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)

Coupling of anthracyclines to high-molecular-weight carriers may alter drug disposition and improve antitumor effects. We have performed a clinical phase I trial of doxorubicin coupled to dextran (70000 m.w.). The drug was administered as single dose i.v. every 21-28 days. Thirteen patients have received a total of 24 courses (median 2; range 1-3). At the starting dose of 40 mg/m2 doxorubicin equivalent (DOXeq), WHO grade IV thrombocytopenia was noted in 2/2 patients. WHO grade IV hepatotoxicity and WHO grade III cardiotoxicity were noted in a patient with preexisting heart disease. Five patients were treated with 12.5 mg/m2 DOXeq. Maximal toxicity at this dose level was WHO grade III thrombocytopenia and local phlebitis (WHO grade II) in 1/5 patients, elevation of alkaline phosphatase (WHO grade III) and WHO grade III vomiting in another patient. Subsequently, five patients received 20 mg/m2 DOXeq. Hepatotoxicity was noted in 5/5 patients (1 x WHO grade IV, 1 x WHO grade III). Thrombocytopenia was noted in 3/5 patients (1 x WHO grade IV, 2 x WHO grade III). At 12.5 mg/m2 DOXeq, a patient diagnosed with a malignant fibrous histiocytoma had stable disease for 4 months. Pharmacokinetic analyses of total and free doxorubicin were performed in plasma and urine. The maximum peak plasma concentration (ppc) for total DOX was 12.3 micrograms/ml at 40 mg/m2 DOXeq. The area under the plasma concentration time curve (AUC) ranged from 28.83-80.21 micrograms/ml*h with dose-dependent elimination half lives (t1/2 alpha: 0.02-0.87 h; t1/2 beta: 2.69-11.58 h; t1/2 gamma: 41.44-136.58 h).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phase I clinical and pharmacokinetic trial of dextran conjugated doxorubicin (AD-70, DOX-OXD). 750 68

Prostaglandins (PGs) have complex and multiple effects on bone metabolism. Although the osteogenic effect of PGE in humans was initially found in an infant with a congenital heart disease, there have been few reports on the effect of PGE in human in vivo. The aim of this study was to investigate the effect of PGE1 on human bone metabolism, using biochemical bone markers. A total of 18 subjects were treated with PGE1 in lipid microspheres. Six subjects were given 10 microg of lipo-PGE, intravenously daily for 14 days, and twelve subjects were given the same dose twice a week for 7 weeks. Before and after the administration of PGE1, blood and a spot urine was obtained in the morning. Bone formation markers (alkaline phosphatase, osteocalcin, procollagen I carboxy-terminal peptide) did not change. In the subjects with daily administration for 2 weeks, type I collagen pyridinolines crosslinked C-telopeptide (ICTP) increased significantly. In the subjects treated twice a week, free deoxypyridinoline (Dpd) increased significantly. When all subjects were analyzed, bone resorption markers (ICTP and Dpd) increased, but not significantly (p=0.055 for ICTP, p=0.055 for Dpd). Therefore, PGE1 at the dosage used in this study did not increase bone formation but increased bone resorption in humans.
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PMID:The effect of prostaglandin E1 on human bone metabolism: evaluation by biochemical markers for bone turnover. 1071 28

One hundred and forty-four patients with osteosarcoma of the extremity treated with neoadjuvant chemotherapy at the authors' institution between 1986 and 1989 were retrospectively analyzed to evaluate the relationship between the dose-intensity of chemotherapy actually received (RDI) and the prognosis. Preoperative chemotherapy consisted of high-dose methotrexate i.v., cisplatin i.a., and doxorubicin i.v. After surgery "good responder" patients (90% or more tumor necrosis) had a 31-weeks of chemotherapy with the same drugs, while "poor responder" patients (less than 90% tumor necrosis) received a 40 weeks treatment with ifosfamide and etoposide added to the three drugs used preoperatively. Due to delays and dose-reductions, only 17 patients (12%) received the treatment exactly as scheduled by the protocol, 66 (46%) received a dose-intensity between 90 and 99%, and 61 (42%) a dose-intensity between 63 and 89%. At a follow-up ranging between 10 and 13 years, 97 patients (67%) remained continuously free of disease, 45 relapsed, and two died of doxorubicin-induced cardiopathy. The continuous disease-free survival (CDFS) was not related to patients' gender and age, tumor histology, site and size, serum value of alkaline phosphatase, type of surgery and histologic response to chemotherapy. According to the RDI, CDFS resulted significantly higher for those 81 patients who received 90% or more of the scheduled dose-intensity than for those 61 who had less than 90% of the scheduled dose-intensity (76.5% v.s. 57.3%; p<0.02). These results seem to suggest that in neoadjuvant treatment of osteosarcoma the dose-intensity of chemotherapy is crucial for outcome, therefore every effort should be made to avoid reductions of doses and/or delays in performing the cycles of chemotherapy.
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PMID:Relationship between dose-intensity of treatment and outcome for patients with osteosarcoma of the extremity treated with neoadjuvant chemotherapy. 1141 Aug 3

