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In image-guided surgery, imaging systems such as (stereo-)endoscopes allow intra-operative 3D reconstructions in form of point clouds. However, endoscopes provide only a narrow field of view, resulting in a confined point cloud. In this paper, we present an analysis and registration pipeline for confined point clouds acquired by stereo endoscopes into a fused representation. For a coarse registration, TEASER is applied, while a refinement is conducted utilizing point-to-plane ICP. The pipeline is tested on two datasets: acquired point clouds of a head phantom using a EinsteinVision® 3.0 endoscope and point clouds from the Stereo Correspondence And Reconstruction of Endoscopic Data challenge. The results for both datasets show that 3D reconstructions of anatomical structures by utilizing stereo-endoscopes and point cloud registration is a promising contactless and radiation-free method. However, non-rigid deformations are not yet incorporated and evaluation of the method compared to reference data is challenging.

We present a stereo-multispectral microscope equipped with an additional illumination unit allowing further narrow-band illumination in the spectral range of 400n.m up to 800nm. The combination of the normal microscope illumination with the multispectral light unit allows different illumination modalities to be realized, which enables intraoperative spectral tissue analysis with direct visualization. Two illumination methods were tested in two cholesteatoma surgeries. In addition, two cholesteatom samples were illuminated and analyzed ex vivo. Cholesteatoma showed :fluorescent characteristics in our ex vivo analysis. This behavior could be used intraoperatively using a combination of white light and strong near-UV to blue illumination to highlight cholesteatoma tissue in the microscopic image. Thus, the visual differentiability of different tissue types can be improved and the clinical decision-making process can be accelerated.

Existing challenges in surgical education (See one, do one, teach one) as well as the Covid-19 pandemic make it necessary to develop new ways for surgical training. This is also crucial for the dissemination of new technological developments. As today’s live transmissions of surgeries to remote locations always come with high information loss, e.g. stereoscopic depth perception, and limited communication channels. This work describes the implementation of a scalable remote solution for surgical training, called TeleSTAR (Telepresence for Surgical Assistance and Training using Augmented Reality), using immersive, interactive and augmented reality elements with a bi-lateral audio pipeline to foster direct communication. The system uses a full digital surgical microscope with a modular software-based AR interface, which consists of an interactive annotation mode to mark anatomical landmarks using an integrated touch panel as well as an intraoperative image-based stereo-spectral algorithm unit to measure anatomical details and highlight tissue characteristics.We broadcasted three cochlea implant surgeries in the context of otorhinolaryngology. The intervention scaled to five different remote locations in Germany and the Netherlands with lowlatency. In total, more than 150 persons could be reached and included an evaluation of a participant’s questionnaire indicating that annotated AR-based 3D live transmissions add an extra level of surgical transparency and improve the learning outcome.

Tracking of surgical instruments is an essential step towards the modernization of the surgical workflow by a comprehensive surgical landscape guidance system (COMPASS). Real-time tracking of a laparoscopic camera used in minimally-invasive surgery is required for applications in surgical workflow documentation, machine learning, image-localization, and intra-operative visualization. In our approach, an inertial measurement unit (IMU) assists the tool tracking in situations when no line-of-sight is available for infrared (IR) based tracking of the laparoscopic camera. The novelty of this approach lies in the localization method adjusted for the laparoscopic visceral surgery, particularly when the line-of-sight is lost. It is based on IMU tracking and the positioning of the trocar entry point. The trocar entry point is the remote center of motion (RCM), reducing degrees of freedom. We developed a method to tackle localization and a real-time tool for position and orientation estimation. The main error sources are given and evaluated in a test scenario. It reveals that for small changes in penetration length (e.g., pivoting), the IMU’s accuracy determines the error.

We present a stereo-multispectral endoscopic prototype using a filter-wheel to guide the removal of cholesteatoma tissue in the middle ear. An image-based method is used that combines multispectral tissue classification for the detection of tissue to be removed and 3Dreconstruction to determine its metric dimensions. The multispectral illumination used for tissue classification ranges from λ = 400 nm to λ = 500 nm with step-size of 20 nm, which results in six different narrow-band illumination modes. For classical RGB imaging and metric calculations, a broadband illumination mode is applied before and after the narrow-band illumination. The spectral information is augmented into the broadband mode using an overlay technique. The combination of multispectral imaging with stereoscopic 3D-reconstruction results in new valuable visualization of intraoperative data. This allows to generate a 3D-model of the patients anatomy highlighting the identified malicious tissue and compare the anatomical dimensions with pre-operative CT data.

