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Biomedical subjects

J K Harrison

Publications and source records attributed to J K Harrison.

At least 19 recordsLinked to original sources
PubMed2001

Comparison of results of percutaneous balloon mitral commissurotomy in patients aged > or = 65 years with those in patients aged < 65 years.

Percutaneous balloon mitral commissurotomy (PBMC) is now first-line therapy in patients with symptomatic mitral stenosis (MS) and favorable valve morphology. Unfortunately, the outcome of Medicare-aged patients undergoing this procedure has not previously been defined. The results of PBMC in 55 patients > or = 65 years old (71 +/- 6 years) with moderate or severe MS were compared with 268 younger patients (47 +/- 10). Preprocedural New York Heart Association functional class and pulmonary pressures did not differ. The older patients had higher blood pressure, were more likely to be in atrial fibrillation and had higher valve scores (9.9 +/- 2.5 vs 8.6 +/- 2.2, p = 0.001). Procedural success was higher in the younger group (71% vs 55%, p = 0.013), with a greater increase in mitral valve area. Complications were similar in both groups and there were no periprocedural deaths. At 6 months a significant improvement in function class was seen in both groups. Restenosis, as assessed by serial echocardiography, occurred at a rate of 0.06 cm(2)/year in both groups, and functional class remained unchanged over 3 years. Event-free survival was similar at 48 months: 76% in the younger group and 69% in the older group. Our data thus demonstrates that PBMC can be safely performed in the Medicare-aged population. Despite less acute success in the older population, complication rates do not differ and decrement in valve area over time occurs at a similar rate. Functional class remains improved and event-free survival over 4 years appears similar in both groups. PBMC should thus be offered to patients with MS and suitable anatomy regardless of their age.

Adult↗
PubMed2001

Mutational analysis of the fractalkine chemokine domain. Basic amino acid residues differentially contribute to CX3CR1 binding, signaling, and cell adhesion.

Fractalkine (FKN/CX3CL1) is a unique member of the chemokine gene family and contains a chemokine domain (CD), a mucin-like stalk, a single transmembrane region, and a short intracellular C terminus. This structural distinction affords FKN the property of mediating capture and firm adhesion of FKN receptor (CX3CR1)-expressing cells under physiological flow conditions. Shed forms of FKN also exist, and these promote chemotaxis of CX3CR1-expressing leukocytes. The goal of the present study was to identify specific residues within the FKN-CD critical for FKN-CX3CR1 interactions. Two residues were identified in the FKN-CD, namely Lys-7 and Arg-47, that are important determinants in mediating an FKN-CX3CR1 interaction. FKN-K7A and FKN-R47A mutants exhibited 30-60-fold decreases in affinity for CX3CR1 and failed to arrest efficiently CX3CR1-expressing cells under physiological flow conditions. However, these mutants had differential effects on chemotaxis of CX3CR1-expressing cells. The FKN-K7A mutant acted as an equipotent partial agonist, whereas the FKN-R47A mutant had marked decreased potency and efficacy in measures of chemotactic activity. These data identify specific structural features of the FKN-CD that are important in interactions with CX3CR1 including steady state binding, signaling, and firm adhesion of CX3CR1-expressing cells.

Amino Acid Sequence↗
PubMed2001

Aortic dissection after angioplasty and stenting of an aortic coarctation: detection by intravascular ultrasonography but not transesophageal echocardiography.

In this case report, an iatrogenic dissection of the descending aorta occurred during balloon angioplasty and stenting of a recurrent coarctation. The dissection was not seen by transesophageal echocardiography, but intravascular ultrasonography, performed routinely during such procedures at this institution, identified the dissection and guided further therapeutic stent placement.

Adult↗
PubMed2001

Correlation between quantitative left atrial spontaneous echocardiographic contrast and intact fibrinogen levels in mitral stenosis.

