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)

The paper reports two siblings, 6 and 3 3/4 years old, with a congenital nephropathy (nephronophthisis), retinitis pigmentosa, heart failure and peripheral dysostosis. The severe histological changes of the kidneys with tubular atrophy and interstitial fibrosis caused the death of the older sister at the age of 7 years. The symptoms of our patients are discussed in comparison to the syndrome described by MAINZER et al.
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PMID:[Familial nephropathy with retinitis pigmentosa and peripheral dysostosis]. 61 82

Refsum's disease is a polyneuropathy due to a hereditary error in the metabolism of a fatty acid, phytanic acid, usually leading to cardiac failure only at an advanced stage of the disease. The authors report the case of two brothers with Refsum's disease revealed by a heart failure before the clinical stage of the peripheral neuropathy. In the younger brother, the affection started at the age of 22 years by an acute pulmonary oedema which revealed a dilated, hypokinetic myocardiopathy, associated with retinitis pigmentosa, ptosis, anosmia and biological myolysis. The normal plasma concentration of phytanic acid measured several times led to the conclusion of Kearns-Sayre syndrome even if certain aspects were atypical (moderate conduction disorders, no characteristic aspect in the muscle biopsy). Five years later, the older brother, aged 28, presents a dyspnea on effort which leads to the discovery of a hypokinetic, hypertrophic myocardiopathy, slightly dilated, associated with cardiac conduction disorders, retinitis pigmentosa, anosmia and biological myolysis. The plasma concentration of phytanic acid being very high. Refsum's disease was diagnosed and the diagnosis of younger brother was corrected. From the study of these two cases, the characteristics of the cardiac disorders can be specified: the cardiopathy can reveal the disease and correspond to a dilated or hypertrophic myocardiopathy. The diagnosis of the disease can be difficult because the plasma phytanic acid may remain at normal level, thus requiring the assay of the activity of phytanate oxydase. The existence of ophthalmologic signs (retinitis pigmentosa or progressive ophthalmoplegia externa) associated with a myocardiopathy must systematically lead to a search for Refsum's disease, this diagnosis having fundamental therapeutic implications (died, even plasmapheresis).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Refsum's disease. Apropos of 2 cases disclosed by myocardiopathy]. 169 53

Fourteen patients with familial juvenile nephronophthisis are described, eight of whom displayed one or more additional disorders. One boy with short limbed dwarfism and an abnormal chest was considered to have Jeune's syndrome; review of the published reports supports the view that nephronophthisis is the principal cause of renal failure in this disorder. Another patient with renal failure and retinitis pigmentosa at presentation developed progressive neurological and neuromuscular impairment leading to the discovery of ragged red fibre disease (mitochondrial cytopathy). Cardiomyopathy was present in this and one other patient. Tapeto-retinal degeneration, hepatic fibrosis, cerebellar ataxia, and oculomotor apraxia were among the other disorders encountered. Three patients presented in extremis with acute heart failure and irreversible oligo-anuria and this complication developed in another child who was already known to have nephronophthisis. Awareness of this disease and its associations is important for early diagnosis and appropriate management.
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PMID:Familial juvenile nephronophthisis, Jeune's syndrome, and associated disorders. 401 47

Mitochondrial disorders are a group of diseases that can affect virtually all organ systems. A 19 year old man was seen in 1993 with neurologic abnormalities consisting of impaired function of muscles, diplopia, progressive loss of vision, impaired phonation and swallowing, during the last 10 years. Physical examination disclosed moderate wasting of the four limb muscles, mild motor weakness of neck muscles, symmetrical hyporeflexia, cerebellar dysfunction, severe external ophtalmoplegia and ptosis. Fundii oculi examination showed retinitis pigmentosa. The electromyogram demonstrated myopathic changes with normal nerve conduction velocities. The cerebrospinal fluid was normal, except for a mild increase in lactic acid. Histochemical study of a muscle biopsy specimen demonstrated ragged red fibers and increase of the subsarcolemal oxidative activity of mitochondriae. The diagnosis of Kearns-Sayre disease was confirmed and he was discharged advising physical therapy. On February 1995, he was again admitted, this time with right cardiac failure and worsening of all his previous symptoms and signs. He complained of myalgias and his muscle weakness was more striking on clinical examination. Echocardiography showed biventricular dilatation and left ventricular hypertrophy with preserved systolic function. A new muscle biopsy revealed an heteroplasmic deletion of 5 Kb with 80% of mutant mitochondrial DNA. In brief, we report a patient with the clinical phenotype of Kearns-Sayre syndrome who presented an acute congestive cardiac failure due to cardiomyopathy, an association which has seldom been, reported in the literature.
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PMID:[Severe cardiac failure in Kearns-Sayre syndrome]. 943 73

