Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hearts of eight patients aged 22 to 67 years (mean, 41 years) who died during or within 4 days of interleukin-2 (IL-2) based immunotherapy for treatment of renal cell carcinoma or melanoma were studied at necropsy. Death resulted from combined cardiorespiratory failure in two patients, sepsis in four patients, acute myocardial infarction in one patient, and myocarditis in one patient. Transmural left ventricular necrosis was present in one of the two patients with significant atherosclerotic coronary artery narrowing. Noninfectious myocarditis was present in five patients: the inflammatory infiltrate was lymphocytic in four and composed of a mixture of eosinophils and lymphocytes in one. Although treatment-related deaths associated with high-dose IL-2 therapy are uncommon (1.5% in 652 consecutive patients), the potential for significant myocardial ischemia or myocarditis exists, and careful monitoring for arrhythmias or myocardial failure is warranted.
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PMID:Myocarditis or acute myocardial infarction associated with interleukin-2 therapy for cancer. 220 2

Magnetic resonance is a unique, noninvasive imaging modality which allows direct, multiplanar imaging and the possibility of obtaining biochemical information in vivo. Presently, MR appears most applicable to the evaluation of central nervous system abnormalities. The high sensitivity of MR in the evaluation of intracranial pathology suggests that it may eventually replace CT for many suspected diseases, if future investigations are able to improve its specificity. As previously noted, MR may be more diagnostic than other radiologic studies in the evaluation of suspected Chiari malformation, syringomyelia, congenital abnormalities, tumors of the spinal axis, and disc space infection. In the chest, MR appears to be more accurate than CT in the determination of the extent of mediastinal tumor, but at present cannot replace CT because of the lack of experience in imaging parenchymal nodules and benign diseases. MR of the breast is promising, but the size of the lesion may prove to be a limiting factor with magnetic field strengths commonly being utilized. There are inherent difficulties in the evaluation of cardiac disease with MR, but it offers a noninvasive method of investigating congenital heart disease and may provide valuable information in suspected myocardial ischemia and altered cardiac function. MR provides a new method of evaluating the vascular system, both in terms of providing anatomic information on large and medium-sized vessels and flow analysis. In the abdomen, MR appears to be most sensitive in the evaluation of suspected hepatic masses, but as with the brain, greater specificity will be needed to replace CT. At the present time, MR offers no distinct advantage over conventional imaging modalities in the evaluation of pancreatic disease, it maybe more accurate than CT in the staging of renal cell carcinoma. Larger studies are needed to determine the role of MR in the investigation of retroperitoneal adenopathy and adrenal abnormalities. In the pelvis, MR offers the hope of earlier diagnosis of prostatic carcinoma and may replace CT for staging of prostatic carcinoma and transitional cell carcinoma of the bladder. Limited MR experience with benign disease of the female pelvis suggests that it is currently more accurately evaluated with ultrasound. MR appears to be highly sensitive and specific for the diagnosis of avascular necrosis and may provide an early clue in suspected osteomyelitis. Finally, in vivo MR spectroscopy may provide unique metabolic information that was unobtainable prior to the advent of magnetic resonance, if this proves to be technically feasible.
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PMID:Magnetic resonance. Principles and applications. 639 70

