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Inadequacy of low-volume resuscitation with hemoglobin-based oxygen carrier hemoglobin glutamer-200 (bovine) in canine hypovolemia.

Stroma-free hemoglobin-based oxygen carriers (HBOC) have been developed to overcome problems associated with transfusion of allogeneic blood. We have studied the efficacy of the first licensed veterinary blood substitute, hemoglobin glutamer-200 bovine (Oxyglobin; Biopure, Cambridge, MA, USA, Hb-200), in a canine model of acute hypovolemia and examined whether clinically commonly used criteria are adequate to guide fluid resuscitation with this product. Twelve anesthetized dogs were instrumented for measurements of physiological variables including hemodynamic, oxygenation, and blood gas and acid-base parameters. Dogs were bled to a mean arterial pressure (MAP) of 50 mmHg for 1 h followed by resuscitation with either shed blood (controls) or Hb-200 until heart rate (HR), MAP and central venous pressure (CVP) returned to baseline. Recordings were repeated immediately and 3 h after termination of fluid resuscitation. Hemorrhage (average 32 mL/kg) caused significant decreases in total hemoglobin (Hb), mean pulmonary arterial pressure (PAP), cardiac output (CO) and oxygen delivery (DO2I), increases in HR and systemic vascular resistance (SVRI), and lactic acidosis. In controls, only re-transfusion of all shed blood returned HR, MAP and CVP to prehemorrhage values, whereas in other dogs this endpoint was reached with infusion of 10 mL/kg Hb-200. Unlike blood transfusion, Hb-200 infusion failed to return CI and DO2I to baseline and to increase arterial oxygen content (CaO2) and total Hb; SVRI further increased. Thus, commonly used criteria (HR, MAP, CVP) to guide transfusion therapy in patients posthemorrhage prove insufficient when HBOCs with pronounced vasoconstrictive action are used and lead to inadequate volume repletion.

Animals↗

Mayo's Older Americans Normative Studies: Age- and IQ-Adjusted Norms for the Boston Naming Test, the MAE Token Test, and the Judgment of Line Orientation Test.

Although many extant normative data sets for standardized neuropsychometric instruments feature adjustments for subject variables, there are reasons to believe that improvements in interpretive accuracy that result from such adjustments are less than optimal. In particular, several theoretical considerations suggest that years of formal education may be less closely related to test performances than is general intellectual functioning. In this first of four reanalyses of results from the Mayo Clinic's Older Americans Normative Studies (MOANS) databases, age-adjusted scores on the Boston Naming Test, the MAE Token Test, and the Judgment of Line Orientation Test were indeed found to be more strongly associated with Mayo Age-adjusted WAIS-R Full Scale IQ scores (rs=.608, .473, and .502, respectively) than with education (rs=.310, .306, and .236, respectively) for healthy older examinees (56-99 years). Consistent with the remarks of Dodrill (19971999), these correlations generally decreased at higher levels of intelligence. The magnitude and pattern of such declines varied across the three tests, however, suggesting that IQ-test score associations must be empirically determined rather than assumed to be linear. Tables of Age- and IQ-Adjusted percentile equivalents of MOANS Age-adjusted BNT, Token Test, and JLO scaled scores are presented for eleven age ranges and seven IQ ranges. The article concludes with a discussion of factors that may underlie observed relations among age, intelligence, and neuropsychometric test performances.

Age Factors↗

Factors predictive of physician location.

The results of a survey of 182 graduates from the University of South Dakota School of Medicine between 1969 and 1973 are reported and discussed. The study was designed to determine which factors are predictive of practice location. Individual factors found to be related significantly to physician location were size of community where the physician grew up, size of community where the physician's spouse was raised, size of the physician's high school graduating class, number of contacts with other physicians, importance to the physician of continuing medical education opportunities, importance to the physician of professional growth opportunities, and importance of the availability of medical facilities. In addition, a multiple regression procedure was used to determine the viability of a number of independent variables in predicting physician location. From a total of 29 independent variables obtained from the survey instrument, nine factors were found to contribute significantly to the overall prediction of practice location.

Humans↗

Vasopressin improves vital organ blood flow after prolonged cardiac arrest with postcountershock pulseless electrical activity in pigs.

