanical aortic valve replacement. One criticism of the Ross procedure is that it may have a higher operative mortality, morbidity, and cost. Several groups have shown that this operation can be performed safely with less than 3% mortality. The issue of higher cost has not been resolved. In this retrospective study we compared a consecutive group of patients undergoing the Ross procedure with an age- and disease-matched group of patients who underwent mechanical aortic valve replacement. METHODS: From 1993 to 1996, 22 consecutive adult patients (age range, 20 to 57 years; mean, 38 +/- 14 years) underwent the Ross procedure. Twenty-seven patients (age range, 17 to 57 years; mean, 41 +/- 10 years) underwent mechanical aortic valve replacement between 1991 and 1996. The hospital cost (in 1996 dollars) and postoperative length of stay were calculated for each patient using Transition I, a hospital-wide cost accounting system. RESULTS: There was no hospital mortality in either group. The incidence of significant valve-related complication was 5% (1/22 patients) in the Ross procedure group and 22% (6/27 patients) in the mechanical valve group. There were two late deaths in the group with mechanical aortic valve replacement. The length of stay for the Ross procedure group was 5.9 +/- 2.1 days, versus 8 +/- 1.85 days for the mechanical valve group (p < 0.01). The mean hospital costs were not significantly different, $23,140 +/- $7,825 for the mechanical valve group and $23,226 +/- $6,960 for the group having the Ross procedure. CONCLUSIONS: The data from this review demonstrate that the Ross procedure can be done safely, with short hospital stays, decreased morbidity, and costs comparable with those of standard mechanical aortic valve replacement in patients with isolated aortic valve disease.

Adolescent↗

PubMed1998

Determinants of 15-year outcome with 1,119 standard Carpentier-Edwards porcine valves.

BACKGROUND: The determinants of long-term outcome 15 years or more after porcine valve replacement are poorly documented. METHODS: A retrospective review was performed of patients undergoing valve replacement with standard Carpentier-Edwards aortic (n = 531), mitral (n = 492), and tricuspid (n = 96) valves. RESULTS: Patient survival was 26%+/-3%, 23%+/-2%, and 31%+/-8% 15 years after aortic, mitral, and tricuspid valve replacements, respectively. Independent determinants of impaired long-term survival for aortic or mitral valve replacement were multiple valve replacement, older age, renal disease, lung disease, or coronary disease. Actual (versus actuarial) freedom from reoperation at 15 years was 86%+/-2%, 76%+/-2%, and 95%+/-2% after aortic, mitral, and tricuspid valve replacement, respectively. Risk factors for reoperation were young age for aortic or mitral valve replacement, previous operation for aortic valve replacement, and large valve size for mitral valve replacement. Freedom from thromboembolism was 77%+/-4%, 62%+/-9%, and 80%+/-5%; from hemorrhage, 95%+/-5%, 87%+/-4%, and 82%+/-6%; and from endocarditis, 94%+/-1%, 96%+/-1%, and 89%+/-5% 15 years after aortic, mitral, and tricuspid valve replacement, respectively. Risk factors for thromboembolism or hemorrhage were multiple valve replacement and age. CONCLUSIONS: The standard Carpentier-Edwards bioprosthesis continues to provide relatively low complication rates at 15 years, especially in the aortic and tricuspid positions, and especially in patients older than 60 years or with significant comorbdity.

Actuarial Analysis↗

PubMed1998

Expression of CCR5 increases during monocyte differentiation and directly mediates macrophage susceptibility to infection by human immunodeficiency virus type 1.

The stage of differentiation and the lineage of CD4+ cells profoundly affect their susceptibility to infection by human immunodeficiency virus type 1 (HIV-1). While CD4(+) T lymphocytes in patients are readily susceptible to HIV-1 infection, peripheral blood monocytes are relatively resistant during acute or early infection, even though monocytes also express CD4 and viral strains with macrophage (M)-tropic phenotypes predominate. CCR5, the main coreceptor for M-tropic viruses, clearly contributes to the ability of CD4+ T cells to be infected. To determine whether low levels of CCR5 expression account for the block in infection of monocytes, we examined primary monocyte lineage cells during differentiation. Culturing of blood monocytes for 5 days led to an increase in the mean number of CCR5-positive cells from <20% of monocytes to >80% of monocyte-derived macrophages (MDM). Levels of CCR5 expression per monocyte were generally lower than those on MDM, perhaps below a minimum threshold level necessary for efficient infection. Productive infection may be restricted to the small subset of monocytes that express relatively high levels of CCR5. Steady-state CCR5 mRNA levels also increased four- to fivefold during MDM differentiation. Infection of MDM by M-tropic HIV-1JRFL resulted in >10-fold-higher levels of p24, and MDM harbored >30-fold more HIV-1 DNA copies than monocytes. In the presence of the CCR5-specific monoclonal antibody (MAb) 2D7, virus production and cellular levels of HIV-1 DNA were decreased by >80% in MDM, indicating a block in viral entry. There was a direct association between levels of CCR5 and differentiation of monocytes to macrophages. Levels of CCR5 were related to monocyte resistance and macrophage susceptibility to infection because infection by the M-tropic strain HIV-1JRFL could be blocked by MAb 2D7. These results provide direct evidence that CCR5 functions as a coreceptor for HIV-1 infection of primary macrophages.