Treatment of hypertension with angiotensin II receptor antagonists (AIIA) was first limited to diabetics and patients with microalbuminuria. So far, results of several large clinical trials with AIIAs were published, confirming significant renoprotective effect of these agents compared to placebo (RENAAL and IRMA), amlodipin (MARVAL and IDNT) and a combination of ACEI and AIIA (CALM). In 2002, results of 2 large comparator studies in hypertension were published: LIFE - Losartan Intervention For Endpoints and SCOPE - the Study on COgnition and Prognosis in Elderly hypertensives. In 2003, a series of the CHARM studies involving patients with heart failure were published and, from than, AIIA have been used as an alternative to ACEI or in a combination with ACEI. MOSES study - Morbidity and mortality after stroke, eprosartan compared with nitrendipine for secondary prevention - results were published in 2005 and ONTARGET study, focusing on secondary prevention of ischemic heart disease, was published in 2008. The CORD study - Comparison of recommended doses - and the ACTIVE I study (AF Clopidogrel Trial with Irbesartan for prevention of Vascular Events) were published in 2009. Candesartan was used in the CALM, SCOPE, RESOLVED and CHARM studies, irbesartan in the IRMA, IDNT and ACTIVE I.
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PMID:[AII antagonists (candesartan and irbesartan) in the treatment of cardiovascular diseases]. 2312 Oct 62

The link between heart and skeletal muscle disorders is based on similar molecular, anatomical and clinical features, which are shared by the 'primary' cardiomyopathies and 'primary' neuromuscular disorders. There are, however, some peculiarities that are typical of cardiac and skeletal muscle disorders. Skeletal muscle weakness presenting at any age may indicate a primary neuromuscular disorder (associated with creatine kinase elevation as in dystrophinopathies), a mitochondrial disease (particularly if encephalopathy, ocular myopathy, retinitis, neurosensorineural deafness, lactic acidosis are present), a storage disorder (progressive exercise intolerance, cognitive impairment and retinitis pigmentosa, as in Danon disease), or metabolic disorders (hypoglycaemia, metabolic acidosis, hyperammonaemia or other specific biochemical abnormalities). In such patients, skeletal muscle weakness usually precedes the cardiomyopathy and dominates the clinical picture. Nevertheless, skeletal involvement may be subtle, and the first clinical manifestation of a neuromuscular disorder may be the occurrence of heart failure, conduction disorders or ventricular arrhythmias due to cardiomyopathy. ECG and echocardiogram, and eventually, a more detailed cardiovascular evaluation may be required to identify early cardiac involvement. Paediatric and adult cardiologists should be proactive in screening for neuromuscular and related disorders to enable diagnosis in probands and evaluation of families with a focus on the identification of those at risk of cardiac arrhythmia and emboli who may require specific prophylactic treatments, for example, pacemaker, implantable cardioverter-defibrillator and anticoagulation.
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PMID:Skeletal muscle involvement in cardiomyopathies. 2414 64

The aim of this review is to present the research results and draw new conclusions about the impact of alterations in the signal transmission through the G protein-coupled receptors (GPCRs) on the formation of diseases and drug therapy. GPCR family is the largest and the most diverse group of membrane receptors. They transmit signals into the cell by interaction with different ligands, which include, inter alia, hormones, neurotransmitters, and photons. GPCRs are responsible for the proper conduction of many physiological processes such as vision, intercellular communication, the neuronal transmission, hormonal signaling and are involved in many pathological processes. They are also point on the binding pathway of multiple drugs. They are targets of nearly one third of the drugs at the current pharmaceutical market. The genes encoding GPCRs represent about 4% of the human genome. Mutations that occur in them are associated with a broad spectrum of diseases of diverse etiology. As a mutations result, there is a change in receptor activity (GPCR become inactive, overactive, or constitutively active), in the process of ligand binding and signal transduction. Changes in the GPCRs functioning can cause diseases such as retinitis pigmentosa (rhodopsin mutations), nephrogenic diabetes insipidus (vasopressin receptor mutations), obesity (melanocortin receptor mutations). Many mutational changes in genes encoding GPCR can change drug therapy of already existed diseases: heart failure (adrenergic receptors), asthma (cysteinyl leukotriene receptors). Studies concerning the structure and function of genetically modified GPCRs allow to get know a variety of mechanisms of its action, which in turn can contribute to broaden the knowledge on the etiology and pharmacotherapy of many currently incurable diseases.
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PMID:G protein-coupled receptors: abnormalities in signal transmission, disease states and pharmacotherapy. 2527 42

Although heart transplantation and mechanical circulatory support are effective therapies for patients with advanced heart failure (HF), many patients are ineligible due to co-morbidities. Continuous home intravenous with positive inotropes such as milrinone are used in these patients to improve quality of life. We hypothesized that, unlike previous studies with oral milrinone, a slow-release formulation that provides stable lower plasma levels may be better tolerated and provide symptomatic benefit. Accordingly, we developed an extended release milrinone formulation (CRD-102) and evaluated its effects in 26 patients with no-option Stage D HF. One month after open-label therapy there were significant improvements in NYHA class, Minnesota Living with Heart Failure score and 6-minute walk distance. There was no evidence of hypotension or increased arrhythmic burden. In conclusion, the present study demonstrates evidence of beneficial actions of extended release milrinone in advanced HF. Longer-term randomized clinical trial data are required.
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PMID:Extended Release Oral Milrinone, CRD-102, for Advanced Heart Failure. 3006 57