Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 37-year-old man with progressive exertional dyspnea had pulmonary hypertension associated with pulmonary arterial and venous obstruction. An autopsy revealed that the cause of death was idiopathic pulmonary hilar fibrosis, a variant of mediastinal fibrosis. Pulmonary hilar fibrosis can mimic thromboembolic pulmonary hypertension, pulmonary veno-occlusive disease, and pulmonary venous hypertension.
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PMID:Idiopathic pulmonary hilar fibrosis: an unusual cause of pulmonary hypertension. 833 79

Pentoxifylline (PTX) has recently been shown to modulate TNF-alpha production and to reduce the incidence and severity of all major complications after BMT, including mucositis, veno-occlusive disease, renal insufficiency, hypertension, and graft-versus-host disease. To analyze in detail the effect of PTX on immune complications after BMT, we investigated the immunomodulatory effect of PTX on immune responses in vitro. The continuous presence of PTX significantly reduced the proliferative response of PBMC to PHA stimulation and to alloantigens in a dose-dependent manner. Starting at concentrations of 100 micrograms/ml, PTX was able to inhibit and, at 1000 micrograms/ml, completely block mitogen-induced proliferation. Maximal inhibition of more than 90% (91 +/- 4%) was also observed at PTX concentrations of 1000 micrograms/ml in the mixed lymphocyte culture (MLR) and by addition on day 0. However, lower but still significant suppression (13 +/- 7%) was achieved at concentrations of 10 micrograms/ml PTX. The inhibitory capacity of PTX was increased by mAbs against TNF-alpha (34 +/- 5% additional suppression at 100 micrograms/ml PTX) and not reversed by the addition of rTNF-alpha. The effect of PTX on the generation of CTLs in vitro was studied in the cell-mediated lymphotoxicity assay. PTX (100 micrograms/ml) significantly inhibited (P = 0.0178) the in vitro generation of CTLs when PTX was added to the culture on day 0. PTX also showed profound modulatory properties in the NK assay, with a reduction of 23 +/- 3% in specific lysis at 10 micrograms/ml PTX and maximal reductions of 88 +/- 3% at 1000 micrograms/ml PTX. Immunomodulatory properties of PTX were not only associated with blockage of TNF-alpha, as shown by decreased mRNA expression and TNF-alpha values in the culture supernatants, but also with an impaired production of other cytokines and secondary messages such as IFN-gamma and neopterin. PTX treatment, however, did not affect IFN-alpha or IL-1 beta production, and IL-6 release was even increased. PTX, therefore, has profound immunomodulatory properties in vitro, which are associated with selective inhibition of cytokine release and can be enhanced by the addition of mAbs against TNF-alpha, but not reversed by the addition of rTNF-alpha.
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PMID:Immune response modulation by pentoxifylline in vitro. 833 42

Hepatic veno-occlusive disease (VOD) is a non-thrombotic obliteration of the lumina of small intrahepatic veins. VOD has been reported after exposure to a wide variety of pathogens. It has been suggested that the chemoradiotherapy used as the conditioning regimen for bone marrow transplant (BMT) is now the main cause of this disease. However, the pathogenesis of VOD after BMT is probably multifactorial. Endothelial injury of sinusoids and small hepatic veins is considered to be the initial event in genesis of VOD. This injury is followed by deposition of fibrin-related aggregates in the subendothelial zone. These aggregates, and the intramural entrapment of fluid and cellular debris, occlude progressively the hepatic venous outflow and generate a postsinusoidal intrahepatic hypertension. Clinically, VOD is characterized by jaundice, weight gain, ascites, painful hepatomegaly and platelet refractoriness developing early post transplant, although other posttransplant liver disturbances can produce a similar syndrome. VOD diagnosis is usually established by applying the clinical criteria proposed by the Seattle and Baltimore groups. When clinical diagnosis of VOD is uncertain, a transjugular liver study including a transvenous biopsy and measurement of the gradient between wedged and free hepatic venous pressure, is recommended in order to establish an accurate diagnosis. According to the literature data, the incidence of VOD ranges from 0 to 70% and its mortality from 20 to 50%. This very wide range is attributable to the different incidence of risk factors in the different series and to the differences in applying the diagnostic criteria.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hepatic veno-occlusive disease after bone marrow transplant. 846 32

