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)

Alzheimer's disease (AD), the leading cause of disability in people older than 75 years of age, has direct and indirect medical costs estimated at $100 billion per year. Yet underdiagnosis, coding, and reimbursement barriers result in most patients with AD receiving inadequate care. The vast majority of managed care organizations (MCOs) still lack formal disease management programs for AD. In several documented studies, the total costs for managing patients with AD increased significantly over age- and comorbidity-matched controls without AD. Importantly, these extra costs include not only nursing home care but also medical claims for inpatient stays, emergency department visits, and outpatient care. The extra costs are especially high in those patients with comorbidities such as diabetes or heart failure. Emerging pharmacoeconomic data indicate potential savings in medical care costs associated with early treatment of AD and the potential cost effectiveness of cholinesterase inhibitors such as donepezil. These studies document that Medicare MCOs are in need of directed efforts to improve medical management for members with AD.
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PMID:The pharmacoeconomics of Alzheimer's disease. 1114 78

Sleep disordered breathing (SDB), i.e., obstructive, central or mixed sleep apneas, has been recognized as a common occurrence in the elderly. Aging is per se associated with a decrease in the quality of sleep; SDB may further disrupt the sleep architecture in older subjects. The prevalence of obstructive sleep apnea (OSA) increases with aging; available studies report prevalence rates of 11-62%. Furthermore, OSA has been associated with increased mortality in older adults. Central apneas and periodic breathing occur with increased frequency either in subjects with neurological disorders such as infarction, tumor, sequelae of infection, diffuse encephalopathies, or in chronic heart failure. Patients with cerebrovascular disease (stroke, or transient ischemic attacks) have a markedly high prevalence of SDB, mainly OSA. In these patients, SDB is associated with a poorer functional prognosis at 3 and 12 months after the acute event, and a higher mortality. The clinical impact of SDB on cognitive function appears to be modest in patients without dementia, although there is a moderate increase in daytime sleepiness. In Alzheimer's disease (AD) however, SDB occurs more frequently than in non-demented older subjects, and its severity is correlated with the degree of cognitive impairment. The hypothesis of a causal relationship between AD and SDB remains a subject of controversy. The possibility of SDB should be considered in the elderly in the differential diagnosis of "reversible dementias", increased daytime sleepiness, or unexplained right-sided heart failure.
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PMID:Sleep disordered breathing in the elderly. 1121 51

Dexanabinol is a non-psychotropic cannabinoid NMDA receptor antagonist under development by Pharmos Corp for the potential treatment of cerebral ischemia, glaucoma, Alzheimer's disease, cardiac failure, head injury and multiple sclerosis (MS) [311522]; it is in phase III trials for traumatic brain injury (TBI) [388709]. Dexanabinol was licensed to Pharmos for development from its originator, the Hebrew University of Jerusalem [180441]. Pharmos is seeking to enter into a strategic agreement with another company to develop and commercialize dexanabinol [317369]. Unlike its enantiomer, HU-210 (Yissum Research Development Co), dexanabinol does not interact with cannabinoid receptors [223330]. It has also exhibited more effective antioxidant and anti-inflammatory properties than MK-801 (dizocilpine; Merck & Co Inc) [167980], [168212]. In addition, dexanabinol is generally well tolerated and appears toxicologically safe [170116]. Pharmos has been awarded a Small Business Innovation Research grant from the National Institutes of Health (NIH) National Institute of Neurological Disorders and Stroke, Division of Stroke and Trauma. The grant covers the development of new prodrugs and novel formulations of dexanabinol and will support additional study of dexanabinol compounds for various indications. The prodrugs being studied are part of the group of compounds that include dexanabinol [247958]. A Notice of Allowance was received in March 1999 on a patent covering the use of the drug in the treatment of MS [324163]. The use of dexanabinol and its derivatives to treat MS is described in US-05932610 [358503]. An oral formulation of dexanabinol is claimed in US-05891468. Dexanabinol analogs with special utility in acute and chronic pain are claimed in US-04876276, while dexanabinol analogs for neuroprotection are claimed in US-06096740. Pharmos estimates that the worldwide market for dexanabinol in the treatment of severe head trauma may reach $1 billion per year [319244].
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PMID:Dexanabinol Pharmos. 1124 4

