Traumatic infarction of the right ventricle caused by coronary dissection

A case is reported of a 47 year-old man who suffered from a right ventricular myocardial infarct which occurred as a result of right coronary arterial dissection after non-penetrating anteroposterior chest compression. The patient was admitted with right heart failure and a central venous pressure of 17 cm H2O. The ST segment in leads V1 to V3 (V2: 7mm) was significantly elevated. Echocardiography showed dilatation of both right atrium and ventricle, with a deviated septum. Emergency cardiac angiography confirmed a hypokinetic right ventricle, with no other abnormal finding. Coronary angiography, performed 24 h after admission, revealed a dissection of the second part of the right coronary artery, with a normal left coronary system which reperfused that part of the right coronary arterial territory located beyond the dissection. The ST segment elevation stopped at the 10th hour. Initially, the patient's condition worsened. Thereafter, he slowly improved under treatment (5.5 micrograms.kg-1.min-1 dobutamine, and fluids so as to maintain a pulmonary wedged pressure of about 15 mmHg). As post-traumatic myocardial infarction is rare, the diagnostic and therapeutic strategies are discussed.     

Disease stage variation in CD4+ and CD8+ T-cell reactivity to the receptor tyrosine kinase EphA2 in patients with renal cell carcinoma

We have evaluated CD8+ and CD4+ T-cell responses against a new tumor-associated antigen, the receptor tyrosine kinase EphA2, which is broadly expressed in diverse cancer histologies and is frequently overexpressed in advanced stage/metastatic disease. We report herein that EphA2 is overexpressed in renal cell carcinoma (RCC) cell lines and clinical specimens of RCC, and find that the highest levels of EphA2 are consistently found in the most advanced stages of the disease. We identified and synthesized five putative HLA class I-binding and three class II-binding peptides derived from EphA2 that might serve as targets for immune reactivity. Each peptide induced specific, tumor-reactive CD8+ or CD4+T-cell responses as measured using IFN-gamma enzyme-linked immunospot assays. The EphA2 peptides elicited relatively weak responses from CD8+ T cells derived from normal healthy volunteers or from RCC patients with active disease. In marked contrast, immune reactivity to EphA2-derived epitopes was greatly enhanced in CD8+ T cells that had been isolated from patients who were rendered disease-free, after surgery. Furthermore, enzyme-linked immunospot analyses demonstrated prominent EphA2-restricted T-helper 1-type CD4+ T cell activity in patients with early stage disease, whereas T-helper 2-type and T regulatory-type responses predominated in patients with more advanced forms of RCC. These data suggest that the immune system of cancer patients actively monitors EphA2-derived epitopes, and that the magnitude and character of T-cell responses to EphA2 epitopes may convey much-needed predictive information about disease stage and outcome.     

Review of the epidemiological evidence relating toluene to reproductive outcomes

This review examines the epidemiological evidence for adverse reproductive outcomes from those occupational studies that present toluene-specific findings. Clinical investigations of the reproductive effects of toluene abuse are also examined. Six occupational studies reported associations between toluene and spontaneous abortion, two between toluene and congenital malformation, and three between toluene and reduced fertility. The spontaneous abortion studies provided the most suggestive evidence for an association with toluene. However, the potential for bias in some of these studies, the relatively homogeneous nature of the populations examined (e.g., four of the six studies evaluated similar groups of Finnish workers), and the multiple chemicals to which most workers were simultaneously exposed suggest cautious interpretation of these findings. Also, spontaneous abortion has generally not been observed as a major problem among highly exposed women who abuse toluene during pregnancy. The results of the occupational studies should be considered "hypothesis generating". Truly prospective studies with individually monitored data on toluene exposure and early fetal loss are needed to more definitively investigate this issue.     

Hormesis and health: a little of what you fancy may be good for you

The term hormesis refers to beneficial effects from low doses of potentially harmful substances. Although there are many laboratory examples of this phenomenon, it remains controversial and has never become widely accepted by the health community. This review goes beyond the laboratory and describes many clinical and common sense, real-world examples of hormesis that often go unrecognized. Many vitamins and minerals are essential for life at low doses but toxic at higher ones. Similarly, exercise, caloric restriction, and alcohol consumption are examples of processes that are harmful in the extreme but beneficial in moderation. This review also highlights possible reasons why acceptance of the hormetic paradigm has lagged. These include high-dose toxicologic testing that precludes the demonstration of low-level effects and the threat posed by hormesis to the currently accepted precautionary principle, which assumes that any dose of a chemical is potentially harmful.     

