Phenotypic relationships between docility and reproduction in Angus heifers.

The objective of this study was to elucidate the phenotypic relationships between docility and first-service AI conception rate in heifers. Data ( = 337) collected from 3 cooperator herds in Kansas at the start of synchronization protocol included exit velocity (EV), chute score (CS), fecal cortisol (FC), and blood serum cortisol (BC). Data were analyzed using logistic regression with 30-d pregnancy rate as the dependent variable. The model included the fixed effect of contemporary group and the covariates FC, BC, EV, CS, BW, and age. Correlation coefficients were calculated between all continuous traits. Pregnancy rate ranged from 34% to 60% between herds. Blood cortisol positively correlated with EV ( = 0.22, < 0.01), negatively correlated with age ( = -0.12, < 0.03), and tended to be negatively correlated with BW ( = -0.10, = 0.09). Exit velocity was positively correlated with CS ( = 0.24, < 0.01) and negatively correlated with BW ( = -0.15, < 0.01) and age ( = -0.12, < 0.03). Chute score negatively correlated with age ( = -0.14, < 0.01), and age and BW were moderately positively correlated ( = 0.42, < 0.01), as expected. Older, heavier animals generally had better temperament, as indicated by lower BC, EV, and CS. The power of our test could detect no significant predictors of 30-d pregnancy for the combined data from all ranches. When the data were divided by ranch, CS ( < 0.03) and BW ( < 0.01) were both significant predictors for 30-d pregnancy for ranch 1. The odds ratio estimate for CS has an inverse relationship with pregnancy, meaning that a 1-unit increase in average CS will reduce the probability of pregnancy at ranch 1 by 48.1%. Weight also has a negative impact on pregnancy because a 1-kg increase in BW will decrease the probability of pregnancy by 2.2%. Fertility is a complex trait that depends on many factors; our data suggest that docility is 1 factor that warrants further investigation.

Spatial and temporal variation of algal assemblages in six Midwest agricultural streams having varying levels of atrazine and other physicochemical attributes.

Potential effects of pesticides on stream algae occur alongside complex environmental influences; in situ studies examining these effects together are few, and have not typically controlled for collinearity of variables. We monitored the dynamics of periphyton, phytoplankton, and environmental factors including atrazine, and other water chemistry variables at 6 agricultural streams in the Midwest US from spring to summer of 2011 and 2012, and used variation partitioning of community models to determine the community inertia that is explained uniquely and/or jointly by atrazine and other environmental factors or groups of factors. Periphyton and phytoplankton assemblages were significantly structured by year, day of year, and site, and exhibited dynamic synchrony both between site-years and between periphyton and phytoplankton in the same site-year. The majority of inertia in the models (55.4% for periphyton, 68.4% for phytoplankton) was unexplained. The explained inertia in the models was predominantly shared (confounded) between variables and variable groups (13.3, 30.9%); the magnitude of inertia that was explained uniquely by variable groups (15.1, 18.3%) was of the order hydroclimate>chemistry>geography>atrazine for periphyton, and chemistry>hydroclimate>geography>atrazine for phytoplankton. The variables most influential to the assemblage structure included flow and velocity variables, and time since pulses above certain thresholds of nitrate+nitrite, total phosphorus, total suspended solids, and atrazine. Time since a ≥30 µg/L atrazine pulse uniquely explained more inertia than time since pulses ≥ 10 µg/L or daily or historic atrazine concentrations; this result is consistent with studies concluding that the effects of atrazine on algae typically only occur at ≥30 µg/L and are recovered from.

Seasonal synchronicity of algal assemblages in three Midwestern agricultural streams having varying concentrations of atrazine, nutrients, and sediment.