An association between left atrial spontaneous echocardiographic contrast (LASEC) and thromboembolic events has been recognized. However, the appearance of LASEC and the assessment of its intensity are gain dependent. To evaluate the relation between LASEC intensity and coagulation activity, 11 patients with mitral stenosis underwent transesophageal echocardiography with quantitative integrated backscatter assessment of LASEC. Right and left atrial blood samples were evaluated for concentrations of coagulation markers, including intact fibrinogen, fibrinopeptide A, D-dimer, prothrombin fragment 1+2, and thrombin-antithrombin III complex. The patients were found to have significantly higher mean left atrial concentrations compared with right atrial concentrations of thrombin-antithrombin III (28.46 +/- 21.05 versus 3.21 +/- 7.16 ng/mL, respectively; P =.001) and fibrinopeptide A (32.78 +/- 17.54 versus 7.42 +/- 8.27 nmol/L, respectively; P <.001). Intact fibrinogen levels were similar in both atria, and a strong, direct correlation existed between left and right atrial intact fibrinogen levels (r = 0.78, P =.005). Quantitative integrated backscatter of LASEC correlated directly with left atrial fibrinogen level (r = 0.78, P =.013) but not with markers of thrombin generation (thrombin-antithrombin III) or activity (fibrinopeptide A). Our results confirm that patients with mitral stenosis have evidence of a regional hypercoagulable state in the left atrium. However, the intensity of LASEC assessed by quantitative integrated backscatter correlates with both right and left atrial intact fibrinogen level, a systemic marker of coagulation.

Adult↗
PubMed2001

Congenital unilateral pulmonary vein atresia: radiologic findings in three adult patients.

OBJECTIVE: The purpose of our study is to describe the radiologic findings of adult patients presenting with congenital unilateral pulmonary vein atresia. CONCLUSION: Chest radiography in affected patients typically reveals a small hemithorax and ipsilateral pulmonary artery as well as ipsilateral septal thickening. CT shows, in addition, ground-glass attenuation, the absence of a pulmonary vein connection to the left atrium, and abundant mediastinal venous collateral vessels. MR imaging is helpful in further characterizing the vascular abnormalities. Angiography may help to confirm the diagnosis.

Adult↗
PubMed2000

Randomized trial of contrast media utilization in high-risk PTCA: the COURT trial.

BACKGROUND: Previous in vitro and in vivo studies have suggested an association between thrombus-related events and type of contrast media. Low osmolar contrast agents appear to improve the safety of diagnostic and coronary artery interventional procedures. However, no data are available on PTCA outcomes with an isosmolar contrast agent. METHODS AND RESULTS: A multicenter prospective randomized double-blind trial was performed in 856 high-risk patients undergoing coronary artery intervention. The objective was to compare the isosmolar nonionic dimer iodixanol (n=405) with the low osmolar ionic agent ioxaglate (n=410). A composite variable of in-hospital major adverse clinical events (MACE) was the primary end point. A secondary objective was to evaluate major angiographic and procedural events during and after PTCA. The composite in-hospital primary end point was less frequent in those receiving iodixanol compared with those receiving ioxaglate (5.4% versus 9.5%, respectively; P=0.027). Core laboratory defined angiographic success was more frequent in patients receiving iodixanol (92.2% versus 85. 9% for ioxaglate, P=0.004). There was a trend toward lower total clinical events at 30 days in patients randomized to iodixanol (9.1% versus 13.2% for ioxaglate, P=0.07). Multivariate predictors of in-hospital MACE were use of ioxaglate (P=0.01) and treatment of a de novo lesion (P=0.03). CONCLUSIONS: In this contemporary prospective multicenter trial of PTCA in the setting of acute coronary syndromes, there was a low incidence of in-hospital clinical events for both treatment groups. The cohort receiving the nonionic dimer iodixanol experienced a 45% reduction in in-hospital MACE when compared with the cohort receiving ioxaglate.

