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)

A 54-year-old woman with progressive systemic sclerosis (PSS) was admitted to hospital because of dyspnea and chest pain. Echocardiogram revealed diffuse hypokinesis of the left ventricle (ejection fraction 24%). Methylprednisolone, heparin, and diuretics were administered, without benefit. Anemia, thrombocytopenia, and renal dysfunction rapidly progressed, and she died of heart failure on the 14th hospital day. Immunohistochemical study of the myocardial tissue showed mild to moderate cell infiltration, mainly consisting of natural killer (NK) cells, macrophages, cytotoxic T lymphocytes (CTLs), and T helper cells. Perforin, a cytolytic factor, was expressed in the infiltrating CTLs and NK cells, indicating that these cells were activated killer cells. Furthermore, human leukocyte antigen classes I and II, intercellular adhesion molecule-1, as well as costimulatory molecules B7-1, B7-2, and CD40, all of which are known not to be expressed in cardiac myocytes under normal conditions, were moderately to strongly expressed in cardiac myocytes. There was no detectable level of enterovirus genomes in the polymerase chain reaction products from the myocardial tissue of this patient. These findings strongly suggest that the infiltrating killer cells recognized cardiac myocytes as target cells and directly damaged them by releasing perforin. Enhanced expression of these antigens may have played an important role in the activation and cytotoxicity of the infiltrating killer cells. Absence of enterovirus genomes in the myocardial tissue may suggest that this autoimmune process is primarily induced by PSS.
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PMID:Evidence of cell-mediated cardiac myocyte injury involved in the heart failure of a patient with progressive systemic sclerosis. 1008 93

The authors analyze three cases of hepatosplenic (gamma-delta) T-cell lymphoma which is a newly defined unit in the spectrum of primary splenic lymphomas. The first two were diagnosed in sequential biopsies of bone marrow, splenectomic material and the liver of female patients aged 38 and 67 years. In the clinical picture dominated symptoms of progressing splenomegaly, hepatomegaly, haemolytic anaemia and different manifestations of leuco- and thrombocytopenia with expulsion of tumour cells into the peripheral blood. The first patient died after complete remission with signs of heart failure, the second one is surviving for 11 months in partial remission. The third case, a 66-year-old male patient, died suddenly during a 16-day hospitalization on account of diagnosis of hepatopathy and anaemic syndrome, as a result of cardiorespiratory failure. The diagnosis was established only post mortem. In none of the patients signs of affected lymph nodes were present. The authors analyze problems of bioptic diagnosis of the mentioned lymphoma, in particular biopsy of bone marrow in the stage of its initial infiltration. The key to diagnosis is in addition to knowledge of clinical manifestations the typical morphology and intrasinusoid propagation of tumour cells and immunohistochemical evidence of their T-phenotype. The predominance of initial manifestations of haemolytic anaemia calls for differential diagnosis of haemolytic conditions and confirmation of their secondary character.
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PMID:[Primary hepatosplenic (gamma delta) T-cell lymphoma: clinico-pathologic analysis of 3 cases]. 1035 63

To increase the dose-intensity of two drugs in metastatic breast cancer, we tested the feasibility, in phase I studies, of two schedules of epirubicin (E) and cyclophosphamide (C) - sequential (E--> C) and alternating (E/C) - with respect to the standard combination (EC). Drugs were given at three planned-dose levels, plus either G-CSF or GM-CSF. Patients with metastatic (30), inoperable stage IIIb (2) or inflammatory (7) breast cancer were treated. The doses of EC, given every 21 days (4 cycles), were 75/1500, 82.5/2250, 90/3000 mg/m2. In the E/C schedule, epirubicin was given at cycles 1, 3 and 5, and cyclophosphamide at cycles 2, 4 and 6. In the E--> C schedule, three cycles of epirubicin then three cycles of cyclophosphamide were administered. In both experimental schedules, drugs were given every 14 days for 6 cycles at doses of 100, 110, 120 mg/m2 (E) and 2000, 3000, 4000 mg/m2 (C). The average relative dose-intensity was 1.2-fold and 2-fold greater with E/C and E--> C, respectively, than with EC. The third level dose was feasible with all schedules. Grade 4 leucopenia occurred in 77% of patients. Thrombocytopenia was absent in 6 cases and grade 4 in 12 (30.8%). Eighty-one percent of patients on experimental schedules required red blood cell support versus 44.4% of patients on EC. At the third level, platelet transfusions were more frequent among patients treated with EC (27. 8%). Non-haematological toxicity was mild: about 20% of patients experienced grade 3 vomiting, irrespective of schedule. Only 2 patients had grade 3 mucositis; no patient developed heart failure. Fever (61% of patients) and bone pain (55.5% of patients) were relevant in the GM-CSF treated groups and 12 patients shifted to G-CSF. The overall response rate was 84.6%: 5/39 (12.8%) complete response and 28/39 (71.8%) partial response. At 30/9/98, median survival was 29.5 months, with no difference between patients with metastatic and stage IIIb/inflammatory breast cancer. Median follow-up of surviving patients was 62 months (range 17-83). The 5-year estimated survival was 19% (95% confidence intervals = 7-31%). Rapidly alternating or sequential cycles of epirubicin and cyclophosphamide with CSF support is a feasible strategy that allows a higher increase of dose-intensity of the single drugs. Hospitalization and anemia were more frequent with the experimental schedules, and thrombocytopenia with the standard schedule. Overall, this intensified therapy was very active.
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PMID:The impact of schedule on acute toxicity and dose-intensity of high-dose chemotherapy with epirubicin and cyclophosphamide plus colony stimulating factors in advanced breast cancer. 1040 45

