Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Infections are thought to be important in the pathogenesis of many heart diseases. Coxsackievirus B3 (CVB3) has been linked to chronic dilated cardiomyopathy, a common cause of progressive heart disease, heart failure and sudden death. We show here that the sarcoma (Src) family kinase Lck (p56lck) is required for efficient CVB3 replication in T-cell lines and for viral replication and persistence in vivo. Whereas infection of wild-type mice with human pathogenic CVB3 caused acute and very severe myocarditis, meningitis, hepatitis, pancreatitis and dilated cardiomyopathy, mice lacking the p56lck gene were completely protected from CVB3-induced acute pathogenicity and chronic heart disease. These data identify a previously unknown function of Src family kinases and indicate that p56lck is the essential host factor that controls the replication and pathogenicity of CVB3.
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PMID:The tyrosine kinase p56lck is essential in coxsackievirus B3-mediated heart disease. 1074 50

There are now 3 commercially approved intracorporeal left ventricular assist devices (LVADs). Product similarities include (1) LV apex, to pump, to ascending aorta flow patterns, (2) excellent hemodynamic support with reversal of heart failure and neurohormone/cytokine milieu, and (3) the requirement of major surgery for device implantation and later explantation, with or without transplant. Two electrically powered models allow a tether-free existence and hospital discharge. All complications are being addressed, and in the past decade, device failure and thromboemboli have been reduced. Infection continues to be an obstacle to more widespread adoption of therapy. Despite pre-LVAD shock, most patients (65% to 78% by Food and Drug Administration data) survive until transplant (averaging 80 to 96 days of LVAD support), and posttransplant survival is equal to nonbridged patients. As the problem of infection is reduced, more widespread LVAD use can be anticipated.
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PMID:Clinically available intracorporeal left ventricular assist devices. 1093 56

Introduction of the constitutively active calcineurin gene into neonatal rat cardiomyocytes by adenovirus resulted in decreased mitochondrial membrane potential (P < 0.05). Infection of H9c2 cells with calcineurin adenovirus resulted in increased superoxide production (P < 0.001). Transgenic mice with cardiac-specific expression of a constitutively active calcineurin cDNA (CalTG mice) exhibit a two- to threefold increase in heart size that progresses to heart failure. We prepared mitochondria enriched for the subsarcolemmal population from the hearts of CalTG mice and transgene negative littermates (control). Intact, well-coupled mitochondria prepared from one to two mouse hearts at a time yielded sufficient material for functional studies. Mitochondrial oxygen consumption was measured with a Clark-type oxygen electrode with substrates for mitochondrial complex II (succinate) and complex IV [tetramethylpentadecane (TMPD)/ascorbate]. CalTG mice exhibited a maximal rate of electron transfer in heart mitochondria that was reduced by approximately 50% (P < 0.002) without a loss of respiratory control. Mitochondrial respiration was unaffected in tropomodulin-overexpressing transgenic mice, another model of cardiomyopathy. Western blotting for mitochondrial electron transfer subunits from mitochondria of CalTG mice revealed a 20-30% reduction in subunit 3 of complex I (ND3) and subunits I and IV of cytochrome oxidase (CO-I, CO-IV) when normalized to total mitochondrial protein or to the adenine nucleotide transporter (ANT) and compared with littermate controls (P < 0.002). Impaired mitochondrial electron transport was associated with high levels of superoxide production in the CalTG mice. Taken together, these data indicate that calcineurin signaling affects mitochondrial energetics and superoxide production. The excessive production of superoxide may contribute to the development of cardiac failure.
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PMID:Calcineurin transgenic mice have mitochondrial dysfunction and elevated superoxide production. 1239 29

