Suppression of crosstalk in multielectrode arrays with local shielding.

Electrical crosstalk can constrain the performance of multielectrode arrays in electro- and neurophysiology, in terms of both stimulation and recording. This is especially so at high electrode density, desirable for spatiotemporal mapping of bioelectrical signals from multiple cells. Channel interference due to crosstalk is currently only partially addressed, via continuous interleaved sampling or post-data acquisition spike sorting. Here, we show that a locally-shielded electrode architecture significantly suppresses crosstalk, and enables multi-site recording at high electrode density without the need for spike sorting. Arrays of shielded electrodes, prepared by micro- and nanofabrication techniques in a vertically-oriented coaxial geometry, demonstrate at least a 400 times improvement in spatial density over the unshielded case.

Deep-ocean basalts: inert gas content and uncertainties in age dating.

The radiogenic argon and helium contents of three basalts erupted into the deep ocean from an active volcano (Kilauea) have been measured. Ages calculated from these measurements increase with sample depth up to 22 million years for lavas deduced to be recent. Caution is urged in applying dates from deep-ocean basalts in studies on ocean-floor spreading.

Helium/Carbon dioxide ratios as premonitors of volcanic activity.

The composition of the gaseous emissions of two fumaroles at the summit of Kilauea Volcano was monitored for môre than 2 years. Magma was released from the summit reservoir on three occasions during this period; prior to or during each event the ratios of helium to carbon dioxide in the fumarole gases decreased substantially from that observed during periods of quiescence.

Helium Flux from the Earth's Mantle as Estimated from Hawaiian Fumarolic Degassing.

Averaged helium to carbon dioxide ratios measured from systematic collections of gases from Sulphur Bank fumarole. Kilauea, Hawaii, when coupled with estimates of carbon in the earth's crust, give a helium flux of 1 x 105 atoms per square centimeter per second. This is within the lower range of other estimates, and may represent the flux from deep-seated sources in the upper mantle.

An extended core nanocoax pillar architecture for enhanced molecular detection.

Biosensors that incorporate nanomaterials and nanofabrication techniques enable molecular detection of chemical and biological macromolecules with a high degree of specificity and ultrasensitivity. Here, we present a novel fabrication process that yields a nanostructure capable of detecting biological macromolecules. The extended core nanocoax (ECC) structure builds on a previously reported nanocoaxial-based sensor. The fabrication of the device incorporates an extended inner pillar, with controllable extension above the annulus and into the surrounding solution. This new design eliminates structural constraints inherent in the original nanocoax architecture. We also provide results demonstrating improvement in biosensing capability. Specifically, we show the capability of the new architecture to detect the B subunit of the Vibrio cholerae toxin at improved sensitivity (100 pg/ml) in comparison to optical enzyme-linked immunosorbant assay (1 ng/ml) and previously reported coaxial nanostructures (2 ng/ml).

Uterine myometrium as a cell patch as an alternative graft for transplantation to infarcted cardiac myocardium: a preliminary study.

PURPOSE: Currently, only a small fraction of patients are able to receive reperfusion therapy for myocardial infarctions. We hypothesize that myometrial cell patch transplantation could be an alternative approach for the treatment of myocardial infarction. DESIGN: We performed a preliminary study to determine the feasibility of this novel therapeutic approach in a rabbit model. PROCEDURES: Six adult female New Zealand rabbits were used. Myocardial infarction was induced by left anterior descending artery ligation. A segment of uterus was removed via a laparotomy incision, and this uterine segment was transplanted as an autologous graft over the infarcted myocardium, which was then reinforced by greater omentum. Statistical methods and outcome measures: Hemodynamic measurements and histological studies. MAIN FINDINGS: All uterine myometrial patches survived in the test animals. Fluoroscopic hemodynamic measurements were made for ejection fractions at 8 weeks after the application of the uterine patch. Histological study demonstrated well-healed myometrial-myocardium junctions with minimum scar tissue. Angiogenesis occurred in the transplanted myometrium. Connexin 43 expression was demonstrated in the transplanted patches. CONCLUSION: Our noncontrolled preliminary rabbit experiments indicate that patches of uterine myometrium reinforced by greater omentum can be used as autologous transplant therapy for infracted myocardium. This is an innovative technique that could lead to future treatment for individuals who may suffer from an infarcted myocardium and may not be eligible for traditional reperfusion therapy.