Fetal and neonatal hyperthyroidism are usually produced by transplacental passage of thyroid-stimulating immunoglobulins. Most commonly, the thyroid-stimulating immunoglobulins are a component of active maternal Graves' disease. However, such antibodies may continue to be produced after ablation of the thyroid by surgery, radioiodine, or by the immune mechanisms of Hashimoto's thyroiditis. Other mechanisms that have produced fetal and neonatal hyperthyroidism include activating mutations of the stimulatory G protein in McCune-Albright syndrome and activating mutations of the thyrotropin (TSH) receptor. Fetal hyperthyroidism may be associated with intrauterine growth retardation, nonimmune fetal hydrops, craniosynostosis, and intrauterine death. Features of this condition in the neonate include hyperkinesis, diarrhea, poor weight gain, vomiting, ophthalmopathy, cardiac failure and arrhythmias, systemic and pulmonary hypertension, hepatosplenomegaly, jaundice, hyperviscosity syndrome, thrombocytopenia, and craniosynostosis. The time course of thyrotoxicosis depends on etiology. Remission by 20 weeks is most common in neonatal Graves' disease; remission by 48 weeks is nearly always seen. A subset of these patients may have persistent disease when there is a strong family history of Graves' diseases. Disease persistence is characteristic of patients with activating mutations of the TSH receptor. Treatment of fetal hyperthyroidism comprises administration of antithyroid drugs to the mother. Fetal heart rate and fetal growth should be monitored. Ultrasonography may reveal changes in thyroid size. At times, cordocentesis may be useful for monitoring fetal thyroid function. Hyperthyroid neonates may be treated with antithyroid drugs, beta-adrenergic receptor blocking agents, iodine, or iodinated contrast agents, and at times, with glucocorticoids and digoxin. Nonremitting causes of neonatal hyperthyroidism require ablative treatments such as thyroidectomy.
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PMID:Fetal and neonatal hyperthyroidism. 1044 21

Profound thrombocytopenia resulting from portal hypertension may exacerbate gastrointestinal bleeding, precipitate spontaneous bleeding, preclude surgical intervention for associated disorders, and severely limit life-style because of the danger of splenic injury. Although splenectomy can reverse the thrombocytopenia, the procedure should be avoided in children. We reviewed our experience with distal splenorenal shunting (DSRS) in children, particularly when performed for the sole purpose of reversing severe thrombocytopenia resulting from portal hypertension. DSRS was performed in 11 children between the ages of 7 and 15 years: five for severe thrombocytopenia (group 1), four for advanced hypersplenism and congenital hepatic fibrosis prior to renal transplantation (group 2), and two for esophageal bleeding (group 3). One child in group 1 with severe heart disease and Child's class C cirrhosis due to hepatitis C died of progressive cardiac failure and was excluded from further analysis. Of the eight remaining patients in groups 1 and 2, four children had congenital hepatic fibrosis, two had portal vein thrombosis, one had hepatitis B, and one had Wilson's disease. After DSRS, the mean platelet count increased from 37,000 +/- 18,000 to 137,600 +/- 81,000 (P = 0.01). The platelet count improved significantly in all seven children with presinusoidal portal hypertension or stable cirrhosis but did not increase in the child with hepatitis B and Child's class B cirrhosis. The white blood cell count increased from an average of 3.3 +/- 1.1 to 5.4 +/- 2.6 (P= 0.02). There were no postoperative complications in this group. The improved platelet count allowed the four children with congenital hepatic fibrosis and renal failure to undergo renal transplantation with full posttransplant immunosuppression including azathioprine. Postoperative Doppler ultrasound examination demonstrated shunt patency at 6 months in all cases. Spleen size decreased appreciably in all children in groups 1 and 2. All children were able to resume full activity including contact sports. In summary, DSRS effectively controls profound thrombocytopenia resulting from presinusoidal portal hypertension or stable cirrhosis without sacrificing the spleen and should be the treatment of choice for this condition.
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PMID:Distal splenorenal shunts for the treatment of severe thrombocytopenia from portal hypertension in children. 1045 41