In renal failure, blood urea nitrogen and serum creatinine usually rise in tandem; the normal BUN: Cr ratio is 10-15: 1. Disproportionate rises in BUN: Cr (> 20: 1) often imply pre-renal azotemia but may be caused by increased protein catabolism or an excessive protein load. In this study we looked at intensive care patients who acutely developed markedly increased BUN (> or = 100 mg/dL) with only modest elevation of Cr (< or = 5 mg/dL) for possible causes of the disproportionate azotemia. There were 19 such cases collected over 6 months, nine women and ten men, with mean age 69.2 +/- 4.4 years (13/19 > 75 years). Peak BUN was 156 +/- 11 mg/dL; peak Cr 4.3 +/- 0.5 mg/dL. Eleven patients expired. Mean serum albumin at the time of consultation was 2.7 +/- 0.2 g/dL; mean total lymphocyte count 1.0 +/- 0.1/mm3. Of possible factors causing the azotemia, nine patients had documented hypovolemia; eight had congestive heart failure; six were in septic or hypovolemic shock, and two received high-dose steroids. As contributing factors, eight patients had Salb < 2.5 g/dL; eight were given a high protein intake > 100 g/d; two had HIV, and two others had gastrointestinal bleeding. Infection was present in 14 patients; seven had sepsis (bacteremia with hypotension). All patients had at least one of these factors present and 16/19 had two or more. Fractional Na excretion was < 1% (consistent with pre-renal azotemia) in only four of the 11 patients in whom it was measured. We conclude that severely disproportionate BUN : Cr is frequently multifactorial and is most common in the elderly, perhaps due to their lower muscle mass, and in ICU patients given a high protein intake. It is often not indicative of uncomplicated renal hypoperfusion, although low renal perfusion (hypovolemia, shock, or heart failure) is common. Mortality is high due to the severe illnesses, especially infection, worsened by decreased renal function and hypercatabolic state.
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PMID:Massive and disproportionate elevation of blood urea nitrogen in acute azotemia. 1254 57

The role of Galpha(i)-2 overexpression in desensitization of beta-adrenergic signaling in heart failure is controversial. An adenovirus-based approach was used to investigate whether overexpression of Galpha(i)-2 impairs beta-adrenergic stimulation of adenylyl cyclase (AC) activity and cAMP levels in neonatal rat cardiac myocytes (NRCM) and cell shortening of adult rat ventricular myocytes (ARVM). Infection of NRCM with Ad5Galpha(i)-2 increased Galpha(i)-2 by 50-600% in a virus dose-dependent manner. Overexpression was paralleled by suppression of GTP- and isoprenaline-stimulated AC by 10-72% (P<0.001) in a PTX-sensitive manner. Isoprenaline-stimulated shortening of Ad5Galpha(i)-2-infected ARVM was attenuated by 34% (P<0.01). Ad5Galpha(i)-2/GFP (Galpha(i)-2, green fluorescent protein; bicistronic) was constructed to monitor transfection homogeneity and target Galpha(i)-2 overexpression to levels found in heart failure. At Galpha(i)-2 levels of 93% above control, isoprenaline-stimulated AC activity and cAMP levels were reduced by 17% and 40% (P<0.02), respectively. Beta1- and beta2-adrenergic stimulation was reduced similarly. Our results suggest that (a) the Galpha(i)-2 system exhibits tonic inhibition of stimulated AC in cardiac myocytes, (b) Galpha(i)-2-mediated inhibition is concentration-dependent and occurs at Galpha(i)-2 levels seen in heart failure, and (c) Galpha(i)-2-mediated inhibition affects both beta1- and beta2-adrenergic stimulation of AC. The data argue for an important, independent role of the Galpha(i)-2 increase in heart failure.
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PMID:Overexpression of wild-type Galpha(i)-2 suppresses beta-adrenergic signaling in cardiac myocytes. 1263 86