OBJECTIVE: Although a benefit of vasopressin when compared with epinephrine was shown during cardiopulmonary resuscitation (CPR) after a short duration of ventricular fibrillation cardiac arrest, the effect of vasopressin during prolonged cardiac arrest with pulseless electrical activity is currently unknown. DESIGN: Prospective, randomized laboratory investigation using an established porcine model with instrumentation for measurement of hemodynamic variables, vital organ blood flow, blood gases, and return of spontaneous circulation. SETTING: University hospital laboratory. SUBJECTS: Eighteen domestic pigs. INTERVENTIONS: After 15 mins of cardiac arrest and 3 mins of chest compressions, 18 animals were randomly treated with either 0.8 units/kg vasopressin (n = 9) or 200 microg/kg epinephrine (n = 9). MEASUREMENTS AND MAIN RESULTS: Compared with epinephrine, vasopressin resulted, at both 90 secs and 5 mins after drug administration, in significantly higher (p < .05) median (25th-75th percentiles) left ventricular myocardial blood flow (120 [range, 96-193] vs. 54 [range, 11-92] and 56 [range, 41-80] vs. 21 [range, 11-40] mL/min/100 g, respectively) and total cerebral blood flow (85 [78-102] vs. 24 [18-41] and 50 [44-52] vs. 8 [5-23] mL/min/100 g, respectively). Spontaneous circulation was restored in eight of nine animals in the vasopressin group and in one of nine animals in the epinephrine group (p = .003). CONCLUSIONS: Compared with a maximum dose of epinephrine, vasopressin significantly increased left ventricular myocardial and total cerebral blood flow during CPR and return of spontaneous circulation in a porcine model of prolonged cardiac arrest with postcountershock pulseless electrical activity.

Animals↗

Intraosseous vasopressin improves coronary perfusion pressure rapidly during cardiopulmonary resuscitation in pigs.

OBJECTIVE: Intravenous administration of vasopressin during cardiopulmonary resuscitation (CPR) may be more effective than optimal doses of epinephrine. The main purpose of this study was to determine whether intraosseous vasopressin achieves serum drug levels comparable with intravenous doses during CPR and, additionally, to evaluate the effects of intraosseous vasopressin during CPR. DESIGN: Prospective, randomized laboratory investigation using an established porcine model with instrumentation for measurement of hemodynamic variables, blood gases, and return of spontaneous circulation. SETTING: University hospital laboratory. SUBJECTS: Twelve domestic pigs. INTERVENTIONS: After 4 mins of untreated ventricular fibrillation and 3 mins of CPR, 12 pigs were randomized to be treated with intravenous administration of vasopressin (0.8 unit/kg vasopressin; n = 6) or intraosseous vasopressin (0.8 unit/kg vasopressin; n = 6). Defibrillation was performed 5 mins after drug administration to attempt the return of spontaneous circulation. MEASUREMENTS AND MAIN RESULTS: At both 90 secs and 5 mins after drug administration, intravenous and intraosseous administration of vasopressin resulted in comparable mean (+/-SEM) coronary perfusion pressure (43+/-4 vs. 44+/-3 and 30+/-2 vs. 37+/-2 mm Hg, respectively) and vasopressin plasma concentrations (13,706+/-1,857 vs. 16,166+/-3,114 pg/mL and 10,372+/-883 vs. 8246+/-2211 pg/mL, respectively). All animals in both groups were successfully resuscitated; pigs that received intraosseous vasopressin had a significantly higher (p < .05) mean arterial (92+/-6 vs. 129+/-12 mm Hg) and coronary perfusion pressure (84+/-11 vs. 119+/-11 mm Hg) at 5 mins of return of spontaneous circulation. CONCLUSIONS: Intraosseous vasopressin resulted in comparable vasopressin plasma levels, hemodynamic variables, and return of spontaneous circulation rates as did intravenous vasopressin. Intraosseous vasopressin may be an alternative for vasopressor administration during CPR, when intravenous access is delayed or not available.

Animals↗

Vasopressin decreases endogenous catecholamine plasma concentrations during cardiopulmonary resuscitation in pigs.