Numerous studies characterizing the potential effects of atrazine on algal assemblages have been conducted using micro- or mesocosms; however, few evaluations focused on in situ lotic algal communities, potentially confounding risk assessment conclusions. This exploratory study, conducted at several sites in the midwestern United States where atrazine is commonly used, presents in situ observations of native algal communities relative to atrazine exposure and other parameters. Planktonic and periphytic algae from three streams in three Midwestern states, having historically differing atrazine levels, were sampled over a 16-week period in 2011 encompassing atrazine applications and the summer algal growth period at each site. Changes in abundance, diversity, and composition of algal communities were placed in the context of hydrological, climatic, and water quality parameters (including components sometimes present in agricultural runoff) also collected during the study. Diatoms dominated communities at each of the three sites and periphyton was much more abundant than phytoplankton. As expected, significant variations in algal community and environmental parameters were observed between sites. However, correspondence analysis plots revealed that patterns of temporal variation in algal communities at each site and in periphyton or phytoplankton were dominated by seasonal environmental gradients. Significant concordance in these seasonal patterns was detected among sites and between phytoplankton and periphyton communities (via procrustes Protest analysis), suggesting synchronicity of algal communities across a regional scale. While atrazine concentrations generally exhibited seasonal trends at the study watersheds; no effects on algal abundance, diversity or assemblage structure were observed as a result of atrazine pulses. This lack of response may be due to exposure events of insufficient concentration or duration (consistent with previously reported results) or the composition of the algal assemblages present. This was in contrast to the effects of elevated flow events, which were associated with significant changes in periphyton abundance, diversity and assemblage.

Loss of OPA1 disturbs cellular calcium homeostasis and sensitizes for excitotoxicity.

Optic atrophy 1 (OPA1) mutations cause dominant optic atrophy (DOA) with retinal ganglion cell (RGC) and optic nerve degeneration. The mechanism for the selective degeneration of RGCs in DOA remains elusive. To address the mechanism, we reduced OPA1 protein expression in cell lines and RGCs by RNA interference. OPA1 loss results in mitochondrial fragmentation, deficiency in oxidative phosphorylation, decreased ATP levels, decreased mitochondrial Ca(2+) retention capacity, reduced mtDNA copy numbers, and sensitization to apoptotic insults. We demonstrate profound cristae depletion and loss of crista junctions in OPA1 knockdown cells, whereas the remaining crista junctions preserve their normal size. OPA1-depleted cells exhibit decreased agonist-evoked mitochondrial Ca(2+) transients and corresponding reduction of NAD(+) to NADH, but the impairment in NADH oxidation leads to an overall more reduced mitochondrial NADH pool. Although in our model OPA1 loss in RGCs has no apparent impact on mitochondrial morphology, it decreases buffering of cytosolic Ca(2+) and sensitizes RGCs to excitotoxic injury. Exposure to glutamate triggers delayed calcium deregulation (DCD), often in a reversible manner, indicating partial resistance of RGCs to this injury. However, when OPA1 is depleted, DCD becomes irreversible. Thus, our data show that whereas OPA1 is required for mitochondrial fusion, maintenance of crista morphology and oxidative phosphorylation, loss of OPA1 also results in defective Ca(2+) homeostasis.

Effects of dietary protein and bacterial lipopolysaccharide infusion on nitrogen metabolism and hormonal responses of growing beef steers.