Monocrotaline (MONO), a pyrrolizidine alkaloid, causes veno-occlusive disease of the liver, pulmonary arterial hypertension, and right ventricular hypertrophy. Toxicity is due to the hepatic formation of a pyrolic metabolite that can be detoxified by conjugation with glutathione (GSH). We have shown that the GSH content of the liver affects the quantity of the pyrrolic metabolite that is released from the liver. We have now examined whether MONO, in turn, affects GSH metabolism. Twenty-four hours after administration of MONO to rats (65 mg/kg, i.p.), the highest concentration of bound pyrrolic metabolites was found in the liver, followed by the lung and kidney. Heart and brain contained lower concentrations of these metabolites. Significantly higher levels of GSH were found in liver and lungs of MONO-treated rats than in saline-injected control animals. In the liver, activities of the following enzymes were elevated: gamma-glutamylcysteine synthetase, GSH synthetase, gamma-glutamyl transpeptidase, dipeptidase, and microsomal GSH transferase. The same changes were seen in the lung. In the heart, gamma-glutamyl transpeptidase activity was decreased markedly, and cytosolic GSH transferase activity was elevated. In the kidney, the activities of GSH synthetase, gamma-glutamyl transpeptidase, and cytosolic GSH transferase were increased. Our results establish a mutual interaction of MONO and sulfur metabolism. It appears that an early metabolic action of MONO is to modify sulfur amino acid metabolism, diverting cysteine metabolism from oxidation to taurine towards synthesis of GSH.
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PMID:Effects of monocrotaline, a pyrrolizidine alkaloid, on glutathione metabolism in the rat. 857 5

The safety and potential efficacy of FK506 in combination with a short course of methotrexate (MTX) for the prevention of acute graft-versus-host disease (GVHD) after marrow transplantation from HLA-matched unrelated donors was evaluated in a single-arm Phase II study conducted at two centers. Forty-three patients, 15 to 54 (median 41) years of age, were transplanted for hematologic malignancies. Thirty-seven of 43 evaluable patients had evidence of sustained marrow engraftment. Five patients died before day 17 after transplantation. The median time to an absolute neutrophil count of > 0.5 x 10(5)/L was 21 (range, 14 to 30) days. Nephrotoxicity (serum creatinine concentration > 2 mg/dL or doubling of baseline) occurred in 32 patients (74% cumulative incidence during the first 100 days after transplant). Other adverse effects included hypertension (n = 27), hyperglycemia (n = 27), neurotoxicity (n = 9) and thrombotic thrombocytopenic purpura (n = 2). Severe veno-occlusive disease of the liver occurred in 9 (21%) of the 43 patients. Eighteen patients (42%) developed grades II to IV acute GVHD and five (12%) developed grades III to IV acute GVHD. Twelve of 25 evaluable patients developed extensive chronic GVHD within 1 year of marrow transplantation resulting in an estimate of the probability of developing this complication of 48%. The cumulative incidence of transplant-related mortality during the first 100 days was 37%. Kaplan-Meier estimates of disease-free survival at 2 years for good-risk, poor-risk, and all patients were 65%, 4%, and 32%, respectively. FK506 in combination with a short course of MTX appears active in preventing acute GVHD after marrow transplantation from unrelated donors. Further studies comparing the combination of FK506 and MTX with cyclosporine and MTX for the prevention of acute GVHD are warranted.
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PMID:FK506 in combination with methotrexate for the prevention of graft-versus-host disease after marrow transplantation from matched unrelated donors. 889 34

Pulmonary veno-occlusive disease (VOD) is a rare cause of pulmonary hypertension (HTN) which has been described in association with a variety of clinical conditions. Rapidly progressive occlusion of pulmonary veins and venules develops that is usually fatal. Recently, a number of cases have been reported in patients with malignancies. To date, 33 patients have developed pulmonary VOD in association with a malignancy or after chemotherapy and/or radiation therapy. Two-thirds of the cases occurred following allogeneic bone marrow transplantation (BMT). We describe the first case of pulmonary VOD following autologous BMT and review the experience of pulmonary VOD in patients with malignancies.
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PMID:Malignancy-associated pulmonary veno-occlusive disease: report of a case following autologous bone marrow transplantation and review. 889 91

The pathogenesis of pulmonary veno-occlusive disease (PVOD) is not known. The diagnosis of PVOD frequently relies on its histological changes since it is often difficult to distinguish clinically from primary pulmonary hypertension. This study carried out a systematic analysis of the pulmonary venous and arterial remodelling that occurs in PVOD (n=5) and compared these changes to two other diseases affecting the pulmonary veins, mitral stenosis (MS; n=6) and fibrosing mediastinitis (FM; n=2), using established morphometric techniques. In PVOD, pronounced intimal and adventitial thickening were noted in veins of all sizes and arterialization of veins >50 microm external diameter was found. Similar changes were evident in the arterial wall, but intimal thickening was less severe than in the veins and medial thickening was more pronounced in arteries <300 microm external diameter. Eccentric intimal fibrosis of the veins was also noted for the first time in PVOD, although this feature occurred less frequently (approximately one third) than in MS. Less pronounced structural remodelling was also encountered in the veins in cases of MS and FM. The severity of the venous changes in PVOD may aid its diagnosis and lend insight into its pathogenesis. However, the similarity of the vascular changes in each form of venous hypertension also suggests that pathology alone may not always differentiate between these disease states. The similarity of the vascular changes in the three forms of venous hypertension suggests that, as in pulmonary artery hypertension, pressure, per se, is one of the triggers to vascular remodelling.
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PMID:Venous and arterial changes in pulmonary veno-occlusive disease, mitral stenosis and fibrosing mediastinitis. 1067 31

