Biomedical subjects

I Palacios

Publications and source records attributed to I Palacios.

At least 37 records · Page 2Linked to original sources

PubMed1997

SAMe restores the changes in the proliferation and in the synthesis of fibronectin and proteoglycans induced by tumour necrosis factor alpha on cultured rabbit synovial cells.

S-Adenosyl-L-methionine (SAMe) is a naturally occurring compound involved in transmethylation and trans-sulphuration reactions. The administration of SAMe to patients with osteoarthritis (OA) seems to have a protective effect, although the mechanisms of its action are largely unknown. We have studied the effect of SAMe as a protective agent against the modifications induced by tumour necrosis factor alpha (TNF alpha) on synovial cell proliferation and extracellular matrix protein synthesis, two important hallmarks of progressive articular diseases. The stimulation of cells with 100 U/ml TNF alpha for 24 h decreased the proliferative rate (58 +/- 14% with TNF alpha vs basal 100%, P < 0.05), fibronectin (FN) mRNA expression (36 +/- 14% vs basal, P < 0.05) and FN synthesis (79 +/- 20% vs basal, P > 0.05). By contrast, TNF alpha raised total protein and proteoglycan synthesis (127 +/- 12% vs basal and 239 +/- 40% vs basal, respectively, P < 0.05). The addition of increasing concentrations of SAMe (10(-10)-10(-6) M) to synoviocytes incubated with TNF alpha reversed the effects induced by the cytokine, while SAMe alone did not modify significantly the metabolic processes studied. These results indicate that, in cultured synovial cells, SAMe restores basal conditions after cell damage elicited by TNF alpha stimulation.

Animals↗

PubMed1996

Amrinone stimulation test: ability to predict improvement in left ventricular ejection fraction after coronary bypass surgery in patients with poor baseline left ventricular function.

OBJECTIVES: This study sought to determine whether the response to amrinone in patients with severe baseline left ventricular dysfunction can predict improvement in left ventricular ejection fraction after coronary artery bypass graft surgery. BACKGROUND: Previous studies have suggested that the inotropic response to dobutamine can identify viable myocardium in the setting of chronic coronary disease and left ventricular dysfunction. However, increased oxygen demand stimulated by dobutamine can lead to superimposition of ischemia on the hibernating state, potentially confounding interpretation of results. Amrinone is an inotropic agent that does not critically augment myocardial oxygen demand and may be useful for identification of hibernating myocardium in the chronically ischemic state. METHODS: Forty-four consecutive patients with coronary artery disease and left ventricular ejection fraction < 40% referred for coronary artery bypass graft surgery underwent amrinone stimulation (1 mg/kg body weight). Left ventricular ejection fraction was determined before amrinone stimulation, 20 min after infusion and 21 days after bypass surgery. RESULTS: Baseline ejection fraction was 28 +/- 7% (mean +/- SD). Ejection fraction increased to 35 +/- 5% after amrinone stimulation (p < 0.0001) and to 33 +/- 6% after bypass surgery (p < 0.0001). Postbypass ejection fraction was significantly correlated with postamrinone ejection fraction (r = 0.65, p < 0.0001). Furthermore, the change in ejection fraction from baseline to after bypass surgery was highly correlated with the change in ejection fraction after amrinone stimulation (r = 0.75, p < 0.0001). Of 13 patients with an increase in ejection fraction > or = 10% after amrinone, all 13 had an increase of at least 8% and 11 (85%) of 13 had an increase > or = 10% after bypass surgery. In contrast, of 31 patients with an increase in ejection fraction < 10% after amrinone, only 2 (6%) had an increase > or = 10% (p < 0.0001) and 28 (90%) of 31 had an increase < 5% after bypass surgery. CONCLUSIONS: Augmentation of myocardial contraction by amrinone in patients with chronic coronary artery disease and severe baseline left ventricular dysfunction predicts improvement in left ventricular ejection fraction after coronary artery bypass graft surgery.

Aged↗

PubMed1996

Endothelin-1 induces loss of proteoglycans and enhances fibronectin and collagen production in cultured rabbit synovial cells.