Dementia in the elderly used to be rare, but why has it become a major social threat today? There can be many potential answers, but an ultimate one is clear: the longer life expectancy today. This knowledge indicates that "advanced aging" is a primary suspect in the origin of senile dementia. If so, then why can many elderly remain healthy at the same old age? We know, for example, that elderly people commonly have a certain degree of atherosclerosis and osteoporosis, but only some of them develop severe clinical symptoms at the same age. These different outcomes generally can be explained by "risk factors" in life (exercise, diet, individual background, etc). It thus appears to be a general pattern that advanced aging (after age 80) will set the stage for various senile disorders, but risk factors largely determine the onset age as well as individual specificity of their clinical manifestations. In this context, senile disorders including senile dementia would differ fundamentally from the pathogen-caused conventional diseases (AIDS, polio, cancer, Down's, etc.) by origin, incidence, and intervention strategy. This view would call into question the current definition of senile dementia as a conventional "disease" (Alzheimer's). The term "Alzheimer's disease" originally referred to "midlife" dementia, but it is defined today to be the same medical entity as senile dementia on the basis that they both display the same hallmarks and symptoms despite their onset age difference. Now, after in-depth scrutiny, we finally come to realize that they are not the same disease, but as different as heart failure at midlife versus the "same" failure at advanced age (i.e., a conventional disease versus a senile condition). Thus, by eliminating the age difference, the new definition has converted a senile condition into a conventional "disease", thereby changing the course of its scientific inquiry to miss the main targets. This may be why after extensive studies for 25 years, the origin of senile dementia has remained an enigma.
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PMID:Alzheimer movement re-examined 25 years later: is it a "disease" or a senile condition in medical nature? 1150 85

Research on different types of stem cells is of major interest because of its apparent very promising therapeutic prospects, such as for Parkinson's and Alzheimer's disease, spinal cord injuries, stroke, diabetes, cardiac failure, liver failure, cartilage injuries, severe blood diseases, cancer etc. Stem cells can be derived from different sources: adult tissue, foetal tissues, and from in vitro fertilised embryos. Depending on their origin they have varying capacity to multiply and differentiate to other cell types. It is at present not possible to predict which types of cells will be best suitable for various therapeutic situations. Embryonic stem cells have been shown capable of differentiating into all the different tissues and cell types of the body, but they cannot form a new individual. Because of the ethics question involved, The European Group on Ethics on Science and New Technologies for the European Commission and Parliament (EGE), and the Ethics Committee of the Nordic Council of Ministers have prepared reports and given guidelines for research on stem cells. According to the guidelines, every country should regulate the research. Only embryos, which cannot be used in infertility treatment, and have been donated for research, can be used. Creation of embryos solely for research purposes, including somatic cell nuclear transfer, is not regarded as acceptable for the time being. Both partners of the donating couple have to sign an informed consent document. Ongoing research in Sweden is well in line with these European and Nordic recommendations.
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PMID:[Ethical aspects of stem cell research. Legislation and guidelines in Europe]. 1157 92

Often ignored, neurocognitive dysfunction in chronic heart failure represents a daunting morbidity progressing to loss of self-reliance. Although the precise mechanisms arbitrating the development of this disorder remain elusive, microembolization and cerebral hypoperfusion are implicated. Other causes of cognitive decline may include prior cardiac surgery, chronic hypertension, sleep disordered breathing, hyperhomocysteinemia, dementia of aging, and more traditional causes such as Alzheimer's disease. The discovery of neurocognitive defects in heart failure must prompt a well-constructed diagnostic evaluation to search for the underlying causes since this process may be at least partially reversible in many cases.
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PMID:Difficult cases in heart failure: the challenge of neurocognitive dysfunction in severe heart failure. 1214 48

