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

Twenty-four patients with histologically proven metastatic malignant melanoma were included in a phase II trial of recombinant IL-2 (rIL-2, RU 49637). Twenty million international units (IU)/m2/day were given by continuous intravenous infusion on days 1 to 5, 15 to 18, and 29 to 31, and then monthly for 5 days until disease progression or major intolerance developed. All patients were evaluable for response and toxicity. Toxicity was consistent with one case of myocardial ischemia, 13 cases of grade III and IV hypotension, and 15 cases of proven sepsis. There were 8 objective responses: 4 of them were of short duration as they were observed on day 31 only. An activation of the immune system was detected in all patients. It was demonstrated by an increase in lymphocyte populations, especially in activated NK cells. A tendency for higher numbers of cytotoxic cells was found in patients with objective tumor responses. These results indicate a role for rIL-2 RU 49637 in treating patients with metastatic malignant melanoma. However, further trials are required to determine its optimal dosage and schedule of administration.
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PMID:IL-2 phase II trial in metastatic melanoma: analysis of clinical and immunological parameters. 130 93

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

Mortality was studied among 1271 employees of a cellulose fiber production plant in Rock Hill, South Carolina, in the United States. Each subject was employed for at least three months between 1 January 1954 and 1 January 1977 in jobs that entailed exposure to the highest concentrations of methylene chloride. In the cohort 122 deaths were identified through 1 September 1986, and mortality rates for the cohort were compared with mortality rates for York County, South Carolina. Deficit mortality was observed for cancers of the respiratory system, breast, and pancreas and from ischemic heart disease. Excess mortality was observed for cancers of the buccal cavity and pharynx and the liver and biliary tract, and for melanoma as well. The largest relative excess was for liver and biliary tract cancers. There were only four deaths in this category; however, three of the four deaths were cancer of the biliary tract (3 observed, 0.15 expected, standardized mortality ratio 20).
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PMID:Mortality of cellulose fiber production workers. 238 31

The objectives of this article on epidemiological studies of health risks from oral contraceptives (OCs) is to review major studies of the association between OCs and circulatory disease and cancer. It is also to emphasize methodologic limitations of the existing data, and to identify unresolved and important questions. A brief discourse on the nature and imputation of relative risk is provided. Cardiovascular diseases covered include ischemic heart disease, stroke, and thromboembolism. Current studies on low dose pills from 3 large US populations reveal that there is no impact of death from use of OCs. A Great Britain and the Walnut Creek study from the US found a slight but not statistically significant increase in ischemic heart disease. These studies also found a statistically significant 3-fold increase in stroke among OC users and, from another study, a 2-fold increase. These studies were based on high levels of ethinyl estradiol where the risk becomes apparent. The risk for idiopathic venous thromboembolism was 3- 8 fold for current OC users. The accuracy of these findings is questioned when the data reflect such heterogeneity. Cancer is differentiated as breast cancer, endometrial cancer, ovarian cancer, cervical cancer, malignant melanoma, and hepatocellular adenoma. For breast cancer, both case control studies as well as cohort studies found no increase in breast cancer. Future additional research will continue to explore unanswered questions about this association. Beneficial effects of OCs occur for endometrial cancer for as long as 15 years after taking the pill. Only 1 year's use resulted in a 50% reduction in risk of endometrial cancer regardless of pill dose and particularly for nulliparous women, who have an increased risk. The longer duration of use of the OCs results in a protective effect against ovarian cancer, i.e., 5 years of use yields as relative risk of below 0.5 and the results of a protective effect can be seen as early as 3 months after pill use. There is about 40% protection against ovarian cancer even with low dose pills; the effect lasts 15 years after cessation of OC use. Cervical cancer studies have shown mixed results. The human papilloma viruses 16 and 18 have been shown to be related to cervical cancer but further research is needed to identify the association with OCs. Data are inconclusive but lean in the direction of no association with malignant melanoma. Hepatocellular adenoma has not been identified in large vital statistics studies, although several small studies have suggested an increased risk. It has been shown by Fortney et al. that with a 50% increase in cervical cancer risk and a 3-4 fold increase in cardiovascular disease risk that OC use for 5 years before the age of 30 years adds 4 days to a health women's life.
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PMID:Results of oral contraceptive epidemiologic studies regarding neoplastic and cardiovascular effects. 257 54