Endothelin-1 exerts a wide range of biological actions besides its characteristic vasoconstrictor function. The potential participation of endothelin-1 in rheumatic diseases has hardly been explored. We have studied the possible role of endothelin-1 as a modulator of extracellular matrix turnover in cultured rabbit synoviocytes. In relation to basal levels, endothelin-1 increased the mRNA levels of collagen I and fibronectin at 24 h (130 +/- 9% and 132 +/- 18%, respectively), but did not modify the expression of decorin core proteoglycan. Endothelin-1 also decreased proteoglycan metabolism (about 50% of proteoglycan synthesis inhibition and 270 +/- 32% of degradation rate vs. basal, P < 0.05 in both cases) and enhanced total collagen (1.5 +/- 0.5 vs. 0.8 +/- 0.2 microgram hydroxyproline/microgram DNA in basal, P < 0.05) and fibronectin protein synthesis (157 +/- 14% of [35S] methionine incorporation vs. basal, P < 0.05). The endothelin ETA receptor antagonist BQ-123 (Cyclo D-trp-D-asp-pro-D-val-leu) displaced [125I]endothelin-1 binding and inhibited endothelin-1 effects on extracellular matrix components. The cell incubation with indomethacin totally reversed the endothelin-1 effect. These data suggest that endothelin-1 may be an important mediator of the pathogenesis of joint damage, disturbing the extracellular synovial matrix turnover through the endothelin ETA receptors.

Animals↗

PubMed1996

Anti-inflammatory effect of a PAF receptor antagonist and a new molecule with antiproteinase activity in an experimental model of acute urate crystal arthritis.

Platelet activating factor (PAF) is a potent mediator of allergic and inflammatory reactions in different pathological conditions. During recent years there has been increasing evidence that PAF can play an important role in the pathogenesis of arthritis. The PMN proteinases make an important contribution to the final tissue joint destruction in arthritis. In a rabbit model of acute crystal arthritis, we have compared the anti-inflammatory effect of two new molecules: BN 50727 with anti-PAF activity, and BN 50548 an inhibitor of PMN proteinases. These molecules were administered dissolved in DMSO at doses of 6 mg/kg three times daily i.p., beginning 24 h before the induction of arthritis. Compared with the untreated animals those receiving the drugs, presented a significant diminution in: (1) the synovial fluid volume; (2) the amount of cells infiltrating the joint cavity and the synovial membrane; and (3) the PGE2 concentration. Furthermore, in both groups of treated rabbits there was a significant decrease in synovial IL-6 concentration and in C-reactive protein serum levels and an important decline of histopathological score. The treatment with BN 50548 induced a significant reduction of TNF levels in the synovial fluid vs DMSO-treated and untreated rabbits. These results further strengthen that in an acute experimental arthritis model, molecules with capacity to antagonize the in vivo action of PAF have an anti-inflammatory effect reflecting an important role for this mediator in the pathogenesis of arthritis. We have also seen that an inhibitor of proteinases is capable of improving the joint inflammation apparently through a decrease in tumor necrosis factor (TNF) and interleukin-6 (IL-6) synovial levels. Furthermore, the proteinase inhibitor treatment preserves the loss of articular proteoglycan content, in an acute arthritis model. In conclusion, BN 50727 and BN 50548, two compounds with PAF antagonist and antiproteinase activity, respectively exert an anti-inflammatory effect in an experimental model of acute urate crystal arthritis, probably due to a decrease in TNF alpha and IL-6 synthesis.

Acute Disease↗

PubMed1996

An orally active ETA/ETB receptor antagonist ameliorates proteinuria and glomerular lesions in rats with proliferative nephritis.