Aged↗
PubMed2000

Chemokines and their receptors in neurobiology: perspectives in physiology and homeostasis.

Chemokines are a large family of small secreted proteins (8-14 kDa) associated with the trafficking of leukocytes in physiological immunosurveillance as well as inflammatory cell recruitment in different disease processes. A limited repertoire of chemokines and their specific cognate receptors are detectable in cells of the CNS such as microglia, astrocytes and neurons under physiological conditions. Coupled with distinct patterns of ligand and receptor expression in various pathologies including multiple sclerosis, trauma, neuro-AIDS, Alzheimer's disease, stroke, neuro- and glioblastomas, such phenomena have fueled the strong belief that chemokines must fulfill significant and potentially diverse functional roles in the CNS.

Animals↗
PubMed2000

Percutaneous stenting of right pulmonary artery stenosis in fibrosing mediastinitis.

Pulmonary artery stenosis is an uncommon complication of fibrosing mediastinitis. Previous medical and surgical therapies have provided limited clinical efficacy without objective evidence of clinical improvement. With the advantages of limited invasiveness and absent need for prolonged drug therapy, percutaneous stent deployment to relieve pulmonary artery obstruction represents a novel treatment for this rare disorder.

Adult↗
PubMed2000

Congenital agenesis of the right pulmonary artery.

A 44-year-old woman with recurrent pulmonary infections developed severe hemoptysis. Chest radiography revealed a hypoplastic right lung. Absence of the right pulmonary artery, a very rare congenital anomaly, was demonstrated by computed tomography and cardiac catheterization. Severe pulmonary hypertension in the contralateral lung precluded right pneumonectomy but percutaneous embolization of a large systemic arterial collateral to the right lung provided palliative relief of hemoptysis.

Adult↗
PubMed2000

NF-kappaB-dependent fractalkine induction in rat aortic endothelial cells stimulated by IL-1beta, TNF-alpha, and LPS.

Fractalkine is an endothelial cell-derived CX3C chemokine that is chemotactic mainly to mononuclear cells. Fractalkine was induced in rat aortic endothelial cells (RAEC) by interleukin-1beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), and lipopolysaccharide (LPS) transcriptionally and translationally. This induction correlated with increased NF-kappaB DNA binding activity as determined by gel mobility shift assay. Supershift assays revealed that the NF-kappaB subunits p50 and p65 were responsible for kappaB binding. Accordingly, we examined the role of NF-kappaB in fractalkine induction in RAEC through the use of an adenovirus-mediated mutant IkappaB as a specific inhibitor. Delivery of a dominant-negative form of IkappaBalpha in RAEC dramatically reduced the induction of fractalkine by these stimuli, suggesting a role for NF-kappaB activation in fractalkine induction. The inhibition of fractalkine expression by two potent NF-kappaB inhibitors, sulfasalazine and sanguinarine, further supported the central role of NF-kappaB in fractalkine transcription regulation and suggested a novel therapeutic target aimed at modulating leukocyte endothelial cell interaction.

Animals↗
PubMed2000

Experimental gliosarcoma induces chemokine receptor expression in rat brain.

Macrophage/microglial infiltration is a characteristic feature of brain tumors. The functional role(s) of these cells is complex and could include both trophic and suppressive effects on tumors. Information has recently emerged about the molecular signals that regulate the accumulation and function of monocytes in pathological disorders. Recent data indicate that the chemokine, monocyte chemoattractant protein-1 (MCP-1), a potent monocyte activating and chemotactic factor, is a primary regulator of the macrophage response in brain tumors. We hypothesized that if MCP-1 regulates macrophage/microglial infiltration, then expression of the specific MCP-1 receptor, CCR2, will be induced in peritumoral tissue and/or within brain tumors. Identification of a specific receptor that is preferentially expressed in brain tumors could be important both in terms of tumor biology and as a potential therapeutic target. We used an established experimental gliosarcoma model, induced by intracranial transplantation of cultured 9L cells into adult rat brain, to test this hypothesis. RT-PCR analysis showed high levels of both MCP-1 and CCR2 mRNA and Western blot analysis demonstrated increased CCR2 protein in tumor extracts. Immunocytochemistry showed CCR2 immunoreactive microglia in peritumoral tissue and, unexpectedly, that intrinsic tumor cells, rather than monocytes, were the predominant source of CCR2. These results demonstrate that CCR2 expression is markedly upregulated in this brain tumor model.

