Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ten to twelve million people irregularly distributed mainly through extensive rural areas of Latin America are afflicted by American trypanosomiasis (Chagas disease). Trypanosoma cruzi is the etiological agent, and it is naturally transmitted to humans by hematophagous hemiptera of Triatominae sub-family. These hemiptera feed by biting and usually defecate in the area near the puncture wound. Mucous membranes of breaks in the continuity of skin serve as passage ways for the parasite present in the excrement of the bug. Acute and chronic forms of American trypanosomiasis occur. Nervous system involvement in the acute form may give rise to meningoencephalitis. Central and/or peripheral signs of nervous system involvement can occur in the chronic form. Neuronal depopulation due to cell destruction by direct parasitism during the acute stage of the disease is the main pathogenetic way pointed out to explain chronic forms of nervous system involvement. Chronic Chagas cardiopathy usually produces mural thrombi. Fragments of thrombus situated in the left ventricle may become detached and migrate with the bloodstream to cause embolic phenomena in distant vessels--as in brain vessels--thus causing embolic cerebrovascular insults. Data on clinical and experimental studies are critically analysed.
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PMID:[American trypanosomiasis (Chagas disease) and the nervous system]. 314 93

In 1814, George Maton, first recognized that a mild illness characterized by rash, adenopathy, and little or no fever was a discrete entity. Henry Veale, in 1866, named the disease rubella. The illness attracted little attention until 1942, when Norman Gregg noticed that first-trimester maternal rubella caused serious birth defects. The full spectrum and impact of rubella embryopathy remained unclarified until rubella virus was isolated in tissue culture in 1962 by two independent groups: Parkman, Buescher, and Artenstein; and Neva and Weller. Using the new tools of the virus laboratory, many investigators concentrated on the consequences of a severe rubella epidemic in 1964, which affected approximately 1% of pregnancies. Newly recognized transient manifestations of congenital rubella infection (CRI) include neonatal thrombocytopenic purpura, hepatitis, bone lesions, and meningoencephalitis and late-emerging sequelae such as diabetes mellitus and progressive rubella panencephalitis added to the cataract, heart disease, mental retardation, and deafness previously defined as due to CRI. Sharp contrasts were documented between the patterns of virus excretion and immune response of postnatal vs. congenital rubella. Licensure and widespread distribution of attenuated rubella virus vaccines in 1969 have prevented epidemic rubella. Pockets of illness remain, even in the United States. Continued effort will be required to eliminate the rubella problem.
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PMID:The history and medical consequences of rubella. 389 Jan 5

Data were analyzed on 290 children admitted consecutively to the pediatric intensive care unit (PICU) of the Postgraduate Institute of Medical Education and Research in Chandigarh, India, in 1993 to examine the frequency, severity, risk factors, and mortality of hypokalemia (3.5 mEq/l serum potassium) and the efficacy of treatment. 43 (14.8%) children had 54 episodes of hypokalemia. Most (68.6%) episodes were moderate. Predisposing factors were the nature of primary disease (renal disease 19%, septicemia 19%, acute diarrhea 14%, and heart disease with congestive failure and meningoencephalitis 12% each), malnutrition (weight for age 80% in 72%), and treatment with drugs (diuretics 20%, beta-agonists 13%, and corticosteroids 11%). Diagnoses most common in hypokalemia cases were acute renal failure (25%), septicemia (22.8%), and acute severe bronchial asthma (20%). The most important predisposing factor for hypokalemia prior to hospitalization was poor oral intake (i.e., inability to replace adequate potassium) (27%). All 43 children received 4-6 mEq potassium/100 ml of intravenous fluids. Clinicians administered an infusion of 0.3 mEq potassium/kg/hour to 7 children (9 episodes) who had ECG changes of hypokalemia until the ECG became normal. Potassium levels returned to normal in all 9 episodes requiring rapid correction and in 40 of 45 episodes requiring slow correction. PICU patients with hypokalemia were more likely to die than PICU patients with no hypokalemia (25.6% vs. 10.9%; p 0.05; odds ratio = 2.34). Hypokalemia patients who received slow correction therapy were more likely to die than those who received rapid correction therapy (31% vs 0; p 0.05). Mortality was lower in PICU patients whose hypokalemia was corrected than in PICU patients whose hypokalemia was not corrected (13.5% vs. 100%; p 0.05). Based on these findings, regular monitoring and rapid correction are recommended to improve the outcome of hypokalemia.
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PMID:Hypokalemia in a pediatric intensive care unit. 877 44

Stroke etiologies in childhood differ from those in adulthood. While in children, congenital and acquired heart diseases and sickle cell anemia (SCA) are commonly seen causes, atherosclerosis is the main cause in adults. In this study, 39 children admitted to our hospital with ischemic stroke were evaluated according to etiologic factors and treatment regimens with comparison to the literature. Congenital-acquired heart disease and central nervous system infections (meningoencephalitis) were the most common causes in our series. Only one patient had dual pathology. As a result, cardiologic and infectious causes appeared to be the most important etiologic factors, especially in our region. Furthermore, etiologic factors rather than treatment used may play an important role in stroke recurrence.
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PMID:Evaluation of 39 children with stroke regarding etiologic risk factors and treatment. 1605 49