The proliferation of mesangial cells and the extracellular matrix expansion constitute the most outstanding morphological aspects of the majority of progressive glomerular diseases. In vitro, endothelin-1 (ET-1) is mitogenic for mesangial cells and induces matrix protein synthesis. We studied the possible participation of ET-1 in the pathogenesis of renal damage in a normotensive model of proliferative nephritis. Coincidentally with maximal proteinuria and glomerular lesions, an increase was found in the glomerular mRNA expression of preproET-1 and the ETA receptor (10 and 6 times compared to controls, respectively), but not of the ETB receptor, and in ET-1 urinary excretion (217 +/- 33 vs. 84 +/- 4 pg ET-1/24 hr, N = 4 to 5, P < 0.05). By in situ hybridization, an increase in preproET-1 mRNA expression in glomerular endothelial, epithelial and mesangial cells, and in come tubular cells was observed. The administration of bosentan, an ETA/ETB receptor antagonist, had a beneficial effect on the evolution of nephritis preventing the appearance of intense proteinuria (76 +/- 35 vs. 380 +/- 77 mg/24 hr, N = 4 to 5, P < 0.05), the morphological lesions and the renal function impairment (creatinine clearance 367 +/- 46 vs. 268 +/- 33 microliters/min/100 g, N = 4 to 5). Simultaneously, there was a decrease in ET-1 urinary excretion (88 +/- 14 vs. 217 +/- 33 pgET-1/24 hr, N = 4,5, P < 0.05) and in the renal preproET-1 mRNA expression. The mean systolic blood pressures remained in the normal range in all animals. These data indicate that ET-1 participates in the pathogenesis of proteinuria and glomerular injury in a model of proliferative nephritis. The nonpeptidic orally active ETA/ETB receptor antagonists could be useful in the treatment of some human nephritis.

Animals↗

PubMed1996

RAN/TC4 mutants identify a common requirement for snRNP and protein import into the nucleus.

Kinetic competition experiments have demonstrated that at least some factors required for the nuclear import of proteins and U snRNPs are distinct. Both import processes require energy, and in the case of protein import, the energy requirement is known to be at least partly met by GTP hydrolysis by the Ran GTPase. We have compared the effects of nonhydrolyzable GTP analogues and two mutant Ran proteins on the nuclear import of proteins and U snRNPs in vitro. The mutant Ran proteins have different defects; Q69L (glutamine 69 changed to leucine) is defective in GTP hydrolysis while T24N (threonine 24 changed to asparagine) is defective in binding GTP. Both protein and snRNP import are sensitive either to the presence of the two mutant Ran proteins, which act as dominant negative inhibitors of nuclear import, or to incubation with nonhydrolyzable GTP analogues. This demonstrates that there is a requirement for a GTPase activity for the import of U snRNPs, as well as proteins, into the nucleus. The dominant negative effects of the two mutant Ran proteins indicate that the pathways of protein and snRNP import share at lease one common component.

Amino Acid Sequence↗

PubMed1996

Mutational analysis identifies functional domains in the influenza A virus PB2 polymerase subunit.

A collection of influenza virus PB2 mutant genes was prepared, including N-terminal deletions, C-terminal deletions, and single-amino-acid insertions. These mutant genes, driven by a T7 promoter, were expressed by transfection into COS-1 cells infected with a vaccinia virus encoding T7 RNA polymerase. Mutant proteins accumulated to levels similar to that of wild-type PB2. Immunofluorescence analyses showed that the C-terminal region of the protein is essential for nuclear transport and that internal sequences affect nuclear localization, confirming previous results (J. Mukaijawa and D. P. Nayak, J. Virol. 65:245-253, 1991). The biological activity of these mutants was tested by determining their capacity to (i) reconstitute RNA polymerase activity in vivo by cotransfection with proteins NP, PB1, and PA and a virion-like RNA encoding the cat gene into vaccinia virus T7-infected COS-1 cells and (ii) complete with the wild-type PB2 activity. In addition, when tested at different temperatures in vivo, two mutant PB2 proteins showed a temperature-sensitive phenotype. The lack of interference shown by some N-terminal deletion mutants and the complete interference obtained with a C-terminal deletion mutant encoding only 124 amino acids indicated that this protein domain is responsible for interaction with another component of the polymerase, probably PB1. To further characterize the mutants, their ability to induce in vitro synthesis of viral cRNA or mRNA was tested by using ApG or beta-globin mRNA as a primer. One of the mutants, 1299, containing an isoleucine insertion at position 299, was able to induce cRNA and mRNA synthesis in ApG-primed reactions but required a higher beta-globin mRNA concentration than wild-type PB2 for detection of in vitro synthesis. This result suggested that mutant I299 has diminished cap-binding activity.

