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)

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

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

Patients with markedly elevated pulmonary vascular resistance, whether caused by primary pulmonary hypertension or by congenital heart disease, have a grave prognosis, regardless of the type of therapy they undergo. This brief report presents our experience in treating 6 patients (4 women and 2 men) having pulmonary vascular obstructive disease, by administrating pentoxifylline (Trental), a drug that has been used in patients with chronic occlusive systemic arterial disease. Our patients underwent treadmill testing before the study and again 1 to 3 months after initiation of the study. Duration of exercise was short in all patients; however, it increased significantly while patients were taking pentoxifylline. These preliminary results are encouraging; however, we were unable to confirm other physiologic improvement with noninvasive study, and placebo effect was not ruled out. Therefore, we believe that use of pentoxifylline in patients with pulmonary vascular obstructive disease warrants further investigation by means of detailed direct hemodynamic measurement.
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PMID:Pentoxifylline therapy: a new adjunct in the treatment of pulmonary hypertension? 1522 46

Primary pulmonary hypertension carries a grim prognosis, therefore, it is imperative that prior to reaching this diagnosis, a thorough search be made for all possible causes of pulmonary hypertension. An uncommon cause of pulmonary hypertension amenable to treatment may occasionally be identified. This case report describes a young woman who presented with rapidly progressive right heart failure. Work up for the common secondary causes of pulmonary hypertension was negative, including, congenital intracardiac shunts, left-sided atrial or ventricular heart disease, left-sided valvular heart disease, disorders of the respiratory system including hypoxemia and pulmonary thromboembolic and venoocclusive disease, collagen vascular disease, portal hypertension, HIV infection as well as pulmonary hypertension secondary to drugs and toxins. The only concurrent illness identified was Graves disease. After treatment of hyperthyroidism there was complete resolution of the right heart failure, tricuspid regurgitation, and the pulmonary hypertension. Only a few cases of reversible pulmonary hypertension and right heart failure associated with hyperthyroidism have been reported worldwide. In these patients, the most striking feature has been the normalization of the cardiovascular findings after adequate treatment of hyperthyroidism. The exact reasons for the development of pulmonary hypertension in hyperthyroidism are unclear. Proposed mechanisms include high cardiac output-induced endothelial injury, increased metabolism of intrinsic pulmonary vasodilating substances resulting in elevated pulmonary vascular resistance, and autoimmune phenomenon. Hyperthyroidism should be included in the causes of secondary pulmonary hypertension and/or otherwise unexplained right heart failure. This is especially important because hyperthyroidism is a treatable entity and its cardiac manifestations may be completely reversible.
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PMID:Reversible pulmonary hypertension, tricuspid regurgitation and right-sided heart failure associated with hyperthyroidism: case report and review of the literature. 1547 66

Since 1990, lung transplantation has been performed in infants, children and adolescents in small numbers, and the numbers, in comparison with adult transplants, remain small today. The indications for lung transplantation are similar in childhood when compared with adults, but the disease entities are distinct. In children, severe pulmonary vascular disease is most commonly associated with developmental abnormalities or congenital heart disease, as opposed to idiopathic pulmonary hypertension. Cystic fibrosis is the dominant indication for lung transplantation in older childhood and adolescence. The operative approach to lung transplantation in early life differs from that in adults, in that cardiopulmonary bypass is more likely to be utilised and bilateral lung transplantation is strongly preferred to single lung transplantation. Living donor lung transplantation is proportionately more common in children and adolescents than in adults. Post-transplant complications related to viral infection and post-transplant lymphoproliferative disease are more common and more likely to be severe and life-threatening. Bronchiolitis obliterans is the most important complication after paediatric lung transplantation and limits both the quality of life and duration of survival, as in adults.
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PMID:Paediatric lung transplantation. 1551 81

Pulmonary arterial hypertension is a chronic, persistent elevation in pulmonary artery pressure without evidence of left heart failure. Pulmonary hypertension is common in patients with adult congenital heart disease and is usually the result of an increase of pulmonary blood flow through a large left to right shunt. This condition is progressive and patients are symptomatic and usually die between the third and fifth decades of life. To date, there is no standardized treatment for this condition and a general policy of non-intervention to avoid destabilization of the balanced physiology is recommended. Intravenous prostanoids have been shown to have an effect but they are invasive and associated with major side effects. Lung and combined heart and lung transplantation might be a therapeutic option for selected patients. However, donor shortage is a major issue. Oral advanced therapies have been recently shown to improve haemodynamics and survival in idiopathic pulmonary hypertension or in pulmonary hypertension related to scleroderma and may have a role in patients with pulmonary hypertension secondary to congenital heart disease.
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PMID:[Pulmonary arterial hypertension in adults with congenital heart disease]. 1589 89

Four cases of sudden unexpected death associated with pulmonary hypertension are described. In all cases, the presence of pulmonary hypertension had not been clinically detected. In each case, the underlying etiology of the pulmonary hypertension was different with one case each of occult adult congenital heart disease, pulmonary sarcoidosis, pulmonary tumour microembolism from gastric adenocarcinoma, and familial primary pulmonary hypertension. These cases indicate that the forensic pathologist must be aware of occult pulmonary hypertension as a cause of sudden unexpected death in a variety of age groups.
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PMID:Sudden death with clinically undiagnosed pulmonary hypertension. 1619 69