Characterization of the cytolytic activity of CD4+ and CD8+ tumor-infiltrating lymphocytes in human renal cell carcinoma

Previously we showed that IL2 expanded tumor-infiltrating lymphocytes (TILs) from renal cell carcinoma mediated non-major histocompatibility complex-restricted cytotoxicity. Phenotypic analysis showed that cultured TILs were composed mostly of T-lymphocytes with varying numbers of CD4+, CD8+, and CD56+ (Leu19+) populations. Here we compared the cytolytic activity of the two predominant TIL subsets, CD3+CD4+ and CD3+CD8+, to that of the CD56+ populations. Using magnetic beads coated with antibodies to either CD4 or CD8, CD3+CD4+, and CD3+CD8+ TILs were isolated in a highly enriched form (greater than 92%) and could be expanded for over 40 days in vitro with 1000 units/ml IL2. In a 4-h 51Cr release assay the CD4+ and CD8+ TILs showed minimal lytic activity, whereas unseparated cells exhibited significant levels of non-major histocompatibility complex-restricted cytotoxicity. The lytic activity seen in the 4-h assay with unseparated TILs appeared to be related to the presence of CD56+ populations. With one exception none of the purified CD4+ or CD8+ TILs expressed any significant levels of CD56, while the unseparated TILs contained varying numbers of CD3+CD56+ and CD3-CD56+ populations. Cell-sorting experiments verified that the CD56+ populations were responsible for most of the lytic activity in 4 h even though CD3+CD56- cells represented the predominant cell type. Although CD3+CD56- TILs were minimally lytic in 4 h, we show here that both CD3+CD4+ and CD3+CD8+ subsets displayed substantial cytotoxicity in long-term assays. In the 18-h 51Cr release assay 5 of 6 CD4+ and 2 of 3 CD8+ TILs were lytic for the autologous tumor. In two cases, restimulation with the autologous tumor induced augmented cytolytic activity of TIL subsets and in one case induced lytic activity in 4 h. The cytotoxic activity of TIL subsets was further examined using a 72-h assay in which TILs were cocultured with a confluent layer of tumor cells. The degree of cytotoxicity was quantitated by measuring the amount of crystal violet dye that was incorporated by tumor cells which remained after the incubation period. CD4+ and CD8+ TILs typically caused greater than a 50% reduction of tumor cells in 3 days and the level of reduction was increased when IL2 was added to the cultures. All the CD4+ and CD8+ subset preparations were cytotoxic in the 3-day assay even though some were not lytic for certain targets in the 18-h 51Cr release assay.(ABSTRACT TRUNCATED AT 400 WORDS)     

Phase 1 trial of subcutaneous IL-6 in patients with refractory cancer: clinical and biologic effects

The authors evaluated the clinical and biologic effects of human recombinant interleukin-6 (rhIL-6) in patients with refractory cancer. A phase 1 trial using escalating doses of rhIL-6 (1-50 microg x kg(-1) x d(-1), Monday through Friday for 4 weeks) was performed in 30 patients. Toxicity was moderate and the maximum tolerated dose was determined to be 25 microg x kg(-1)x d(-1) based on cardiac and neurocortical toxicity in one patient each and thrombocytosis (platelets > 800,000/microL) in three patients. One patient with non-small-cell lung cancer had a partial response after three cycles of therapy. The biologic effects of rhIL-6 included anemia and dose-related thrombocytosis. Various proinflammatory activities were induced and included dose-related cyclical increases in peripheral blood monocytes and the CD14+/CD45RB+ +/- CD16C+ mononuclear cell populations. These increases were accompanied by increased levels of C-reactive protein, serum neopterin, and type I soluble tumor necrosis factor receptor. In contrast, rhIL-6 did not affect lymphocyte numbers or function (cytotoxicity, cytokine levels, immunoglobulin levels), with the possible exception of IL-2Ralpha mRNA induction in peripheral blood lymphocytes. rhIL-6 has pleiotropic proinflammatory actions in vivo and moderate toxicity when administered as long-term therapy.