We report a rare case of idiopathic thrombocytopenic purpura (ITP) associated with acute myocardial infarction (AMI). A 72-year-old woman with hypertension and hemorrhoids was admitted because of chest pain, severe anemia (RBC 340 x 10(4)/microliter, Hb 5.4 g/dl, Ht 21.7%) and thrombocytopenia (0.2 x 10(4)/microliter). AMI was diagnosed by electrocardiogram (ST elevation and negative T in V2-5), echocardiogram (hypokinesis in anteroseptal wall) and laboratory (CPK 470 U/l) findings and was treated with only blood transfusion. Chest pain disappeared the day after admission, and neither heart failure nor arrhythmia occurred. Based on bone marrow findings (hyperplasia of erythroblast and megakaryocyte), endoscopic (internal hemorrhoids) and laboratory (antiplatelet antibody positive, platelet associated IgG 257.8 ng/10(7) cells) findings, iron deficiency anemia and ITP were diagnosed. Anemia improved after blood transfusion, but thrombocytopenia (< 1.0 x 10(4)/microliter) without active bleeding continued after steroid and gamma-globulin therapy. At discharge, electrocardiogram showed a negative T in I, aVL and V2-5, and T1 and BMIPP myocardial scintigram showed defects in the anteroseptal and apical wall.
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PMID:[An elderly case of idiopathic thrombocytopenic purpura associated with acute myocardial infarction]. 1061 30

The unique clinical and pathological findings in nine Asian (Elephas maximus) and two African (Loxodonta africana) elephants from North American Zoos with a highly fatal disease caused by novel endotheliotropic herpesviruses are described. Identification of the viruses by molecular techniques and some epidemiological aspects of the disease were previously reported. Consensus primer polymerase chain reaction (PCR) combined with sequencing yielded molecular evidence that confirmed the presence of two novel but related herpesviruses associated with the disease, one in Asian elephants and the second in African elephants. Disease onset was acute, with lethargy, edema of the head and thoracic limbs, oral ulceration and cyanosis of the tongue followed by death of most animals in 1 to 7 days. Pertinent laboratory findings in two of three clinically evaluated animals included lymphocytopenia and thrombocytopenia. Two affected young Asian elephants recovered after a 3 to 4 wk course of therapy with the anti-herpesvirus drug famciclovir. Necropsy findings in the fatal cases included pericardial effusion and extensive petechial hemorrhages in the heart and throughout the peritoneal cavity, hepatomegaly, cyanosis of the tongue, intestinal hemorrhage, and ulceration. Histologically, there were extensive microhemorrhages and edema throughout the myocardium and mild, subacute myocarditis. Similar hemorrhagic lesions with inflammation were evident in the tongue, liver, and large intestine. Lesions in these target organs were accompanied by amphophilic to basophilic intranuclear viral inclusion bodies in capillary endothelial cells. Transmission electron microscopy of the endothelial inclusion bodies revealed 80 to 92 nm diameter viral capsids consistent with herpesvirus morphology. The short course of the herpesvirus infections, with sudden deaths in all but the two surviving elephants, was ascribed to acute cardiac failure attributed to herpesvirus-induced capillary injury with extensive myocardial hemorrhage and edema.
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PMID:Clinical and pathological findings of a newly recognized disease of elephants caused by endotheliotropic herpesviruses. 1068 40

