Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study summarizes the effects of both the rate and the cumulative dose of cigarette smoking on the health of the original Framingham cohort, 5209 individuals aged 30 to 62 years at entry. After 34 years of follow-up, it was observed that cigarette smoking was the prime determinant of chronic cough, and reduced both forced vital capacity and the 1-second forced expiratory volume. A significant relationship was observed between cigarette smoking and the incidence of cancer of the lung, stroke and transient ischemic attacks, intermittent claudication, and total cardiovascular disease, and most especially the average annual death rate. Cigarette smoking was significantly related to coronary heart disease in men 45 to 64 years old, although not related in women or older men. The data confirm and extend the evidence of the detrimental influence of cigarette smoking on health.
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PMID:The health risks of smoking. The Framingham Study: 34 years of follow-up. 827 19

Fabry disease (FD) is a rare disorder resulting from mutations of the alpha-Galactosidase A lysosomal enzyme gene. Accumulation of enzyme substrates leads to multisystemic clinical manifestations and multiorgan progressive damage with high morbidity and mortality. Recombinant enzyme replacement therapy (RERT) now available aims to delay or even avoid the complications of FD. The index case was a 50-year-old man with bone pain since childhood, coarse facies, angiokeratomas, anemia, renal failure, proteinuria, sinus node disease, valvular disease and massive left ventricular hypertrophy and brain ischemic alterations. FD diagnosis was confirmed during hospital admission for bacterial endocarditis leading to death. Family screening revealed an affected brother with acroparesthesia, chronic cough, sinus bradycardia, long QT interval and near-nephrotic proteinuria, now under RERT. Their mother was not screened due to stroke sequelae. This report illustrates the need for early diagnosis, family screening and treatment, aiming to change the natural history of FD.
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PMID:[A family with a rare disease]. 2065 70

We describe the case of a 45-year-old man with a unique constellation of supra-aortic artery aneurysms detected by chest X-ray during work-up for chronic cough. During his diagnostic work-up, the patient suffered an embolic stroke likely secondary to disrupted plaque originating in an aneurysmal right vertebral artery. Endovascular repair was not a viable option due to the diffuse and bilateral nature of aneurysmal disease, including involvement of the innominate and right carotid and vertebral arteries. The patient was successfully treated with a two-stage open surgical approach involving an initial right carotid artery to vertebral artery bypass and subsequent in situ reconstruction utilizing a bifurcated Dacron graft sewn to the proximal aortic arch with distal extension to the right common carotid and axillary arteries.
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PMID:A novel two-stage surgical approach for the treatment of symptomatic supra-aortic artery aneurysms. 2203 Mar 56

This editorial is about the roles that TRP channels play in heat and cold sensation and body temperature regulation. These roles may be exploited for therapeutic purposes (indeed, drugs targeting TRPV1, TRPA1 and TRPM8 channels are currently undergoing clinical trials for indications that range from pain through chronic cough and overactive bladder to cancer) or, conversely, may limit drug development (for example, several TRPV1 antagonists were withdrawn from clinical trials due to the hyperthermic reaction that they caused). In the future, modulation of thermosensitive TRP channels may ultimately find application in the treatment not only of pain, but also itch, stroke, asthma, and metabolic disorders. Of the multitude of targets involved in temperature sensation and body temperature regulation, why TRP channels? And why now?
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PMID:Feeling hot, feeling cold: TRP channels-a great story unfolds. 2722 14

This review is focused on the pathophysiology and therapeutic potential of purinergic signalling. A wide range of diseases are considered, including those of the central nervous system, skin, kidney, musculoskeletal, liver gut, lower urinary tract, cardiovascular, airways and reproductive systems, the special senses, infection, diabetes and obesity. Several purinergic drugs are already on the market, including P2Y12 receptor antagonists for stroke and thrombosis, P2Y2 receptor agonists for dry eye, and A1 receptor agonists for supraventricular tachycardia. Clinical trials are underway for the use of P2X3 receptor antagonists for the treatment of chronic cough, visceral pain and hypertension, and many more compounds are being explored for the treatment of other diseases. Most experiments are 'proof of concept' studies on animal or cellular models, which hopefully will lead to further clinical trials. The review summarises the topic, mostly referring to recent review articles.
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PMID:The therapeutic potential of purinergic signalling. 2873 73