Pulmonary hypertension is the hemodynamic consequence of vascular changes within the precapillary (arterial) or postcapillary (venous) pulmonary circulation. These changes may be idiopathic, as in primary pulmonary hypertension or pulmonary veno-occlusive disease, but more commonly they represent a secondary response to alterations in pulmonary blood flow. The pulmonary and systemic bronchial circulations form broad anastomoses that largely prevent infarction except in settings of markedly elevated pulmonary venous pressure, underlying malignancy, or excessive embolic burden. Causes of precapillary pulmonary hypertension include long-standing cardiac left-to-right shunt, chronic thromboembolic disease, and widespread pulmonary embolism arising from intravascular malignant cells, parasites, or foreign materials. The classic radiologic features of precapillary pulmonary hypertension are central arterial enlargement, sharply pruned peripheral vascularity, and right-sided heart hypertrophy and chamber dilatation. Postcapillary pulmonary hypertension may develop secondary to focal venous constriction or to compromised pulmonary venous drainage due to left atrial neoplasia, mitral stenosis, or left ventricular failure. Radiologic manifestations of postcapillary pulmonary hypertension include prominent septal lines, small pleural effusions, and occasionally air-space opacities. In addition, radiologic evaluation of postcapillary pulmonary hypertension may demonstrate evidence of pulmonary arterial hypertension, secondary to the retrograde transmission of elevated pulmonary venous pressure across the capillary bed.
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PMID:From the archives of the AFIP: pulmonary vasculature: hypertension and infarction. 1071 47

Pulmonary drug toxicity is increasingly being diagnosed as a cause of acute and chronic lung disease. Numerous agents including cytotoxic and noncytotoxic drugs have the potential to cause pulmonary toxicity. The clinical and radiologic manifestations of these drugs generally reflect the underlying histopathologic processes and include diffuse alveolar damage (DAD), nonspecific interstitial pneumonia (NSIP), bronchiolitis obliterans organizing pneumonia (BOOP), eosinophilic pneumonia, obliterative bronchiolitis, pulmonary hemorrhage, edema, hypertension, or veno-occlusive disease. DAD is a common manifestation of pulmonary drug toxicity and is frequently caused by cytotoxic drugs, especially cyclophosphamide, bleomycin, and carmustine. It manifests radiographically as bilateral hetero- or homogeneous opacities usually in the mid and lower lungs and on high-resolution computed tomographic (CT) scans as scattered or diffuse areas of ground-glass opacity. NSIP occurs most commonly as a manifestation of carmustine toxicity or of toxicity from noncytotoxic drugs such as amidarone. At radiography, it appears as diffuse areas of heterogeneous opacity, whereas early CT scans show diffuse ground-glass opacity and late CT scans show fibrosis in a basal distribution. BOOP, which is commonly caused by bleomycin and cyclophosphamide (as well as gold salts and methotrexate), appears on radiographs as hetero- and homogeneous peripheral opacities in both upper and lower lobes and on CT scans as poorly defined nodular consolidation, centrilobular nodules, and bronchial dilatation. Knowledge of these manifestations and of the drugs most frequently involved can facilitate diagnosis and institution of appropriate treatment.
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PMID:Pulmonary drug toxicity: radiologic and pathologic manifestations. 1099 15

Acute renal failure and veno-occlusive disease of the liver are serious complications following stem cell transplantation (SCT) and contribute to the non-relapse mortality associated with this procedure. Endothelins, a family of vasoconstrictor peptides, may be involved in the pathogenesis of a variety of renal and hepatic diseases, including CsA-associated hypertension and the hepatorenal syndrome. In order to study the relevance of endothelins to SCT-related liver and kidney dysfunction, we determined endothelin-1 (ET-1) levels in plasma samples obtained from 65 patients (38 autologous, 27 allogeneic) 7 days before and 7, 14 and 28 days after SCT. A steady increase in plasma ET-1 was observed after SCT (5.36 pg/ml, 95% CI 4.30-6.43 on day +28 vs 3.82 pg/ml, 95% CI 3.21-4.43 on day -7; P = 0.020). No differences in ET-1 levels existed between autologous and allogeneic SCT recipients at any of the time points studied (P = 0.561). In addition, no significant differences were observed among patients with renal dysfunction vs those without (P = 0.187), nor in patient groups with or without hepatic dysfunction (P = 0.075). In conclusion, even though plasma ET-1 levels showed a steady increase following SCT, no correlation could be found with development of SCT-related kidney or liver dysfunction.
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PMID:Plasma endothelin-1 levels after stem cell transplantation. 1114 31


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