Cell Differentiation↗

PubMed1998

Cotransfection of second and third intracellular loop fragments inhibit angiotensin AT1a receptor activation of phospholipase C in HEK-293 cells.

Peptides from the intracellular regions of G protein-coupled receptors are useful probes of receptor-G protein coupling mechanisms. As a first step toward the genetic delivery of such "G protein inhibitors," we describe inhibition of angiotensin II (AII) receptor responses by expressed fragments of the second and third intracellular loops of the AT1a receptor (AT1a/i2 and AT1a/i3). Transient transfection of human embryonic kidney 293 cells with DNA encoding the rat AT1a receptor resulted in AII-dependent increases of inositol phosphates (maximum 4.5-fold). Cotransfection of AT1a/i2 and AT1a/i3 fragments raised the EC50 for AII stimulation of phospholipase C activity 5-fold (from 0.18 nM to 0.99 nM, n = 12, P < .001) and 3-fold (from 0.38 nM to 1.2 nM, n = 8, P < .002), respectively. The combined effect of AT1a/i2 and AT1a/3 was additive, and transfection of an alpha-1b adrenergic receptor third intracellular loop (alpha1b/i3) fragments also increased the EC50 for AII. Neither AT1a/i1 nor C-terminus (AT1a/Ct) constructs had significant effects on angiotensin responses. These data confirm a role for the second and third intracellular loops in angiotensin receptor responses and show the potential of this approach to blocking multiple phospholipase C-linked receptors.

Animals↗

PubMed1997

Lossy (15:1) JPEG compression of digital coronary angiograms does not limit detection of subtle morphological features.

BACKGROUND: Development of the "all-digital" cardiac catheterization laboratory has been slowed by substantial computer archival and transfer requirements. Lossy data compression reduces this burden but creates irreversible changes in images, potentially impairing detection of clinically important angiographic features. METHODS AND RESULTS: Fifty image sequences from 31 interventional procedures were viewed both in the original (uncompressed) state and after 15:1 lossy Joint Photographic Expert's Group (JPEG) compression. Experienced angiographers identified dissections, suspected thrombi, and coronary stents, and their results were compared with those from a consensus panel that served as a "gold standard." The panel and the individual observers reviewed the same image sequences 4 months after the first session to determine intraobserver variability. Intraobserver agreement for original images was not significantly different from that for compressed images (89.8% versus 89.5% for 600 pairs of observations in each group). Agreement of individual observers with the consensus panel was not significantly different for original images from that for compressed images (87.6% versus 87.3%; CIs for the difference, -4.0%, 4.0%). Subgroup analysis for each observer and for each detection task (dissection, suspected thrombus, and stent) revealed no significant difference in agreement. CONCLUSIONS: The identification of dissections, thrombi, and coronary stents is not substantially impaired by the application of 15:1 lossy JPEG compression to digital coronary angiograms. These data suggest that digital angiographic images compressed in this manner are acceptable for clinical decision-making.

Coronary Angiography↗

PubMed1997

Role of right ventricular and pulmonary functional abnormalities in limiting exercise capacity in adults with congenital heart disease.

