Multiparametric Analysis of Heart Rate Variability Used for Risk Stratification Among Survivors of Acute Myocardial Infarction

A multiparametric heart rate variability analysis was performed to prove if combined heart rate variability (HRV) measures of different domains improve the result of risk stratification in patients after myocardial infarction. In this study, standard time domain, frequency domain and non-linear dynamics measures of HRV assessment were applied to 572 survivors of acute myocardial infarction. Three parameter sets each consisting of 4 parameters were applied and compared with the standard measurement of global heart rate variability HRVi. Discriminant analysis technique and t-test were performed to separate the high risk groups from the survivors. The predictive value of this approach was evaluated with receiver operator (ROC) and positive predictive accuracy (PPA) curves. Results - The discriminant analysis shows a separation of patients suffered by all cause mortality in 80% (best single parameter 74%) and sudden arrhythmic death in 86% (73%). All parameters of set I show a high significant difference (p<0.001) between survivors and non-survivors based on two-tailed t-test. The specificity level of the multivariate parameter sets is at the 70% sensitivity level (ROC) about 85–90%, whereas HRVi shows maximum levels of 70%. The PPA in the all cause mortality group is at the 70% sensitivity level twice as high as the univarihate HRV measure and increases to more than fourfold as high within the VT/VF group. In conclusion, in this population, the multiparametric approach with the combination of four parameters from all domains especially from NLD seems to be a better predictor of high arrhythmia risk than the standard measurement of global heart rate variability.     

The future of smoking cessation therapy in the United States

Six trends that are likely to influence the future content, format, delivery and reach of smoking cessation therapy in the United States are discussed: (1) changing characteristics of smokers (e.g. more likely to be poor, have psychiatric co-morbidity and be more nicotine dependent), (2) health care reform demands for cost-effectiveness, (3) development of guidelines/algorithms that recommend stepped-care approaches, (4) continued emphasis on smoking as a form of drug dependence requiring intensive pharmacological and behavior therapy for some smokers, (5) interest in harm-reduction strategies for smokers unable or unwilling to qua (and 6) smoking cessation therapies become reimbursable on par with other drug dependencies.     

Alternans of the ST Segment and T Wave. A Sign of Electrical Instability in Prinzmetal''s Angina

In an effort to determine the incidence of ventricular arrhythmias associated with ST segments alternans, the patterns of ST segment and T-wave electrical alternans (STEA) were analyzed in 93 patients during spontaneous Prinzmetal's angina. Twenty-eight of 93 patients, or 30% (Group I), showed STEA during episodes of ST segment elevation. SIxty-five of 93 patients, or 70% (Group II), showed no alternans during episodes of ST segment elevation. In Group I, ventricular arrhythmias, defined as all ventricular ectopic activity greater than 5 beats per minute and complex Lown grades III to V, occurred during 52 of 55 episodes, or 95%; whereas in Group II, ventricular arrhythmias occurred in only 51 of 125 episodes, or 41% (p less than 0.01). The difference in the incidence of ventricular fibrillation (VF) or ventricular tachycardia (VT) in the two groups was more striking. VT or VF occurred in 20 of 55 in Group I (36%) versus 5 of 125 in Group II (4%). Although there were no significant differences in age or sex between Group I and II patients, there was a significant difference in the magnitude of the maximum ST segment elevation (5 mm in Group I versus 3 mm in Group II, p less than 0.01). This study demonstrates that the occurrence of STEA and T wave alternans frequently heralds the onset of ventricular arrhythmias in Prinzmetal's angina. Both the arrhythmias and the alternans occur during the time of maximal ST segment elevation.     

