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Biomedical subjects

J K Harrison

Publications and source records attributed to J K Harrison.

At least 73 records · Page 4Linked to original sources
PubMed1995

Predictors of outcome of tricuspid valve replacement in carcinoid heart disease.

The cardiac valvular surgical experience of patients in the Duke Carcinoid Database was reviewed to assess operative outcome. Of the 604 patients in the database, 19 patients with carcinoid heart disease were identified by cardiac catheterization or echocardiography, or both. Eight of these underwent tricuspid valve replacement surgery with bioprostheses (2 also had open pulmonic valvuloplasty). Compared with patients medically managed, surgically treated patients were similar with the exception that they had higher right atrial mean (17 +/- 6 vs 9 +/- 4 mm Hg, p = 0.03) and v-wave (27 +/- 6 vs 17 +/- 7 mm Hg, p = 0.04) pressures. Of the 8 surgical patients, 5 (63%) died within 30 days. Causes of death included tricuspid valve thrombosis, cerebral vascular accident, coagulopathy, renal failure, and intractable right heart failure. High comorbidity was present in all 8 patients. There was a weak trend (p = 0.17) toward lower Charlson comorbidity indexes in survivors (6.7 +/- 0.6) compared with nonsurvivors (7.6 +/- 0.9). Age was significantly lower (p = 0.036) in survivors (46 +/- 13 years) compared with nonsurvivors (69 +/- 4 years). Extended follow-up revealed 2 patients who survived beyond a decade. Review of 47 carcinoid valve replacement cases (Duke Carcinoid Database and 39 published cases) revealed a 30-day mortality of 56% for patients > 60 years of age, and 0% for those < or = 60 years of age (p < 0.0001). Although valve replacement surgery can afford prolonged palliation from carcinoid heart disease, it is associated with a significant mortality risk. Careful preoperative risk stratification by age and comorbidity may provide a means for optimal selection of surgical candidates.

Adult↗
PubMed1995

Transesophageal echocardiographic assessment of reversal of systolic pulmonary venous flow in mitral stenosis.

Transesophageal echocardiography and diagnostic cardiac catheterization were performed in 36 patients with symptomatic mitral stenosis to assess the incidence and significance of systolic flow reversal in the pulmonary veins. Mitral regurgitation was graded by contrast ventriculography, and left atrial pressure was directly measured after transseptal puncture. Pulmonary venous flow was recorded with transesophageal Doppler imaging from the left upper pulmonary vein. Early systolic flow reversal was identified in 11 patients (31%) and began an average of 58 +/- 13 ms after QRS onset. This pattern correlated strongly with the presence of atrial fibrillation or flutter. Late systolic flow reversal was identified in 8 patients (22%), beginning an average of 245 +/- 46 ms after the QRS complex. These patients had higher left atrial V-wave pressure (36 +/- 10 vs 29 +/- 8 mm Hg; p < 0.05) and V-wave peak-X-descent trough (18 +/- 7 vs 11 +/- 5 mm Hg; p < 0.01) than patients without systolic flow reversal. Neither pattern of pulmonary venous flow reversal was related to the severity of angiographic mitral regurgitation. Systolic reversal of pulmonary venous flow is not specific for angiographically severe mitral regurgitation in patients with mitral stenosis. Similar limitations to pulmonary venous flow analysis likely apply to other patient groups with elevated left atrial pressure and poor left atrial compliance.

Adult↗
PubMed1995

The forgotten chamber: the importance of the right ventricle.

Historically, the right heart was viewed as less important than the left heart in the maintenance of normal overall hemodynamic performance. However, there is now considerable evidence that emphasizes the significance of intact right ventricular (RV) function. The RV's anatomy and physiology are reviewed in order to provide insight into how changes in volume can be accommodated within a low-pressure environment and how this contributes to hemodynamic stability. The interdependent relationship between the right and left ventricles is also explored. The contribution of RV performance to overall hemodynamics is best exemplified when the RV becomes diseased. RV infarction, atrial septal defect, and cor pulmonale are used as examples to illustrate the dramatic sequelae associated with RV dysfunction, as well as to identify the RV's specific adaptive mechanisms.

Heart Septal Defects, Atrial↗
PubMed1995

NF-kappa B and transcriptional control of renal epithelial-inducible nitric oxide synthase.