Purified lipopolysaccharide (LPS) infusion in cattle induces clinical and metabolic responses similar to gram-negative bacterial infection. Effects of LPS and dietary protein on rectal temperature, serum hormones, haptoglobin, plasma urea N and AA, and N balance were evaluated in 24 steers (250 +/- 2.8 kg of BW). Treatments were a 2 x 3 factorial of LPS (0 vs. 1.5 microg/kg of BW; -LPS vs. +LPS) and diets containing (DM basis) 1) 14.5% CP, 11.6% ruminally degradable protein (RDP), and 2.9% ruminally undegradable protein (RUP; CP14.5CON); 2) 16.3% CP, 13.4% RDP, and 2.9% RUP (CP16RDP); and 3) 16.1% CP, 11.2% RDP, and 4.9% RUP (CP16RUP). Diet RDP and RUP were altered using casein, fish meal, and corn gluten meal. Steers were adapted to diets (1.1 Mcal/kg of NE(g); DM fed at 1.8% BW) for 14 d and were infused (intravenously 1 mL/min) with LPS (in 100 mL of saline) on d 15. Rectal temperature and serum cortisol, prolactin, haptoglobin, and insulin increased, glucose initially increased and then declined, and serum thyroxine and triiodothyronine decreased for +LPS vs. -LPS steers (LPS x hour; P < 0.01). Serum IGF-I was less (P < 0.01) for +LPS vs. -LPS steers. Plasma urea N increased in response to LPS (LPS x hour; P = 0.02) and was greater for +LPS steers fed CP16RDP and CP16RUP vs. CP14.5CON, but greater in -LPS steers fed CP16RUP vs. CP16RDP and CP14.5CON (LPS x diet; P = 0.04). Plasma Met, Thr, Leu, Ile, Phe, Trp, Gly, Ser, Asn, and Tyr decreased, and plasma Ala increased in response to LPS (LPS x hour; P < 0.01). Plasma Orn initially increased and then decreased in +LPS vs. -LPS steers (LPS x hour; P < 0.01). No LPS x diet interactions (P > or = 0.15) occurred for DM, OM, NDF and N intake, fecal excretion, or apparent digestibility. Dietary DM, OM, NDF, and N intake, and retained N were less (P < 0.01) for +LPS than -LPS steers. Total N intake, apparent N digestibility, and retained N were greater (P < or = 0.05) for steers fed CP16RDP and CP16RUP vs. CP14.5CON. An LPS x diet interaction (P = 0.05) occurred for N retention (% N intake) because N retention was less for +LPS than -LPS steers when fed CP14.5CON, but not different between +LPS and -LPS steers when fed CP16RDP and CP16RUP. These results demonstrate that LPS infusion alters serum hormones, plasma AA, and N balance in cattle and imply that growing steers exposed to LPS may require greater dietary protein concentrations to account for altered intake and metabolic AA demand.

Effects of rumen-protected methionine supplementation and bacterial lipopolysaccharide infusion on nitrogen metabolism and hormonal responses of growing beef steers.

Metabolic demand for sulfur-containing AA increases during inflammation in nonruminants. Therefore, Met supplementation may alleviate the negative effects of infection on N balance. Effects of gram-negative bacterial lipopolysaccharide (LPS) and supplemental dietary Met on N balance, serum hormones and haptoglobin, and plasma urea-N and AA were evaluated in 20 Angus-cross steers (BW = 262 +/- 6.3 kg). Treatments (2 x 2 factorial) were infusion of no LPS (-LPS) or a prolonged low dose of LPS (+LPS) and dietary supplementation of no (-MET) or 14 g/d (+MET) of rumen-protected Met (providing 7.9 g/d of dl-Met). Steers were adapted to a roughage-based diet (DMI = 1.4% of BW daily) and supplemental Met for 14 d, and were then infused (1 mL/min via intravenous catheter) with LPS on d 1 (2 microg/kg of BW) and 3 (1 microg/kg of BW) of a 5-d collection period. Blood was collected on d 1, before LPS infusion, and at 2, 4, 6, 8, 10, 12, and 24 h after LPS challenge. Diet samples, feed refusals, feces, and urine were collected daily for 5 d. Rectal temperature and serum concentrations of cortisol, prolactin, tumor necrosis factor-alpha, and haptoglobin increased, whereas thyroxine and triiodothyronine decreased for +LPS vs. -LPS steers (LPS x h; P < 0.01). Plasma urea-N was greater for +LPS than -LPS steers (LPS; P = 0.03), and serum IGF-1 was not affected (P > or = 0.26) by LPS or Met. Plasma concentrations of Thr, Lys, Leu, Ile, Phe, Trp, Asn, Glu, and Orn decreased, plasma Ala increased, and Gly and Ser initially increased, then declined in +LPS vs. -LPS steers (LPS x h; P < or = 0.04). Plasma Met was greater for +MET than -MET steers before LPS infusion, but declined in +MET steers after LPS infusion (LPS x Met x h; P < 0.01). By design, DMI was not different, but DM digested was less (P = 0.04) for +LPS than -LPS steers. Infusion of LPS did not affect (P > or = 0.24) N intake, fecal N excretion, or N digested, but resulted in greater (P < 0.01) urinary N excretion and less (P < 0.01) N retention. The absence of an LPS x Met interaction (P = 0.26) for N retention indicates that supplemental Met does not improve the N utilization of growing beef steers exposed to a gram-negative bacterial endotoxin. Decreases in plasma concentrations of several essential AA in +LPS steers suggest that metabolic demand for these AA likely increased in steers exposed to endotoxin.