Information processing and coping style during the wake/sleep transition

Information processing of meaningful events (subject's own name, neutral name and tones) was studied during the transition from wakefulness to sleep in two groups of subjects with opposing information processing styles, Monitors and Blunters. In two experimental sets, subjects were instructed to execute a fingerlift response to a predetermined stimulus type. Subject's own name produced the greatest number of K-complexes and arousals relative to other name and tones. A task relevance effect was found for arousals but not for K-complexes. The overall P3 amplitude was larger for Monitors than for Blunters, whereas Blunters showed a larger N350 to target stimuli than Monitors. The findings suggest that higher level processing continues during light sleep and that N350 may reflect a process related to sleep maintenance.     

Research at the Auction Block

The “fair benefits” approach to international research is designed to produce results that all can agree are fair without taking a stand on divisive questions of justice. But its appealing veneer of collaboration masks ambiguities at both a conceptual and an operational level. An attempt to put it into practice would look a lot like an auction, leaving little reason to think the outcomes will satisfy even minimal conditions of fairness.     

A FEASIBILITY STUDY OF GENE GUN MEDIATED IMMUNOTHERAPY FOR RENAL CELL CARCINOMA

PURPOSE: Gene modified autologous tumor cell vaccines have demonstrated a protective and therapeutic effect in murine tumor model systems. The majority of trials to date have used viral methods of gene transfer for vaccine construction. An alternative approach to transfer genes into tumor cells is to use the gene gun, which is a physical method of gene transfection that produces high levels of gene expression without viral agents. We establish the feasibility of generating cytokine secreting autologous renal tumor cell vaccines for use in gene therapy for metastatic renal cell carcinoma. MATERIALS AND METHODS: We obtained 1 cm3 tumor tissue from 12 patients undergoing resection of primary or metastatic renal cell carcinoma. The tumor was disaggregated and placed in culture. The phenotype of the primary renal cell lines was established by microscopy and immunohistochemistry. The 1x10(7) lethally irradiated tumor cells were transfected with plasmid deoxyribonucleic acid containing the human (h) granulocyte-macrophage colony-stimulating factor (GM-CSF) gene under control of a cytomegalovirus promoter using the gene gun. The hGM-CSF production was assayed by enzyme-linked immunosorbent assay in the cell culture media 24 hours after transfection. RESULTS: Of 12 tumor samples 8 grew rapidly to produce a mean of 1.8x10(8) cells after 4 to 5 passages in culture, which was sufficient to produce between 24 and 32 vaccines. Immunocytochemistry confirmed that all cultures were almost exclusively renal tumor cells. Gene gun mediated transfection of lethally irradiated tumor cells resulted in high levels of hGM-CSF production (mean 330 ng./10(6) cells per 24 hours). CONCLUSIONS: We have demonstrated the feasibility of producing cytokine secreting tumor cell vaccines from primary and metastatic human renal tumors, and plan to use this approach in phase I clinical trials of gene therapy for metastatic renal cell carcinoma.     

Haem in the gut. I. Fate of haemoproteins and the absorption of haem

Haem (FeII-protoporphyrin-IX) is presented to the gut lumen as haemoproteins derived from exogenous dietary) and endogenous (mucosal cell desquamation and bleeding) sources. Haemoproteins such as haemoglobin, myoglobin and catalase undergo hydrolysis by luminal proteases to release the haem. Released haem is maintained in a soluble form in the gut lumen by the products of haemoprotein digestion. Chelators of elemental iron do not bind haem-iron and so haem-iron is better absorbed than elemental iron. Haem-iron does not exchange with luminal elemental iron. Mucosal uptake of haem is limited. Less than 10% binds to the brush border of the villus cell. Although the mechanisms by which haem binds to the brush border and is transported to the intracellular environment are poorly understood, it is known that some haem is transferred to secondary lysosomes where the porphyrin ring is split to release iron and form bilirubin. Depending upon the composition of the diet, the iron released from haem within the villus cell can be the major physiological source of iron. In iron-deficiency in humans, absorption of haem-iron can increase threefold whereas absorption of elemental-iron can increase tenfold. These observations indicate that haem-iron and elemental-iron are absorbed via different mechanisms which are subject to different regulation. For haem-iron to be absorbed, the haem itself must be taken up by the mucosa.