Carnitine is an ammo acid derivative found in high energy demanding tissues (skeletal muscles, myocardium, the liver and the suprarenal glands). It is essential for the intermediary metabolism of fatty acids. Carnitine is indispensable for beta-oxidation of long-chain fatty acids in the mitochondria but also regulates CoA concentration and removal of the produced acyl groups. AcylCoAs act as restraining factor for several enzymes participating in intermediary metabolism. Transformation of AcylCoA into acylcarnitine is an important system for removing the toxic acyl groups. Although primary deficiency is unusual, depletion due to secondary causes, such as a disease or a medication side effect, can occur. Primary carnitine deficiency is caused by a defect in plasma membrane carnitine transporter in muscle and kidneys. Secondary carnitine deficiency is associated with several inborn errors of metabolism and acquired medical or iatrogenic conditions, for example in patients under valproate and zidovuline treatment. In cirrhosis and chronic renal failure, carnitine biosynthesis is impaired or carnitine is lost during hemodialysis. Other chronic conditions like diabetes mellitus, heart failure, Alzheimer disease may cause carnitine deficiency also observed in conditions with increased catabolism as in critical illness. Preterm neonates develop carnitine deficiency due to impaired proximal renal tubule carnitine re-absorption and immature carnitine biosynthesis. Carnitine stabilizes the cellular membrane and raises red blood cell osmotic resistance but has no metabolic influence on lipids in dialysis patients. L-Carnitine has been administered in senile dementia, metabolic nerve diseases, in HIV infection, tuberculosis, myopathies, cardiomyopathies, renal failure anemia and included in baby foods and milk.
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PMID:Carnitine metabolism and deficit--when supplementation is necessary? 1276 64

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

Semicarbazide-sensitive amine oxidase (SSAO) catalyzes the conversion of methylamine to formaldehyde. This enzyme is located on the surface of the cytoplasmic membrane and in the cytosol of vascular endothelial cells, smooth muscle cells, and adipocytes. Increased SSAO activity has been found in patients with diabetes mellitus, chronic heart failure, and multiple types of cerebral infarcts and is associated with obesity. Increased SSAO-mediated deamination may contribute to protein deposition, the formation of plaques, and inflammation, and thus may be involved in the pathophysiology of chronic vascular and neurological disorders, such as diabetic complications, atherosclerosis, and Alzheimer's disease. In the present study, we demonstrate the induction of cross-linkage of formaldehyde with the lysine moiety of peptides and proteins. Formaldehyde-protein adducts were reduced with sodium cyanoborohydride, hydrolyzed in hydrochloric acid, and the amino acids in the hydrolysates were derivatized with fluorenylmethyl chloroformate and then identified with high-performance liquid chromatography. We further demonstrate that incubation of methylamine in the presence of SSAO-rich tissues, e.g., human brain meninges, results in formaldehyde-protein cross-linkage of particulate bound proteins as well as of soluble proteins. This cross-linkage can be completely blocked by a selective inhibitor of SSAO. Our data support the hypothesis that the SSAO-induced production of formaldehyde may be involved in the alteration of protein structure, which may subsequently cause protein deposition associated with chronic pathological disorders.
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PMID:Protein cross-linkage induced by formaldehyde derived from semicarbazide-sensitive amine oxidase-mediated deamination of methylamine. 1512 65

Dysphagia is most common in geriatric medicine. Aspirations may cause chronic inflammatory syndrome or acute pneumonia or heart failure. At-risk patients should be recognised: some risks are caused by an acute condition, some by chronic disease or handicap. Alzheimer's disease is the most common at-risk condition; it is causes a loss of the conscious part of mastication and early swallowing. Psychiatric disorders with anorexia should not be overlooked as a cause for dysphagia and malnutrition. Due to a longer life, elderly people are more likely to have multiple causes for dysphagia. Management of dysphagia in geriatric patients is sometimes curative but more often readaptative and palliative. It is not restricted to the time of the meals. It first starts with avoiding decubitus and maintaining a walking ability. Proper positioning in seats and bed involves an occupational therapist. The nutritionist selects tasty and appealing meals for each patient. Nurses detect acute confusion as opposed to, or in, dementia. The speech therapist takes charge in tutoring the staff in knowing what is the secure way to manage an assisted meal, and helps finding the best fitted texture for food and drink. Sometimes a proper rehabilitation will be feasible. Per endoscopic gastrostomies are mostly restricted to neuro-vascular patients and need discussed for their benefit/risk balance. The holistic approach needed to manage dysphagia in polypathology elderly patients calls for a "cultural" approach of the whole gerontologic team, never the less, accurate specialised diagnosis in mandatory.
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PMID:[Dysphagia, a geriatric point of view]. 1514 31


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