Purinergic signalling, i.e., the role of nucleotides as extracellular signalling molecules, was proposed in 1972. However, this concept was not well accepted until the early 1990's when receptor subtypes for purines and pyrimidines were cloned and characterised, which includes four subtypes of the P1 (adenosine) receptor, seven subtypes of P2X ion channel receptors and 8 subtypes of the P2Y G protein-coupled receptor. Early studies were largely concerned with the physiology, pharmacology and biochemistry of purinergic signalling. More recently, the focus has been on the pathophysiology and therapeutic potential. There was early recognition of the use of P1 receptor agonists for the treatment of supraventricular tachycardia and A2A receptor antagonists are promising for the treatment of Parkinson's disease. Clopidogrel, a P2Y12 antagonist, is widely used for the treatment of thrombosis and stroke, blocking P2Y12 receptor-mediated platelet aggregation. Diquafosol, a long acting P2Y2 receptor agonist, is being used for the treatment of dry eye. P2X3 receptor antagonists have been developed that are orally bioavailable and stable in vivo and are currently in clinical trials for the treatment of chronic cough, bladder incontinence, visceral pain and hypertension. Antagonists to P2X7 receptors are being investigated for the treatment of inflammatory disorders, including neurodegenerative diseases. Other investigations are in progress for the use of purinergic agents for the treatment of osteoporosis, myocardial infarction, irritable bowel syndrome, epilepsy, atherosclerosis, depression, autism, diabetes, and cancer.
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PMID:Purinergic Signalling: Therapeutic Developments. 2899 32

Cough is a physiological reflex to protect airways against aspiration, but also it is one of the most frequent problems that lead patients to seek medical care. Chronic cough is more prevalent in the elderly than younger subjects, and more challenging to manage due to frequent comorbidities and possible side effects from drug treatment. Meanwhile, cough reflex does not decrease with natural aging but is often impaired by pathologic conditions like stroke. The impairment in cough reflex may lead to fatal complication like aspiration pneumonia. In this paper, we reviewed epidemiology and clinical considerations for chronic cough in the elderly, and summarized aging-related changes in cough reflex and also possible ways to normalize cough reflex and prevent aspiration pneumonia.
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PMID:The double-sidedness of cough in the elderly. 2933 68

Purinergic signaling was proposed in 1972, after it was demonstrated that adenosine 5'-triphosphate (ATP) was a transmitter in nonadrenergic, noncholinergic inhibitory nerves supplying the guinea-pig taenia coli. Later, ATP was identified as an excitatory cotransmitter in sympathetic and parasympathetic nerves, and it is now apparent that ATP acts as a cotransmitter in most, if not all, nerves in both the peripheral nervous system and central nervous system (CNS). ATP acts as a short-term signaling molecule in neurotransmission, neuromodulation, and neurosecretion. It also has potent, long-term (trophic) roles in cell proliferation, differentiation, and death in development and regeneration. Receptors to purines and pyrimidines have been cloned and characterized: P1 adenosine receptors (with four subtypes), P2X ionotropic nucleotide receptors (seven subtypes) and P2Y metabotropic nucleotide receptors (eight subtypes). ATP is released from different cell types by mechanical deformation, and after release, it is rapidly broken down by ectonucleotidases. Purinergic receptors were expressed early in evolution and are widely distributed on many different nonneuronal cell types as well as neurons. Purinergic signaling is involved in embryonic development and in the activities of stem cells. There is a growing understanding about the pathophysiology of purinergic signaling and there are therapeutic developments for a variety of diseases, including stroke and thrombosis, osteoporosis, pain, chronic cough, kidney failure, bladder incontinence, cystic fibrosis, dry eye, cancer, and disorders of the CNS, including Alzheimer's, Parkinson's. and Huntington's disease, multiple sclerosis, epilepsy, migraine, and neuropsychiatric and mood disorders.
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PMID:Introduction to Purinergic Signaling. 3164 77

Angiotensin-converting enzyme inhibitors (ACEIs) represent an important group of pharmacological compounds, largely prescribed for more than 30 years. They have been extensively evaluated in clinical trials, demonstrating significant reduction of morbidity and mortality of patients with cardiovascular diseases, mainly high blood pressure, myocardial infarction, heart failure and stroke. Besides their beneficial effects and a general good safety profile, it was proven that ACEIs might also induce adverse effects in some patients, most notably angioedema (AE) and chronic cough. The occurrence rate of adverse events induced by ACEIs is low, but the number of suffering patients is relatively high, since ACEIs is one of the most frequently prescribed medication worldwide. The aim of our study was to evaluate clinical pattern, risk factors and general management of ACEI-induced angioedema in a cohort of patients addressed for allergist evaluation in one university hospital in Romania, during a period of 32 months. It was found that ACEI-induced angioedema (ACEI-AE) represented more than half of the total number of patients addressed for angioedema without urticaria, with variable clinical and time-patterns. Most of the patients were referred by general practitioners (GPs) with diagnosis of urticaria or other skin allergy and continued to take ACEIs for months and years after onset of angioedema. We concluded that the awareness of acquired, non-allergic angioedema induced by ACEI therapy in medical practice is still low and there is a need for improved knowledge and interdisciplinary collaboration in this field.
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PMID:Acquired angioedema induced by angiotensin-converting enzyme inhibitors - experience of a hospital-based allergy center. 3250 96