OBJECTIVE: The purpose of this study was to evaluate the effect of vasopressin vs. saline placebo on catecholamine plasma concentrations during cardiopulmonary resuscitation (CPR). DESIGN: Prospective, randomized laboratory investigation by using an established porcine CPR model with instrumentation for measurement of hemodynamic variables, vital organ blood flow, and return of spontaneous circulation. SETTING: University hospital laboratory. SUBJECTS: Sixteen domestic pigs. INTERVENTIONS: After 15 mins of untreated cardiac arrest and 3 mins of CPR, 16 pigs were randomized to be treated with either 0.8 U/kg vasopressin (n = 8) or placebo (normal saline; n = 8). Arterial epinephrine and norepinephrine plasma concentrations were sampled at prearrest, after 1.5 mins of chest compressions, and at 1.5 mins and 5 mins after drug administration during CPR. MEASUREMENTS AND MAIN RESULTS: In comparison with placebo pigs at 1.5 and 5 mins after drug administration, animals resuscitated with vasopressin had significantly (p < .01) higher mean +/- SEM left ventricular myocardial (131+/-27 vs. 10+/-1 mL x mins(-1) x 100 g(-1) and 62+/-13 vs. 9+/-2 mL x mins(-1) x 100 g(-1)); total cerebral (90+/-8 vs. 14+/-3 mL x mins(-1) x 100 g(-1) and 51+/-4 vs. 12+/-2 mL x mins(-1) x 100 g(-1)); and adrenal gland perfusion (299+/-36 vs. 38+/-7 mL x mins(-1) x 100 g(-1) and 194+/-23 vs. 29+/-5 mL x mins(-1) x 100 g(-1)). Significantly lower mean +/- SEM epinephrine concentrations in the vasopressin pigs compared with the placebo group were measured 1.5 mins and 5 mins after drug administration, (24167+/-7919 vs. 80223+/-19391 pg/mL [p < .01] and 8346+/-1454 vs. 71345+/-10758 pg/mL [p < .01]). Mean +/- SEM norepinephrine plasma concentrations in the vasopressin animals in comparison with placebo were at 1.5 and 5 mins after drug administration significantly lower (41729+/-13918 vs. 82756+/-9904 pg/mL [p = .01] and 10642+/-3193 vs. 62170+/-8797 pg/mL [p < .01]). CONCLUSIONS: Administration of vasopressin during CPR resulted in significantly superior vital organ blood flow, but significantly decreased endogenous catecholamine plasma concentrations when compared with placebo.

Animals↗

Effect of phased chest and abdominal compression-decompression cardiopulmonary resuscitation on myocardial and cerebral blood flow in pigs.

OBJECTIVE: This study was designed to assess the effects of a phased chest and abdominal compression-decompression cardiopulmonary resuscitation (CPR) device, Lifestick, vs. standard CPR on vital organ blood flow in a porcine CPR model. DESIGN: Prospective, randomized laboratory investigation using an established porcine model with instrumentation for measurement of hemodynamic variables, vital organ blood flow, blood gases, and return of spontaneous circulation. SETTING: University hospital research laboratory. SUBJECTS: Twelve domestic pigs. INTERVENTIONS: After 4 mins of untreated ventricular fibrillation, either the Lifestick CPR device (n = 6) or standard CPR (n = 6) was started and maintained for an additional interval of 6 mins before attempting defibrillation. MEASUREMENTS AND MAIN RESULTS: During CPR, but before epinephrine, use of the Lifestick CPR device resulted in significantly higher (p < .05) mean (+/- SD) coronary perfusion pressure (23+/-9 vs. 10+/-7 mm Hg), cerebral perfusion pressure (29+/-11 vs. 18+/-10 mm Hg), mean arterial pressure (49+/-10 vs. 36+/-13 mm Hg), end-tidal carbon dioxide (32+/-11 vs. 20+/-7 mm Hg), left ventricular myocardial blood flow (44+/-19 vs. 19+/-12 mL x min(-1) x 100 g(-1)), and total cerebral blood flow (29+/-10 vs. 14+/-12 mL x min(-1) x 100 g(-1)). After 45 microg/kg epinephrine, hemodynamic and vital organ blood flow variables increased to comparable levels in both groups. CONCLUSIONS: Compared with standard CPR, the Lifestick CPR device increased significantly hemodynamic variables and vital organ blood flow during CPR before epinephrine administration.

Abdomen↗

Prosody impairment in depression measured through acoustic analysis.

