Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a prospective study, 44 children receiving Adriamycin (ADR) for various neoplastic diseases underwent serial estimations of the systolic time intervals (STI) for the noninvasive assessment of left ventricular myocardial performance. Five of the 44 children developed clinical signs of ADR-related congestive heart failure at a cumulative dose of less than 550 mg/m2 body surface area. Clinical symptoms, changes in the electrocardiogram and in the chest X-ray were preceded in every case by changes of the STI, mainly a prolongation of the left ventricular pre-ejection period (PEP), or a decrease of the ejection time (ET)/pre-ejection period (PEP) ratio (ET/PEP). A continous increase of the PEP and a decrease of the ET/PEP-ratio also gave an indication of myocardial dysfunction during ADR treatment in the other children without clinical signs of congestive heart failure. This subclinical cardiotoxic effect of ADR below the critical cumulative dose of 550 mg/m2 was observed in children with pre-existent myocardial damage, with preceding thoracic irradiation, or during concurrent chemotherapy, of which cyclophosphamide seemed to be most important. Thus, the estimation of the STI proved helpful and reliable in the early detection of incipient heart failure and in the selection of high risk patients in children receiving ADR treatment.
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PMID:Assessment of adriamycin cardiotoxicity in children by systolic time intervals. 43 54

Right ventricular endomyocardial biopsy, right heart catheterization, and systolic time intervals were done in 33 adult patients receiving doxorubicin (AdriamycinTM). Doxorubicin administration was associated with a dose-related increase in the degree of myocyte damage, and 27 of 29 patients biopsied at doses greater than or equal to 240 mg/m2 had doxorubicin-associated degenerative changes identified on biopsy. The pre-ejection period to left ventriculr ejection time ratio (PEP/LVET) showed a threshold phenomenon and did not begin to increase until a total dose of 400 mg/m2 had been reached. Seven patients with catheterization-proven heart failure had a significantly greater amount of myocyte damage on biopsy than dose-matched control subjects (P less than 0.01). Preveious mediastinal radiation appeared to potentiate the doxorubicin-associated degenerative process. Mediastinal radiation and age greater than or equal to 70 years appeared to be risk factors for doxorubicin-associated heart failure. Dose limitation by combined clinical, noninvasive, invasive, and morphologic criteria offered an advantage over empirical dose limitation or dose limitation by PEP/LVET alone.
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PMID:Doxorubicin cardiomyopathy: evaluation by phonocardiography, endomyocardial biopsy, and cardiac catheterization. 62 45

A 20-year-old man with metastatic Ewing Sarcoma developed severe congestive heart failure. Because he had been treated with a large amount of Adriamycin, the diagnosis was initially thought to be Adriamycin cardiotoxicity. However, ante- and post-mortem studies revealed the presence of massive cardiac metastases. At post-mortem, there was no evidence of Adriamycin cardiotoxicity. This case emphasizes that cardiac metastases must be considered in the differential diagnosis of heart failure in patients treated with Adriamycin.
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PMID:Metastatic Ewing sarcoma to the heart simulating adriamycin cardiotoxicity. 74 91

Between December 1982 and November 1990, 31 patients with advanced urothelial carcinoma were treated with one of two combination chemotherapy regimens. A total of 20 patients were treated with 3 mg/m2 mitomycin C and 300 mg/m2 cyclophosphamide given intravenously every 10-14 days and with 180 mg/m2 5-fluorouracil (5-FU) given intravenously every day for as long as possible (CF-Mito regimen). After the patient had been discharged from the hospital, the same treatment with CF-Mito was performed except that 180 mg/m2 5-FU was replaced by 400 mg/m2 UFT (a mixture of tegafur and uracil) given orally. A total of 11 patients whose tumor had relapsed during the first-line treatment were given 60 mg/m2 cisplatin, 40 mg/m2 Adriamycin, and 40 mg/m2 methotrexate intravenously every 28 days (PAM regimen). In all, 20 patients received 4-44 (mean, 9.7) courses of CF-Mito over a period of 1.5-24 (mean, 5.3) months. The results obtained in these 20 patients with evaluable lesions included no complete remission (CR), 4 partial remissions (PRs), 9 cases of stable disease (SD), and 7 cases of progressive disease (PD). The PR duration was 1.5-22 (mean, 7.5) months. The side effects encountered in this group included anorexia, nausea, vomiting, myelosuppression, diarrhea, stomatitis, liver damage, and heart failure. In all, 11 patients received 3-7 (mean, 4.1) courses of PAM over a period of 3-14.5 (mean, 5.2) months. All 11 patients had evaluable lesions, and their responses included no CR, 5 PRs, 3 cases of SD, and 3 cases of PD. The PR duration was 1-3 (mean, 1.6) months. The side effects encountered in this group included anorexia, nausea, vomiting, myelosuppression, heart failure, and hair loss.
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PMID:Combination chemotherapy for advanced urothelial-tract carcinoma. 139 20

