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

In this randomized study involving patients with limited-stage small-cell lung cancer (LD-SCC), we compared treatment with either cyclophosphamide; doxorubicin, and vincristine (CAV) or CAV plus etoposide (CAVE). All patients received identical thoracic radiation consisting of 3,750 cGy in 15 fractions and prophylactic cranial radiation (3,000 cGy in 10 fractions). Among 231 evaluable patients, the two treatment arms were well matched with respect to sex, age, performance score, and presence or absence of heart disease. A major regression (REGR) was observed in 83% of all patients and a complete response (CR) in 60%. There was no difference in the response rate between the two treatment regimens. The median time to progression is 10.4 months (95% confidence interval [Cl], 8.9 to 12 months) for CAVE versus 8.9 months (95% Cl, 7.9 to 10.4 months) for CAV (P = .04). The median survival is 15.1 months (95% Cl, 11.7 to 17.8 months) for CAVE versus 12.4 months (95% Cl, 11 to 14.4 months) for CAV. This difference is not significantly different (P = .13). Toxicity was primarily myelosuppression and was significantly greater for the four-drug regimen. Fatal treatment-related toxicity was observed in two patients on the CAVE regimen and no treatment-related deaths were observed on the CAV treatment. In conclusion, the addition of etoposide to the CAV regimen resulted in increased toxicity but did not lead to a meaningful improvement in survival.
 ...
PMID:Treatment of limited-stage small-cell lung cancer with cyclophosphamide, doxorubicin, and vincristine with or without etoposide: a randomized trial of the North Central Cancer Treatment Group. 215 93

An analysis of clinical and laboratory parameters and the results of treatment of 14 children with Down Syndrome and acute leukaemia was performed. The children were treated between 1986-1997. Their age ranged from 1 day to 13 years (average 5.5). There were 9 girls and 5 boys. Four of them had congenital heart disease. ALL was observed in 10, AML in 3 and TAM (Transient Abnormal Myelopoesis) in 1. Half of the children with ALL was classified as L1 according to FAB with the majority of common phenotypes and M6 in ANLL group. Remission was achieved in all ALL patients, six of them are still free of symptoms, the remaining four died of brain haemorrhage as a consequence of myelosuppression. Only 1 of 3 children with ANLL achieved remission. The child died of cardiac arrest after induction phase of BFM 95 programme (ADE). The 2 remaining children with ANLL also died of circulation failure before initiation of chemotherapy. The children had complicated cyanotic heart disease. The neonate with TAM is in clinical and hematological remission. In conclusion all children with ALL achieved hematological remission but tolerance of treatment was a problem. The majority of patients had diminished bone marrow reserve. Mortality was frequently related to circulatory failure in children with associated heart defects. It seems necessary to discuss the modification of accepted programmes for leukemia for the treatment of children with Down Syndrome.
 ...
PMID:[Acute leukemia in children with Down syndrome: analysis of cases]. 1073 84

Daunorubicin (DNR) is one of the most important cytotoxic agents in the treatment of acute myeloid leukemia (AML). Its use is usually limited by drug-induced cardiotoxicity depending on the cumulative dose administered. Liposomal encapsulation of DNR (DaunoXome, DNX) seems to reduce the risk of this severe side effect. To investigate the toxicity of DNX in heavily pretreated patients, we conducted a phase I trial, including patients (pts) older than 60 years with relapsed or refractory AML. DNX was used at doses of 40, 60, 75 and 90 mg/m(2), biweekly. Fourteen patients with a median age of 69 years (range, 63-77) were enrolled. A total of 49 courses of DNX were administered [3 pts at 40 mg/m(2) (for a total of 13 courses), 5 at 60 mg/m(2) (20 courses), 4 at 75 mg/m(2) (12 courses), and 2 at 90 mg/m(2) (4 courses)]. The mean cumulative dose of DNX administered was 340 mg (range, 120-1200). A 20% decline in the left ventricular ejection fraction (LVEF) without clinical signs and symptoms of heart failure was noted in 2 patients after a cumulative DNX dose of 480 mg, both with pre-existing heart disease. Even at the highest cumulative doses of DNX, no further decline in LVEF was noted. Nausea, vomiting, alopecia and mucositis were absent. All patients had significant myelosuppression requiring transfusion support. During treatment, 3 patients showed a 25% reduction of leukemic blasts in the bone marrow, 3 patients had to be excluded due to AML progression after the 2nd DNX course, and 7 patients died during the first 6 weeks of treatment. We conclude from these data that DNX offers a less toxic alternative to DNR and other anthracyclines. Using DNX dosages of 40 to 90 mg/m(2) biweekly seems to have little anti-leukemic activity in a patient population heavily pretreated with anthracyclines.
 ...
PMID:Phase I study of liposomal daunorubicin in relapsed and refractory acute myeloid leukemia. 1279 45