Evaluation of two-dimensional ultrasonography and computed tomography in the mapping and measuring of canine urinary bladder tumors.

Determining the dimensions of transitional cell carcinomas (TCCs) of the urinary bladder in dogs is important in assessing tumor progression and the response to treatment. The primary aim of this study was to evaluate the reliability of a standardized two-dimensional (2-D) ultrasound (US) protocol performed by a single experienced operator. Secondary aims were to compare World Health Organization (WHO) and Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, and to compare measurements by two operators following these guidelines. These were evaluated by inter-operator and intra-operator reliability using the concordance correlation coefficient (CCC) and Cohen's κ statistics, which demonstrated substantial to better agreement by an experienced operator using either set of guidelines. It was demonstrated that 2-D US provides a reliable means to determine the dimensions of urinary bladder TCC when an experienced operator used a standardized protocol. In a subset of dogs, urinary bladder distension was varied, which resulted in differences in measurement with 2-D US and computed tomography.

Effects of dietary butter enrichment on the fatty acid distribution of phospholipid fractions isolated from rat platelets and aortae.

Rats were maintained for 2 weeks on a low-fat basal diet (5% energy) and a diet from which 50% of the energy was derived from butter. Lipids were extracted from aortae and platelets and the fatty acid profiles of individual phospholipids were examined. Similar responses to dietary butter enrichment occurred in PI, PS, PE and PC fractions from either tissue: 20:4(n - 6) and all other n - 6 series longer-chain polyunsaturated fatty acids except 20:3(n - 6) decreased in percentage; all n - 3 series polyunsaturated fatty acids increased, including 20:5(n - 3) and 22:6(n - 3); n - 9 series polyunsaturated fatty acids, derived from 18:1(n - 9), increased. Despite the considerable redistribution of polyunsaturated fatty acids, the percentages of total polyunsaturated fatty acids in each phospholipid were, in every case, independent of diet. None of the changes were localized in a particular phospholipid fraction. Quantitation of fatty acids using heptadecanoic acid as an internal standard revealed that the concentrations of 20:4(n - 6) in platelet and aortic PE and PC was higher than in PI fractions. Therefore, in terms of substrate amount, it appears that PC and PE as well as PI have the potential to provide endogenous 20:4(n - 6) for oxygenation to the prostanoids thromboxane A2 and prostacyclin I2.

Results of a multicenter randomized clinical trial of exercise and long-term survival in myocardial infarction patients: the National Exercise and Heart Disease Project (NEHDP).

BACKGROUND: This study examined whether a supervised exercise program improved 19-year survival in 30- to 64-year-old male myocardial infarction patients. METHODS AND RESULTS: The men (n=651) were participants in the National Exercise and Heart Disease Project, a 3-year multicenter randomized clinical trial conducted in the United States (1976-1979). The treatment group (n=315) exercised for 8 weeks in a laboratory. Thereafter, they jogged, cycled, or swam in a gymnasium/pool setting guided by an individualized target heart rate. Participants in the control group (n=319) were to maintain normal routines but not participate in any regular exercise program. Participants were followed up until their death or December 31, 1995. Cox proportional hazards analysis revealed the all-cause mortality risk estimates (95% CIs) in the exercise group compared with controls to be 0.69 (0.39 to 1.25) after an average follow-up of 3 years, 0.84 (0.55 to 1.28) after 5 years, 0.95 (0.71 to 1.29) after 10 years, 1.02 (0.79 to 1.32) after 15 years, and 1.09 (0.87 to 1. 36) after 19 years. Cardiovascular disease (CVD) mortality risk estimates (95% CI) for the same follow-up periods were 0.73 (0.37 to 1.43), 0.98 (0.60 to 1.61), 1.21 (0.79 to 1.60), 1.14 (0.84 to 1.54), and 1.16 (0.88 to 1.52). However, each 1-MET increase in work capacity from baseline to the end of the original trial resulted in consistent reductions in all-cause and CVD mortality risk at each follow-up period, regardless of initial work-capacity level. CONCLUSIONS: These findings indicate exercise-program participation resulted in nonsignificantly reduced mortality risks early in the follow-up period. Benefits diminished as time since participation increased, which suggests that the protective mechanisms associated with the program may be short term. Contamination between groups over time could also explain the diminished effects, because increased work capacity provided survival benefits up to 19 years.