Expression of the inducible isoform of nitric oxide synthase (iNOS) is subject to strict tissue specific transcriptional control. Recently, the NF-kappa B/Rel family of transcription factors, and particularly c-rel, was shown to mediate bacterial lipopolysaccharide (LPS) induction of iNOS in macrophages. Since LPS is only a weak inducer of iNOS in most nonimmune cells, we investigated the role of NF-kappa B in the regulation of iNOS expression in mouse renal epithelial cells. We report that LPS activates NF-kappa B in renal epithelium, but that this is not sufficient for induction of iNOS activity. The NF-kappa B complexes activated by LPS in renal epithelium differ from those in macrophages in that they lack c-rel, which may explain the absence of iNOS induction in renal epithelium. Conversely, LPS and interferon-gamma (IFN) synergize to induce renal epithelial iNOS. Functional iNOS promoter analysis indicate that this synergistic induction requires NF-kappa B. We conclude that NF-kappa B is necessary but not sufficient for the induction of renal epithelial iNOS expression, and that in contrast to macrophages, c-rel does not appear to play a major role in the regulation of renal epithelial iNOS.

Animals↗
PubMed1994

Value of transthoracic echocardiography in predicting embolic events in active infective endocarditis. Duke Endocarditis Service.

The purpose of this study was twofold: (1) to determine interobserver variability of echocardiographic characteristics of vegetations in patients with infective endocarditis, and (2) to assess the value of these vegetation characteristics in predicting embolic events. Although echocardiography contributes to the diagnosis of patients with infective endocarditis, its prognostic role in predicting embolic events is controversial. The echocardiograms of 41 patients with infective endocarditis were independently reviewed by 4 echocardiographers blinded to the clinical data. If a vegetation was present, the following characteristics were analyzed: involved site, size, mobility, shape, and pedunculated or sessile attachment. Each echocardiographer also made a "gestalt" estimate of embolic risk based on these vegetation characteristics. Interobserver agreement on vegetation characteristics and their relation to embolic events was then determined using kappa statistics and logistic regression analysis. Interobserver agreement was 98% with regard to echocardiographic vegetation presence and 97% with regard to the involved site. Of the 30 patients in whom vegetations were observed, complete observer agreement was achieved with regard to size in 22 (73%), mobility in 17 (57%), shape in 11 (37%), and attachment in 12 (40%). Vegetations with a maximal diameter of > 10 mm were associated with a 50% incidence of embolic events, compared with a 42% incidence of emboli in patients with vegetations measuring < or = 10 mm. Interobserver variability was great with respect to vegetation shape, mobility, and attachment characteristics. Echocardiographic vegetation characteristics were not helpful in defining the risk of embolic complications in patients with endocarditis.

Echocardiography, Transesophageal↗
PubMed1994

cDNA cloning of a G-protein-coupled receptor expressed in rat spinal cord and brain related to chemokine receptors.

A series of cDNAs and a genomic clone (named RBS11) were isolated, from a variety of rat brainstem, pituitary and/or spinal cord cDNA libraries and a genomic library by low-stringency hybridization screening with a rat angiotensin receptor cDNA. The RBS11 protein, as conceptualized from these DNAs, is a novel member of the rhodopsin family of the G-protein-coupled receptor (GCR) superfamily. Comparison of RBS11 to other members of the GCR superfamily suggests that the RBS11 protein might be a receptor for a peptide ligand in the chemokine family. The RBS11 protein sequence is unusual in that it is without N-linked glycosylation consensus sequences in the putative exofacial regions. Northern analysis indicates that the mRNA for RBS11 accumulates widely and unevenly in the adult rat, with the mRNA being most prominent in extracts of spinal cord, brain, kidney, gut, uterus and testes.

Animals↗
PubMed1994

Regulation of rat renal alpha 2 B-adrenergic receptors by potassium depletion.

Potassium depletion and alpha 2-adrenergic receptor (alpha 2-AR) agonists produce similar physiological effects on renal function. Both stimuli increase Na-H exchange in proximal tubule cells, inhibit water transport in collecting tubule cells, and alter blood pressure regulation. The purpose of this study was to determine whether potassium depletion and renal alpha 2-AR subtype expression were linked. Kidney membrane proteins and RNA were harvested from anesthetized rats fed a potassium-deficient diet for 4-20 days (LK 4 to LK 20). Using a selective alpha 2-AR antagonist, [3H]MK-912, we observed that potassium depletion led to a dramatic increase in maximum binding (270% of control) without a change in dissociation constant. Competitive binding studies in LK 14 kidney membranes employing chlorpromazine, prazosin, and oxymetazoline suggested that the increase in alpha 2-ARs in response to potassium depletion was due primarily to an increase in the B subtype of alpha 2-AR. Northern blot analysis demonstrated that renal alpha 2B-AR mRNA levels increased (190% of control) after 4 or 14 days on a potassium-deficient diet. In contrast, there was no difference in steady-state alpha 2A-receptor protein levels by Western blot analysis. We conclude that potassium depletion selectively increases the expression of the B subtype of alpha 2-AR with no detectable effect on alpha 2A-AR expression.