Previous studies using wild-type Encephalomyocarditis virus (EMCV) and Mengo virus, which have long poly(C) tracts (61 to 146 C's) at the 5' nontranslated region of the genome, and variants of these viruses genetically engineered to truncate or substitute the poly(C) tracts have produced conflicting data on the role of the poly(C) tract in the virulence of these viruses. Analysis of the nucleotide sequence of an EMCV strain isolated from an aborted swine fetus (EMCV 30/87) revealed that the virus had a poly(C) tract that was 7- to 10-fold shorter than the poly(C) tracts of other EMCV strains and 4-fold shorter than that of Mengo virus. Subsequently, we investigated the virulence and pathogenesis of this naturally occurring short-poly(C)-tract-containing virus in rodents, pigs, and nonhuman primates. Infection of C57BL/6 mice, pigs, and cynomolgus macaques resulted in similar EMCV 30/87 pathogenesis, with the heart and brain as the primary sites of infections in all three animals, but with different disease phenotypes. Sixteen percent of EMCV 30/87-infected pigs developed acute fatal cardiac failure, whereas the rest of the pigs were overtly asymptomatic for as long as 90 days postinfection (p.i.), despite extensive myocardial and central nervous system (CNS) pathological changes. In contrast, mice infected with >/==" BORDER="0">4 PFU of EMCV 30/87 developed acute encephalitis that resulted in the death of all animals (n = 25) between days 2 and 7 p.i. EMCV 30/87-infected macaques remained overtly asymptomatic for 45 days, despite extensive myocardial and CNS pathological changes and viral persistence in more than 50% of the animals. The short poly(C) tract in EMCV 30/87 (CUC(5)UC(8)) was comparable to that of strain 2887A/91 (C(10)UCUC(3)UC(10)), another recent porcine isolate.
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PMID:A wild-type porcine encephalomyocarditis virus containing a short poly(C) tract is pathogenic to mice, pigs, and cynomolgus macaques. 1291 30

We describe a 40-year-old man with limited scleroderma who presented with acute heart failure following a flu-like illness. He was known to have incomplete left anterior bundle branch block, initial isolated pulmonary hypertension with enlarged right atrium, and no pulmonary fibrosis. He received therapy for acute heart failure and was transferred to a scleroderma centre for specific treatment of scleroderma cardiomyopathy. Investigations showed raised inflammatory markers and diffuse hyperechogenic thickening of the myocardium on echocardiography. Contrast-enhanced (Gd-DOTA) cardiovascular magnetic resonance imaging (CV-MRI) showed multiple areas of non-homogeneous delayed hyperenhancement in the left ventricle, suggestive of myocarditis. Antiadenovirus IgM antibodies were detected with a titer consistent with recent infection. Six weeks later a repeat Gd-DOTA CV-MRI showed an almost complete resolution of the areas of hyperenhancement and there was a significant reduction in the adenovirus antibody titer with serological conversion to IgG. To our knowledge this is the first report of viral myocarditis in scleroderma. Infections are important causes of morbidity and mortality in this disease and should always be included in the differential diagnosis of cardiac symptoms. We propose that contrast-enhanced CV-MRI is valuable in a non-invasive diagnosis of heart disease in patients with scleroderma.
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PMID:Acute myocarditis associated with adenoviral infection in a patient with scleroderma. 1467 36

Parvovirus infection during pregnancy is an important cause of hydrops fetalis. It is attributed to anemia caused by viral-induced destruction of red blood cells. Infection of other organs has been reported including the heart, liver, and lungs. Few of these reports, however, convincingly demonstrate virions within the functional parenchyma of the tissue. This is of particular concern regarding myocardium in the context of hydrops fetalis which is, in part, due to cardiac failure. The problem in routine pathology practice is that most fetuses with the infection are macerated. This, in part, probably explains the paucity of published information on cardiac involvement. This study examined five cases of fatal hydrops fetalis with variable maceration with serologically proven parvovirus B19 infection. Transmission electron microscopy of cardiac tissue demonstrated intranuclear virions in both erythroid precursor cells and in cardiac myocytes in three of these cases. In each of these, immuno-gold electron microscopy provided confirmatory evidence of parvovirus infection. Virions were not identifiable where maceration had caused disintegration of nuclei in the myocytes. In addition, virions were absent in the three negative control cases where retroplacental hemorrhage was confirmed as the cause of death. This study suggests that parvovirus infection of cardiac myocytes may play a more important role in causing hydrops fetalis than previously realized. It also demonstrates that maceration should not discourage the use of electron microscopy.
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PMID:Parvovirus infects cardiac myocytes in hydrops fetalis. 1470 34