This work attempts to explore the association between depression and prosody impairment through acoustic techniques of voice analysis. For this purpose, we selected 10 quantitative vocal parameters, obtained instrumentally, and related to the variability and psychomotor control of phonation, which we have considered as prosody indicators. The sample consisted of 23 patients with diagnosis DSM-III-R of major depression and a control group of 20 healthy volunteers. We obtained results in 7 of the 10 acoustic parameters that suggest reduced prosody in depressed subjects. In a second voice test, carried out 2 months after baseline situation, and while patients were under antidepressant treatment, it was not possible to demonstrate that all these prosody indicators change to normality in those 13 subjects who clinically improved.

Adolescent↗

Ongoing assessment of health status in patients with diabetes mellitus.

In 1990, the Division of Endocrinology and Metabolism of Henry Ford Hospital established an Outcomes Management data base for patients with Type I and Type II diabetes. A first cohort of 117 patients completed a baseline and 6-month follow-up assessment; a second cohort of 116 patients completed the baseline assessment. Assessment at each time point includes: the Short Form--36 Questions (SF-36) health status instrument; a set of clinical variables known as the Diabetes TyPE scale Form 2.2 abstracted from the medical record; and the physicians' ratings of patient's health status along the major dimensions of the SF-36. Success with both face-to-face and mailed administration of the SF-36 has been good, with response rates of over 85% using both methods. Comparison of patient and physician ratings of patient health status indicated a significant discrepancy on ratings of general health status, with physicians' ratings higher than those of patients themselves. "Tight" glycemic control (as measured by glycosylated hemoglobin) was associated with somewhat lower ratings on the various SF-36 dimensions for all patients in the first cohort and for Type I patients in the second cohort. However, this effect did not seem to be attributable to those features of a complex regimen used to achieve tight control, but rather reflected a complex combination of age, education level, and number of daily injections associated with achieving good control.

Activities of Daily Living↗

Characteristics of a video-type pupillometer.

In using a video-type pupillometer, the adjustment of the clipping level, the illumination of the target, the focus of the camera, and the viewing angle have been shown to affect the measurement. The focus of the camera and the viewing angle are the most important variables. The precision of this instrument can be as good as 0.01 mm. The accuracy of the instrument is good with regard to clinical standards; however, all measurements vary slightly from the known value. Interexaminer variation appears to be small.

Computers↗

Immigration, lack of control and psychological distress: findings from the Oslo Health Study.

The aims of this study are to compare the level of psychological distress between Norwegian born and immigrants from countries with different income levels and culture, and to investigate the explanatory effect of socioeconomic and psychosocial factors, with special emphasis on lack of control (powerlessness and self-efficacy). A cross-sectional survey with self-administered questionnaire was conducted in 2000-2001 in a sample of 15,723 adults living in Oslo. Psychological distress was measured by a ten-item shortened version of Hopkins Symptom Checklist-25 items, whereas psychosocial variables were measured by various instruments. The results show that the level of psychological distress is significantly higher in immigrants from low- and middle-income countries than in the Norwegian born and the immigrants from high-income countries. They also report more powerlessness, more negative life events, less social support, less income and less paid work. It is concluded that negative life events, mainly related to social network, somatic health and economic situations, as well as lack of social support, are important mediators between immigration from low- and middle-income countries to Norway and psychological distress. Powerlessness also plays a role, but this is mainly because of a concept overlap between psychological distress and powerlessness.

Adult↗

Spectrum of acute renal failure in the intensive care unit: the PICARD experience.

BACKGROUND: Acute renal failure (ARF) in the critically ill is associated with extremely high mortality rates. Understanding the changing spectrum of ARF will be necessary to facilitate quality improvement efforts and to design successful interventional trials. METHODS: We conducted an observational cohort study of 618 patients with ARF in intensive care units at five academic medical centers in the United States. Participants were required to sign (or have a proxy sign) informed consent for data collection. A comprehensive data collection instrument captured more than 800 variables, most on a daily basis, throughout the course of ARF. Patient characteristics, dialysis status, and major outcomes were determined and stratified by clinical site. RESULTS: The mean age was 59.5 years, 41% were women, and 20% were of minority race or ethnicity. There was extensive comorbidity; 30% had chronic kidney disease, 37% had coronary artery disease, 29% had diabetes mellitus, and 21% had chronic liver disease. Acute renal failure was accompanied by extrarenal organ system failure in most patients, even those who did not require dialysis. Three hundred and ninety-eight (64%) patients required dialysis. The in-hospital mortality rate was 37%, and the rate of mortality or nonrecovery of renal function was 50%. The median hospital length of stay was 25 days (26 days, excluding patients who died). CONCLUSION: There is a changing spectrum of ARF in the critically ill, characterized by a large burden of comorbid disease and extensive extrarenal complications, obligating the need for dialysis in the majority of patients. There is wide variation across institutions in patient characteristics and practice patterns. These differences highlight the need for additional multicenter observational and interventional studies in ARF.