The authors invoke a population health perspective to assess the distribution of environmental hazards according to race/ethnicity, social class, age, gender, and sexuality and the implications of these hazards for health. The unequal burden of environmental hazards borne by African American, Native American, Latino, and Asian American/Pacific Islander communities and their relationship to well-documented racial/ethnic disparities in health have not been critically examined across all population groups, regions of the United States, and ages. The determinants of existing environmental inequities also require critical research attention. To ensure inclusiveness and fill important gaps, scientific evidence is needed on the health effects of the built environment as well as the natural environment, cities and suburbs as well as rural areas, and indoor as well as outdoor pollutants. [ABSTRACT FROM AUTHOR]

Introduction: Inpatient telemetry monitoring is a commonly used technology designed to detect and monitor life-threatening arrhythmias. However, residents are rarely educated in the proper use and interpretation of telemetry monitoring., Methods: We developed a training module containing an educational video, PowerPoint presentation, and hands-on interactive learning session with a telemetry expert. The module highlights proper use of telemetry monitoring, recognition of telemetry artifact, and interrogation of telemetry to identify clinically significant arrhythmias. Learners completed pre- and postcurriculum knowledge-based assessments and a postcurriculum survey on their experience with the module. In total, the educational curriculum had three 60-minute sessions., Results: Thirty-two residents participated in the training module. Residents scored higher on the posttest (77% ± 12%) than on the pretest (70% ± 12%), t (31) = -4.3, p < .001. Wilcoxon signed rank tests indicated PGY-3s performed better on the posttest ( Mdn = 0.86) than on the pretest ( Mdn = 0.72), z = -2.19, p = .031. PGY-2s also performed better on the posttest ( Mdn = 0.86) than on the pretest ( Mdn = 0.76), z = -2.04, p = .042. There was no difference between pretest ( Mdn = 0.66) and posttest ( Mdn = 0.71) scores for PGY-1s, z = -1.50, p = .142. The majority of residents reported that the telemetry curriculum boosted their self-confidence, helped prepare them to analyze telemetry on their patients, and should be a required component of the residency., Discussion: This module represents a new paradigm for teaching residents how to successfully and confidently interpret and use inpatient telemetry., Competing Interests: None to report.

Objective: Previous studies have found biological conceptualizations of psychopathology to be associated with stigmatizing attitudes and prognostic pessimism. This research investigated how biological and psychosocial explanations for a child's ADHD symptoms differ in affecting laypeople's stigmatizing attitudes and prognostic beliefs., Method: Three experiments were conducted online with U.S. adults, using vignettes that described a child with ADHD and attributed his symptoms to either biological or psychosocial causes. Dependent measures gauged social distance and expectations about the child's prognosis., Results: Across all three studies, the biological explanation yielded more doubt about treatability but less social distance-a result that diverges from previous research with other disorders. Differences in the amount of blame ascribed to the child mediated the social distance effect., Conclusion: The effects of biological explanations on laypeople's views of ADHD seem to be a "double-edged sword," reducing social rejection but exacerbating perceptions of the disorder as relatively untreatable., (© The Author(s) 2012.)

Background: Permanent pacemakers (PPMs) are capable of recording tachyarrhythmic events including nonsustained ventricular tachycardia (NSVT), though the clinical significance of NSVT on routine PPM evaluation is unknown. Our goals: assess the prevalence of NSVT on routine PPM follow-up and survival of PPM patients with NSVT, without NSVT, and with ventricular high rate (VHR) episodes of undefined origin., Methods: A single-center retrospective, cohort study was performed on patients implanted with PPMs capable of recording NSVT, defined as ≥5 consecutive ventricular beats at ≥170/minutes lasting <30 seconds. Patients were categorized: (1) no NSVT; (2) NSVT; or (3) VHR episodes of uncertain etiology. The primary endpoint was all-cause mortality within 6 months of last follow-up., Results: Note that in 1,125 enrollees (51.8% male, age 74.2 ± 15.5 years, ejection fraction 57.0 ± 9.0%), 742 (66%) had no NSVT, 223 had NSVT (20%), and 160 (14%) had VHR. There were no differences in ejection fraction, diabetes, hypertension, coronary disease, prior myocardial infarction, baseline creatinine, QRS duration, prevalence of left bundle branch block, or β-blocker use among groups. "No NSVT" patients were older (P = 0.013), NSVT patients had more males (P = 0.012); atrial fibrillation and digoxin use were more prevalent in VHR patients (P < 0.01). During median follow-up of 2.8 years there were 93 deaths within 6 months of last follow-up with no differences in survival among groups (log rank P = 0.47). Age, ejection fraction at time of implant, and β-blocker use were independent predictors of survival., Conclusion: NSVT detected on routine PPM follow-up in this patient population with a preserved ejection fraction is not associated with long-term mortality., (© 2015 Wiley Periodicals, Inc.)

Background: The role of a percutaneous ventricular assist device (VAD) for left heart support in the management of patients in cardiogenic shock is not well defined., Methods: All patients who received LV support using the percutaneous TandemHeart (percTH) ventricular support device (Cardiac Assist, Pittsburgh, PA) were retrospectively reviewed. Indications for insertion included bridge to decision (BTD) or "salvage" and bridge to transplant (BTT)., Results: Between April 2005 and December 2008, 22 percTH devices were successfully implanted in patients (13 men) with isolated left heart failure. Mean duration of support was 6.8 +/- 9.4 days (median, 4; maximum, 45 days). Of patients requiring percTH support for at least 3 days, mean pump flows were 3.77 +/- 1.10, 4.22 +/- 0.69, and 4.04 +/- 0.41 L/min on at days 1, 2, and 3. Mean serum aspartate aminotransferase levels were 455 +/- 994 mg/dL before percTH, 551 +/- 1046 mg/dL at day 1, and 231 +/- 225 mg/dL at day 3 after percTH. No mechanical device failure, device-related infections, or cerebrovascular accidents occurred. Ten of 11 BTT patients were successfully bridged. Support was withdrawn in 7 of 11 BTD patients. The percTHs were successfully explanted in 4 BTD patients: 1 as recovery, 1 direct to transplant, and 2 to VAD., Conclusions: The percTH was reliable, with no mechanical device failures and minimal associated adverse events. We support the use of the percTH in the BTD mode, allowing time for a more complete evaluation of neurologic and end-organ status without the added expense and morbidity of a long-term VAD.