Experimental evaluation of new therapy for congestive heart failure has been hampered by the lack of a simple and reliable animal model of heart failure. This study was undertaken to develop a canine model of chronic left ventricular dysfunction. A left thoracotomy was performed in 9 adult mongrel dogs. A 1.5-mm Silastic (Dow Corning) catheter with an attached subcutaneous access port was positioned in the left main coronary artery. Six animals received five weekly infusions of Adriamycin (doxorubicin hydrochloride) (10 mg/wk), and 3 received saline solution. Hemodynamic studies were performed before insertion of the catheter and 2 weeks after completion of the infusions. In animals that received Adriamycin, rest ejection fraction declined from 0.54 +/- 0.03 to 0.35 +/- 0.03, cardiac output fell from 5.6 +/- 0.6 to 3.9 +/- 0.5 L/min, and left ventricular end-diastolic volume increased from 76 +/- 9 to 99 +/- 12 mL (p less than 0.05). There was a small increase in right atrial pressure (2.7 +/- 1 versus 5.7 +/- 1 mm Hg) but no change in right ventricular ejection fraction (0.31 +/- 0.04 versus 0.30 +/- 0.03). In no animal did alopecia, weight loss, neutropenia, or anemia develop. Histological changes consistent with Adriamycin-induced cardiac toxicity were found in each dog. No significant hemodynamic or histological changes occurred in the control animals. Administration of Adriamycin into the left main coronary artery causes left ventricular dysfunction without resulting in systemic side effects or compromising right ventricular function. This animal model could be used to evaluate the effects of new possible therapy, such as cardiomyoplasty, on left ventricular failure.
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PMID:A model of left ventricular dysfunction caused by intracoronary adriamycin. 157 Sep 84

The effects of cardiomyoplasty were evaluated with multiple-gated equilibrium radionuclide angiocardiography and catheterization in a canine model of chronic heart failure. Doxorubicin was administered to 12 dogs at a dose of 1 mg/kg/wk intravenously for 10 weeks. Left ventricular ejection fraction was reduced from a mean of 53.6% +/- 3.4% to 33.5% +/- 2.3% preoperatively. Two dogs died of presumed arrhythmia during this period. Cardiomyoplasty with the left latissimus dorsi muscle was performed on 10 dogs. The muscle was wrapped around both the left and right ventricles. Five dogs died of infection or arrhythmia after the operation. Postoperatively the muscle remained unstimulated for 2 weeks to allow adhesion to the heart. After this period, the latissimus dorsi muscle was conditioned by a progressive stimulation protocol. After the muscle was conditioned, multiple-gated equilibrium radionuclide angiocardiography studies showed that left ventricular global ejection fraction was 18.4% +/- 7.2% at 0 volts (nonstimulation), 26.2% +/- 3.7% at 5-volt stimulation (p less than 0.05), and 31.0% +/- 5.4% at 10-volt stimulation (p less than 0.05). Regional ejection fractions in low lateral, apical, and low septal regions at 5 volts and 10 volts were higher than those at 0 volts (p less than 0.05). Regional wall motion (percent radial shortening) of the low lateral region was higher than that during nonstimulation (p less than 0.05). Peak emptying rate was 2.07 +/- 0.95 end-diastolic counts per second at 0-volt, 3.10 +/- 0.67 at 5-volt, and 3.34 +/- 0.89 at 10-volt stimulation (p less than 0.05). Peak filling rate was 1.81 +/- 0.52 end-diastolic counts per second at 0-volt, 2.67 +/- 1.18 at 5-volt, and 3.11 +/- 0.65 at 10-volt stimulation (p less than 0.05). Cardiac catheterization data showed a nonsignificant increase in left ventricular rate of pressure rise with increasing voltage (1302 +/- 355 mm Hg/sec at 0 volts, 1450 +/- 413 mm Hg/sec at 5 volts, and 1568 +/- 455 mm Hg/sec at 10 volts). Left ventricular systolic pressures were unchanged. End-diastolic pressures decreased (11.2 +/- 1.48 mm Hg at 0 volts, 10.4 +/- 2.30 mm Hg at 5 volts, and 9.6 +/- 1.52 at 10 volts; p less than 0.05). These data show that cardiomyoplasty can improve indices of systolic and diastolic function in a canine model of chronic heart failure.
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PMID:Effects of dynamic cardiomyoplasty on indices of left ventricular systolic and diastolic function in a canine model of chronic heart failure. 159 87

