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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiovascular diseases are increasingly recognised as an important cause of morbidity and mortality in developing countries. This is due to the ageing of the population and better control of communicable disease and malnutrition. We review the published data on the epidemiology of heart failure in such countries. Rheumatic heart disease remains a major cause of heart failure in Africa and Asia, especially in the young. Hypertension is an important cause of heart failure especially in the African and African-American population. Chagas' disease is still a cause of heart failure in South America. However, as countries go through epidemiological transition and undergo socio-economic development, the epidemiology of heart failure becomes increasingly similar to that of Western Europe and North America with coronary artery disease being the single most common cause of heart failure. Preventive and public health strategies need to be specific to the local epidemiological characteristics.
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PMID:The epidemiological features of heart failure in developing countries: a review of the literature. 1157 17

The nonviral gene transfer technologies include naked DNA administration, electrical or particle-mediated transfer of naked DNA, and administration of DNA-synthetic macromolecule complex vectors. Each method has its advantage, such as low immunogenicity, inexpensiveness, ease in handling, etc., but the common disadvantage is that the transfection efficiency has been relatively poor as far as conventional plasmid vectors are involved. To improve the nonviral gene transfer systems, Epstein-Barr virus (EBV)-based plasmid vectors (also referred to EBV-based episomal vectors) have been employed. These vectors contain the EBNA1 gene and oriP element that enable high transfer efficiency, strong transgene expression and long term maintenance of the expression. In the current article, I review recent preclinical gene therapy studies with the EBV plasmid vectors conducted against various diseases. For gene therapy against malignancies, drastic tumor suppression was achieved by gancyclovir administrations following an intratumoral injection with an EBV plasmid vector encoding the HSV1-TK suicide gene. Equiping the plasmid with carcinoembryonic antigen (CEA) promoter sequences enabled targeted killing of CEA-positive tumor cells, which was not accomplished by conventional plasmid vectors without the EBV genetic elements. Transfection with an apoptosis-inducing gene was also effective in inhibiting tumors. Interleukin (IL)-12 and IL-18 gene transfer, either local or systemic, induced therapeutic antitumoral immune responses including augmentation of the cytotoxic T lymphocyte (CTL) and natural killer (NK) activities, while an autologous tumor vaccine engineered to secrete Th1 cytokines via the EBV system also induced growth retardation of tumors. Non-EBV conventional plasmids were much less effective in eliciting these therapeutic outcomes. Intracardiomuscular transfer of the beta-adrenergic receptor gene induced a significant elevation in cardiac output in cardiomyopathic animals, suggesting the usefulness of the EBV system in treating heart failure. The EBV-based nonviral delivery also worked as genetic vaccine that triggered prophylactic cellular and humoral immunity against acute lethal viral infection. All the nonviral delivery vehicles so far tested showed an improved transfection rate when combined with the EBV-plasmids. Collectively, the EBV-based plasmid vectors may greatly contribute to nonviral gene therapy against a variety of disorders, including malignant, congenital, chronic and infectious diseases.
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PMID:Improvement of nonviral gene therapy by Epstein-Barr virus (EBV)-based plasmid vectors. 1218 22

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

It is often assumed that aging is a uniform process throughout adulthood because of the approximately linear increase of logarithmic mortality. We explored this assumption by analyzing cause-specific mortality increases in France (1979-1994). Rising rapidly at ages 30-54 years ("middle age") are death rates from malignant neoplasms at various sites, acute myocardial infarction, hypertensive disease, and liver cirrhosis. Steeply increasing at 65-89 years ("old age") are death rates from certain infectious diseases, particularly of the respiratory system; certain types of accidents; nonalcoholic mental disorders (probably due mainly to Alzheimer's disease and senile dementia); heart failure; cerebrovascular disease; and some "vague" categories. The processes at work may be fundamentally different in these two life history stages, such that the mortality rise in middle age reflects specific chronic diseases that develop prematurely in some high-risk individuals, whereas the mortality increase in old age is dominated by senescent processes that eventually raise the vulnerability of almost all individuals to multiple pathologies.
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PMID:Differential patterns of age-related mortality increase in middle age and old age. 1463 Aug 73

We describe a case in which an elderly woman is hospitalised for acute medical illness and ask how this patient's risk of venous thromboembolism should be assessed and managed. Venous thromboembolism was previously regarded as a surgical problem, but occurs at least as frequently among medical patients. The risk of venous thromboembolism varies, but recent studies have provided detailed data on the risk in patients with acute medical illness, in particular those patients with acute heart failure, respiratory failure and acute infectious disease. As the evidence has accumulated, specific guidelines recommend provision of thromboprophylaxis to patients at risk. An approach to venous thromboembolic risk assessment and prevention in acutely ill medical patients is presented.
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PMID:Venous thromboembolic risk and prevention in acute medical illness. 1284 49

Epidemiologic data have shown that the risk of venous thromboembolism (VTE) in medical patients is comparable to the risk in surgical patients. Moreover, autopsy studies demonstrated that 75% of all in-hospital deaths for pulmonary embolism occur in nonsurgical patients. Hospitalized medical patients represent a very heterogeneous population. Patients with medical disorders who are at significant risk include those with heart failure, acute respiratory failure, acute infectious diseases, acute rheumatic disorders, inflammatory bowel diseases, and cancer. Recent consensus conferences have produced detailed recommendations for thrombosis prophylaxis in both surgical and medical patients. Both unfractionated heparin and low-molecular-weight heparins (LMWHs) have been shown to be effective when compared with placebo and are recommended in high-risk medical patients. When LMWHs were compared with unfractionated heparin, they were shown to have equivalent efficacy and greater safety than the parent compound. As for surgical patients, routine prophylaxis is still underused in the general medical population.
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PMID:Deep venous thrombosis in the medically ill. 1290 Nov 27

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

Heart failure is still associated with a poor prognosis despite great advances in drug therapy, so that surgical procedures are necessary in patients with end-stage cardiac failure. Cardiac transplantation was the therapy of choice during the last decades, but due to its disadvantages and the increasing scarcity of donor organs other surgical procedures were developed. Multisite pacing improves quality of life, but a longterm survival benefit remains to be proved. Coronary artery bypass grafting and valve surgery demonstrated to improve quality of life and to increase long-term survival. Ventricular assist devices are effective in bridging up to 70% of patients to cardiac transplantation, but the number of complications must be reduced. Partial left ventriculectomy may be performed with results similar to those obtained of cardiac transplantation, but long-term results are not yet available. Dynamic cardiomyoplasty and Myosplint implantation were not successful, but it must be awaited, if passive cardiomyoplasty leads to better results. Xenotransplantation is under intense investigation, but cannot be used clinically until now due to the hurdles of rejection and transfer of infectious diseases. This work provides a summary of today's knowledge about surgical procedures for end-stage heart failure.
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PMID:[Surgical therapy of end-stage heart failure]. 1292 37


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