Limiting amino acids for growing lambs fed a diet low in ruminally undegradable protein.

Ruminally cannulated Rambouillet wether lambs were used in three 6 x 6 Latin square experiments (n = 6/experiment) to determine which essential AA limit N retention. Lambs (BW = 36.9 +/- 1.9 kg for Exp. 1, 35.1 +/- 1.4 kg for Exp. 2, and 46.0 +/- 1.3 kg for Exp. 3) were housed in metabolism crates and limit-fed (DMI = approx. 1.8% of BW daily) twice daily a soybean hull-based diet low in ruminally undegradable protein. Treatments for Exp. 1 were continuous abomasal infusions of a solution (500 mL/d) containing 1) no AA (CON), 2) a mixture of 10 essential AA and 2 nonessential AA (10EAA), 3) 10EAA with Met removed, 4) 10EAA with Lys removed, 5) 10EAA with His removed, and 6) 10EAA with Thr removed. Treatments for Exp. 2 were abomasal infusions of 1) CON, 2) 10EAA, 3) 10EAA with Leu, Ile, and Val removed (-BCAA), 4) 10EAA with Arg removed, 5) 10EAA with Phe removed, and 6) 10EAA with Trp removed. Treatments for Exp. 3 were abomasal infusions of 1) CON, 2) 10EAA, 3) -BCAA, 4) 10EAA with Leu removed, 5) 10EAA with Ile removed, and 6) 10EAA with Val removed. All lambs received continuous infusions of acetate and propionate into the rumen and dextrose into the abomasum to supply additional energy. Periods were 7 d: 3 d for adaptation to abomasally infused treatments and 4 d for fecal and urinary collections. Blood samples were collected 3 h after feeding on d 7. In all 3 experiments, N retention was greater (P < 0.10) for lambs receiving 10EAA vs. CON, demonstrating that the basal AA supply from CON was limiting. Removal of each of the essential AA from 10EAA decreased (P < 0.10) their concentrations in plasma (except for Trp), indicating that 10EAA supplied these AA in excess of the animal's requirement. In Exp. 1, N retention (g/d) decreased (P < 0.10) in response to the removal of Met and Thr, but was not affected by removal of Lys and His from 10EAA. In Exp. 2, N retention decreased (P < 0.10) in response to removal of all 3 branched-chain AA, Arg, and Trp, whereas the removal of Phe from 10EAA did not affect N retention. In Exp. 3, N retention decreased (P < 0.10) in response to removal of branched-chain AA and Val, but was not affected by the omission of Leu and Ile from 10EAA. The results of this research demonstrated that Met, Thr, Arg, Trp, and Val limited N retention of lambs fed a diet low in ruminally undegradable protein.

Suppression of bloodfeeding by Ochlerotatus dorsalis and Ochlerotatus melanimon on cattle treated with python ear tags.

Adult mosquitoes were collected by drop traps to compare bloodfeeding rates between cattle treated with 2 Python ear tags (10% zeta-cypermethrin and 20% piperonyl butoxide) per animal and animals that were untreated. Mosquitoes were collected both 2 and 4 wk after application of the ear tags. Bloodfeeding by Ochlerotatus dorsalis was reduced by 79 and 77%, respectively, and bloodfeeding by Ochlerotatus melanimon was reduced by 84 and 81%, respectively, at 2 and 4 wk. Based on chi-square analysis, differences in bloodfeeding rates due to treatment were significant. The effect of the treatment appeared to be repellency, because no mosquito mortality was observed at the time of collection and no mortality was observed among bloodfed mosquitoes that were collected and held for 24 h.

Suppression of mosquito (Diptera: Culicidae) and black fly (Diptera: Simuliidae) blood feeding from Hereford cattle and ponies treated with permethrin.