The functional integrity of the beta-adrenergic stimulatory pathway in a rabbit model of heart failure induced by long-term adriamycin treatment was investigated. Adriamycin-induced cardiomyopathy was produced in 46 rabbits by injecting 0.75 mg/kg of adriamycin, three times per week, for a period of 11 weeks. Biochemical studies performed on isolated membrane preparations revealed a 40 and 55% decrease in basal adenylyl cyclase activity in the left and right ventricles of the adriamycin treated rabbits, respectively. Furthermore, the Vmax of forskolin stimulation was significantly lower in both ventricles with no change in Kact. The Vmax of 5'-guanylylimidodiphosphate stimulation of the stimulatory guanylyl nucleotide binding protein Gs and beta-adrenergic receptor stimulation by isoproterenol were also significantly decreased (42%) in both ventricles of the adriamycin-treated rabbits with no change in Kact. Despite the decrease in receptor-mediated cyclic AMP production, no decrease in beta-adrenergic receptor population was found. Mechanical studies on the isolated right ventricular papillary muscle revealed a decrease in baseline total tension (3.1 +/- 0.4 g/mm2 to 1.8 +/- 0.2 g/mm2) and dT/dt (15.1 +/- 1.6 g/mm2 s to 7.9 +/- 0.8 g/mm2 s) in the adriamycin-treated rabbits. Furthermore, tension generation and dT/dt response to increasing concentrations of forskolin or isoproterenol were both significantly lower in the adriamycin-treated rabbits as compared to normal. We suggest that a decrease in the activity of the adenylyl cyclase component of the beta-adrenergic stimulatory pathway is largely responsible for the decrease in cyclic AMP generation in the adriamycin-treated rabbits. This defect may play an important role in the decrease of contractility in this model of heart failure.
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PMID:Adriamycin-induced changes to the myocardial beta-adrenergic system in the rabbit. 165 46

Preoperative intraarterial (IA) cisplatin (CDP) was administered to 92 patients with nonmetastatic osteosarcoma. The ages of the patients ranged from 4 to 28 years. Sixty-four patients (70%) received 2 or 3 preoperative courses and 28 (30%) received 4 or more. Sixty-two specimens were available for pathologic examination to assess the degree of tumor necrosis. More than 90% tumor destruction was observed in 16 of 42 patients (38%) who received 1 to 3 preoperative courses as opposed to 17 of 20 (85%) who received 4 or more courses. Patients who received 4 or more courses had a 2-fold probability of achieving more than 90% tumor necrosis, and 68% underwent conservative surgery. Of those who received 3 or less courses, 23% underwent conservative surgery. Postoperatively, patients were treated with intravenous (IV) CDP alternating with doxorubicin (ADR) (Adriamycin, Adria Laboratories, Columbus, OH). Pulmonary metastases developed in 36 patients, bone metastases in 2, and local recurrence in 6. Two patients died of cardiac failure without evidence of disease. Thus, 46 patients (50%) were continuously free of disease 18 to 78 months after diagnosis. Univariate and multivariate analyses showed that male sex, low grade preoperative chemotherapy-induced necrosis, and nonosteoblastic histologic condition were prognostic factors predictive of recurrence, while male sex and large tumor size were prognostic factors predictive of death. These results are comparable with those reported by other centers and are superior to our previous experiences that yielded survival rates of 5% to 10%. A substantial number of patients also had the opportunity to achieve tumor removal with conservative surgery.
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PMID:Increased survival, limb preservation, and prognostic factors for osteosarcoma. 185 72

Five patients with high risk multiple myeloma not responsive to standard chemotherapy were treated by high-dose chemotherapy (Melphalan, Cyclophosphamide) (HDC) and total body irradiation (TBI) followed by autografting with blood stem cells. These cells were previously collected by leukaphereses from eight to twelve occasions during hematopoietic recovery following profound aplasia induced by each course of intensive chemotherapy (Vincristine, Adriamycin, Cyclosphosphamide, Prednisone) when the patient reached a neutrophil count of 1,000/microliters and a platelet count of 100,000/microliters. No patients had evidence of tumor plasmacells in leukaphereses products using cytology, immunocytochemistry and immunofluorescence. At this time the patient 5 is not evaluable because of the short follow-up. One died at day 30 from heart failure. All living patients achieved a complete remission which persisted at a follow-up of 300, 261 and 136 days. Autologous blood derived hematopoietic stem cells induced successful and sustained engraftment in all living patients. Our results indicate the feasibility of this therapeutic approach over allogenic or autologous bone marrow transplantation in selected patients with high tumour mass multiple myeloma.
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PMID:Blood stem cells autografts in patients with high risk multiple myeloma. 197 31

Three hundred fifteen patients with operable gastric cancer were randomized to receive fluorouracil, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and mitomycin (FAM) or no adjuvant treatment between September 1981 and July 1984. After excluding ineligible patients, 281 patients are included in this analysis. Treatment was moderately well tolerated by the majority of patients, the common side effects being nausea and vomiting (58%) and alopecia (57%). Three possible treatment-related deaths were seen, all due to cardiac failure. At median follow-up of 68 months, 164 patients have died, 73 in the treated arm and 91 in the control arm. There was no significant difference in disease-free or overall survival between the two arms of the study (P = 0.21). There is some evidence that patients with more advanced carcinoma (T3-T4) derived some benefit from treatment (P = 0.04). The interpretation of this finding must take into account that all subgroups were defined retrospectively, and this could, therefore, be a chance finding. We conclude that adjuvant chemotherapy as given in this trial is not indicated as routine treatment in operable gastric cancer, but that further evaluation in stage T3-T4 patients is warranted.
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PMID:A randomized trial comparing adjuvant fluorouracil, doxorubicin, and mitomycin with no treatment in operable gastric cancer. International Collaborative Cancer Group. 219 22


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