Hospital admissions, cancer statistics, causes of death and data from general practice consultations have been reviewed to identify the challenges to health within the working life. Morbidity resulted commonly from trauma, malignant neoplasms especially of the female breast, melanoma, colorectal and cervical tumours, locomotor disorders especially of the spine, ischaemic heart disease, obstructive respiratory disorder, gynaecological problems, psychiatric disorders, hearing impairment and diabetes mellitus. Support for basic research and studies relating to approaches aimed at influencing community attitudes are discussed. Areas of particular research possibilities in New Zealand are identified in psychiatry, cost benefit studies in surgery, and health screening. A case is made for a strong improved complementary research effort within the clinical areas of the health service both in hospitals and in general practice especially in clinical conditions such as asthma and diabetes. Seeding money for voluntary societies and foundations closely involved with research and scientific merit may facilitate further financial support to such voluntary organisations and the prospect of expansion by them of the support of peer-reviewed research projects.
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PMID:Challenges to health in working life. 318 24

The present level of understanding of the known risks of oral contraceptive (OC) use are summarized. The findings of many investigations in the late 1960s and early 1970s may no longer be totally appropriate because OCs available then had higher dosages than today. Also, early studies enrolled predominantly women in their 20s, who are now almost all more than 35 years old. Thus, the risks observed in these studies may not be applicable to younger women using OCs today. Another consideration has been underscored by the results of the Walnut Creek Study. Behavioral characteristics such as smoking, drinking, and sexual activity are factors which can strongly confound risks of OC use and must be considered when assessing current and future investigations. Many studies have clearly shown that the most serious life threatening danger associated with OC use is that of cardiovascular complications arising from the interaction of OC use and smoking. The increased risks attributable to smoking while using OCs account for a substantial number of the deaths recorded. The Walnut Creek Study showed a somewhat different outcome. Its data suggest no significant risk of myocardial infarction (MI), ischemic heart disease, cerebral thrombosis, or ischemic cerebrovascular disease associated with OC use, but there were nonsignificant increases noted in some cardiovascular diseases which appeared to be explained by a synergism between current use and heavy smoking. Age also has a strong influence on risk for cardiovascular disease. The results of earlier studies seem to indicate that OC use is associated with a risk of subarachnoid hemorrhage. The Walnut Creek Study also noted an increased risk of subarachnoid hemorrhage associated with OC use and found that risk increased with use. Several studies have shown that the incidence of venous thrombosis seems dependent on the dosage of the OC used. An overwhelming majority of studies on the carcinogenicity of OCs have found no increased incidence of cancer of the ovaries, uterus, or breast among users. In regard to both ovaries and endometrium, there is some evidence that OCs may be protective. Several studies have concluded that OC users have a slightly increased risk of developing malignant melanoma. The results of the Oxford/Family Planning Study show that although previous use of OC by nulliparous women may delay future childbearing by several months, it does not impair longterm potential for pregnancy. No increase in risk of clinically apparent diabetes mellitus has been reported in users. In addition to their possible protection against ovarian and endometrial cancer, OCs may reduce the risk of at least 5 other diseases: benign breast disease; deficiency anemia; arthritis, pelvic inflammatory disease; and ovarian cysts.
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PMID:The pill: an evaluation of recent studies. 704 36