Effect of long-term moderate physical exercise on plasma lipoproteins. The National Exercise and Heart Disease Project.

As part of the National Exercise and Heart Disease Project, 223 postcoronary men, aged 30 to 64, were randomly assigned to moderate exercise or control groups. Levels of total plasma cholesterol, high- and low-density lipoprotein (HDL and LDL) cholesterol, and triglycerides were measured. At baseline, alcohol intake, weight, and skin-fold thickness but not treadmill work capacity correlated with triglyceride or HDL cholesterol levels. After one year, no clinically important change in lipid levels was observed in either group. Using multiple regression analysis of the combined groups, changes in several independent variables, including work capacity change, were not predictive of changes in lipid levels. Thus, changes in levels of fitness and/or regular exercise did not substantially influence HDL cholesterol or other lipid levels.

Cefamandole kinetics in uremic patients undergoing hemodialysis.

A single intravenous 15 mg/kg dose of cefamandole was given to 6 patients in chronic renal failure before hemodialysis, and 3 were examined during an interdialysis period. Mean cefamandole clearance by hemodialysis was 24 +/- 12 ml/min; 35 +/- 15% of the dose was recovered in the dialysate. The cefamandole half-life (1 1/2) on dialysis was 4.0 +/- 0.29 hr; off dialysis it was 13.9 +/- 4.2 hr. High urine concentrations of cefamandole in these patients suggests usefulness in urinary tract infection.

Role of physical activity as a secondary intervention for healed myocardial infarction.

Five exercise clinical trials were conducted to determine the effectiveness of physical activity on selected outcomes, especially mortality and morbidity rates, in patients recovered from myocardial infarction. Although the design of every trial differed, each evaluated the effects of medically prescribed and supervised regular physical activity. In 3 studies there were substantially lower mortality rates in the exercise patients compared with control patients, but statistically significant differences occurred in only 1 of the 3 trials. No differences between treated and control patients were observed in another trial. In the fifth trial, a slight excess mortality rate was reported for the treatment group. However, both groups in this trial were assigned to an exercise regimen in which only the frequency of attendance and intensity of regimen differed. Although regular physical activity tended to reduce mortality rates in the first 3 trials, it is apparent that it did not affect recurrence rates of nonfatal myocardial infarction. In fact, this condition generally occurred more frequently in treated than in control patients. It is clear that more clinical investigations are required before a definitive statement confirming the effectiveness of regular physical activity as a secondary intervention for myocardial infarction can be made.

Prognostic value of peak exercise systolic blood pressure on long-term survival after myocardial infarction.

This study examined the association between peak exercise systolic blood pressure and other exercise test parameters and the long-term (19-year) survival of 625 patients with myocardial infarction who were original participants of the National Exercise and Heart Disease Project, a 3-year (1976 to 1979) multicenter randomized exercise clinical trial. Results show that low peak exercise systolic blood pressure (< or =140 mm Hg) was associated with increased mortality throughout the 19 years of follow-up, and men with this finding obtained no survival benefit from participating in an exercise program.

Maximal exercise systolic pressure, exercise training, and mortality in myocardial infarction patients.