The commonest causes of pulmonary hypertension are secondary to endstage pulmonary disease or congenital heart disease (including structural abnormalities of the pulmonary veins). Less obvious causes include sleep disordered breathing due to obstructive sleep apnoea or neuromuscular disease, and occult interstitial lung disease. When these have been excluded, the primary pulmonary vascular diseases should be considered. These are primary pulmonary hypertension; pulmonary veno-occlusive disease; pulmonary embolic disease (thromboembolism, and non-thrombotic embolism) and invasive pulmonary capillary haemangiomatosis. The clinical signs and chest X-ray appearances are often non-specific. Echocardiography can often estimate pulmonary artery pressure and exclude congenital heart disease. Right heart catheterization is usually needed to confirm the diagnosis, estimate any reversibility of elevated pulmonary vascular resistance and exclude other causes. Precise diagnosis may require an open lung biopsy. For many of these conditions, treatment is difficult and the prognosis poor unless the child has a lung transplant.
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PMID:Pulmonary hypertensive diseases. 1626 65

The Eisenmenger syndrome is a complication of congenital heart disease with significant left-to-right shunts, such as large ventricular septal defects, and corresponds to fixed pulmonary hypertension with shunt reversal. Bosentan, an inhibitor of endothelin A and B receptors, is a new molecule previously validated in the treatment of primary pulmonary hypertension. The authors report their monocentric experience of bosentan in 11 consecutive patients with the Eisenmenger syndrome treated for at least one year. This retrospective study comprised 7 females and 4 males with an average age of 34 years (range 17 to 51 years). The underlying lesion was ventricular septal defect (n = 4), atrial septal defect (n = 3), pulmonary atresia with septal defect (n = 4 of which 2 were treated palliatively). Before treatment, the patients were classified according to the NHYA functional class (I, II, IIIa and IIIb, IV or, respectively from 1 to 5) with a distribution in this series between Classes IIIa and IV (average 3.81 +/- 0.75) and from 3 to 10 on Borg's dyspnoea scale (average 6.54 +/- 2.29). The ambient oxygen saturation (SaO2) at rest was, on average 77 +/- 9%, the haemoglobin concentration 16.6 +/- 2.4 g/dl; hepatic transaminase levels were normal. The 6 minute walk test before treatment was 216 +/- 111 m with marked desaturation on exercise (49 +/- 18%). With Bosentan, patients were globally much better clinically with a decrease in dyspnoea, improvement in NHYA class and increased 6 minute walking perimeter. Improvement in NYHA class was observed from 3 months' treatment (3.0 +/- 0.8, p = 0.0002) and was sustained to one year (2.54 +/- 0.7, p< 0.001). An improvement of dyspnoea on Borg's scale was observed from the second month's treatment (5.56 +/- 1.65, p = 0.0201) and persisted throughout follow up to one year (3.81 +/- 1.32, p < 0.0001). Similarly, the 6 minute walking perimeter increased from the first control at 6 months (323 +/- 82 m, p < 0.0001) and at one year (322 +/- 62 m, p <0.0004). Finally, although a significant increase in SaO2 was observed at 6 months (p = 0.0032), this was hardly significant at one year (82 +/- 10 %, p = 0.0512). Transaminase levels did not rise significantly at the follow up visits (p = ns) and the haemoglobin concentration was unchanged. No patient died during the study period. This study showed a clear functional improvement in patients with Eisenmenger's syndrome treated with bosentan. The drug was well tolerated clinically with few adverse effects and a good safety margin of usage.
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PMID:[The effect of an endothelin receptor antagonist in Eisenmenger syndrome: a single-center experience of 11 patients]. 1680 35

CMV infection causes morbidity and mortality after transplantation. Despite a wide range of prevention strategies among pediatric lung transplant programs, the optimal duration of prophylactic therapy against CMV infection in pediatric lung transplantation is unknown. To assess the feasibility, safety, and short-term efficacy of extending intravenous ganciclovir administration from six wk duration to 12 wk duration in pediatric lung transplant recipients. An open-label pilot study was performed in primary pediatric lung transplant recipients with donor and/or recipient CMV seropositivity. Intravenous ganciclovir was given for 12 wk post-transplantation. Subjects were tracked for protocol completion. Toxicities monitored included renal dysfunction, myelosuppression, gastrointestinal and neurological complications, as well as infection related to indwelling catheter placement. Serial CMV levels were measured to determine short-term efficacy of the intervention. Nine of nine subjects enrolled completed the pilot study. Subjects' ages ranged from six to 18 yr. Indications for lung transplantation included cystic fibrosis (n = 7), idiopathic pulmonary hypertension (n = 1), and complex congenital heart disease with pulmonary hypertension (n = 1). Seven subjects underwent deceased donor bilateral lung transplantation and two subjects underwent heart-lung transplantation. No subjects had protocol-defined drug toxicity. No episodes of neutropenia, thrombocytopenia, or renal toxicity occurred. Five subjects had catheter-related infections (three after week 12 of ganciclovir). Seven of nine subjects had CMV detected by PCR (four prior to ganciclovir completion) with only one subject having a positive viral culture for CMV viremia (prior to ganciclovir completion). No subjects had UL-97 mutation for ganciclovir resistance detected. The use of prolonged prophylactic administration of ganciclovir for 12 wk duration is a feasible, safe, and effective treatment to prevent CMV viremia based on viral culture in at risk pediatric lung transplant recipients. Further clinical studies are underway to determine optimal CMV prevention strategies.
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PMID:Safety and efficacy of prolonged cytomegalovirus prophylaxis with intravenous ganciclovir in pediatric and young adult lung transplant recipients. 1743 Apr 89


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