Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The brain natriuretic peptide (BNP) assay is a new, relatively inexpensive, and simple test that has the potential to be an early, cost-effective, and reliable marker for HIV-related cardiomyopathy. We report 1 case of HIV-related cardiomyopathy and 10 cases of of HIV infection with unknown heart disease in which we measured BNP levels and performed echocardiography. We found a significant inverse relationship between BNP and left ventricular function in these patients. Further basic and epidemiologic research on BNP measurement for the detection of HIV-related cardiomyopathy is needed to support these findings, which if confirmed, could have important clinical and public health implications.
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PMID:Brain natriuretic peptide and HIV-related cardiomyopathy. 1249 56

Biosimulation uses mathematics to quantitatively represent the dynamics of biological systems and thereby analyze and predict system behavior. Biosimulations can be classified into two general categories: small-scale models designed to address a specific problem, and large-scale models of detailed regulatory mechanisms used to address a broad scope of questions. Both classes of biosimulations have been applied to problems important for drug discovery and development. Small-scale biosimulations have been particularly useful for interpreting clinical data and developing novel biomarkers. Large-scale biosimulations typically integrate a wide variety of data and can provide insights into how complex biological systems are regulated in both health and disease. Because large-scale biosimulations represent detailed regulatory mechanisms and their interactions, they can predict the overall clinical effect of modulating individual pathways or targets. In this mini-review, we describe several examples of how small- and large-scale biosimulations have been applied to problems important for drug development in diabetes, HIV, heart disease and asthma.
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PMID:Small- and large-scale biosimulation applied to drug discovery and development. 1254 5

Methamphetamine (MA) not only affects the nervous system but also has cardiac toxicity and immunosuppressive properties. This manuscript will provide support that there is a relationship between MA use and heart disease as well as immune dysfunction. The cardiovascular manifestations of acute MA use include tachycardia, atrioventricular arrhythmias, myocardial ischemia, myocardial ischemia and hypertension, resulting in cardiac lesions. Chronic use of MA causes cardiomyopathy including cellular infiltration, myocardial hypertrophy, myocardium rupture and fibrosis. The increased catecholamine levels are responsible for the cardiac lesions induced by MA. The additional problem with MA use is its potential to disrupt the immune system function leading to suppression of mitogen-stimulated lymphocyte, a reduction in circulating lymphocyte numbers and alternation T-lymphocyte cytokine secretion as well as B cell proinflammatory cytokine secretion. Concomitant MA use and Human Immunodeficiency Virus (HIV) infection not only enhances immunosuppression associated with HIV but also increases the heart disease occurrence with a coincidentally complication of AIDS or AIDS medications.
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PMID:Heart disease, methamphetamine and AIDS. 1273 29

Heart disease in AIDS, particularly cardiomyopathy (CM), is an increasingly recognized clinical problem with as yet undefined pathogenetic mechanisms. Among the potential etiologies of AIDS CM are HIV-1 infection of cardiac myocytes and subsequent cardiac dysfunction, opportunistic infection, inflammatory reactions, cytokine effects, and cardiotoxicity of prescribed or illicit drugs. It seems probable that multiple factors may impact on the development of CM in AIDS. Transgenic mice (TG) are useful biological tools to explore mechanisms of cardiac function and disease. In AIDS models, TG offer novel ways to elucidate mechanisms of AIDS CM through combined in vivo and in vitro studies. With targeted and non-targeted TG, structural and functional effects of specific HIV-1 gene products on heart tissue may be addressed. The impact of environmental agents including therapeutics or cardiotoxins may also be defined. To address the complexity of AIDS CM using TG, an experimental approach has been employed in our laboratories to model the clinical condition. We utilize AIDS TG with generalized expression of HIV-1 gene products in CM models with combined antiretroviral regimens to define the cardiovascular effects of AIDS and its therapy on the structure and function of the murine heart. We are developing a series of cardiac specific TG bearing selected HIV-1 genes. These TG target the selected HIV-1 genes expressed in cardiac ventricular myocytes. Tissue-specific targeting of this type enables us to define structural and functional effects of specific HIV-1 gene products on the cardiac myocyte.
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PMID:Use of the transgenic mouse in models of AIDS cardiomyopathy. 1287 May 29

