Hypothermia protects brain function in acute carbon monoxide poisoning

The role of body temperature in the morbidity and mortality resulting from acute severe carbon monoxide (CO) poisoning (2400 ppm CO, 90 min) was investigated using an unanesthetized animal model. Modified Levine prepared female rats (left common carotid artery and jugular cannulated) displayed a lower rate of recovery period (4 hr) re-warming, and an increased mortality rate and behaviorally-assessed neurologic index (NI) compared to normal rats. This indicated their greater susceptibility to CO hypoxia, although the degree of CO-induced hypothermia was the same in both groups. The whole-body cooling of Levine rats to a similar extent prior to CO exposure increased somewhat the post-CO re-warming rate, and marginally decreased NI and mortality during CO exposure (in-CO). In contrast, maintenance of constant body temperature by external heating during CO exposure resulted in a negative post-CO re-warming rate and sharply increased NI and in-CO mortality. Normal euthermic rats were much less severely affected by CO. The results suggest that hypothermia, whether CO-induced or produced by prior cooling, provides measurable protection of brain function during acute severe CO poisoning, and that maintenance of body temperature increases in-CO mortality and interferes with ability to thermoregulate and increases NI in survivors.     

Zinc, copper, manganese, and iron balance of parenterally fed very low birth weight preterm infants receiving a trace element supplement

To evaluate a pediatric trace element supplement (Ped-El, Pharmacia) 18 metabolic balance studies were completed in 13 infants (mean birth weight 909 +/- 67 g, x +/- SEM; mean gestational age 27.2 +/- 1 weeks) who received total parenteral nutrition. The supplement supplied 40 micrograms/kg/day of zinc resulting in negative retention of 226 micrograms/kg/day. Copper infused at 20 micrograms/kg/day led to a positive retention of 8 micrograms/kg/day and an increase in serum Cu (p less than 0.05) not related to Cu intakes. Manganese infused at 40 micrograms/kg/day was nearly all retained (88 +/- 16% retention). Iron infused at 120 micrograms/kg/day led to a positive retention of 93 micrograms/kg/day. Although plasma ferritin and percent transferrin saturation were elevated, only plasma Fe values were correlated with Fe intake. This trace element supplement does not appear suitable for very low birth weight preterm infants.     

Outcomes of cardiopulmonary resuscitation in dialysis patients.

Patients with renal failure are believed to have a poor survival rate after cardiopulmonary resuscitation, but there is little specific information about the outcomes of cardiopulmonary resuscitation in dialysis patients. To be better able to inform dialysis patients and assist them in decision making about cardiopulmonary resuscitation, the eight-year experience with cardiopulmonary resuscitation in dialysis patients at a university dialysis program was analyzed and outcomes were compared with those of a control group of nondialysis patients undergoing cardiopulmonary resuscitation during the same time period in the same hospital. Of 221 dialysis patients experiencing cardiopulmonary arrest, 74 (34%) had CPR compared with 247 (21%) of 1,201 control patients (P = 0.0002). Six of 74 (8%; 95% confidence interval, 2 to 14%) dialysis patients survived to hospital discharge compared with 30 of 247 (12%; 95% confidence interval, 8 to 16%) control patients (P = not significant). At 6 months after CPR, 2 (3%) of 74 dialysis patients were still alive compared with 23 (9%) of 247 controls (P = 0.044); this difference was not explained by age or comorbid conditions. Twenty-one (78%) of the 27 successfully resuscitated dialysis patients died a mean of 4.4 days later; 95% were on mechanical ventilation in an intensive care unit at the time of death. It was concluded that cardiopulmonary resuscitation is a procedure that rarely results in extended survival for dialysis patients. In discussions about cardiopulmonary resuscitation with dialysis patients, nephrologists should provide this information.     

A theophylline dosage regimen which reduces round-the-clock variations in plasma concentrations resulting from diurnal pharmacokinetic variation

Summary Slower drug absorption at night can leave residual drug from an evening dose of a sustained-release product remaining to be absorbed at the time of the next morning's dose, thereby giving higher plasma concentrations of the drug during the day than the night.When a capsule product releasing theophylline over 12 h after a morning dose was given repetitively at 8 a.m. and 8 p.m. for 4 days, daytime plasma concentrations from 4 h to 8 h after the dose were about 40% greater than corresponding night-time concentrations, and the mean steady-state concentration during the night-time interval was only 81% of that during the daytime interval.Altering the regimen to one capsule at 12 noon and one at 10 p.m. eliminated all significant differences between a.m. and corresponding p.m. plasma concentrations of theophylline and between the mean steady-state concentrations for each of the interdose intervals within a day.     