Base Sequence↗

PubMed1995

Proximal jet size by Doppler color flow mapping predicts severity of mitral regurgitation. Clinical studies.

BACKGROUND: Recent studies have shown that many instrument and physiological factors limit the ability of color Doppler total jet area within the receiving chamber to predict the severity of valvular regurgitation. In contrast, the proximal or initial dimensions of the jet as it emerges from the orifice have been shown to increase directly with orifice size and to correlate well with the severity of aortic insufficiency. Only limited data, however, are available regarding the value of proximal jet size in mitral regurgitation, and it has not been examined in short-axis or transthoracic views. The purpose of the present study, therefore, was to evaluate the relation between proximal jet size and other measures of the severity of mitral regurgitation. METHODS AND RESULTS: In 49 patients, the anteroposterior height of the proximal jet as it emerges from the mitral valve was measured in the parasternal long-axis view; proximal jet width and area were measured in the short-axis view at the same level. Results were compared with regurgitant volume and fraction by pulsed Doppler subtraction of aortic and mitral flows in 47 patients without more than trace aortic insufficiency; with angiographic grade determined within 24 hours in 33 catheterized patients; and with angiographic regurgitant fraction in 13 patients who were in normal sinus rhythm and had no significant aortic and tricuspid insufficiency. Proximal jet height, width, and area correlated well with Doppler regurgitant volume and fraction (r = .86 to .95; SEE = 7.7 to 9.0 mL; 5.9% to 7.3%). Proximal jet size could also be used to distinguish angiographic grades of mitral regurgitation with minimal overlap (P < .0001) and correlated well with angiographic regurgitant fraction (r = .85 to .91; SEE = 4.1% to 5.1%). CONCLUSIONS: Proximal jet size correlates well with established measures of the severity of mitral regurgitation. It is conveniently available with transthoracic clinical scanning and should be useful in the routine evaluation of patients with mitral regurgitation.

Adult↗

PubMed1995

IL-1 beta and IL-6 stimulate the production of platelet-activating factor (PAF) by cultured rabbit synovial cells.

The aim of this study was to determine whether synovial cells are capable of producing PAF in the presence of cytokines such as IL-1 beta and IL-6 and other stimuli. Synovial cells were obtained from joints of healthy rabbits. PAF production was assayed by measurement of serotonin release in rabbit platelets and the incorporation of 3H-acetate into PAF. Synovial cells produced PAF after 5 min of incubation with ionophore A23187, reaching the maximal amount at 15 min (4.3 +/- 0.7 x 10(-3) pmol of PAF/mg protein, P < 0.005, n = 4), and declining afterwards. The treatment of synoviocytes with IL-1 beta and IL-6 induced synthesis of PAF after 5 min of stimulation, reaching the greatest production at 15 min with IL-6 and 30 min with IL-1 beta (3.6 +/- 1.1 x 10(-3) and 3.3 +/- 1.2 pmol of PAF/mg protein, respectively, P < 0.05, n = 4). The incubation of the cells with PMSF, an inhibitor of acetylhydrolase, before the addition of the stimuli, increased the incorporation rate of 3H-acetate, suggesting a rapid degradation of PAF by synoviocytes. These results demonstrate that synovial cells can produce PAF after stimulation with agonists, such as ionophore, and cytokines. Thus, PAF, acting alone or with other mediators, could amplify the inflammatory joint reaction.

Animals↗

PubMed1995

Nuclear retention of RNA as a mechanism for localization.