Little is known about the hospital inpatient care of patients with idiopathic Parkinson's disease (PD). Here, we describe the features of the emergency hospital admissions of a geographically defined population of PD patients over a 4-year period. Patients with PD were identified from a database for a Parkinson's disease service in a district general hospital with a drainage population of approximately 180,000. All admissions of this patient subgroup to local hospitals were found from the computer administration system. Two clinicians experienced in both general medicine and PD then reviewed the notes to identify reasons for admission. Admission sources and discharge destinations were recorded. Data regarding non-PD patients was compared to PD patients on the same elderly care ward over the same time period. The total number of patients exposed to analysis was 367. There was a total exposure of 775.8 years and a mean duration of 2.11 years per patient. There were 246 emergency admissions to the hospital with a total duration of stay of 4,257 days (mean, 17.3 days). These days were accounted for by 129 patients (mean age, 78 years; 48% male). PD was first diagnosed during 12 (4.9%) of the admissions. The most common reasons for admission were as follows: falls (n=44, 14%), pneumonia (n=37, 11%), urinary tract infection (n=28, 9%), reduced mobility (n=27, 8%), psychiatric (n=26, 8%), angina (n=21, 6%), heart failure (n=20, 6%), fracture (n=14, 4%), orthostatic hypotension (n=13, 4%), surgical (n=13, 4%), upper gastrointestinal bleed (n=10, 3%), stroke/transient ischemic attack (n=8, 2%), and myocardial infarction (n=7, 2%). The mean length of stay for the PD patients on the care of elderly ward specializing in PD care was 21.3 days compared to 17.8 days for non-PD patients. After hospital admission, there was a reduction in those who returned to their own home from 179 to 163 and there was an increase in those requiring nursing home care from 37 to 52. Infections, cardiovascular diseases, falls, reduced mobility, and psychiatric complications accounted for the majority of admissions. By better understanding the way people with PD use hospital services, we may improve quality of care and perhaps prevent some inpatient stays and care-home placements.
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PMID:Emergency hospital admissions in idiopathic Parkinson's disease. 1588 38

Emergent mechanical support for the failing ventricle, with eventual transfer for definitive care, is often required at non-transplant centers. Transfer for definitive care, in terms of bridge to transplant, may require ventricular assist device (VAD) placement at the primary institution or at the transplant center. Review of consecutive single transplant center referrals was conducted to decipher optimal management. From January 1997 to December 2000, 104 patients were transferred to the University of Pennsylvania Heart Failure/Transplant Service. Most were transferred from active cardiac surgical programs, with 56 patients having post-cardiotomy failure at the primary site. A VAD was placed in procedures done at the outside hospital (OSH) in 28 patients, most commonly (60%) an Abiomed device. Of the 76 patients that received a VAD at the transplant center (TxpC), 86% received a TCI or Thoratec device. Biventricular support was required in 34 patients. Overall survival was 57%, with 54 patients bridged to transplantation and 5 patients undergoing recovery. Patients having a VAD placed at the OSH had a 32% (9 of 28) survival, whereas at the TxpC survival was 65% (45 of 76) (p < 0.05). Mid-term follow-up showed that all 5 patients weaned are presently alive, and 52 patients are alive at >1-year post-transplant. The most common cause of death was multi-system organ failure (19 of 45), followed by major neurologic event (15 of 45). Infection was the cause of death in only 6 patients. Left ventricular failure can be treated by emergent VAD placement. Overall survival is substantial if these patients are referred to a transplant center with multiple options. In contrast to previous reports, survival rates may be improved by earlier referral, before VAD placement at non-transplant centers and use of a VAD with longer-term capability.
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PMID:Emergent mechanical support in the community: improvement with early transplant center referral. 1594 38


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