The relation of maximal exercise systolic pressure to physical conditioning and to mortality was determined in 641 men with > or =1 myocardial infarctions. Each performed a standardized multistage exercise test before randomized assignment either to an exercise group or a control group and at scheduled periodic intervals over 3 years. This study compares 123 men with maximal exercise systolic pressures (MESP) of < or =140 mm Hg with 518 men whose maximal exercise systolic pressure was > or =140 mm Hg. At baseline, the 2 groups were comparable for age, entry time since the occurrence of the qualifying cardiac event, and reported use of antihypertensive medications. Men with low MESP used more beta blockers, had lower systolic pressure measurements at rest and by definition at maximal exercise, and lower work capacity than men with higher levels of MESP. Men with low MESP experienced: (1) no reduction in mortality with exercise conditioning (p<0.86), and (2) a significantly higher mortality rate over 3 years (p<0.003) compared with men with higher levels of MESP. The relation of a low MESP to mortality persisted: (1) whether MESP or work capacity increased from the baseline exercise test to the last performed exercise test, and (2) whether it was measured at low (<6 METs) or high (> or =6 METs) levels of work capacity. We conclude that low maximal exercise systolic blood pressure is a predictor of mortality and is associated with an ineffective training response in men with myocardial infarction.

Work and leisure time physical activity and mortality in men and women from a general population sample.

PURPOSE: The purpose of this study was to examine the long-term relationships between total physical activity and mortality from all causes and coronary heart disease (CHD) in the general population. METHODS: A prospective design was used, following participants for 29 years, beginning in 1960. The study population consisted of a randomly selected sample of white male (n = 698) and female (n = 763) residents of Buffalo, New York with a 79.0% participation rate and follow-up rates of 96.0% and 90.2% in males and females, respectively. At baseline, comprehensive information was obtained regarding participants' usual physical activity at work and during leisure time. RESULTS: As of December 31, 1989, three hundred and two (43.3%) men and 276 (41.0%) women died, 109 (15.6%) and 81 (10.6%) from CHD, respectively. In men, a significant interaction was found between activity and body mass index (BMI) for both outcomes. In women, a significant activity by age interaction was observed. In non-obese men (BMI<27.02), activity was inversely associated with all-cause [relative risk (RR) = 0.59; 95% confidence interval (CI), 0.39-0.89] and CHD mortality (RR = 0.39; 95% CI, 0.18-0.83), independent from the effects of age and education. No such associations were found in obese men and increased risks could not be ruled out. Among women, younger participants (age <60 years) had a significantly reduced risk of CHD death with increased activity (RR = 0.26; 95% CI, 0.07-0.99). No other significant associations were observed. CONCLUSIONS: Physical activity favorably influences mortality risks in non-obese men and younger women. Gender-specific factors should be considered for potential effect modification.

Effect of exercise on left ventricular ejection time in patients with prolapsing mitral leaflet syndrome.

The effect of exercise on left ventricular ejection time was determined in 12 subjects with prolapsing mitral valve leaflet syndrome (PML). A single lead ECG (CM5), phonocardiogram and carotid pulse contour were recorded simultaneously with the subjects at supine rest before and immediately after multistage treadmill exercise. Systolic time intervals were measured from five consecutive complexes to determine the pre-ejection period (PEP), left ventricular ejection time (LVET) and total electromechanical systole (QS2). LVET was corrected for heart rate and defines as LVETc. In nine subjects, an increase of 1 to 49 msec was observed in the LVETc following exercise. A shorter resting LVETc and greater afterload at peak exercise was related to an increase in LVETc of 10 msec or more. Exercise elicited or evoked evidence of left ventricular dysfunction. The results support the concept that impaired left ventricular performance is a concomitant of this syndrome.

Isosorbide dinitrate and cardiovascular adaptation to exercise.

Sixteen men with well-documented angina pectoris and without previous myocardial infarction performed a multistage exercise stress test to determine their levels of exercise-induced limitations, characterized by onset of chest discomfort or electrocardiographic ischemic changes, or both. Following a control study, each subject was assigned randomly to either a placebo- or vasodilator-treated group, received chewable medication, and was retested 30 minutes after chewing the medication. Blood pressure, heart rate, and electrocardiographic changes were measured during rest, peak exercise, and recovery. A phonocardiogram, carotid-pulse contour, and single-lead electrocardiogram were recorded simultaneously at supine rest before and immediately after exercise, and systolic time intervals were measured. Results indicated that chewable isosorbide dinitrate reduced systolic blood pressure and the triple product (systolic blood pressure X heart rate X ejection time) significantly during rest and reduced the left ventricular ejection time corrected for heart rate both at rest and peak exercise; no significant differences were observed in the placebo group. The ability to achieve an increased workload was observed in both groups, and the threshold for ischemic manifestations occurred at comparable triple-product levels in both during pretreatment and posttreatment studies.