Acute Kidney Injury↗

Run-specific limits of detection and quantitation for STR-based DNA testing.

STR-based DNA profiling is an exceptionally sensitive analytical technique that is often used to obtain results at the very limits of its sensitivity. The challenge of reliably distinguishing between signal and noise in such situations is one that has been rigorously addressed in numerous other analytical disciplines. However, an inability to determine accurately the height of electropherogram baselines has caused forensic DNA profiling laboratories to utilize alternative approaches. Minimum thresholds established during laboratory validation studies have become the de facto standard for distinguishing between reliable signal and noise/technical artifacts. These minimum peak height thresholds generally fail to consider variability in the sensitivity of instruments, reagents, and the skill of human analysts involved in the DNA profiling process over the course of time. Software (BatchExtract) made publicly available by the National Center for Biotechnology Information now provides an alternative means of establishing limits of detection and quantitation that is more consistent with those used in other analytical disciplines. We have used that software to determine the height of each data collection point for each dye along a control sample's electropherogram trace. These values were then used to determine a limit of detection (the average amount of background noise plus three standard deviations) and a limit of quantitation (the average amount of background noise plus 10 standard deviations) for each control sample. Analyses of the electropherogram data associated with the positive, negative, and reagent blank controls included in 50 different capillary electrophoresis runs validate that this approach could be used to determine run-specific thresholds objectively for use in forensic DNA casework.

DNA Fingerprinting↗

Level of ventilation influences the cardiovascular response to hypoxemia in lambs.

Newborn animals of a number of species display a brisk increase in ventilation followed by a gradual drop toward or below baseline within minutes of exposure to acute hypoxemia. Heart rate and cardiac output (a determinant of systemic oxygen transport along with the arterial oxygen content) appear to follow a similar pattern, but whether or not the cardiovascular response is influenced by the respiratory response is unknown. We therefore carried out experiments in which the level of ventilation was controlled during normoxemia and hypoxemia to test the hypothesis that the level of ventilation influences the cardiovascular response to acute hypoxemia. Six lambs ranging in age from 17 to 22 days were anesthetized, tracheostomized, and instrumented for measurement of cardiovascular variables. A recovery period of at least 3 days was allowed before the study when each lamb was artificially ventilated with a mixture of 70% nitrous oxide and 30% oxygen in nitrogen. A control respiratory frequency (f) of 30 breaths per min was set and a control tidal volume (VT) was chosen to achieve normocapnia. Cardiovascular measurements were made during normoxemia and hypoxemia (FIO2 0.10) 5 min after f or VT was changed to simulate a decrease, no change, or an increase in ventilation. During normoxemia, the level of ventilation had little effect on the measured cardiovascular variables. At control levels of ventilation, hypoxemia caused an increase in cardiac output that was due solely to an increase in stroke volume as heart rate decreased; blood pressure was unchanged. Increasing ventilation during hypoxemia did not augment cardiac output or alter blood pressure as compared with that observed at control levels of ventilation. Decreasing ventilation during hypoxemia, however, decreased cardiac output due to a profound bradycardia; blood pressure increased significantly. Our data provide evidence that the level of ventilation significantly influences the cardiovascular response to hypoxemia in young lambs.

Animals↗

Effects of topical anesthesia on upper airway resistance during wake-sleep transitions.