Worker displacement has become a common feature of employment in the "flexible economy." While studies of income losses and the duration of unemployment after displacement abound, and popular accounts argue that workers often lose status, less empirical attention has been paid to the quality or prestige of employment displaced workers are able to secure after a downsizing event. This paper helps to fill this gap in the literature by focusing on changes in occupational prestige among a nationally representative sample of displaced workers who became reemployed from the January 2004 Displaced Workers and Employee Tenure Supplement of the Current Population Survey. Our findings show that displaced workers with higher levels of education, net of other factors, fared significantly better than others in job quality upon reemployment, highlighting the importance of education in retaining status and privilege in the new economy.

Climate change may increase the frequency and intensity of ozone episodes in future summers in the United States. However, only recently have models become available that can assess the impact of climate change on O3 concentrations and health effects at regional and local scales that are relevant to adaptive planning. We developed and applied an integrated modeling framework to assess potential O3-related health impacts in future decades under a changing climate. The National Aeronautics and Space Administration-Goddard Institute for Space Studies global climate model at 4 degrees x 5 degrees resolution was linked to the Penn State/National Center for Atmospheric Research Mesoscale Model 5 and the Community Multiscale Air Quality atmospheric chemistry model at 36 km horizontal grid resolution to simulate hourly regional meteorology and O3 in five summers of the 2050s decade across the 31-county New York metropolitan region. We assessed changes in O3-related impacts on summer mortality resulting from climate change alone and with climate change superimposed on changes in O3 precursor emissions and population growth. Considering climate change alone, there was a median 4.5% increase in O3-related acute mortality across the 31 counties. Incorporating O3 precursor emission increases along with climate change yielded similar results. When population growth was factored into the projections, absolute impacts increased substantially. Counties with the highest percent increases in projected O3 mortality spread beyond the urban core into less densely populated suburban counties. This modeling framework provides a potentially useful new tool for assessing the health risks of climate change.

Background: Poor or reverse R-wave progression (PRWP) is a common statement on electrocardiogram (ECG) interpretations, but its value in diagnosing anterior myocardial infarction (MI) is disputed. We assessed the accuracy of PRWP criteria in diagnosing anterior MI., Methods: We searched MEDLINE (1960-1998) and found 3 criteria for PRWP. We included a modified version of the Marquette Muse system's criteria and multiple novel criteria. We interpreted resting ECGs of consecutive patients undergoing pharmacologic stress tests with dual isotope gated single photon emission computed tomography. Subjects with Q-wave anterior MI, bundle branch block, or Wolf-Parkinson-White syndrome were excluded. We established whether patients met the PRWP criteria. A nuclear cardiologist blinded to PRWP classifications reviewed the scintigrams. Chi2 methods were used for statistical analysis., Results: Inclusion criteria were met by 122 subjects. The standard PRWP criteria were met in 15% to 42% of ECGs. Of subjects meeting PRWP criteria, 2% to 9% had anterior MI and 27% to 33% had anterior MI or ischemia. These proportions were similar to those expected by chance. The performance of PRWP criteria did not improve when subjects with electrocardiographic left ventricular hypertrophy were excluded or when more stringent criteria for right precordial R-wave amplitude were tested., Conclusions: In our study of patients undergoing cardiac stress tests, only a small percentage of patients who met various criteria for PRWP (a proportion no different than would be expected by chance) had anterior MI. Conclusions about the presence of anterior MI solely on the basis of PRWP have little usefulness.

The authors invoke a population health perspective to assess the distribution of environmental hazards according to race/ethnicity, social class, age, gender, and sexuality and the implications of these hazards for health. The unequal burden of environmental hazards borne by African American, Native American, Latino, and Asian American/Pacific Islander communities and their relationship to well-documented racial/ethnic disparities in health have not been critically examined across all population groups, regions of the United States, and ages. The determinants of existing environmental inequities also require critical research attention. To ensure inclusiveness and fill important gaps, scientific evidence is needed on the health effects of the built environment as well as the natural environment, cities and suburbs as well as rural areas, and indoor as well as outdoor pollutants.