Two mutant RNAs, one derived from tRNA(imet), the second from U1 snRNA, that are defective in export from the nucleus to the cytoplasm have been studied. In both cases, the RNAs are shown to be transport competent but prevented from leaving the nucleus by interaction with saturable binding sites. This contradicts previous hypotheses to explain the behavior of the tRNA mutant, and highlights a general problem in using mutant RNAs to study nuclear export. In the case of these mutants, it is argued that nuclear retention is likely to be artifactual. However, the additional example of U6 snRNA is described. In this case, nuclear retention appears to be a physiological mechanism by which intranuclear localization is achieved. Evidence that the site of interaction with the La protein in U6 snRNA is important for its nuclear retention is presented.

Animals↗

PubMed1994

Involvement of angiotensin II and endothelin in matrix protein production and renal sclerosis.

PURPOSE: To review the evidence that links angiotensin II and endothelin as growth factors and as modifiers of extracellular matrix synthesis in renal cells, with particular reference to the effects of angiotensin converting enzyme (ACE) inhibition in models of renal injury. IN VITRO STUDIES: In cultured mesangial cells, both angiotensin II and endothelin promote contraction, proliferation/hypertrophy, signal transduction pathways, the activation of early growth genes, and the generation of inflammatory mediators, cytokines and growth factors. Both hormones have been shown to promote the synthesis of fibronectin and collagen in a dose-dependent manner. ACE inhibition attenuates the effect of endothelin-1, one of three isoforms of endothelin. ANIMAL STUDIES: In experimental models of renal injury, chiefly in those characterized by increased intraglomerular pressure, ACE inhibition has reduced proteinuria and glomerular and interstitial sclerosis. HUMAN STUDIES: ACE inhibition has been shown to have major beneficial effects in patients with diabetic nephropathy, even in those with normal blood pressure. CONCLUSIONS: Although the renal-protective effects of ACE inhibitors in experimental and human renal injury may reflect systemic and/or local hemodynamic effects of these drugs, their modulatory actions on extracellular matrix synthesis and proteinuria may contribute to the benefit of ACE-inhibitor therapy.

Angiotensin II↗

PubMed1994

The potential role of inflammatory and fibrogenic cytokines in the glomerular diseases.

In recent years increasing evidence has been accumulated on the role of cytokines in mediating glomerular and renal damage. Many such cytokines are released in the inflamed glomeruli by leukocytes and intrinsic glomerular cells. Cytokines not only recruit inflammatory cells into the injured glomeruli, but also induce a variety of responses on glomerular cells that range from a direct toxic effect to shape changes, proliferation, and induction of the release of inflammatory mediators and extracellular matrix, and could promote further glomerular damage. Moreover, exogenous administration of cytokines has induced glomerular injury in healthy animals and has enhanced renal damage in animals with glomerulonephritis. Anti-cytokine strategies have proved to be effective therapeutical alternatives in experimental models of glomerular diseases and may provide a more specific approach to the management of human glomerulonephritis.

Animals↗

PubMed1992

Viral myocarditis mimicking acute myocardial infarction.

Anecdotal reports have shown that myocarditis can mimic acute myocardial infarction with chest pain, electrocardiographic (ECG) abnormalities, serum creatine kinase elevation and hemodynamic instability. Thirty-four patients with clinical signs and symptoms consistent with acute myocardial infarction underwent right ventricular endomyocardial biopsy during a 6.5-year period after angiographic identification of normal coronary anatomy. Myocarditis was found on histologic study in 11 of these 34 patients. Cardiogenic shock requiring intraaortic balloon support developed within 6 h of admission in three (27%) of the patients with myocarditis. The mean age of the group with myocarditis was 42 +/- 5 years. A preceding viral illness had been present in six patients (54%). The ECG abnormalities were varied and included ST segment elevation (n = 6), T wave inversions (n = 3), ST segment depression (n = 2) and pathologic Q waves (n = 2). The ECG abnormalities were typically seen in the anterior precordial leads but were diffusely evident in three patients. Left ventricular function was normal in six patients and globally decreased in the remaining five patients, whose ejection fraction ranged from 14% to 45%. Lymphocytic myocarditis was diagnosed in 10 patients, and giant cell myocarditis was detected in the remaining patient. Four patients with impaired left ventricular function received immunosuppressive therapy with prednisone and either azathioprine (n = 2) or cyclosporine (n = 2). All six patients whose left ventricular function was normal on admission remain alive in functional class I. Of the five patients with impaired systolic function, ejection fraction normalized in three of the four patients who received immunosuppressive therapy within 3 months of treatment and in the one patient who received only supportive therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Atrial septal occlusion improves the accuracy of mitral valve area determination following percutaneous mitral balloon valvotomy.