Acute massive chloral hydrate intoxication treated with hemodialysis: a clinical pharmacokinetic analysis.

A 38-year-old female became comatose and exhibited signs of cardiac toxicity 2 hours after ingestion of approximately 38 Gm chloral hydrate. Hemodialysis was initiated 21 hours after ingestion, using twin coils in series, and was continued for 4.5 hours. Trichloroethanol, the active metabolite of chloral hydrate, was measured in plasma and dialysate. Two hours after ingestion, the plasma level was 330 micrograms/ml (average therapeutic level is 12 micrograms/ml or less). The predialysis level was 216 micrograms/ml and after dialysis declined to 141 micrograms/ml. The pre- and post-plasma half-life values were 35 hours, while on dialysis the half-life was only 6 hours. The average dialysis clearance was 120 ml/minute, and the amount of chloral hydrate removed by dialysis was 5.79 Gm. By the end of dialysis, the patient could respond to verbal commands and was ambulatory 36 hours later. In conclusion, hemodialysis can be a clinically important method of treating chloral hydrate overdose.

Arachidonic acid and linoleic acid supplementation increase prostanoid production in rats fed a butter-enriched diet.

Male Sprague Dawley rats were fed a butter-enriched diet (50% fat) for 2 weeks and then supplemented orally with either 90 mg of ethyl arachidonate or ethyl linoleate daily for 2 weeks. For comparative reasons, one group of animals was fed standard laboratory rat chow for 4 weeks. Aortic prostacyclin (PGI2) production, platelet aggregation and thromboxane A2 (TXA2) production and plasma and aortic phospholipid (PL) fatty acids were measured. When compared to butter-fed rats, aortic PGI2 production, collagen-induced platelet aggregation and TXA2 production were significantly increased in rats supplemented with ethyl arachidonate to levels similar to those seen in chow-fed rats. Ethyl linoleate supplementation also tended to increase aortic PGI2 production, collagen-induced platelet aggregation and TXA2, but not to the same extent. These changes were accompanied by increases in the level of arachidonic acid and linoleic acid in aortic and plasma PL and a decrease in the level of eicosapentaenoic acid (EPA) and docsahexaenoic acid (DHA). These data indicate that supplementation with small doses of preformed arachidonic acid was more effective than supplementation with its precursor, linoleic acid, in reversing the effects on prostanoid production and phospholipid fatty acid composition in rats fed diets enriched with butter.

Arachidonic acid supplementation dose-dependently reverses the effects of a butter-enriched diet in rats.

Male Sprague Dawley rats were fed a butter-enriched diet (50% fat) for 2 weeks which was supplemented orally with 9, 18, 36, or 72 mg/day of ethyl arachidonate for a further 2 weeks. The control group of animals were fed a 5% fat diet for 4 weeks. Aortic prostacyclin (PGI2) production, platelet aggregation and thromboxane A2 (TXA2) production and plasma and aortic phospholipid (PL) fatty acids were measured. 50% butter-feeding resulted in a significant reduction in aortic PGI2 production and collagen-induced platelet aggregation and TXA2 production. These changes were accompanied by a reduction in plasma and aortic PL arachidonic acid levels and an increase in eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), 5,8,11-eicosatrienoic acid (ETA) and dihomo-gamma-linolenic acid (DGLA). These changes in prostanoid production, platelet aggregation and PL fatty acid composition were dose-dependently reversed by the daily oral administration of ethyl arachidonate (9, 18, 36, or 72 mg). The threshold dose being as little as 9 mg of ethyl arachidonate/rat/day for reversal of PL fatty acid composition, collagen-induced platelet aggregation and TXA2 production, and 18 mg of ethyl arachidonate/rat/day for reversal of aortic PGI2 production. Full reversal was seen generally with 36 or 72 mg of ethyl arachidonate/rat/day. The data highlight the responsiveness of tissue eicosanoid production to small quantities (ppm) of dietary eicosanoid precursors.