Atmospheric deposition is a significant loading pathway for polychlorinated dibenzo-p-dioxins and dibenzofurans (dioxin) to the Great Lakes. An innovative approach using NOAA's HYSPLIT atmospheric fate and transport model was developed to estimate the 1996 dioxin contribution to each lake from each of 5,700 point sources and 42,600 area sources in a U.S./Canadian air emissions inventory. These unusually detailed source-receptor modeling results show that deposition to each lake arises from a broad geographical region, with significant contributions from up to 2,000 km away. The source categories contributing most significantly to 1996 dioxin deposition appear to be municipal waste incineration, iron sintering, medical waste incineration, and cement kilns burning hazardous waste. Model-predicted air concentrations and deposition fluxes were consistent with ambient measurement data, within the uncertainties in each, but there may be a moderate tendency toward underestimation using midrange emissions estimates. The most likely reason for this tendency appears to be missing or underestimated emissions sources, but in-situ atmospheric formation of octachlorinated dibenzo-p-dioxin (OCDD) and heptachlorinated dibenzo-p-dioxin (HpCDD) may have also contributed. Despite uncertainties, the findings regarding the relative importance of different sources types and source regions appear to be relatively robust and may be useful in prioritizing pollution prevention efforts.

There are no standardized definitions for anti-incontinence therapy outcomes. The present study was conducted to evaluate whether the incorporation of several non-invasive outcome measures into a new score may serve as a meaningful outcome instrument. Ninety-four consecutive sphincteric incontinent women who underwent a pubovaginal sling by a single surgeon were enrolled. All patients underwent a full clinical evaluation, including pre- and post-operative questionnaires, 24-hour voiding diary, and 24-hour pad test. Surgery outcomes were classified twice: First, by analyzing the patient questionnaire, voiding diary, and pad test separately, according to previously published criteria, and second, by combining the three outcome tools into a new response score. The new score was constructed in a simple, easy-to-remember format and divided into five categories: cure, good response, fair response, poor response, and failure. All patients were evaluated at least 1 year post-operatively. Comparison of the old and new classifications suggests that the new response score provides a more accurate evaluation of the surgical outcomes. Although 64 to 69% of the patients were originally classified as cure according to the old classification, only 44.7% were re-classified as cure by the strict criteria employed in the new score. Furthermore, the response score also differentiates between various degrees of clinical improvement (i.e., good, fair, or poor response). Twenty-five (26.6%) patients, most of whom were previously classified as cure, were re-classified as good response, whereas 20 others were re-classified as fair (13. 9%), or poor (7.4%) response. Seven (7.4%) patients were re-classified as surgical failures. All were diagnosed pre-operatively as having complex sphincteric incontinence. Specific failure rates were therefore 11.3% for complex and 0% for simple cases. In conclusion, the suggested post-operative response score incorporates in a user-friendly format three popular outcome tools (i.e., 24-hour diary, 24-hour pad test, and patient questionnaire) and seems to reflect the surgical results more accurately. Further studies are needed to assess its validity and reproducibility in other treatment modalities. Neurourol Urodynam. 19:127-135, 2000., (Copyright 2000 Wiley-Liss, Inc.)

Purpose: Presently to our knowledge there are no standardized techniques to assess outcomes after surgery for stress incontinence. We performed a prospective blinded study to assess the correlation among physician and patient assessments, and a validated 24-hour pad test and voiding diary., Materials and Methods: A total of 84 women were evaluated before and after pubovaginal sling for stress incontinence with a voiding diary, pad test and symptom questionnaire (patient assessment) administered by a blinded third party. The operating surgeon evaluated the patient using history, physical examination, pad test and voiding diary but was blinded to results of the outcome questionnaire. Preoperative focused neurourological examination and video urodynamics confirmed stress incontinence. Patients were assessed at least 1 year postoperatively. We compared patient assessment (cured, improved, failure) to the outcome of the pad test, voiding diary and physician assessment. The physician and questioner were blinded to each other. We considered patients with a pad test of 0 to 2 ml. as cured, 50% or more volume reduction as improved and less than 50% volume reduction as failure. Postoperative assessment did not differentiate between stress and urge incontinence. The kappa coefficient was used for statistical comparison., Results: Average patient age was 58 years and average followup for the entire group was 4 years. Agreement among the 4 instruments to assess outcome was excellent (k >0.9) with respect to cured/improved versus failure but only good for cured versus improved versus failure (k >0.5)., Conclusions: Outcomes following incontinence surgery may vary depending on how the analysis was performed, patient selection, definition of success and so forth. Our results indicate that a pad test and voiding diary are reliable and should be part of the normal followup after pubovaginal sling for sphincteric incontinence. When these tests are used in conjunction with defined parameters of success, there is excellent agreement with patient feelings in regard to success or failure of surgery. Nevertheless, these instruments and methods are imperfect at best.