Adrenergic alpha-Antagonists↗
PubMed1994

Relief of superior vena cava syndrome due to fibrosing mediastinitis using the Palmaz stent.

Relief of superior vena cava (SVC) syndrome due to non-neoplastic mediastinal disease presents a formidable challenge. Long-term patency of surgically created bypass grafts has been poor, and the morbidity associated with these procedures is substantial. We report a case of SVC syndrome, caused by fibrosing mediastinitis, treated with Palmaz balloon expandable intravascular stents. Intravascular stents are a promising alternative for relief of non-neoplastic SVC obstruction.

Adult↗
PubMed1994

Aortic valve replacement in adults after balloon aortic valvuloplasty.

BACKGROUND: Percutaneous balloon aortic valvuloplasty is limited by a high risk of procedural morbidity, transient clinical benefit, and a high restenosis rate. The management of patients with symptomatic aortic valve restenosis after percutaneous balloon aortic valvuloplasty is unclear. We hypothesized that aortic valve replacement would produce superior midterm survival compared with repeat balloon aortic valvuloplasty or medication alone in patients with symptomatic aortic valve restenosis after prior balloon aortic valvuloplasty. METHODS AND RESULTS: Baseline clinical, echocardiographic, and hemodynamic data were collected on 165 patients who underwent percutaneous balloon aortic valvuloplasty as treatment for symptomatic degenerative calcific aortic stenosis. In 144 of these patients (87%), aortic valve replacement was originally considered to carry excessive risk. The survival of three subgroups was calculated during a median follow-up period of 3.9 years (range, 1 to 6 years). Ninety-four patients (57%) had no further mechanical intervention (subgroup 1-BAV), 31 patients (19%) developed symptomatic aortic valve restenosis and underwent a repeat balloon aortic valvuloplasty (subgroup 2-BAV), and 40 patients (24%) subsequently underwent aortic valve replacement (subgroup BAV+AVR). Follow-up was 99% complete. Patients in subgroup BAV+AVR tended to be younger and have a lower prevalence of coronary artery disease or mitral regurgitation. Only 1 patient (2.5%) suffered a perioperative death during aortic valve replacement. The probability of survival 3 years from the date of the last mechanical intervention was 13% for subgroup 1-BAV, 20% for subgroup 2-BAV, and 75% for subgroup BAV+AVR. At the conclusion of follow-up, only 2 patients had symptoms of congestive heart failure or angina after aortic valve replacement. CONCLUSIONS: Aortic valve replacement may be performed with a low mortality rate, excellent palliation of symptoms, and prolongation of survival in selected high-risk patients with a history of previous balloon aortic valvuloplasty.

Actuarial Analysis↗
PubMed1994

Complications related to percutaneous transvenous mitral commissurotomy.

Recent randomized studies have demonstrated that percutaneous transvenous mitral commissurotomy (PTMC) has similar efficacy compared to surgical commissurotomy. Compared with surgery, PTMC is associated with shorter hospital stays, reduced patient discomfort, and significantly lower costs. The challenge of PTMC remains to provide increased safety. The most serious risks of balloon commissurotomy include cardiac perforation and embolic stroke. The creation of severe mitral regurgitation also limits the effectiveness of the procedure and occasionally leads to the requirement for emergency mitral valve replacement. Since 1986, procedure-related mortality has ranged from 0-2.7% with lower mortality rates reported recently. The most frequent cause of procedure-related death has been left ventricular (LV) perforation. This is almost exclusively a complication associated with the double balloon technique, which requires LV guidewires. Cardiac perforation due to inadvertent atrial perforation during transseptal catheterization may occur with the Inoue technique as well, but this tends to be less severe and has not resulted in death. Embolic stroke has occurred in 1.1-5.4% of cases. The incidence of embolic events has been favorably influenced by routine preprocedure transesophageal echocardiography (TEE), eliminating patients with left atrial thrombi. Significant mitral regurgitation occurs in 3.3-10.5% of patients undergoing balloon mitral commissurotomy. Fortunately, mitral regurgitation infrequently requires emergency surgery (0.3-3.3% of cases). Iatrogenic atrial septal defects are usually of no clinical consequence. Their frequency has been reduced with the use of the Inoue balloon catheter system and they rarely require surgical repair.(ABSTRACT TRUNCATED AT 250 WORDS)

Catheterization↗
PubMed1994

Adult patients with congenital heart disease.