Animals↗
PubMed2000

Acute excitotoxic injury induces expression of monocyte chemoattractant protein-1 and its receptor, CCR2, in neonatal rat brain.

Chemokines are a family of structurally related cytokines that activate and recruit leukocytes into areas of inflammation. The "CC" chemokine, monocyte chemoattractant protein (MCP)-1 may regulate the microglia/monocyte response to acute brain injury. Recent studies have documented increased expression of MCP-1 in diverse acute and chronic experimental brain injury models; in contrast, there is little information regarding expression of the MCP-1 receptor, CCR2, in the brain. In the neonatal rat brain, acute excitotoxic injury elicits a rapid and intense microglial response. To determine if MCP-1 could be a regulator of this response, we evaluated the impact of excitotoxic injury on MCP-1 and CCR2 expression in the neonatal rat brain. We used a reproducible model of focal excitotoxic brain injury elicited by intrahippocampal injection of NMDA (10 nmol) in 7-day-old rats, to examine injury-induced alterations in MCP-1 and CCR2 expression. RT-PCR assays demonstrated rapid stimulation of both MCP-1 and CCR2 mRNA expression. MCP-1 protein content, measured by ELISA in tissue extracts, increased >30-fold in lesioned tissue 8-12 h after lesioning. CCR2 protein was also detectable in tissue extracts. Double-immunofluorescent labeling enabled localization of CCR2 both to activated microglia/monocytes in the corpus callosum adjacent to the lesioned hippocampus and subsequently in microglia/monocytes infiltrating the pyramidal cell layer of the lesioned hippocampus. These results demonstrate that in the neonatal brain, acute excitotoxic injury stimulates expression of both MCP-1 and its receptor, CCR2, and suggests that MCP-1 regulates the microglial/monocyte response to acute brain injury.

Animals↗
PubMed2000

Effect of variability in the interpretation of coronary angiograms on the appropriateness of use of coronary revascularization procedures.

BACKGROUND: Evidence from numerous studies of coronary angiography show differences between observers' assessments of 15% to 45%. The implication of this variation is serious: If readings are erroneous, some patients will undergo revascularization procedures unnecessarily and others will be denied an essential treatment. We evaluated the variation in interpretation of angiograms and its potential effect on appropriateness of use of revascularization procedures. METHODS AND RESULTS: Angiograms of 308 randomly selected patients previously studied for appropriateness of angiography, coronary artery bypass grafting (CABG), and percutaneous transluminal coronary angioplasty (PTCA) were interpreted by a blinded panel of 3 experienced angiographers and compared with the original interpretations. The potential effect on differences on the appropriateness of revascularization was assessed by use of the RAND criteria. Technical deficiencies were found in 52% of cases. Panel readings tended to show less significant disease (none in 16% of vessels previously read as showing significant disease), less severity of stenosis (43% lower, 6% higher), and lower extent of disease (23% less, 6% more). The classification of CABG changed from necessary/appropriate to uncertain/inappropriate for 17% to 33% of cases when individual ratings were replaced by panel readings. CONCLUSIONS: The general level of technical quality of coronary angiography is unsatisfactory. Variation in the interpretation of angiograms was substantial in all measures and tended to be higher in individual than in panel readings. The effect was to lead to a potential overestimation of appropriateness of use of CABG by 17% and of PTCA by 10%. These findings indicate the need for increased attention to the technical quality of studies and an independent second reading for angiograms before recommending revascularization.