We investigated the impact of the atrial communication on the mitral valve area calculation after percutaneous mitral balloon valvotomy in 17 patients (15 women, 2 men; mean age 56 +/- 4 years). The hemodynamic measurements and mitral valve area calculations were performed with and without balloon occlusion of the atrial septal puncture site. The mitral valve area determined with balloon occlusion was significantly smaller than the mitral valve area determined without occlusion (1.6 +/- 0.1 vs. 1.9 +/- 0.1 cm2, P less than 0.01), and was similar to the echocardiographically determined valve area (1.6 +/- 0.1 cm2). This decrease in the calculated mitral valve area with occlusion was associated with a decrease in the measured cardiac output, without a change in the mitral valve gradient or the diastolic filling period. Occlusion of the atrial septal puncture site may permit more accurate determination of the mitral valve area and thus provide a better reference point for future comparison should the question or restenosis arise.

Cardiac Catheterization↗

PubMed1991

The safety of intraaortic balloon pump catheter insertion through suprainguinal prosthetic vascular bypass grafts.

To determine the safety of intraaortic balloon pump catheter insertion for critical coronary ischemia through suprainguinal prosthetic bypass grafts, we examined our experience of 19 intraaortic balloon pumps placed through grafts in 17 patients by means of surgical exposure (8) or the percutaneous (11) approach. Fourteen intraaortic balloon pumps were placed through matured grafts at a time remote (2 to 13 years; mean, 7 years) from their vascular bypass surgery. Five were inserted through nonmatured grafts during the same hospitalization as their vascular reconstructive surgery (1 to 12 days; mean, 4 days). One patient, a day after an aortoiliac bypass, died during an urgent, surgical intraaortic balloon pump insertion for cardiogenic shock. All other patients had prompt reversal of their cardiac ischemia. Decreased limb perfusion developed during use of the intraaortic balloon pump in three patients, all of whom had their intraaortic balloon pump placed percutaneously through mature grafts. Two of these required surgical thrombectomy. Ten intraaortic balloon pump insertions in eight patients survived the hospitalization and were followed for a mean of 24 months (range, 2 weeks to 64 months). No localized groin or graft infections were identified. No bleeding complications or pseudoaneurysms occurred. Thus in patients with unstable, severe, cardiac disease, intraaortic balloon pumps can be safely placed through indwelling suprainguinal bypass grafts.

Aged↗

PubMed1991

Giant cell versus lymphocytic myocarditis. A comparison of their clinical features and long-term outcomes.

BACKGROUND: Giant cell myocarditis has rarely been diagnosed premortem, and little is known about its natural history. In addition, no comparative studies with lymphocytic myocarditis exist. METHODS AND RESULTS: The clinical features, serial change in left ventricular fraction (LVEF), and outcomes of all patients with histologically verified myocarditis were retrospectively evaluated. Ten patients (22%) were found to have giant cell myocarditis (group 1), whereas the remaining 36 (78%) had lymphocytic myocarditis (group 2). Age at presentation, gender distribution, duration of symptoms, initial LVEF, and resting hemodynamics did not differ between groups. Ventricular tachycardia was detected in 90% of group 1 patients compared with only 25% of group 2 (p = 0.0007). Atrioventricular block that required pacemaker insertion was also more common in group 1 (60%) than in group 2 (8.3%) (p = 0.001). Left ventricular systolic function declined during follow-up in group 1 patients (LVEF, 0.43 +/- 0.07-0.26 +/- 0.05, p = 0.11) but increased in group 2 patients (LVEF, 0.33 +/- 0.03-0.41 +/- 0.03, p = 0.02). When the net change between initial and final LVEF was assessed, a significant difference was evident (giant cell group, -0.17 +/- 0.06; lymphocytic group, +0.07 +/- 0.03; p = 0.0008). Although a greater proportion of patients in group 1 died or required transplantation (seven of 10 versus 11 of 36, p = 0.03), actuarial survival over 4 years was not different for the giant cell group (50%) than for the lymphocytic group (62%). CONCLUSION: Giant cell myocarditis was more prevalent than previously recognized and highly associated with both ventricular tachycardia and pacemaker requirement. The likelihood of an adverse event, either cardiovascular mortality or cardiac transplantation, was significantly greater for patients with giant cell myocarditis than for those with lymphocytic myocarditis, perhaps because of the progressive decline in left ventricular systolic function that was observed in those with giant cell myocarditis.