OBJECTIVE: The objective of this study was to analyze the incidence and significance of hepatic dysfunction after cardiac surgery in children. DESIGN: Prospective, observational study. SETTING: Pediatric intensive care unit of a university hospital. PATIENTS: The study consisted of 232 children ranging in age from newborn to 17 years with no history of liver disease. MEASUREMENTS AND MAIN RESULTS: Aspartate aminotransferase (AST), alanine aminotransferase (ALT), gammaglutamyltranspeptidase (GGT), alkaline phosphatase, total and conjugated bilirubin, blood glucose, urea, creatinine, and coagulation studies were determined at admission, at 24 and 48 hrs, and at 7 days. Hepatic dysfunction was taken as an ALT of > 100 IU/L or a moderate or high hepatic score. The statistical study included bivariate analysis and multivariate logistic regression to study the risk factors for hepatic dysfunction. Twenty-one patients (9%) showed an ALT > 100 IU/L, and 29.3% had a moderate or high hepatic score. A relationship was found between hepatic dysfunction and the type of cardiopathy (D-transposition of the great arteries and coarctation of the aorta), shock, the administration of dopamine or epinephrine, renal insufficiency, the presence of pulmonary changes (pulmonary edema, atelectasis, pulmonary hypertension, hypoxemia), hematologic disturbances (prothrombin time, kaolin-cephalin time, fibrinogen, and platelets), and the need for a greater number of transfusions of packed cells, plasma, and platelets. Compared with 7.6% of the rest of the patients (p <.001), 38% of patients with an ALT > 100 IU/L died. The hepatic score of those patients who died was 4.2 (2.3)-higher than that of the survivors at 1.5 (1.8), (p <.001). Shock and renal insufficiency were the factors most significantly related to the development of hepatic dysfunction. CONCLUSIONS: Hepatic dysfunction is an uncommon complication in children after cardiac surgery. This complication is related mainly to hemodynamic disturbances and renal insufficiency and is an indicator of poor prognosis.
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PMID:Hepatic dysfunction after cardiac surgery in children. 1279 88

The common side effects associated with the use of prostaglandins in newborn infants include apnoea, hyperthermia, diarrhoea, skin flushing and oedema. Periosteal reaction or cortical thickening of the bones, also known as cortical hyperostosis, is associated with a prolonged use of prostaglandins. This is a radiological diagnosis; therefore, its occurrence is most likely underestimated. We describe an infant who developed cortical hyperostosis simulating osteomyelitis with elevated alkaline phosphatase. The radiologic changes were initially attributed to congenital syphilis. This occurred after a prolonged infusion of prostaglandin E(1) for a cyanotic congenital heart disease.
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PMID:Cortical hyperostosis in an infant on prolonged prostaglandin infusion: case report and literature review. 1506 99

Impairment of venous outflow from the liver manifests as zone 3 sinusoidal dilatation and congestion (SDC) in liver biopsy. The spectrum of histologic changes in portal tracts has not been described. We studied liver biopsies from 34 patients with a confirmed diagnosis of venous outflow impairment (VOI). Liver transplant recipients and biopsies with cirrhosis and hepatic neoplasms were excluded. Clinical records were reviewed for laboratory tests and radiographic findings. In all, 19 patients had right heart disease, 13 had classic Budd-Chiari syndrome and two had veno-occlusive disease. Liver chemistry tests showed elevated liver transaminases (n=21; 61.8%), elevated alkaline phosphatase (n=31; 91.2%) and GGT (all 13 cases tested). The elevation in ALT and AST was mild (below 200 U/l in all cases), while alkaline phosphatase (ALP) was elevated above 500 U/l in nine (26.5%) patients and above 1000 U/l in three cases. On biopsy, all cases showed SDC. The portal tracts showed (a) portal expansion with bile ductular proliferation (n=16; 47.1%) accompanied by lymphoplasmacytic infiltrate (n=10), lymphocytic cholangitis (n=3) and portal or periportal fibrosis (n=11), (b) Portal and/or periportal fibrosis without ductular proliferation (n=3; 8.8%) or (c) Normal portal tracts (n=15; 44.1%). The combination of elevated ALP and bile ductular changes on biopsy suggested chronic bile duct disease. Ultrasound/CT scan evaluation of bile ducts in 26 patients showed no biliary tree abnormality. Antimitochondrial antibody testing in eight cases also yielded negative results. In conclusion, bile ductular proliferation, portal inflammation and portal-based fibrosis are commonly seen in liver biopsies of patients with VOI even in the absence of bile duct disease. These changes are often accompanied by elevated ALP and GGT and can lead to the suspicion of chronic biliary disease. In the absence of demonstrable abnormalities in the biliary tree, these changes can be attributed to venous outflow impairment.
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PMID:Histologic changes mimicking biliary disease in liver biopsies with venous outflow impairment. 1509 6