Angioplasty, Balloon, Coronary↗
PubMed2000

Inhaled nitric oxide selectively dilates pulmonary vasculature in adult patients with pulmonary hypertension, irrespective of etiology.

OBJECTIVES: We sought to compare the responses of patients with pulmonary hypertension from primary and secondary causes (PPH and SPH, respectively) to inhaled nitric oxide (iNO) in the cardiac catheterization laboratory. BACKGROUND: Pulmonary hypertension can lead to right ventricular pressure overload and failure. Although vasodilators are effective as therapy in patients with PPH, less is known about their role in adults with SPH. Inhaled nitric oxide can accurately predict the response to other vasodilators in PPH and could be similarly utilized in SPH. METHODS: Forty-two patients (26 to 77 years old) with pulmonary hypertension during cardiac catheterization received iNO. Demographic and hemodynamic data were collected. Their response to iNO was defined by a decrease of > or =20% in mean pulmonary artery (PA) pressure or pulmonary vascular resistance (PVR). RESULTS: Mean PA pressures and PVR were lower during nitric oxide (NO) inhalation in all patients with pulmonary hypertension. Seventy-eight percent of patients with PPH and 83% of patients with SPH were responders to iNO. A trend was seen toward a greater response with larger doses of NO in patients with SPH. Nitric oxide was a more sensitive predictor of response (79%), compared with inhaled oxygen (64%), and was well tolerated, with no evidence of systemic effects. Elevation in right ventricular end-diastolic pressure appeared to predict poor vasodilatory response to iNO. CONCLUSIONS: Nitric oxide is a safe and effective screening agent for pulmonary vasoreactivity. Regardless of etiology of pulmonary hypertension, pulmonary vasoreactivity is frequently demonstrated with the use of NO. Right ventricular diastolic dysfunction may predict a poor vasodilator response.

Administration, Inhalation↗
PubMed2000

Contrast Agents for Cardiac Angiography: Osmolality and Contrast Complications.

Radiographic contrast agents have undergone a tremendous evolution over the past several decades. The creation of contrast agents with greater iodine carrying capacity and lower osmolality has improved imaging quality and reduced complications, including nausea, vomiting, congestive heart failure, and cardiac rhythm abnormalities. Whether differences exist among agents in terms of thrombotic complications remains controversial. Several characteristics including potential complications, toxicity, and cost must factor into the decision to use a particular contrast agent in cardiac procedures.

Journal Article↗
PubMed1999

Cultured rat microglia express functional beta-chemokine receptors.

We have investigated the functional expression of the beta-chemokine receptors CCR1 to 5 in cultured rat microglia. RT-PCR analysis revealed constitutive expression of CCR1, CCR2 and CCR5 mRNA. The beta-chemokines MCP-1 (1-30 nM) as well as RANTES and MIP-1alpha (100-1000 nM) evoked calcium transients in control and LPS-treated microglia. Whereas, the response to MCP-1 was dependent on extracellular calcium the response to RANTES was not. The effect of MCP-1 but not that of RANTES was inhibited by the calcium-induced calcium release inhibitor ryanodine. Calcium responses to MCP-1- and RANTES were observed in distinct populations of microglia.

Animals↗
PubMed1999

Predictors and significance of atrial rhythm before and six months after percutaneous balloon mitral commissurotomy.

Clinical, echocardiographic, and cardiac catheterization data were evaluated in 263 patients with mitral stenosis who were undergoing balloon commissurotomy to determine the predictors of atrial rhythm and its effect on functional status. Conversion from atrial fibrillation to sinus rhythm at 6 months after the procedure occurred in 16 of 86 patients (19%) and was predicted by the duration of atrial fibrillation, baseline functional class, and antiarrhythmic therapy; patients who remained in atrial fibrillation had a poorer functional status compared with those in sinus rhythm despite similar procedural results.

Adult↗