The blood feeding of mosquitoes and black flies from Hereford cattle and ponies treated with commercial formulations of permethrin was evaluated using an animal enclosure trap sample system that allowed comparison of insect blood-feeding levels between treated and nontreated animals. Blood feeding of both Aedes dorsalis Meigen and A. melanimon Dyar from heifers treated with pour-on concentrate and whole body spray treatments was reduced significantly by 79-88% at 4 d posttreatment, with apparent but not significant reductions of 61-68% at 11 d posttreatment. Simulium bivittatum Malloch and S. griseum Coquillett blood feeding was reduced significantly by 96% to >99% at 4 d posttreatment, but apparent reductions of 30-87% at 11 d posttreatment were not significant. Blood feeding of S. bivittatum from ponies treated with a permethrin fly wipe was reduced significantly by 98 and 87% at 1 and 7 d posttreatment, respectively. No evidence of treatment-induced mortality was observed for recently blood-fed female mosquitoes or black flies captured from treated animals and held for 24 h. The potential benefit of using permethrin to protect livestock from insect-transmitted pathogens was estimated with a model based on level of host attack, pathogen infection rate in the vector, and suppression of blood feeding. Suppression of blood feeding by 90% is predicted to prevent the exposure of a host to a pathogen for up tolO d at 1,000 insect feedings per d when the vector population infection rate is one insect per 1,000. If insect feedings are lower (100/d) and the insect infection rate remains at one per 1,000, protection is predicted for 100 d. In contrast, a 90% suppression of blood feeding is predicted to provide protection for less than 1 d at 1,000 feeding per day and a vector infection rate of one insect per 100.

The effect of changing transfusion practice on rates of perioperative stroke and myocardial infarction in patients undergoing carotid endarterectomy: a retrospective analysis of 1114 Mayo Clinic patients. Mayo Perioperative Outcomes Group.

OBJECTIVE: To evaluate changes in the institution's red blood cell (RBC) transfusion practice during the past 15 years and the influence of these changes on neurologic or cardiac morbidity after carotid endarterectomy. PATIENTS AND METHODS: Based on a retrospective analysis of the Mayo Clinic database, 1,114 patients who underwent carotid endarterectomy were stratified into 1 of 2 groups: (1) 1980 to 1985 (ie, pre-human immunodeficiency virus screening, early-practice group [n=552]) and (2) 1990 to 1995 (ie, recent-practice group [n=562]). Data were compared between time periods using the chi2 test for categorical variables and the rank sum test for continuous variables. Logistic regression was used to assess the association between perioperative transfusion practice and the occurrence of stroke or myocardial infarction. Two-tailed P values < or = 05 were considered statistically significant. RESULTS: Patients in the recent-practice group were significantly older (mean +/- SD age, 69.6 +/- 8.7 years) vs 65.9 +/- 8.3 years in the early-practice group (P<.001). The proportion of patients receiving perioperative RBC transfusion decreased dramatically from 72.9% in 1980-1985 to 8.7% in 1990-1995 (P<.001). Additionally, the mean +/- SD number of RBC units transfused decreased from 1.10 +/- 1.30 U in 1980-1985 to 0.27 +/- 1.22 U in 1990-1995 (P<.001). Mean +/- SD discharge hemoglobin concentration decreased from 13.7 +/- 1.4 g/dL in 1980-1985 to 11.8 +/- 1.5 g/dL in 1990-1995 (P<.001). Rates of perioperative stroke and myocardial infarction did not differ between the 2 time periods (early-practice group vs recent-practice group: stroke, 5.1% vs 3.6% [P=.22]; myocardial infarction, 1.5% vs 2.3% [P=.29]). CONCLUSIONS: Our results suggest that elderly patients undergoing carotid endarterectomy (ie, individuals known to be at high risk for cerebral and cardiac ischemia) can tolerate modest perioperative anemia despite a considerable change in the institution's transfusion practice (lower "transfusion trigger," the hemoglobin concentration or hematocrit value below which RBC transfusion is indicated).

Persistent efficacy of doramectin topical solution against induced infestations of Bovicola bovis and Solenopotes capillatus.