This study evaluates right ventricular (RV) and pulmonary function during exercise in adults with congenital heart disease (CHD). Thirty-one patients with CHD involving the right side of the heart underwent symptom-limited bicycle exercise testing with simultaneous expired gas analysis and measurement of RV ejection fraction (EF). Twenty-one age-matched normal controls underwent the identical exercise protocol. Maximal oxygen consumption was lower in the CHD than in normal controls (19.5 +/- 6.4 vs 30.5 +/- 0.8 ml/kg/min, p = 0.0001 patients vs controls). Both heart rate (156 +/- 25 vs 171 +/- 13 beats/min, p = 0.01) and oxygen pulse (9.3 +/- 3.7 vs 12.3 +/- 3.7 ml/beat, p = 0.01), an indirect measure of stroke volume, were found to be lower in the CHD group at peak exercise. Pulmonary dysfunction was evidenced in the CHD group by decreased forced expiratory volume, forced vital capacity and maximum voluntary ventilation, and by a higher ventilation/expired carbon dioxide ratio at peak exercise (37.2 +/- 6.9 vs 33.0 +/- 5.4, p = 0.02), suggesting an increase in dead space ventilation. Maximal oxygen consumption was lower in patients whose RVEF decreased with exercise (17.6 +/- 5.4 vs 22.8 +/- 6.4 ml/kg/min, p = 0.03 "decrease RVEF" group vs "increase RVEF" group). Maximal oxygen consumption correlated with the change in RVEF only in the group whose RVEF decreased with exercise (r = 0.5, p = 0.03). In the group that had increased RVEF with exercise, maximal oxygen consumption correlated with forced expiratory volume (r = 0.7, p = 0.02). Thus, adults with CHD have a reduced functional capacity compared with normal controls. This phenomenon appears to be associated with both RV and pulmonary abnormalities.

Adult↗

PubMed1997

Effect of inadequate cardiac output reserve on exercise tolerance in patients with moderate mitral stenosis.

Twenty-nine patients with moderate mitral stenosis and 29 age-matched normal controls underwent symptom-limited upright bicycle exercise testing with simultaneous hemodynamic monitoring. Exercise tolerance in the mitral stenosis group was found to be limited by inadequate cardiac output reserve and not by resting mitral valve area or exercise pulmonary capillary wedge pressure.

Adult↗

PubMed1997

Simultaneous biplane coronary and pulmonary arteriography: a novel technique for defining the course of an anomalous left main coronary artery originating from the right sinus of Valsalva.

We present a novel technique employing biplane cineangiography with simultaneous left coronary and pulmonary angiography to define the anomalous course of the left main coronary artery when it originates from the right sinus of Valsalva. These biplane cinearterlograms clearly define the relationship of the left main coronary artery to the great vessels, allowing confident delineation of the interarterial variant from the other, benign variants. We illustrate the advantages of this technique with two cases in which the course of the anomalous left main coronary artery was incorrectly diagnosed using standard coronary arteriography and magnetic resonance imaging.

Adult↗

PubMed1997

Agonist-independent effect of an allosteric enhancer of the A1 adenosine receptor in CHO cells stably expressing the recombinant human A1 receptor.

The allosteric enhancer PD 81,723, a 2-amino-3-benzoylthiophene derivative, has been shown to potentiate agonist binding to A1 adenosine receptors (A1AdoRs) and to enhance the functional effects of adenosine and adenosine analogs. The objective of this study was to determine whether the apparent agonist-independent effect of PD 81,723 observed in CHO cells stably expressing the recombinant human A1AdoR was due to the potentiation of the action of endogenous adenosine, to the presence of constitutive receptor activity and/or to the binding of PD 81,723 to the agonist binding site of the A1AdoR. The allosteric enhancer PD 81,723, the A1AdoR agonist (R)-N6-(2-phenylisopropyl)adenosine and adenosine all significantly inhibited forskolin-stimulated cAMP accumulation in intact cells and increased [35S]-5'-(gamma-thio)triphosphate binding to cell membranes. The effects of adenosine on cAMP formation and [35S]-5'-(gamma-thio)triphosphate binding were attenuated by adenosine deaminase, but the effects of PD 81,723 were not. In the presence of ADA, the A1AdoR antagonist 8-cyclopentyl-1,3-dipropylxanthine increased forskolin-stimulated cAMP accumulation in cells expressing the recombinant human A1AdoR but not in nontransfected CHO cells. In binding experiments, the agonist (R)-N6-(2-phenylisopropyl)adenosine, but not PD 81,723, significantly displaced the specific binding of the A1AdoR agonist [3H]-N6-cyclohexyladenosine and the antagonist [3H]-8-cyclopentyl-1,3-dipropylxanthine. The results of this study demonstrate that in CHO cells stably expressing the recombinant human A1AdoR, the agonist-independent effect of PD 81,723 is not due to potentiation of the action of endogenous adenosine or mediated by the binding of the allosteric enhancer to the agonist binding site of the recombinant human A1AdoR. It is possible that these effects are due to potentiation of constitutive receptor activity by PD 81,723.