Background: Occupational stress may affect measured hemodynamic and electrocardiographic variables. Data describing the physiologic effects of work on the emergency physician (EP) are sparse., Objective: To determine whether blood pressure (BP) and heart rate variability (HRV) of the EP are affected during a night shift in the ED., Methods: This prospective study evaluated BP and HRV in attending EPs at an urban academic medical center for a 24-hour period during which a night shift was scheduled. Participants were fitted with an oscillometric ambulatory BP device and a Holter monitor at 1500 hours on the day of a night shift. The monitors were worn continuously before, during, and after a night shift (2300-0700) in the ED and were removed at 1500. Systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), heart rate (HR), measures of HRV, and occurrence of cardiac dysrhythmias were evaluated. Comparisons were made for ED and non-ED awake periods and non-ED sleep periods., Results: Twelve participants completed the study. Eight (67%) subjects were men and 4 (33%) were women. Age ranged from 28 to 40 years (mean 34.1+/-4.1). Results were analyzed using repeated-measures ANOVA. An elevation of mean DBP (5.5 mm Hg+/-4.37; p < 0.05; 95% CI 1-10) during night shift activity was seen. A trend toward elevation of SBP, MAP, and HR was discernible. HRV measures indicated a significant relative increase in sympathetic vs parasympathetic tone and an increase in HR of prework and work compared with postwork. Dysrhythmias observed included sinus tachycardia, sinus bradycardia, sinus pause, atrial premature beats, atrial couplets and triplets, supraventricular tachycardia, and premature ventricular contractions., Conclusions: The elevation of DBP during a night shift suggests that these patterns of BP variability are activity- or stress-related rather than a result of a true diurnal variation. HRV analysis suggests that sympathetic tone is heightened both before work and during work. The implications of such findings to the health of the EP warrant further investigation.

Twenty-four-hour acquisition of QT dispersion (QTd) from the Holter and the circadian variation of QTd were evaluated in 20 survivors of sudden cardiac death (SCD), in 20 healthy subjects, and in 14 control patients without a history of cardiac arrest who were age, sex, diagnosis and therapy matched to 14 SCD patients. Computer-assisted QT measurements were performed on 24-hour Holter recordings; each recording was divided into 288 5-minute segments and templates representing the average QRST were generated. QTd was calculated as the difference between QT intervals in leads V1 and V5 for each template on Holter. The 24-hour mean QTd was significantly greater in SCD patients (40 +/- 28 ms) than in healthy subjects (20 +/- 10 ms) and control patients (15 +/- 5 ms) (p <0.05). There was a circadian variation in QTd with greater values at night (0 to 6 A.M.) than at daytime (10 A.M. to 4 P.M.) in healthy subjects (25 +/- 13 vs 15 +/- 8 ms, p <0.001) and control patients (18 +/- 10 vs 12 +/- 4 ms p <0.05), whereas in SCD patients there was no significant difference between night and day values (45 +/- 31 vs 37 +/- 28 ms, p = NS). It is concluded that QTd measured by Holter was greater in SCD patients than in healthy subjects and matched control patients during the entire day. QTd has a clear circadian variation in normal subjects, whereas this variation is blunted in SCD patients. QTd measured on Holter differentiates survivors of cardiac arrest and may be a useful tool for risk stratification.

To evaluate and compare QT correction formulas in healthy subjects, we used 24-hour Holter monitoring because it allows the assessment of QT intervals over a large range of rates. Computer-assisted QT-interval measurements were obtained from 21 subjects. QT-RR relations for individuals and the group were fitted by regression analysis to 5 QT prediction formulas: simple Bazett's, modified Bazett's, linear (Framingham), modified Fridericia's and exponential (Sarma's). There were no significant differences in mean squared residuals between formulas. When using individually calculated regression parameters, each formula gave good or acceptable QT correction over the entire range of RR intervals. Simple Bazett's formula (which uses no regression parameters) was unreliable at high rates. Akaike information criteria rank was: Sarma's, Framingham, modified Bazett's, Fridericia's, and simple Bazett's. When group-based regression parameters were applied to individuals, no formula had a clear advantage over simple Bazett's. We conclude that any formula that invokes regression parameters unique to each individual provides satisfactory QT correction. Determination of these parameters requires long-term recording to obtain an adequate range of rates. Group-based regression parameters give poor correction. When individual parameters cannot be determined, as in a 12-lead electrocardiogram, no formula provides an advantage over the familiar simple Bazett's.

Objectives: This study sought to evaluate the range and variability of the QT and corrected QT (QTc) intervals over 24 h and to assess their pattern and relation to heart rate variability., Background: Recent Holter monitoring data have revealed a high degree of daily variability in the QTc interval. The pattern of this variability and its relation to heart rate variability remain poorly characterized., Methods: We developed and validated a new method for continuous measurement of QT intervals from three-channel, 24-h Holter recordings. Average RR, QT, QTc and heart rate variability were measured from 5-min segments of data from 21 healthy subjects., Results: Measurement of 6,048 segments showed mean (+/- SD) RR, QT and QTc intervals of 830 +/- 100, 407 +/- 23 and 445 +/- 16 ms, respectively (mean QTc interval for men 434 +/- 12 ms, 457 +/- 10 ms for women, p < 0.0001). The average maximal QTc interval was 495 +/- 21 ms and the average QTc range 95 +/- 20 ms. The maximal QTc interval was > or = 500 ms in 6 subjects and > or = 490 ms in 13. The 95% upper confidence limit for the mean 24-h QTc interval was 452 ms (men 439 ms, women 461 ms). The RR, QT and QTc intervals and the high frequency component of heart rate variability were greater during sleep. Both the QTc interval and the variability between hourly minimal and maximal QTc intervals reached their circadian peak shortly after awakening, before declining to daytime levels., Conclusions: The maximal QTc interval over 24 h in normal subjects is longer than heretofore thought. Both QT and QTc intervals are longer during sleep. The QTc interval and QTc variability reach a peak shortly after awakening, which may reflect increased autonomic instability during early waking hours, and the time of the peak value corresponds in time to the period of reported increased vulnerability to ventricular tachycardia and sudden cardiac death. These findings have implications regarding the definition of QT prolongation and its use in predicting arrhythmias and sudden death.