A study was conducted in two locations, Wyoming and Wisconsin, USA, to evaluate the persistent efficacy of doramectin topical solution at a dose rate of 500 microg/kg body weight against artificially induced infestations of Bovicola bovis and Solenopotes capillatus on cattle. At each location, lice-free beef calves were individually housed and randomly allocated to treatment. Both B. bovis and S. capillatus were transferred from untreated donor animals to doramectin-treated cattle at the end of 35, 63, 91 or 126 day post-treatment periods. Cattle treated with a saline pour-on served as the control. Based on the geometric means of lice counts 2 weeks following transfer, the persistent efficacy of a single treatment with doramectin topical solution against induced infestations of B. bovis was 100.0, 100.0, 99.5, and 100.0% at post-treatment days of 35, 63, 91, and 126, respectively. Persistent efficacy against induced infestations of S. capillatus, for the same intervals, were 100.0, 94.9, 86.3, and 74.9%.

Selective convective brain cooling during normothermic cardiopulmonary bypass in dogs.

OBJECTIVE: Although normothermic cardiopulmonary bypass results in improved cardiac outcome, patients do not benefit from hypothermia-mediated brain protection and thus may be at high risk for ischemic brain injury. The present study evaluated the efficacy of selective forced-air cerebral cooling. METHODS: Sixteen dogs were anesthetized with either intravenous pentobarbital or inhaled halothane (n = 8 for each group). Temperatures were monitored in the esophagus (i.e., core), parietal epidural space, and brain parenchyma. Normothermic atrial-femoral cardiopulmonary bypass and forced-air pericranial cooling (to approximately 13 degrees C) were maintained for 150 minutes. Data between groups were compared by means of repeated-measures analysis of variance and two-sample t test. Within each group, brain-to-core temperature gradients were compared to zero by means of the one-sample t test. RESULTS: In pentobarbital-anesthetized dogs, after 30 minutes of cerebral cooling, temperatures in the parietal epidural space and 1 cm and 2 cm beneath the dura were 3.3 degrees +/- 1.4 degrees C (mean +/- standard deviation), 2.6 degrees +/- 1.3 degrees C, and 1.1 degrees +/- 0.6 degrees C cooler than the core temperature, respectively. At the conclusion of the study (i.e., 150 minutes), these temperatures were 4.5 degrees +/- 1.8 degrees C, 3.9 degrees +/- 1.6 degrees C, and 2.0 degrees +/- 0.9 degrees C cooler than the core temperature, respectively. Similar changes were observed in halothane-anesthetized dogs. CONCLUSIONS: Regardless of the background anesthetic, the magnitude of selective cerebral cooling observed in our study was larger than the 1 degree to 2 degrees C changes previously reported to modulate ischemic brain injury.

Efficacy of eprinomectin against Hypoderma spp in cattle.

OBJECTIVE: To determine the efficacy of a topical formulation of eprinomectin against natural infestations of first (L1)-stage, and second and third (L2/L3)-stage larvae of Hypoderma spp. ANIMALS: 140 approximately 6- to 18-month-old cattle of various breeds. PROCEDURE: Cattle, selected from herds with high prevalence of Hypoderma infestation, were treated in 4 experiments: within each replicate, 1 animal received eprinomectin at a dosage of 500 micrograms/kg of body weight against first-stage larvae (L1). The second animal received the same treatment against second or third-stage larvae (L2/L3). The third animal served as an untreated control. In a fifth experiment, visible warbles were treated on half of the cattle. Remaining cattle served as vehicle-treated controls. In 1 experiment, warbles were examined from time of treatment until all lesions were resolved. In 4 experiments, emerging Hypoderma larvae were recovered, speciated, and enumerated, and viability was determined. RESULTS: Eprinomectin (500 micrograms/kg) efficacy was complete against L1. Hypoderma L2/L3 eradication approached 100% efficacy (1 live larva was recorded). Warbles in treated cattle resolved in a significantly shorter time than did those in controls. Adverse reactions related to treatment were not observed in any of the trials. CONCLUSIONS: Eprinomectin (500 micrograms/kg) applied topically was safe and highly efficacious for treatment of all larval stages of Hypoderma spp in these trials. CLINICAL RELEVANCE: Attributes of eprinomectin besides antiparasite efficacy allow treatment of all classes of cattle with no need for meat or milk withdrawal.