A total of 3,868 urban policemen in Rome were investigated through a historical cohort study with emphasis on mortality from cardiovascular disease and cancer. Overall mortality from cardiovascular disease, respiratory conditions, digestive and genitourinary diseases, and accidents was lower than expected. An excess risk of ischemic heart disease was observed among subjects aged less than 50 years [14 deaths, standardized mortality ratio (SMR = 1.63), 95% CI = 0.89-2.73], corresponding to workers with a short duration of employment and a short latency since first employment. Overall cancer mortality was as expected and no excess was found for lung cancer (82 deaths, SMR = 1.05). Increased mortality was observed from colon cancer (16 deaths, SMR = 1.47), melanoma (four deaths, SMR = 2.34), bladder cancer (13 deaths, SMR = 1.27), renal cancer (seven deaths, SMR = 1.39), and non-Hodgkin's lymphoma (six deaths, SMR = 1.51), although none of the excesses were statistically significant. Two deaths from male breast cancer (SMR = 14.36) and three from cancer of endocrine glands were found (SMR = 3.44). Nested case-control studies were conducted to evaluate cancer mortality risk by job category. Bladder cancer was significantly increased among car drivers (OR = 4.17); for kidney cancer, an increased odds ratio (OR = 2.27) was found among motorcyclists; non-Hodgkin's lymphoma clustered among motorcyclists (OR = 5.14). In summary, excess risk for specific cancer sites (colon, male breast, and endocrine glands) might be linked to occupational exposures; professional drivers seem to be at higher risk of bladder cancer, kidney cancer, and non-Hodgkin's lymphoma.
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PMID:Mortality among urban policemen in Rome. 789 29

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

The changes in systemic circulation during hyperthermic isolated lower limb perfusion with carboplatin and interferon-beta were investigated in 19 patients with malignant melanoma. The cardiac output (CO) increased significantly (p < 0.01) from 3.81 +/- 0.22 L/min before the procedure to 5.30 +/- 0.49 L/min 1 h after hyperthermic perfusion. The double product (mean arterial pressure x heart rate) also increased significantly (p < 0.01) from 5,145 +/- 372 mm Hg/min to 6,760 +/- 486 mm Hg/min. In some patients, it increased to more than twice the control value. These changes were accompanied by an increase in body temperature, presumably caused by the systemic leakage of both warmed blood and interferon-beta. Blood chemistry data demonstrated no significant changes in the liver or renal function. However, the serum CPK level increased markedly on the first postoperative day, and persisted for 1 week, thus suggesting that some muscle damage occurred during the procedure. There was no operative death or severe complications. From these data, we concluded that hyperthermic isolated limb perfusion with interferon-beta is a relatively safe therapeutic method for malignant melanoma of the extremities. However, care should be taken in patients with ischemic heart disease who may suffer a heart attack due to the rapid increase in cardiac work during the procedure.
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PMID:Systemic effects of hyperthermic isolated lower limb perfusion with carboplatin and interferon-beta. 1116 57

Recent studies have demonstrated new benefits of pill use, reduced risks associated with the minipill, and the possibility of screening out high risk women. The minipill is as effective as other formulations except in cases of chronic malnutrition or concomitant use of antibiotics or anticonvulsives. Oral contraceptives (OCs) frequently lessen menstrual problems. They prevent functional cysts in the ovaries, and reduce the incidence of benign breast tumors and the relative risk of developing ovarian cancer after 3 years of use. Combined OCs reduce the risk of endometrial cancer although sequentials increase it. OCs offer protection against salpingitis and other pelvic infections, against tubal pregnancies, and against chronic rheumatoid arthritis. Minipills appear to be less frequently associated with bothersome side effects than other OCs. The most significant risk of OCs is of death due to thrombo emboli of venous origin, myocardial ischemia, cerebrovascular accidents, and hypertension in women over 35, particularly those who smoke heavily. In 1981 the 2 British studies reported a reduced risk from these causes compared to results published in 1977. Estrogens are clearly responsible for some of the complications, apparently due to a weakening of the fibrinolytic systems, but progestagens or estrogen-progestagen combinations are also implicated. Arterial hypertension and cerebral and cardiac accidents appear to be due to the effect of progestagens on arterial tension, glucose metabolism, and the level of high density lipoprotein cholesterol. Risks of some liver diseases are elevated in pill users, but the question of tumors of the pituitary is not yet resolved. The incidence of uterine cancer appears to be elevated in pill users although the association is obscured by other factors. Some evidence exists of an association between estrogen-progestagen formulations and melanoma. No increase in abortion or fetal malformations except possibly an increase in twin pregnancies is noted after discontinuation of the pill. Pills should not be prescribed for smokers over 35 or any women over 45. Pills are possibly acceptable for women 35-44 in good health with no signs of diabetes, hypertension, or hyperlipoproteinemia. They should be followed up more frequently and should recognize the signs of complications.
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PMID:[Oral contraception in 1983 (author's transl)]. 1231 9


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