Deformation of the upper airway (UA) by negative transmural pressure alters the activity of UA mechanoreceptors, causing a reflex increase in UA muscle activity. Topical anesthesia of the UA mucosa, which greatly reduces this reflex response, causes an increase in UA resistance during stage 2 sleep. We hypothesized that topical anesthesia of the UA mucosa would predispose to UA instability at sleep onset and, therefore, examined the effect of UA anesthesia on pharyngeal resistance (Rph) in stage 1 sleep. Eleven normal, healthy volunteers were instrumented to record standard polysomnographic variables, respiratory airflow, and UA pressure at the nasal choanae and the epiglottis. Subjects were permitted to sleep until stable stage 2 sleep was reached and were then awoken. This procedure was repeated three times to obtain reproducible wake-sleep transitions. The UA mucosa was then anesthetized with 10% lidocaine to the oropharynx and laryngopharynx, and the pharyngeal mechanics were studied during the subsequent wake-sleep transition. Three subjects were excluded because of failure to resume sleep postanesthesia. Rph was significantly higher after anesthesia during stage 1 sleep [2.88 +/- 0.77 cmH(2)O.l(-1).s (mean +/- SE)] compared with control (0.95 +/- 0.35 cmH(2)O.l(-1).s; P < 0.05), but there was no difference during wakefulness. Furthermore, there was a significant rise in Rph at wake-to-sleep transitions and a significant fall in Rph at sleep-to-wake transitions after anesthesia (P < 0.05) but not in the control condition. We conclude that sensory receptors in the UA mucosa contribute to the maintenance of UA patency at wake-sleep transition in normal humans.

Administration, Topical↗

Effect of dopamine beta-hydroxylase inhibition on systemic hemodynamics in conscious, spontaneously hypertensive rats.

The acute and chronic effects of a potent and selective dopamine beta-hydroxylase inhibitor, SK&F 102698 [1-(3,5-difluorobenzyl)imidazole-2-thiol], on systemic hemodynamic variables were assessed in chronically instrumented spontaneously hypertensive and normotensive Wistar rats. The changes observed in the hypertensive rats were compared with those obtained by vehicle in a different group of rats. Following intragastric administration of SK&F 102698 (75 mg/kg), blood pressure and cardiac output decreased gradually in both strains of rats, while total peripheral vascular resistance remained unchanged. The antihypertensive effect of repeated daily administration of SK&F 102698 in the hypertensive rats was sustained for the duration of treatment. During the acute phase, the decrease in cardiac output was due to bradycardia. In addition, as a result of hemodynamic changes, SK&F 102698 significantly reduced the minute work output of the heart. The results indicate that SK&F 102698 lowers blood pressure primarily by decreasing cardiac output.

Animals↗

A preliminary analysis of a functional model of assessment and treatment for school refusal behavior.

We assessed whether treatment of children and adolescents with school refusal behavior is effective when based upon an individualized, functional analysis. Seven children and adolescents, who were currently experiencing difficulties attending school, were evaluated with the School Refusal Assessment Scale (SRAS), an instrument designed to identify maintaining variables surrounding school refusal behavior. These included specific fearfulness/general overanxiousness, escape from aversive social situations, attention-getting or separation anxious behavior, and tangible reinforcement. Prescriptive treatment was given in accordance with the assessed motivating condition and included systematic desensitization/relaxation training, modeling and cognitive restructuring, shaping and differential reinforcement of other behavior, and contingency contracting for each condition, respectively. Daily measures of anxiety, depression, distress, and school attendance were taken, as well as pretreatment, posttreatment, and 6-month follow-up child and/or parent questionnaires. Results indicated that 6 of the subjects maintained full-time school attendance by posttreatment and at the 6-month follow-up. All reported moderate improvements in daily levels of anxiety, depression, and/or distress. The implications of a prescriptive treatment approach for school refusal behavior are discussed.

Adolescent↗

The revised Personal Lifestyle Questionnaire for early adolescents.

The purposes of this study were to revise the Personal Lifestyle Questionnaire (PLQ), a measure of positive health practices, for use with early adolescents and to provide evidence of reliability and validity for the revised PLQ instrument. The sample consisted of 224 seventh and eighth graders who responded to the revised PLQ and instruments measuring three theoretically relevant variables. Relative to the revised PLQ, content validity was established, construct validity was determined by support of three hypotheses derived from theoretical propositions, and a two-factor solution was accepted in factor analysis procedures using principal components analysis with Varimax rotation. Acceptable reliabilities were obtained on the total revised PLQ and Factor 1; the reliability for Factor 2 fell slightly below the acceptable standard.

Adolescent↗