Myocardial hypoxia and ischemia result in the production of lactate. To study the effect of lactate on the rapid Na+ current (INa), we used the whole cell voltage-clamp technique in enzymatically isolated guinea pig ventricular myocytes. Experiments were conducted at 16 degrees C. Extracellular Na+ concentration ([Na+]o) was maintained in control and test solutions and extracellular pH was 7.4. Lactate (4-10 mM, either sodium lactate or lactic acid) augmented INa in each of eight experiments, increasing the peak Na+ conductance from 75.4 to 84.7 nS (13-16% at all test voltages in the linear portion of the conductance curve). The voltage dependence of steady-state availability and the time course of inactivation remained unchanged. The increase in peak Na+ conductance was concentration dependent, with an apparent dissociation constant of 1.8 mM and Hill coefficient of 1.8. Lactate in the range of 1-10 mM did not significantly reduce the Ca2+ activity of test solutions. These effects of lactate were still observed in Mg(2+)-free test solutions and when the buffering capacity of internal solution was reinforced by increasing N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid concentration from 5 to 20 mM. In conclusion, lactate enhances INa via a mechanism that does not involve chelation of Ca2+ or Mg2+ or changes in intracellular pH. These effects of lactate on the Na+ channel might alter electrophysiological properties during myocardial ischemia and could protect the heart from ischemia-induced conduction abnormalities or, alternatively, could lead to arrhythmias.

1. It has been reported that catecholamines affect intracellular pH (pHi) in a number of tissues, generally by altering the kinetics of the Na(+)-H+ exchanger. We postulated that catecholamines might affect pHi in cardiac tissue. We tested this in resting sheep cardiac Purkinje fibres by measuring transmembrane potential and pHi with standard and H(+)-sensitive microelectrodes. 2. Adrenaline and the beta-adrenergic agonist isoprenaline, both 5.0 x 10(-6) M, resulted in depolarization and intracellular acidification (adrenaline, 0.03 +/- 0.01 pH units, n = 8, P = 0.005; isoprenaline, 0.08 +/- 0.01 pH units, n = 17, P = 0.0001). The alpha-adrenergic agonist phenylephrine, at concentrations up to 200 microM, had no significant effect on membrane potential or pHi. 3. Isoprenaline significantly attenuated the half-time (t0.5) for pHi recovery from intracellular acidification induced via the NH4Cl pulse technique. Isoprenaline also attenuated the hyperpolarization that is normally seen at the onset of pHi recovery. Phenylephrine slightly reduced the t0.5 for recovery, although the reduction did not reach statistical significance. 4. Forskolin, 7.5-10 x 10(-5) M, an agent that raises intracellular cyclic adenosine 3',5'-monophosphate (cyclic AMP), also induced depolarization and acidification, similar to that induced by adrenaline and isoprenaline. 5. In the presence of the Na(+)-H+ exchange blocker 5-dimethyl amiloride, 2-6 x 10(-5) M, isoprenaline-induced acidification was blunted but not abolished. When administered in Na(+)-free Tyrode solution, isoprenaline-induced acidification was also not abolished. Buffering power, tested using the NH4Cl method, was not decreased by isoprenaline, but rather, was slightly increased. Reversal of H+ driving force across the cell membrane from the normally inward direction to outward (achieved by increasing pHo to 8.3-8.5 and depolarizing the membrane with 10 mM K+ solutions) did not prevent intracellular acidification from occurring in the presence of isoprenaline. When glycolysis was inhibited by a 60 min exposure to glucose-free solution containing 5.5 mM 2-deoxyglucose, acidification by isoprenaline was nearly abolished. 6. We conclude that, in resting sheep Purkinje fibres, beta- but not alpha-adrenergic stimulation results in intracellular acidification and depolarization, probably mediated via an increase in cyclic AMP. beta- but not alpha-adrenergic stimulation slows the rate of recovery from intracellular acidification and blunts the hyperpolarization associated with this recovery. 7. The intracellular acidification appears to be due both to partial inhibition of Na(+)-H+ exchange and to stimulation of glycolysis by beta-adrenergic agents.

The ability to predict the RR-QT relation over a range of heart rates was evaluated in 10 patients with atrial fibrillation (AF) and in 10 control subjects in sinus rhythm. The data from each subject were fitted by regression into 3 QT prediction formulas (the square root formula of Bazett, the cube root formula of Fridericia and the exponential formula of Sarma) applied in standard form and modified with a weighted average of the preceding 5 RR intervals. The goodness-of-fit of each formula was evaluated using mean square residual and Akaike information criterion. For AF, the mean square residuals did not differ among the 3 standard QT prediction formulas (Bazett 624 +/- 274, Fridericia 625 +/- 274 and Sarma 611 +/- 267) and among the 3 modified QT prediction formulas (Bazett 507 +/- 325, Fridericia 496 +/- 255 and Sarma 495 +/- 328). The weighted average modification produced a significant decrease in mean square residuals for all 3 equations (p less than 0.05) in all patients. These findings were confirmed by Akaike information criterion. Goodness-of-fit in sinus rhythm was similar to previously published reports, and significantly better than the fit for AF (p less than 0.0001). For 9 of the 10 patients with AF, sinus rhythm electrocardiograms were obtained and the above regression equations were used to predict QT intervals.(ABSTRACT TRUNCATED AT 250 WORDS)