Adult patients with congenital heart disease present complex problems that require individualized management. Unfortunately, few physicians who care for adults with congenital heart disease have received adequate specific training to deal with their problems. Pediatric cardiologists who are familiar with congenital heart disease often refer patients to adult cardiologists after adolescence. And adult cardiologists have not traditionally had much training or experience in dealing with congenital heart disease. The cardiac needs of these patients are often best managed through the collaborative efforts of adult and pediatric cardiologists, cardiac surgeons, specialized nurse clinicians, and social workers. Of course, it is crucial to their optimal care that there be involvement of a primary care physician who can help with their many medical, surgical, and psychosocial problems.

Adult↗
PubMed1993

Molecular cloning of a novel rat G-protein-coupled receptor gene expressed prominently in lung, adrenal, and liver.

A gene and cDNA (named G10d) encoding a novel member of the G-protein-coupled receptor (GCR) superfamily has been isolated from a rat genomic library and a rat liver cDNA library by tandom polymerase chain reaction (PCR) amplification and hybridization screening. Comparison of the sequence of the encoded protein to other members of the rhodopsin family of the GCR superfamily suggests that this new member is a peptide receptor. The G10d gene is present as a single copy in the rat genome and its translational open reading frame is intronless. Northern analysis demonstrates a wide and uneven distribution of G10d mRNA in the adult rat, with the highest mRNA abundance in lung, liver and adrenal gland extracts.

Adrenal Glands↗
PubMed1993

Molecular structure of a protein-tyrosine/threonine kinase activating p42 mitogen-activated protein (MAP) kinase: MAP kinase kinase.

MAP kinases p42mapk and p44mapk participate in a protein kinase cascade(s) important for signaling in many cell types and contexts. Both MAP kinases are activated in vitro by MAP kinase kinase, a protein-tyrosine and threonine kinase. A MAP kinase kinase cDNA was isolated from a rat kidney library by using peptide sequence data we obtained from MAP kinase kinase isolated from rabbit skeletal muscle. The deduced sequence, containing 393 amino acids (predicted mass, 43.5 kDa), is most similar to byr1 (Bypass of ras1), a yeast protein kinase functioning in the mating pathway induced by pheromones in Schizosaccharomyces pombe. An unusually large insert is present in MAP kinase kinase between domains IX and X and may contribute to protein-protein interactions with MAP kinase. Major (2.7 kilobases) and minor (1.7 kilobases) transcripts are widely expressed in rat tissues and appear to be derived from a single gene.

Amino Acid Sequence↗
PubMed1993

Comparison of balloon valvuloplasty with operative treatment for mitral stenosis.

To determine the optimal role for percutaneous balloon mitral valvuloplasty or open mitral commissurotomy, the outcome of 164 consecutive patients undergoing either percutaneous balloon mitral valvuloplasty, open mitral commissurotomy, or mitral valve replacement for mitral stenosis was reviewed. No preoperative differences existed between percutaneous balloon mitral valvuloplasty and open mitral commissurotomy in age, symptoms, or mitral valve characteristics. Symptoms improved similarly in all groups, and median hospital stays after procedures were 2, 9, and 10 days for percutaneous balloon mitral valvuloplasty, open mitral commissurotomy, and mitral valve replacement (p < 0.005). Actuarial survivals at 36 months did not differ significantly (83% +/- 6%, 94% +/- 4%, and 90% +/- 4%). Actuarial freedoms from subsequent mitral valve procedures at 36 months were 66% +/- 7%, 87% +/- 6%, and 100% +/- 13% (p < 0.005), with the linearized rate of subsequent mitral valve procedures being 12% +/- 3%, 4% +/- 2%, and 1.2% +/- 0.8%/patient-year for percutaneous balloon mitral valvuloplasty, open mitral commissurotomy, and mitral valve replacement (p < 0.01). Prior mitral commissurotomy increased the likelihood of subsequent mitral procedures after percutaneous balloon mitral valvuloplasty from 10% +/- 3% to 20% +/- 7%/patient-year.