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.
 ...
PMID:Safety and efficacy of prolonged cytomegalovirus prophylaxis with intravenous ganciclovir in pediatric and young adult lung transplant recipients. 1743 Apr 89

Secondary erythrocytosis in cyanotic congenital heart disease (CCHD) causes substantial morbidity because of complications of hyperviscosity, including stroke and chronic end organ damage. Phlebotomy provides temporary improvement but leads to iron deficiency and can actually increase blood viscosity. We describe the successful use of hydroxyurea (hydroxycarbamide) in four patients with uncorrected CCHD and symptomatic secondary erythrocytosis. In all patients, hydroxyurea improved symptoms of hyperviscosity. Substantial decreases in the red blood cell (RBC) count were observed, along with increases in the mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH), leading to only modest declines in the circulating hemoglobin concentration. Two patients experienced transient mild myelosuppression, which promptly resolved with dose reduction of hydroxyurea. Hydroyxurea provides a novel and useful therapeutic approach to reduce hyperviscosity from secondary erythrocytosis in patients with CCHD, while preserving oxygen carrying capacity and avoiding iron depletion by phlebotomy.
 ...
PMID:Hydroxyurea therapy for management of secondary erythrocytosis in cyanotic congenital heart disease. 1750 64

Mitoxantrone has a broad anti-tumour activity including lymphoma with potentially less cardiotoxicity than doxorubicin, which may be of particular importance in elderly patients. However, an important issue is whether mitoxantrone is as efficacious as doxorubicin in the treatment of aggressive lymphomas. Through search of several relevant databases and contacts with lymphoma investigators worldwide, we identified nine randomised studies of previously untreated patients comparing CHOP and CNOP chemotherapy in aggressive non-Hodgkin lymphoma. Five trials were included where doxorubicin (50 mg/m2) was compared with mitoxantrone (10-12 mg/m2) and the interval between chemotherapy courses was 3-4 wk. In none of these trials rituximab was used. Odds ratios of complete remission (CR) were pooled using a fixed effects model, and odds ratios of overall survival (OS) were pooled using a random effects model. CNOP was significantly inferior to CHOP with regard to CR rate. CNOP was also inferior, but not significantly to CHOP with regard to OS. No formal testing of side effects could be made. However, the two regimens were equally myelosuppressive. Clinical evidence of symptomatic congestive heart disease was not more frequent among patients treated with CHOP. However, gastrointestinal toxicities and alopecia were more common in this group. CHOP chemotherapy is more efficacious than CNOP at equitoxic (myelosuppression) doses. CHOP is, however, associated with more alopecia and gastrointestinal toxicity.
 ...
PMID:CNOP (mitoxantrone) chemotherapy is inferior to CHOP (doxorubicin) in the treatment of patients with aggressive non-Hodgkin lymphoma (meta-analysis). 1833 1

The discovery of adult cardiac progenitor cells (CPCs) provides a promising way for treating heart disease; however, their surface characteristics that play a critical role in regulating their maintenance, self-renewal, migration, and differentiation have not been fully investigated. One subpopulation of Dolichos biflorus agglutinin (DBA)-positive cells was identified in the heart of adult mice. Flow cytometry showed that 3.7% of heart cells could be labeled by FITC conjugated DBA. BrdU pulse-chase showed that 55-75% of DBA(+) cells were CPCs. Evidences from 5-FU-induced myelosuppression along with BrdU pulse-chasing suggests that DBA-positive cells are proliferative. Furthermore, DBA positive cells display a cologenic appearance in vivo. Our findings suggest that DBA-positive cells in the heart of adult mouse contained a subset of CPCs, and DBA reactivity is one novel surface characteristic on CPCs.
...
PMID:The lectin of Dolichos biflorus agglutinin recognises glycan epitopes on the surface of a subset of cardiac progenitor cells. 2388 68