Endothelial cells have complex roles in the pathophysiology of vascular and heart disease and are increasingly being recognized as targets for gene therapy. The intravenous administration of plasmid DNA complexed to lipid tends to target transfection of endothelial cells within the lung; however, expression from the transgene remains transient. Here we utilize the integrating capability of the Sleeping Beauty (SB) transposon for durable gene transfer within lung endothelia. To restrict expression of the transgene, an endothelial cell-specific promoter, endothelin-1, was placed within the transposon. Further refinements to the transposon increased in vitro transposition efficiency by 3.6-fold. Utilizing this optimized transposon we evaluated the expression of two reporter molecules, secreted alkaline phosphatase (SEAP) and intracellular GFP, following administration of DNA-polyethylenimine complexes to mice. Long-term expression (>2 months) of SEAP occurred only with cotransfection of adequate amounts of transposase. Localization studies using the GFP reporter, at 3 days and 6 weeks postinjection, demonstrated that the majority of transgene-expressing cells were of endothelial origin, while the second most abundant cell type was type II pneumocyte. These results suggest that the SB transposon can be adapted to target particular cell types, in this case, endothelial cells. Such an approach may be useful for gene therapy paradigms involving the long-term modulation of vascular and endothelial cell biology.
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PMID:Endothelial targeting of the Sleeping Beauty transposon within lung. 1523 46

Orbital xanthogranuloma is an uncommon tumor. It is usually associated with a systemic or hematological disease. This report presents a rare case of orbital xanthogranuloma associated with heart disease and thrombocytopenia. A 52-year-old female presented with a bilateral periorbital subcutaneous tumor that had existed for 3 years. Although immunoglobulin levels were within the normal limits, thrombocytopenia, slight anemia and increased levels of C-reactive protein and alkaline phosphatase were observed. The mass was excised successfully. The malar flap elevation technique made it easy to approach the periorbital subcutaneous mass. A histopathological study led to a diagnosis of xanthogranuloma based on the presence of infiltration of histiocytes and Touton-type giant cells.
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PMID:A Case of Orbital Xanthogranuloma Treated by Surgical Excision. 2068 34

Etiopathogenetic mechanisms in calcific aortic valve stenosis are still poorly understood despite this being the third major cause of heart disease in western world. In prior in vitro cultures simulating metastatic calcification, pro-calcific effects on aortic valve interstitial cells (AVICs) resulted by adding bacterial endotoxin lipopolysaccharide (LPS) at high inorganic phosphate (Pi) levels. Here we accomplished improved in vitro models simulating either metastatic (Pi = 2.6 mM) or dystrophic calcification (Pi = 1.3 mM), in which LPS-stimulated bovine AVICs underwent extra-stimulation with macrophage-cytokine-containing media derived from parallel cultures of allogeneic monocyte/macrophages in turn stimulated with LPS. In dystrophic calcification-like cultures, lower calcium amount was spectrometrically assessed with parallel reduced alkaline phosphatase activity with respect to metastatic calcification-like cultures, with an about three-fold slower progression of mineralization. Hydroxyapatite crystal precipitation was ultrastructurally found to correlate with AVIC degeneration processes culminating with the formation of phthalocyanin-positive lipidic layers (PPLs) at the surface of cells and cell-derived matrix-vesicle-like bodies, acting as calcium nucleators according to a pattern mirroring those we had previously found in in vivo conditions. In conclusion, an in vitro model has been developed enabling reliable simulations of the effects exerted on AVICs by putatively pro- or anti-calcific agents.
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PMID:Pro-calcific responses by aortic valve interstitial cells in a novel in vitro model simulating dystrophic calcification. 2107 3

Prostaglandin E1 (PGE1) infusion is usually administered for short periods to maintain patency of ductus arteriosus in infants with cyanotic heart disease. Prolonged therapy may be necessary while patients are awaiting surgical treatment. Several side effects occur at the onset of the treatment, most of them reversible once the treatment is discontinued. Cortical hyperostosis is a frequent complication of prolonged PGE1 infusion. Objective is to determine the incidence and severity of cortical hyperostosis in newborn requiring prolonged prostaglandin E1 infusion. 61 newborn babies were admitted in the Neonatal Intensive Care Unit at Bazterrica Clinic, Buenos Aires City, from January 2006 to May 2010. Five newborn received prolonged PGE1 therapy defined as a longer-than-one-week treatment. Four of them had radiologic evidence of cortical hyperostosis and elevated serum alkaline phosphatase. Accurate and rapid diagnosis of this condition is critical to reduce unnecessary laboratory tests and to avoid cardiac surgery cancelling.
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PMID:[Neonatal cortical hyperostosis. A side effect of prolonged prostaglandin E1 infusion]. 2146 75


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