Subtle memory disturbances are widely reported in schizophrenia. We investigated one such disturbance, reduced primacy in serial position recall among 20 schizophrenic patients, 20 depressed patients, and 20 normal controls. The main finding is that schizophrenic subjects show reduced primacy and middle position performance, but are able to match the recency recall of controls. We further demonstrate that primacy performance is associated with another memory anomaly frequently noted in schizophrenia, decreased context associated gain in recall. Among schizophrenic subjects, primacy performance is also related to increased repetition in speech, a feature associated with formal thought disorder in schizophrenia. These observations suggest that memory deviances and disordered speech may have a common pathogenesis.

Isolated canine interventricular septa were studied with standard microelectrode techniques. Focal automaticity was induced by applying depolarizing current through an extracellular pipet in contact with the right bundle branch (RBB) of the ventricular specialized conducting system. Automaticity appeared with depolarization to transmembrane potentials of -50 mV or less. The spontaneous activity was neither depressed nor accelerated when overdrive suppression was attempted. Activity originating within the focus propagated into fully polarized surrounding tissue. However, entrance block, phasically related to the spontaneous cycle length, was an intrinsic property of these foci. Early premature beats initiated outside the focus failed to enter the focus, but the resulting electrotonus delayed the next automatic beat. Late premature beats captured and thereby accelerated the focus. Thus, the automatic foci could be extrafocal activity. Consequently, continous pacing at various rates precipitated complex rhythms with fixed coupling. Similar foci with exit conduction, entrance block, and electrotonic modulation also were demonstrated in focally depolarized papillary muscles in feline septal preparations. The unique properties of focally depolarized areas in which spontaneous activity is generated at low membrane potentials provide a mechanism capable of generating a wide array of arrhythmias.

The purposes of this study were to determine whether amrinone induces oscillatory afterpotentials (OAP) or aftercontractions (AC) in Purkinje tissue or myocardium, to determine whether a relationship exists between the production of OAP or AC and the inotropic effects of amrinone and to determine possible effects of amrinone on the oscillations and the positive inotropic effect produced by digitalis. Isolated canine papillary and trabecullar muscles, as well as false tendons, were exposed to 5.3 X 10(-4) M amrinone. Some of the preparations had been pretreated with acetylstrophanthidin (AS) in a dose just sufficient to induce OAP or AC. Standard electrophysiologic techniques were used to record transmembrane action potentials. Developed tension also was recorded. Amrinone by itself did not induce OAP or AC in myocardium or false tendons. This was true even when the resting membrane potential of the false tendons was reduced by means of focal current application. Amrinone increased the amplitude of AS-induced oscillations in both myocardium and false tendons. Amrinone increased strength of contraction of untreated myocardium at all basic cycle lengths and of AS-treated myocardium, especially at shorter basic cycle lengths. Amrinone decreased strength of contraction both of untreated and AS-treated false tendons at all basic cycle lengths. The results suggest that there may be important differences in the mechanisms of action of amrinone and digitalis.

To assess whether free radicals affect the characteristic sequence of events in an in vitro model of ischemia and reperfusion, isolated canine cardiac Purkinje fibers were exposed to anti-free radical agents, superoxide dismutase 50 U/ml; catalase 600 U/ml; mannitol 2 mM and 20 mM and combined superoxide dismutase, catalase, and mannitol 20 mM. Fibers were superfused for 60 min with altered Tyrode's solution which mimicked some conditions of ischemia (glucose-free, containing lactate, equilibrated with 90% N2-10% CO2), and then re-exposed to normal, oxygenated Tyrode's solution. Anti-free radical agents alone had no electrophysiological effects. Ischemic conditions resulted in moderate depolarization in most preparations (10 control; 43 treated) but in severe depolarization, to less than -60 mV, in some (3 control, 11 treated). Re-exposure to normal, oxygenated solution resulted in prompt initial hyperpolarization followed by marked depolarization, and finally by recovery to baseline maximum diastolic potential. Anti-free radical agents had not effect on maximum diastolic potential during exposure to ischemic conditions or on initial hyperpolarization following re-exposure to oxygenated solution. Preparations that became severely depolarized during exposure to ischemic conditions were not protected by anti-free radical interventions from developing marked depolarization following re-exposure to oxygenated solution. However, in fibers only moderately depolarized by the ischemic conditions, all anti-free radical interventions except mannitol, 2 mM significantly attenuated depolarization following re-exposure to oxygenated solution. Anti-free radical interventions significantly reduced the number of preparations that became markedly depolarized (to less than -65 mV) during re-exposure to oxygenated solution (except for mannitol, 2 mM). Agents had no effect on the occurrence of abnormal automaticity; the occurrence of inexcitability was reduced, but not significantly, except when all agents were used in combination. The results suggest that free radical production may contribute to electrophysiological abnormalities when Purkinje fibers are re-exposed to oxygenated Tyrode's solution after they have been exposed to ischemic conditions.