Infantile choriocarcinoma of the liver is an extremely rare entity, and outcome has been fatal in almost all published cases. To the authors' knowledge, this is the first report on successful treatment with preoperative chemotherapy. A 10-week-old girl presented with a large liver tumor, ovarian cysts, cardiac insufficiency, progressive hemolytic anemia, and thrombocytopenia. Ultrasound scan and magnetic resonance tomography (MRT) showed the typical pattern of infantile hemangioendothelioma. An emergency laparotomy was performed because of increasing cardiac insufficiency with ligation of the right hepatic artery, tumor biopsy, and subtotal resection of the ovarian cysts. Histology findings showed a choriocarcinoma of the liver and corpus luteum cysts of the ovaries. Serum beta-human chorionic gonadotropin (beta-HCG) was elevated to 1.600.00 U/L. Chemotherapy was initiated with etoposide and cisplatin. When x-ray examination showed development of lung metastases, chemotherapy was intensified with etoposide, cisplatin, and ifosfamid according to the German Study Group of Extracranial Nontesticular Malignant Germ Cell Tumors in Childhood and Adolescence (MAKEI-96). Serum beta-HCG levels decreased further, ultrasound examination showed significant tumor reduction, and pulmonal metastasis could no longer be found in chest x-rays. After the fourth course, a complete tumor resection was achieved by an extended right hemihepatectomy with adjuvant chemotherapy being administered after the operation. The child has been in complete remission for 22 months. The authors' experience shows that chemotherapy is effective for preoperative tumor reduction.
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PMID:Effective treatment of infantile choriocarcinoma in the liver with chemotherapy and surgical resection: a case report. 1091 16

Ten patients with refractory (n = 8) or early relapsing (n = 2) aggressive non-Hodgkin's lymphoma were enrolled in a pilot study evaluating a high-dose sequential chemotherapy regimen with peripheral blood stem cell (PBSC) support. Five treatment phases were scheduled: phase I (cyclophosphamide + etoposide followed by lenograstim (G-CSF), and a PBSC harvest); phase II (cisplatinum + cytarabine + etoposide followed by lenograstim); phases III and IV (cyclophosphamide + cytarabine + etoposide followed by autologous PBSC infusion and lenograstim); and phase V (carmustine + cytarabine + etoposide + melphalan followed by autologous PBSC infusion and lenograstim). Ten, nine, eight, six and four of the 10 patients received one, two, three, four and five of the five scheduled phases of treatment, respectively. Four patients were withdrawn from the study due to progressive disease and two due to thrombotic microangiopathy (TM). Moreover, in the four patients who completed all treatment phases, an additional case of TM was seen. In all three patients with TM, laboratory studies showed evidence of Coombs negative hemolytic anemia, thrombocytopenia, renal dysfunction and in addition cardiac failure in two patients. TM may be a new dose-limiting toxicity of high-dose sequential chemotherapy followed by repeated PBSC transplantation.
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PMID:Thrombotic microangiopathy: a new dose-limiting toxicity of high-dose sequential chemotherapy. 1131 88

Sequential administration of the association of 5-fluorouracil, epirubicin and cyclophosphamide (FEC) and paclitaxel could be better tolerated than the association of an anthracycline and paclitaxel while having a similar antitumour effect. 69 patients with advanced breast cancer previously untreated with anthracyclines or paclitaxel entered a phase II multicentre study in which FEC was followed by paclitaxel. Both regimens were administered 4 times every 21 days. The median follow-up is 20 months and 38/69 patients have died. Grade III-IV toxicity was acceptable. Leukopenia occurred in 26% of patients, thrombocytopenia in 2% and anaemia in 4%. One patient had reversible heart failure during FEC therapy. Peripheral neuropathy and arthralgia-myalgia occurred in 9% and 4% of patients, respectively and one patient had respiratory hypersensitivity during paclitaxel treatment. 9 patients did not complete therapy because of: treatment refusal (n = 1), cardiac toxicity (n = 1), early death during FEC chemotherapy (n = 1), major protocol violations (n = 4), hypersensitivity reaction (n = 1) and early death during paclitaxel chemotherapy (n = 1). The overall response rate was 65% (95% CI = 53-76), and 7% of patients had stable disease. Therapy was defined as having failed in 28% of patients because they were not evaluable (13%) or had progressive disease (15%). The median time to progression and survival are 13.2 and 23.5 months, respectively. Sequential FEC-paclitaxel is a suitable strategy for patients with metastatic breast cancer who have not been previously treated with anthracyclines and/or taxanes. In fact, it avoids major haematologic toxicity and has a good antitumour effect.
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PMID:A phase II study of sequential 5-fluorouracil, epirubicin and cyclophosphamide (FEC) and paclitaxel in advanced breast cancer (Protocol PV BC 97/01). 1146 Oct 67


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