Whether the atherogenic metabolic side effects of highly active antiretroviral therapy (HAART) (lipid disorders and glucose intolerance/diabetes) will translate, in the long term, into an increased incidence of cardiovascular events that would offset the survival benefits of this type of therapy is a matter of intense concern. This concern has been substantiated by a series of case reports of HIV-infected patients who had experienced unexplained cardiovascular disease. However, in the absence of prospective, large cohort studies, the answer to this question at present remains elusive. Indirect evidence, from retrospective cohort analyses and non-invasive imaging of peripheral arteries, indicates that HIV-infected persons are at higher risk for atherosclerosis than HIV-negative individuals. However, this risk does not appear to be attributable to HAART. Pending the availability of further data, a global assessment of the risk for heart disease should be performed in all HAART-treated HIV-infected patients, taking into account age and the presence of major risk factors. There is so far no evidence, from a cardiovascular standpoint, to limit administration of HAART. However, interventions on modifiable risk factors, including smoking cessation, are strongly recommended, particularly in high-risk patients.
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PMID:Atherosclerosis and HIV in the highly active antiretroviral therapy era: towards an epidemic of cardiovascular disease? 1287 May 32

Within the clinical and public health communities, it is often unnoticed that the developing world is experiencing an aging population with its attendant increase in the burden of chronic, noncommunicable diseases. From July 1999 to July 2000, 77% of the world's net gain in elderly persons occurred in developing countries. In Sub-Saharan Africa alone, the number of persons aged 65 years and older is expected to increase by 50% in 2015, from 19.3 million to 28.9 million. This demographic change has profound implications for developing countries that already shoulder a huge burden of communicable diseases, especially the HIV/AIDS epidemic, and continue to be challenged by basic infrastructure needs and economic development. In the 30-year period from 2000 to 2030, the population of elderly persons is projected to double in many Sub-Saharan African countries including the Democratic Republic of Congo, Mozambique, Cameroon, and Ghana. The scale and magnitude of these demographic changes are unprecedented. Since advancing age is the most powerful independent predictor of cardiovascular morbidity and mortality, the impact of these demographic changes on heart disease and stroke will be substantial. Aggressive efforts in promoting healthy aging and the prevention of cardiovascular risk factors will be crucial in preventing an impending cardiovascular epidemic in these countries.
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PMID:Population aging and implications for epidemic cardiovascular disease in Sub-Saharan Africa. 1367 18

Primary pulmonary hypertension (PPH) is characterised by sustained elevations of pulmonary arterial pressure without a demonstrable cause, leading to right ventricular failure and death. Hereditary mutations in the bone morphogenetic protein receptor type II (BMPR2) gene result in familial PPH transmitted as an autosomal dominant trait, albeit with low penetrance. The causes in cases without a BMPR2 mutation are unknown, but a syndrome of pulmonary arterial hypertension (PAH) similar to hereditary PPH is associated with systemic connective tissue disease, congenital heart disease, portal hypertension, and human immunodeficiency virus infection, or with the use of appetite-suppressant drugs. The authors identified a BMPR2 gene mutation in a 27-yr-old female who developed PAH after a short course of the appetite-suppressant drug amfepramone (diethylpropion). This allowed molecular genetic counselling and prevention of potentially harmful drug exposure in the patient's son treated for attention deficit disorder with methylphenidate, an amphetamine-related drug. No BMPR2 mutation was found in four additional, unrelated patients with appetite suppressant-related PPH. The findings provide strong evidence that amfepramone can trigger primary pulmonary hypertension in a bone morphogenetic protein receptor type II gene mutation carrier, and indicate that other genes are probably implicated in genetic susceptibility to appetite suppressants.
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PMID:Primary pulmonary hypertension after amfepramone (diethylpropion) with BMPR2 mutation. 1517 99

This study aimed to identify therapeutic approaches and the tendencies of Gram-positive infections in Spanish hospitals in terms of prevalence, origin, location and etiology, as well as the characteristics of patients with these infections, their underlying illnesses, the severity and predisposing factors. We used statistical analysis to compare the results of two multicenter prevalence studies, the first from 1994-1995, and the second in 1998. We found a statistically significant decrease in the percentage of infected patients (45.8% vs. 32.8%; p <0.001), but an increase in infections by Gram-positive microorganisms (14.4% vs. 20.6%; p <0.001), which was reflected in the increased use of glycopeptides (17.1% vs. 31.2%; p = 0.002). The use of quinolones also increased. The most common underlying illnesses were heart disease and diabetes mellitus, and there was a reduction in the number of patients infected by HIV and in users of parenteral medication. The decrease in outpatient infections indicated that nosocomial infection was more frequent in the second study, in which the number of predisposing factors increased (52.3% vs. 79.2%; p <0.001), the most common of which were peripheral line, immobilization and a bladder catheter. Bacteremia was the most frequent infection, and there was a reduction in lower respiratory tract infections and an increase in skin and soft tissue infections. Staphylococcus aureus was the most frequently found microorganism and showed a significant increase in incidence (27.2% vs. 47.9%; p <0.001), whereas pneumococcus showed a decrease (15.0% vs. 5.2%; p = 0.012). It was concluded that despite the decrease in the percentage of infected patients and severely ill patients, there is an increase in Gram-positive infections, especially bacteremia, and in the use of more aggressive treatments. This may reflect the increase in resistant isolates.
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PMID:[Prevalence and treatment of Gram-positive infections in internal medicine departments of Spanish hospitals: IGP Study]. 1496 Nov 37