Adult↗

PubMed1990

Antimyosin antibody cardiac imaging: its role in the diagnosis of myocarditis.

Right ventricular endomyocardial biopsy currently remains the procedure of choice for identifying patients with symptomatic heart failure due to myocarditis from the larger population with idiopathic dilated cardiomyopathy. Despite its specificity, the sensitivity of right ventricular biopsy remains uncertain because of the focal or multifocal nature of the disease. Because myocyte necrosis is an obligate component of myocarditis, the use of indium-111 antimyosin imaging was evaluated in 82 patients with suspected myocarditis. Seventy-four patients had dilated cardiomyopathy of less than 1 year's duration (mean left ventricular ejection fraction 0.30 +/- 0.02); eight patients had normal left ventricular function (mean ejection fraction 0.59 +/- 0.03). Symptoms at presentation included congestive heart failure (92%), chest pain mimicking myocardial infarction (6%) and life-threatening ventricular tachyarrhythmias (2%). All patients underwent planar and single photon emission computed tomographic (SPECT) cardiac imaging after injection of indium-111-labeled antimyosin antibody fragments and right ventricular biopsy within 48 h of imaging. Antimyosin images were interpreted as either abnormal or normal and correlated with biopsy results. On the basis of the right ventricular histologic examination, the sensitivity of antimyosin imaging was 83%, specificity 53% and predictive value of a normal scan 92%. Improvement in left ventricular function occurred within 6 months of treatment in 54% of patients with an abnormal antimyosin scan compared with 18% of those with a normal scan (p less than 0.01). Antimyosin cardiac imaging may be useful for the initial evaluation of patients with dilated and nondilated cardiomyopathy and clinically suspected myocarditis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1990

"Borderline" myocarditis: an indication for repeat endomyocardial biopsy.

Repeat endomyocardial biopsy was performed in 28 patients with dilated cardiomyopathy of less than or equal to 12 months' duration and either symptomatic heart failure or life-threatening ventricular arrhythmias. Myocarditis was strongly suspected clinically in all cases, yet was unconfirmed on initial right ventricular biopsy. Seventeen patients underwent both right and left ventricular biopsy, seven patients had a repeat right ventricular biopsy and four patients underwent repeat left ventricular biopsy alone. The interval between initial and repeat biopsy averaged 31 +/- 6 days. Myocarditis was confirmed on repeat biopsy in 4 of 6 patients whose initial biopsy revealed "borderline" myocarditis (that is, interstitial inflammation but absence of myocyte necrosis) compared with none of the 22 patients whose initial biopsy showed either myocyte hypertrophy or interstitial fibrosis, or both (p = 0.0007). "Borderline" myocarditis on initial biopsy was the only clinical or histologic finding predictive of myocarditis on subsequent biopsy. Repeat endomyocardial biopsy can identify and potentially modify the treatment of an additional group of patients with dilated cardiomyopathy and nondiagnostic initial endomyocardial histologic features. Right ventricular sampling should be repeated in patients whose initial biopsy demonstrates "borderline" myocarditis.

Azathioprine↗