Interleukin-2 (IL-2) is a cytokine with proven activity against metastatic renal cell carcinoma (RCC) and malignant melanoma (MM). The intravenous administration of high-dose IL-2 is limited by important cardiovascular side effects such as hypotension, fluid retention, arrhythmias, and myocardial ischemia, which often cause dose reduction and/or treatment withdrawal. The occurrence of these toxic events is not predicted by routine pretreatment examinations. The aim of the present study was to test the reliability of serial echocardiography in predicting subsequent cardiac adverse effects in patients undergoing IL-2 administration. In 19 patients (15 men, 4 women; median age: 51 years, range 27-71 years; 10 affected by metastatic RCC and 9 affected by MM) we performed two-dimensional and Doppler echocardiography before and immediately after 28 continuous intravenous infusions (CIVI) of IL-2 at the dose of 18 MIU/m2/day for 4 days. Left ventricular systolic function and the diastolic transmitral flow pattern were assessed before and after IL-2 administration. Significant changes of two indexes of left ventricular filling were noted: a decrease of the ratio of maximal flow velocity in early diastole to that in late diastole (E/A) (basal: 1.12 +/- 0.46, mean +/- SD; posttreatment: 0.83 +/- 0.27; p < 0.01) and an increase of the percentage of the atrial contribution to left ventricular filling (basal: 37.75 +/- 11.58%; posttreatment: 49.43 +/- 16.48%; p < 0.01). Eight major cardiovascular events causing IL-2 infusion withdrawal were observed (two ischemic electrocardiographic modifications, three grade III-IV hypotension, one atrial fibrillation, one pericardial effusion, one acute heart failure). These major cardiovascular events were observed more often when an abnormal basal E/A ratio < 1.0 (p < 0.05) was found. We conclude that Doppler transmitral flow pattern analysis before and subsequent to IL-2 infusion is a useful and easily available procedure for the monitoring of cardiac modifications during CIVI IL-2 administration. It might also predict a major cardiovascular event during IL-2 administration. Patients with basal E/A ratio < 1.0 should be more carefully monitored during treatment and/or should be treated with lower IL-2 doses to avoid cardiovascular toxicity.
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PMID:Isolated left ventricular filling abnormalities may predict interleukin-2-induced cardiovascular toxicity. 873 96

There has been no effective therapy for metastatic renal cell carcinoma (RCC). Cimetidine has been demonstrated to block histamine mediated activation of suppressor T cells in man and in animal models, resulting in an anti-tumor immune response. We treated two patients with cimetidine for matastatic RCC. Case 1: A 61-year-old man presented with a diagnosis of metastatic lung and brain tumor of RCC. Interferon therapy was not effective, but after radiation therapy, his brain metastasis revealed partial response. He received cimetidine 800 mg orally after radiation, his lung metastasis revealed almost complete response. But he died of ischemic heart disease. Case 2: A 58-year-old woman presented with a metastatic lung tumor of RCC. We started interferon therapy. But because of general fatigue and anemia, she required discontinution of interferon therapy. So she received cimetidine 800 mg orally and her lung metastasis revealed complete response. She remained well and had no evidence of disease. Patients with metastatic renal cell carcinoma can occasionally respond to cimetidine and further investigation must be studied.
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PMID:[Successful treatment of metastatic renal cell carcinoma with cimetidine--report of two cases]. 893 17

Originally identified for its ability to induce vascular permeability and stimulate endothelial cell growth, vascular endothelial growth factor (VEGF) is now recognized as a key factor required for growth of tumors and is involved in many other diseases, such as diabetes, arthritis, atherosclerosis and ischemic heart disease. In addition, recent studies show that VEGF is involved in stem cell recruitment and mobilization. A new role of VEGF has been postulated in enhancing the production and release into the circulation of endothelial progenitor cells derived from the bone marrow. These circulating endothelial cells may be targeted to angiogenic sites where they are being incorporated in new vessels. We provide an overview of the biological role of VEGF and summarize the different approaches that are under development to inhibit VEGF activity in the clinic, particularly antiangiogenic cancer treatment. Thus far, more than five inhibitors of the VEGF pathway have entered clinical phase I-III trials. Of these, bevacizumab, an antibody against VEGF, was shown to prolong survival in a phase III trial in renal cell cancer. Although very preliminary, a phase I trial found tumor regressions that were caused by an oral VEGF receptor tyrosine kinase inhibitor, SU11248. Taken together, these data seem very promising for the development of long-term nontoxic treatments against cancer.
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PMID:Vascular endothelial growth factor and its inhibitors. 1498 47