Adult↗
PubMed1993

Identification and characterization of a new mammalian mitogen-activated protein kinase kinase, MKK2.

Mitogen-activated protein (MAP) kinases are serine/threonine protein kinases activated by dual phosphorylation on threonine and tyrosine residues. A MAP kinase kinase (MKK1 or MEK1) has been identified as a dual-specificity protein kinase that is sufficient to phosphorylate MAP kinases p42mapk and p44mapk on the regulatory threonine and tyrosine residues. Because of the multiplicity of MAP kinase isoforms and the diverse circumstances and agonists leading to their activation, we thought it unlikely that a single MKK could accommodate this complexity. Indeed, two protein bands with MKK activity have previously been identified after renaturation following sodium dodecyl sulfate-polyacrylamide gel electrophoresis. We now report the molecular cloning and characterization of a second rat MAP kinase kinase cDNA, MKK2. MKK2 cDNA contains an open reading frame encoding a protein of 400 amino acids, 7 residues longer than MKK1 (MEK1). The amino acid sequence of MKK2 is 81% identical to that of MKK1, but nucleotide sequence differences occur throughout the aligned MKK2 and MKK1 cDNAs, indicating that MKK2 is the product of a distinct gene. MKK1 and MKK2 mRNAs are expressed differently in rat tissues. Both cDNAs when expressed in COS cells displayed the ability to phosphorylate and activate p42mapk and p44mapk, both MKK1 and MKK2 were activated in vivo in response to serum, and both could be phosphorylated and activated by the v-Raf protein in vitro. However, differences between MKK1 and MKK2 in sites of phosphorylation by proline-directed protein kinases predict differences in feedback regulation.

Amino Acid Sequence↗
PubMed1993

Systolic left ventricular function after reperfusion therapy for acute myocardial infarction. Analysis of determinants of improvement. The TAMI Study Group.

BACKGROUND: Contrast ventriculograms of 542 patients treated with intravenous thrombolytic agents for acute myocardial infarction were examined to define changes in left ventricular ejection fraction and regional wall motion that occur during the first week after reperfusion therapy for acute myocardial infarction and define clinical, acute angiographic and treatment variables related to improvement in global and regional left ventricular function. METHODS AND RESULTS: Intravenous tissue-type plasminogen activator and/or urokinase was administered to 805 patients during acute myocardial infarction. Mean time from symptom onset to thrombolytic therapy was 3 hours (22 patients received therapy within the first hour). Acute and 7-day catheterization were performed. Paired left ventricular ejection fraction and centerline regional wall motion were available in 542 patients (67%). Stepwise, multivariable analysis of clinical, acute angiographic and treatment variables was used to develop two models: One related to improvement in left ventricular ejection fraction, and the second related to improvement in infarct zone regional function. Left ventricular ejection fraction did not change (51.2 +/- 11.1% for acute versus 51.9 +/- 11.0% for 1 week, p = 0.19). Improvement in infarct zone regional function was modest (14%) at 1 week (-2.54 +/- 1.07 standard deviation per chord for acute versus -2.17 +/- 1.24 at 1 week, p < 0.001). Subgroup analysis demonstrated modest improvement in ejection fraction (1.4 +/- 9.5%) and greater improvement in infarct zone function (19%) in patients with successful sustained reperfusion at 1 week. Depressed left ventricular ejection fraction and infarct zone regional wall motion at the acute study were strongly associated with improvement of these parameters at 1 week. Resolution of chest pain before acute catheterization, infarct-related artery flow at acute catheterization, and depressed regional wall motion in the noninfarct zone were associated with improvement in both ejection fraction and regional infarct zone function at 1 week. Notably, the time from the onset of symptoms to initiation of thrombolytic treatment was not related to subsequent improvement in ventricular function. CONCLUSIONS: Dramatic improvement in left ventricular systolic function is not common after thrombolytic therapy for acute myocardial infarction. Improvement in global and regional systolic function is most closely related to acutely depressed ventricular function and successful acute coronary recanalization. Thus, patients with the most myocardium in jeopardy and successful coronary reperfusion demonstrate the greatest improvement in global and infarct zone ventricular function. Overall, the magnitude of this improvement is modest, suggesting that the benefits of coronary reperfusion are not solely related to improvement in systolic left ventricular function.

Aged↗