Hepatic and renal clearances of lidocaine in conscious and anesthetized sheep

Sheep were implanted with cannulae to study blood flow through, and drug extraction by, the lungs, kidneys, liver, and gut. Lidocaine, infused to a steady state in conscious sheep, caused no significant changes in cardiac output or regional blood flow, and was cleared principally by the liver, where the extraction ratio usually exceeded 0.9, and by the kidneys, where the extraction ratio was 0.1-0.2. There was no detectable clearance by lungs or gut. Under general anesthesia with 1.5% halothane, the cardiac output and renal and hepatic blood flows were decreased to means of 77, 44, and 79% of mean control values, respectively, but hepatic and renal extraction ratios of lidocaine were not systematically altered, so that regional clearances of lidocaine were not significantly different from those in conscious animals. There was evidence that the total body clearance of lidocaine exceeded the sum of the directly measured regional clearances in both control and general anesthesia studies. These equivocal findings of the effects of general anesthesia on lidocaine clearance are at variance with unequivocal findings of reduced regional clearances of other drugs tested in this preparation.     

The effects of aerobic conditioning and/or caloric restriction in overweight men and women

The purpose of this study was to compare the effects of exercise and/or caloric restriction for 12 wk on body composition, maximal aerobic power (VO2max), and serum lipids and lipoproteins in overweight individuals. Forty-eight males and 48 females (means age = 36.6 yr), 120-140% of ideal body weight, were randomly assigned to groups (N = 12 each) of diet-exercise (DE), diet (D), exercise (E), and sedentary control (C). The dietary regimen consisted of 1,200 kcal X d-1, while exercise consisted of 5 d X wk-1 of 30 min of walk/running. For the males, body weight (BW) and fat weight loss in the DE group (-11.8 and 23%, respectively) were significantly greater than in the D group (-9.1 and -18%), with both groups significantly greater than for E and C. In the females, BW and fat weight loss for DE (-10.4 and -24%) were significantly greater than for D (-7.8 and -20%), with both groups significantly greater than E and C. Both DE and D males and females had a decrease in fat-free weight of -4.5 and -2.4%, respectively. In both sexes, the increase in VO2max-BW (ml X kg -1 X min-1) in DE (25%) was significantly greater than for E (15%), D (11%), and C (0%), with differences between E and D nonsignificant. However, increases in absolute VO2max (1 X min-1) and VO2max-fat-free weight (ml X kg-1 X min-1) were similar (P greater than 0.05) for DE and E (14%) but significantly greater compared to D and C (2%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiovascular, metabolic and neurologic effects of carbon monoxide and cyanide in the rat.

Levine-prepared, female Sprague-Dawley rats were used to investigate the effects of carbon monoxide (CO) and cyanide (CN) on heart rate, blood pressure, hematocrit, body temperature, blood glucose, lactate, and neurologic function. Rats were exposed to either 2400 ppm CO, 1500 ppm CO, 4 mg/kg NaCN, or both 1500 ppm CO and 4 mg/kg NaCN for 90 min, followed by 4 h of room air recovery. Following exposure to 2400 ppm CO, rats exhibited a significant bradycardia which normalized by 2 h of recovery. All groups exhibited an initial hypotension which was either maintained or exaggerated during exposure in all but the rats exposed to CN, and which returned to pre-exposure values by 90 min. All groups experienced a significant hypothermia during the exposure period, with those in the 1500 ppm CO or the CN returning to initial values over the recovery period. The only significant change in hematocrit was due to 2400 ppm CO (4.1% increase). During exposure, all groups experienced an initial surge in glucose concentration which was maintained in all but rats exposed to 2400 ppm CO. The greatest hyperglycemic response resulted from the combination of CO and CN, whereas 2400 ppm CO produced the smallest. CN alone produced no significant rise in lactate concentration. However, lactate concentration in all other groups was significantly elevated during the exposure period, returning to initial values by 4 h of recovery. Lactate concentrations and neurologic deficit in rats exposed to 1500 ppm CO, when added to those rats treated with CN, closely approximated the lactate and neurologic deficit of the combination treatment. Neurologic deficit was greatest in rats exposed to 2400 ppm CO. While in most cases the responses of the rats to CO and CN differed whether the substances were administered alone or in combination, a synergistic relationship is not suggested. An additive or less than additive relationship is more likely.     

Region-specific constitutive gene expression in the adult porcine meniscus.

The knee meniscus exhibits extensive spatial variations in native healing capacity, biochemical composition, and cell morphology that suggest the existence of distinct phenotypes for meniscus cells. Constitutive gene expression levels of appropriate extracellular matrix proteins may serve as useful molecular markers of cellular phenotypes; however, relatively little is known of variations in the gene expression for meniscus cells of different regions of the tissue. The objective of the present study was to evaluate constitutive differences between radial inner and outer regions in gene expression for extracellular matrix proteins relevant to the meniscus. A secondary objective was to determine if these region-specific differences in gene expression are maintained after periods of monolayer culture. The innermost regions of the meniscus were found to constitutively express higher mRNA levels for proteins highly expressed in articular cartilage, including aggrecan, type II collagen, and NOS2. In contrast, the outer meniscus was found to contain higher gene expression for proteins associated with fibrous tissues including type I collagen, and the proteases MMP2 and MMP3. Isolated inner and outer meniscus cells maintained these region-specific gene expression patterns for collagens and proteoglycans during short-term monolayer culture. The results provide new information that suggests the utility of constitutive gene expression levels as molecular markers to distinguish tissue and cells of the inner and outer meniscus.