Automatic foci with membrane potentials in the range characterized by depolarization-induced automaticity exhibit entrance block. The present study demonstrates a role of variable entrance and exit block in arrhythmogenesis. We studied canine interventricular septa with the right bundle branch exposed, isolated false tendons and isolated feline papillary muscle using standard microelectrode techniques. Foci of automaticity were produced either by focal application of electric current or by exposure of the preparations to Tyrode's solution containing 1.5-2.0 mM KCl. Foci induced by mild depolarization exhibited entrance block with exit conduction and were subject to electrotonic modulation. With greater depolarization, varying degrees of exit block developed. Various rhythms, including Wenckebach periodicity, resulted. Delayed emergence of electrotonically accelerated activity led to closely coupled extrasystoles resembling reentrant activity. Exit conduction in some preparations was facilitated by enhanced normal pacemaker activity (membrane potentials -- 70 mV or greater) in tissue peripheral to the focus. Also, when there were two sites of automaticity separated by an area of depressed conduction, intermodulation between the two automatic regions generated complex arrhythmias. Shifts in maximum diastolic potential also changed conduction and led to changes in arrhythmic patterns. In some experiments, focal automaticity was terminated by single stimuli. We conclude that complex and variable behavior of automatic foci may result in activity with characteristics previously attributed to other arrhythmic mechanisms.

Intracranial resistance and compliance were assessed in the cerebrospinal fluid system of rat, dog, and man by means of low-volume, short-duration infusions of artificial CSF into the subarachnoid space. A family of pressure/time response curves was obtained for each species: at low flow rates, steady-state pressure elevations were associated with normal neurological function; at high flow rates, rapid linear pressure elevations were associated with marked neurological dysfunction. From these curves a mathematical model was developed which describes transport and pressure-dependent valvelike characteristics of the CSF outflow resistance. This resistance shows a progressive phylogenetic change in rat, dog, and man which increasingly enhances the species' abilities to vent fluid from the intracranial cavity into the venous circulation. Arachnoid villi appear to be the major structures modulating sustained, nonlethal elevations of intracranial pressure.

A recent study in 1 day old infarcted canine cardiac tissue demonstrated that variations in entrance and exit characteristics of depolarized spontaneous foci could profoundly affect their expression, resulting in behaviors such as modulated parasystole and entrainment, second and third degree exit block "autoentrainment" and annihilation (abrupt termination) of spontaneous activity. Foci with exit and entrance delay should also allow the occurrence of reflected reentry. To test this, the left circumflex coronary artery was ligated and, after 1 day, simultaneous microelectrode impalements were made in infarcted and uninfarcted portions of isolated ventricular preparations. Preparations were stimulated from the uninfarcted portions. Reflected reentry was demonstrated in 5 of 11 preparations. It occurred when exit conduction delay resulted in reexcitation of the focus or, alternatively, when entrance conduction delay resulted in reexcitation of extrafocal tissue. Reflection occurred in which the action potentials were reexcited during phase 2 or 3, resulting in prolongation of action potential duration (type I), and in which reexcitation occurred after full or nearly full repolarization, resulting in a closely coupled extrasystole (type II). Electrotonic modulation and reflection could coexist, the type of behavior depending on the phase relation between focal and extra-focal action potentials. An example is illustrated in which type I reflection occurred only when preceding driven activity induced overdrive suppression of exit conduction from the focus. The results suggest that, in infarcted tissue, entrance and exit conduction delays to depolarized foci may form the basis for the occurrence of reflected reentry.

Hardware arrangements and methods are proposed in which optoelectronic devices, such as image converters and special purpose CRT's, are used for image processing operations, e.g., correlations-integral transforms, such as the Fourier transform, filtering, implementation of special algorithms, and one-dimensional functional representations. These operations are to be performed in parallel or partly in parallel at an over-all speed far exceeding that of a fast digital computer, with the output appearing as sequential electric signals. The accuracy will be adequate for experimental but not for analytic inputs. Specific recommendations are made on needed improvements in the performance of display devices and the standardization of developmental models, which would permit optimization of the proposed systems and increase their range of applicability.

To assess the roles of entrance and exit block after canine myocardial infarction, single stage coronary artery ligations of canine circumflex coronary arteries were performed. After 1 day, atria and ventricles were paced using single stimuli and trains. After isolation, simultaneous microelectrode impalements were made in infarcted and uninfarcted tissue. Spontaneous foci, when identifiable, were always located in infarcted tissue. They could frequently be triggered by one or more driven beats, and their activity could often be terminated ("annihilated") by a properly timed beat. Foci with varying combinations of entrance and exit conduction impairment were observed. Variations in conduction characteristics altered the manifest arrhythmic pattern. With partial entrance block and intact exit conduction, foci could be electrotonically modulated and entrained into regular patterns. Activity that emerged from a focus with sufficient conduction delay could modulate the focus, and entrain it to discharge at a slower rate ("autoentrainment"). The results suggest that modulated parasystole may contribute to arrhythmogenesis after canine myocardial infarction and that variations in entrance and exit characteristics of depolarized foci may result in variable and complex arrhythmic patterns.