RSV is the primary cause of hospitalisation in the first year of life for children in most parts of the world, and nearly 100% of children in the USA are infected with the virus by 2 to 3 years of age. The agent is an enveloped RNA virus with a non-segmented single-stranded negative-sense genome. The viral genome encodes 8 structural and 2 non-structural proteins. Important structural proteins include the fusion (F) protein and the attachment (G) protein which are essential for viral penetration and attachment to the host cells. Both proteins are important in development of immune responses. The virus is estimated to cause 3000 to 4000 deaths annually. Primary infections are as a rule symptomatic. The spectrum of clinical manifestations ranges from mild upper tract illness, infection in middle ear which progresses to acute otitis media, croup, to apnoea in premature infants, pneumonia and bronchiolitis. Premature babies born at 30-35 weeks of gestation, infants with cyanotic congenital heart disease, HIV-infected subjects, and patients on intensive immunosuppressive therapy especially after bone marrow transplant are considered to be at risk for increased mortality and morbidity during RSV infection. The virus does not normally replicate outside of the bronchopulmonary tree and the infection is exquisitely restricted to the respiratory mucosa. However, development of extrapulmonary disease has been observed in certain T and B cell immunodeficiency states. The association of RSV with asthma and reversible reactive airway disease in early childhood has attracted significant attention. Recurrent wheezing for up to 5 to 7 years of age and established airway disease has been observed in a significant number of children with a strong family history of allergy, after primary infection or reinfection with RSV. Immune response to primary infection is relatively small but on reinfection, a significant booster effect with sustained immunologic reactivity is observed in serum and respiratory mucosa. Both CD(4)- and CD(8)-specific as well as Th(1)- and Th(2)-cell specific immune responses have been observed during human infection. In addition, proinflammatory as well as immunoregulatory cytokines and chemokines are induced in the respiratory tract after natural and induced (in vitro) infection. Significant progress has been made in understanding the role of Th(1) vs. Th(2), IgE, viral induced cytokines and chemokines in the mechanisms of pathogenesis of the disease, development of wheezing and in the prevention and treatment of the infection and its sequelae. Respiratory syncytial virus (RSV) is one of the commonest human viral infections, and virtually every child is infected by the third birthday. Because of its restricted mucosal immunopathology, and frequent association with bronchial hyperreactivity and development of wheezing, RSV has served as an important model to investigate mechanisms of mucosal immune responses and development of mucosal disease following infection. The importance of RSV in bronchopulmonary disease and development of bronchial hyperreactivity has been the focus of several recent symposia [Kimpen JL, Simoes EAF. Am J Respir Crit Care Med 2001; 163:S1-S6]. This brief report will only summarise, based on selected references, the historical landmarks of its discovery and current understanding of the mechanisms of immunity, and their possible role in the pathogenesis of bronchopulmonary disease.
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PMID:Respiratory syncytial virus: the virus, the disease and the immune response. 1498 Feb 56

Pulmonary arterial hypertension (PAH) is a rare condition characterised by elevated pulmonary arterial resistance leading to right heart failure. PAH can be sporadic (idiopathic PAH, or primary pulmonary hypertension), familial (caused by germline BMPR2 mutations, a type II member of the TGFbeta receptor superfamily), or related to other conditions including connective tissue disease, congenital heart disease, human immunodeficiency virus infection, portal hypertension, appetite suppressant exposure... Idiopathic PAH has a prevalence of 2 per million per year in France. The lack of specificity of PAH symptoms (mostly dyspnea) presumably lead to underdiagnosis of this condition. Echocardiography is the investigation of choice for non-invasive screening. Measurement of hemodynamic parameters during right-heart catheterism is mandatory to establish the diagnosis (mean pulmonary artery pressure >25 mmHg and pulmonary artery wedge pressure <12 mmHg). Acute pulmonary vasodilator testing should be performed with nitric oxide or prostacyclin during right-heart catheterization. Recent advances in the management of PAH including continuous intravenous prostacyclin infusion and endothelin receptor antagonists have improved markedly the patients' prognosis. Novel treatments such as inhaled iloprost and type 5 phosphodiesterase inhibitors have to be further evaluated in this setting. Lung transplantation is the last option for patients deteriorating despite medical treatment.
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PMID:[Pulmonary arterial hypertension]. 1504 92


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