Adenosine↗

PubMed1996

Identification of two rat genes orthologous to the human interleukin-8 receptors.

The genes encoding two functional human interleukin-8 (IL-8) receptors have been identified by molecular cloning techniques and they are members of the rhodopsin G-protein coupled receptor (GCR) superfamily. We report the molecular cloning of two rat GCR genes (rat CXCR1-like and rat CXCR2) whose conceptualized amino acid sequences are approximately 70% identical to the human IL-8 A and B receptor subtypes. The murine GRO-like peptide, macrophage inflammatory peptide-2 (MIP-2), elevates intracellular calcium levels in HEK293 cells expressing the rat CXCR2 receptor. Southern blot analysis of restriction-digested rodent and human genomic DNAs indicate that rat CXCR1-like and CXCR2 are: 1) each single copy genes in the rat genome; 2) most closely related to the human IL-8 receptor genes; and 3) orthologous to two previously identified murine genes. CXCR2 mRNA is detected in adult rat lung, spleen, and neutrophils. CXCR1-like mRNA can be detected in adult rat lung, native rat macrophages, and a rat alveolar macrophage cell line (NR8383). These data identify the rat orthologs of the human IL-8 receptors, and describe cellular and tissue targets of rat C-X-C chemokine peptides.

Amino Acid Sequence↗

PubMed1996

Esophageal varices in association with unilateral pulmonary vein atresia.

A 27-yr-old woman with recurrent episodes of hemoptysis (and hematemesis due to esophageal varices) was found to have unilateral pulmonary vein atresia. Reversed flow in the left pulmonary artery, a finding highly suggestive of this rare congenital anomaly, was demonstrated during cardiac catheterization. The definitive diagnosis was afforded by pulmonary wedge angiography, which not only demonstrated the atretic leftsided pulmonary veins, but also revealed a serpiginous system of systemic collateral veins to be the cause of her esophageal varices. Pneumonectomy of the nonfunctioning hypoplastic lung, the most successful approach to this disorder, may be complicated by severe bleeding of the numerous systemic arterial collateral vessels transected during surgical mobilization of the affected lung. Percutaneously delivered vascular occlusion coils were used in this case to occlude the large systemic to pulmonary artery collateral arteries immediately prior to pneumonectomy. Intra- and perioperative bleeding was minimal, and the patient has done well without further episodes of hemoptysis or hematemesis. Percutaneous occlusion of systemic to pulmonary collaterals may prove useful as a preoperative step for other congenital heart disease patients requiring lung or heart/lung transplantation.

Adult↗

PubMed1996

Late conduit occlusion after modified Fontan procedure with classic Glenn shunt.

A number of patients with complex congenital heart disease who were initially palliated with a classic Glenn shunt subsequently underwent modified Fontan procedures. This report discusses the operative management of complete occlusion of right atrial-to-right ventricular conduits in patients with patent classic Glenn shunts. The literature is reviewed regarding similar patients, and alternative treatment strategies are discussed.

Adult↗

PubMed1996

Delayed right heart failure following lung transplantation.

Dynamic right ventricular outflow tract obstruction (RVOTO) has been reported following lung transplantation for pulmonary hypertension, usually in association with the use of inotropic agents. This report describes delayed severe right-sided heart failure associated with right ventricular outflow tract obstruction following sequential bilateral lung transplantation and closure of a ventricular septal defect. The patient had no evidence of outflow tract obstruction in the early posttransplant period but developed progressive right heart failure more than 2 months later. Catheterization revealed dynamic RVOTO and an elevated right ventricular end-diastolic pressure. The patient was treated with metoprolol tartrate and diltiazem hydrochloride with resolution of the outflow tract obstruction and heart failure. This case demonstrates that RVOTO can occur in the late posttransplant period and must be included in the differential diagnosis for patients who develop right-sided heart failure.

Adrenergic beta-Antagonists↗

PubMed1996

Total pulmonary artery occlusion immediately after lung transplantation: successful revascularization with intravascular stents.

Occlusion of the pulmonary artery anastomosis is an uncommon early complication of lung transplantation which necessitates emergency surgical revision. Percutaneous correction of such a complication has not been previously reported. We report a patient who had total pulmonary artery occlusion less than 24 hours after right single lung transplantation with successful revascularization achieved by means of percutaneously delivered endovascular stents.