Chagas' disease (American trypanosomiasis) is an endemic parasitic disease in some areas of Latin America. About 16-18 million persons are infected with the aetiological agent of the disease, Trypanosoma cruzi, and more than 100 million are living at risk of infection. There are different modes of infection: (1) via blood sucking vector insects infected with T. cruzi, accounting for 80-90% of transmission of the disease; (2) via blood transfusion or congenital transmission, accounting for 0.5-8% of transmission; (3) other less common forms of infection, eg, from infected food or drinks or via infected organs used in transplants. The acute phase of the disease can last from weeks to months and typically is asymptomatic or associated with fever and other mild nonspecific manifestations. However, life-threatening myocarditis or meningoencephalitis can occur during the acute phase. The death rate for persons in this phase is about 10%. Approximately 10-50% of the survivors develop chronic Chagas' disease, which is characterized by potentially lethal cardiopathy and megacolon or megaoesophagus. There are two drugs available for the aetiological treatment of Chagas' disease: nifurtimox (Nfx) and benznidazole (Bz). Nfx is a nitrofurane and Bz is a nitroimidazole compound. The use of these drugs to treat the acute phase of the disease is widely accepted. However, their use in the treatment of the chronic phase is controversial. The undesirable side effects of both drugs are a major drawback in their use, frequently forcing the physician to stop treatment. The most frequent adverse effects observed in the use of Nfx are: anorexia, loss of weight, psychic alterations, excitability, sleepiness, digestive manifestations such as nausea or vomiting, and occasionally intestinal colic and diarrhoea. In the case of Bz, skin manifestations are the most notorious (e.g., hypersensitivity, dermatitis with cutaneous eruptions, generalized oedema, fever, lymphoadenopathy, articular and muscular pain), with depression of bone marrow, thrombocytopenic purpura and agranulocytosis being the more severe manifestations. Experimental toxicity studies with Nfx evidenced neurotoxicity, testicular damage, ovarian toxicity, and deleterious effects in adrenal, colon, oesophageal and mammary tissue. In the case of Bz, deleterious effects were observed in adrenals, colon and oesophagus. Bz also inhibits the metabolism of several xenobiotics biotransformed by the cytochrome P450 system and its reactive metabolites react with fetal components in vivo. Both drugs exhibited significant mutagenic effects and were shown to be tumorigenic or carcinogenic in some studies. The toxic side effects of both nitroheterocyclic derivatives require enzymatic reduction of their nitro group. Those processes are fundamentally mediated by cytochrome P450 reductase and cytochrome P450. Other enzymes such as xanthine oxidoreductase or aldehyde oxidase may also be involved.
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PMID:Toxic side effects of drugs used to treat Chagas' disease (American trypanosomiasis). 1693 19

Chagas' disease, caused by the parasite Trypanosoma cruzi, remains the leading cause of cardiopathy in Latin America with about 12 million people infected. Classic clinical manifestations derive from infection of muscle cells leading to progressive cardiomyopathy, while some patients develop megacolon or megaesophagus. A very aggressive clinical course including fulminant meningoencephalitis has been reported in patients who contract Chagas' disease in the background of immunodeficiency. This includes patients with human immunodeficiency virus infection as well as patients receiving immunosuppressive therapy for organ transplant. Currently, only two drugs are approved for the treatment of Chagas' disease, nifurtimox and benznidazole. Both have significant limitations due to common and serious side effects as well as limited availability. A promising group of new drug leads for Chagas' disease is cysteine protease inhibitors targeting cruzain, the major protease of T. cruzi. The inhibitor N-methyl-Pip-F-homoF-vinyl sulfonyl phenyl (N-methyl-Pip-F-hF-VS phi) is in late-stage preclinical development. Therefore, the question arose as to whether protease inhibitors targeting cruzain would have efficacy in Chagas' disease occurring in the background of immunodeficiency. To address this question, we studied the course of infection in recombinase-deficient (Rag1(-/-)) and normal mice infected with T. cruzi. Infections localized to heart and skeletal muscle in untreated normal animals, while untreated Rag1(-/-) mice showed severe infection in all organs and predominantly in liver and spleen. Treatment with the dipeptide N-methyl-Pip-F-hF-VS phi rescued immunodeficient animals from lethal Chagas' infection. The majority (60 to 100%) of inhibitor-treated Rag1(-/-) mice had increased survival, negative PCR, and normal tissues by histopathological examination.
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PMID:A cysteine protease inhibitor cures Chagas' disease in an immunodeficient-mouse model of infection. 1769 25