Adult↗

PubMed1995

Balloon aortic valvuloplasty in adults: failure of procedure to improve long-term survival.

OBJECTIVES: This study sought to determine the long-term outcome of adult patients undergoing percutaneous balloon aortic valvuloplasty. BACKGROUND: Percutaneous balloon aortic valvuloplasty has been offered as an alternative to aortic valve replacement for selected patients with valvular aortic stenosis. Although balloon aortic valvuloplasty produces an immediate reduction in the transvalvular aortic gradient, a high incidence of restenosis frequently leads to recurrent symptoms. Therefore, it is unclear whether balloon aortic valvuloplasty impacts on the long-term outcome of these patients. METHODS: Clinical, hemodynamic and echocardiographic data were collected at baseline in 165 patients undergoing balloon aortic valvuloplasty and examined for their ability to predict long-term outcome. RESULTS: The median duration follow-up was 3.9 years (range 1 to 6). Ninety-nine percent follow-up was achieved. During this 6-year period, 152 patients (93%) died or underwent aortic valve replacement, and 99 (60%) died of cardiac-related causes. The probability of event-free survival (freedom from death, aortic valve replacement or repeat balloon aortic valvuloplasty) 1, 2 and 3 years after valvuloplasty was 40%, 19% and 6%, respectively. In contrast, the probability of survival 3 years after balloon aortic valvuloplasty in a subset of 42 patients who underwent subsequent aortic valve replacement was 84%. Survival after aortic valvuloplasty was poor regardless of the presenting symptom, but patients with New York Heart Association functional class IV congestive heart failure had events earliest. Univariable predictors of decreased event-free survival were younger age, advanced congestive heart failure symptoms, lower ejection fraction, elevated left ventricular end-diastolic pressure, presence of coronary artery disease and increased left ventricular internal diastolic diameter. Stepwise multivariable logistic regression analysis found that only younger age and a lower left ventricular ejection fraction contributed independent adverse prognostic information (chi-square 14.89, p = 0.0006). CONCLUSIONS: Long-term event-free and actuarial survival after balloon aortic valvuloplasty is dismal and resembles the natural history of untreated aortic stenosis. Aortic valve replacement may be performed in selected subjects with good results. However, the prognosis for the remainder of patients who are not candidates for aortic valve replacement is particularly poor.

Aged↗

PubMed1995

Left ventricular performance improves late after aortic valve replacement in patients with aortic stenosis and reduced ejection fraction.

EF in patients with aortic stenosis and reduced EF who underwent aortic valve replacement did not improve by 1 week postoperatively despite rectification of afterload mismatch. By 6 months, however, EF significantly improved without any further change in ventricular loading conditions. This implies that the benefit from aortic valve replacement (when measured by LV ejection performance) may not be evident until late postoperatively.

Aged↗

PubMed1995

Carcinoid heart disease. Correlation of high serotonin levels with valvular abnormalities detected by cardiac catheterization and echocardiography.

BACKGROUND: Although serotonin has been postulated as an etiologic agent in the development of carcinoid heart disease, no direct evidence for different ambient serotonin levels in cardiac and noncardiac patients has been reported to date. METHODS AND RESULTS: The present study reviews our experience with 604 patients in the Duke Carcinoid Database. Nineteen patients with proven carcinoid heart disease (by cardiac catheterization and/or echocardiogram) were compared with the remaining 585 noncardiac patients in the database with regard to circulating serotonin and its principal metabolite, 5-hydroxyindole acetic acid (5-HIAA). No significant demographic differences existed between the cardiac and noncardiac groups; however, typical carcinoid syndrome symptoms (ie, flushing and diarrhea) were almost threefold more common in the cardiac group (P < .001). Compared with the noncardiac group, heart disease patients demonstrated strikingly higher (P < .0001) mean serum serotonin (9750 versus 4350 pmol/mL), plasma serotonin (1130 versus 426 pmol/mL), platelet serotonin (6240 versus 2700 pmol/mg protein), and urine 5-HIAA (219 versus 55.3 mg/24 h) levels. The spectrum of heart disease among the 19 patients showed a strong right-sided valvular predominance, with tricuspid regurgitation being the most common valvular dysfunction (92% by cardiac catheterization; 100% by echocardiogram). CONCLUSIONS: These data suggest that serotonin plays a major role in the pathogenesis of the cardiac plaque formation observed in carcinoid patients.

Carcinoid Heart Disease↗