Selective convective brain cooling during hypothermic cardiopulmonary bypass in dogs.

BACKGROUND: Neurologic complications, primarily resulting from ischemic insults, represent the leading cause of morbidity and disability, and the second most common source of death, after cardiac operations. Previous studies have reported that increases (as occur during the rewarming phase of cardiopulmonary bypass [CPB]) or decreases in brain temperature of a mere 0.5 degrees to 2 degrees C can significantly worsen or improve, respectively, postischemic neurologic outcome. The purpose of the present study was to evaluate a novel approach of selectively cooling the brain during hypothermic CPB and subsequent rewarming. METHODS: Sixteen dogs were anesthetized with either intravenous pentobarbital or inhaled halothane (n = 8 per group). Normocapnia (alpha stat technique) and a blood pressure near 75 mm Hg were maintained. Temperatures were monitored by placing thermistors in the esophagus (i.e., core), parietal epidural space, and brain parenchyma at depths of 1 and 2 cm beneath the dura. During CPB, core temperature was actively cycled from 38 degrees C to 28 degrees C, and then returned to 38 degrees C. Forced air pericranial cooling (air temperature of approximately 13 degrees C) was initiated simultaneous with the onset of CPB, and maintained throughout the bypass period. Brain-to-core temperature gradients were calculated by subtracting the core temperature from regional brain temperatures. RESULTS: In halothane-anesthetized dogs, brain temperatures at all monitoring sites were significantly less than core during all phases of CPB, with one exception (2 cm during systemic cooling). Brain cooling was most prominent during and after systemic rewarming. For example, during systemic rewarming, average temperatures in the parietal epidural space, and 1 and 2 cm beneath the dura, were 3.3 degrees +/- 1.3 degrees C (mean +/- standard deviation), 3.2+/-1.4 degrees C, and 1.6 degrees +/-1.0 degrees C, cooler than the core, respectively. Similar trends, but of a greater magnitude, were noted in pentobarbital-anesthetized dogs. For example, during systemic rewarming, corresponding brain temperatures were 6.5 degrees +/-1.7 degrees C, 6.3 degrees +/-1.6 degrees C, and 4.2+/-1.3 degrees C cooler than the core, respectively. CONCLUSIONS: The magnitude of selective brain cooling observed in both study groups typically exceeded the 0.5 degrees to 2.0 degrees C change previously reported to modulate ischemic injury, and was most prominent during the latter phases of CPB. When compared with previous research from our laboratory, application of cold forced air to the cranial surface resulted in brain temperatures that were cooler than those observed during hypothermic CPB without pericranial cooling. On the basis of the assumption that similar beneficial brain temperature changes can be induced in humans, we speculate that selective convective brain cooling may enable clinicians to improve neurologic outcome after hypothermic CPB.

Mephenytoin disposition and serum bile acids as indices of hepatic function in chronic viral hepatitis.

BACKGROUND AND OBJECTIVES: The effect of chronic viral hepatitis on liver function may vary from none to hepatic failure. Changes in function are usually the result of impaired hepatocyte function or altered vascular flow and architecture. Conventional liver function tests usually cannot distinguish contributions from these mechanisms or indicate degree of hepatic metabolic dysfunction. An alternative approach is to measure the hepatic metabolism of a highly extracted compound whose oral clearance and systemic bioavailability are dependent on both hepatocyte function and degree of portosystemic shunt. METHODS: The stereoselective metabolism of racemic mephenytoin (100 mg oral dose) was investigated in 35 patients with chronic viral hepatitis and compared with 153 healthy subjects. The mephenytoin R/S enantiomeric ratio and cumulative excretion of the 4'-hydroxymephenytoin metabolite in a 0- to 8-hour urine sample were used in addition to serum bile acid levels and pathologic examination of biopsy specimens to assess the severity of hepatic dysfunction and portosystemic shunting. RESULTS: The patients as a group excreted less 4'-hydroxymephenytoin and had a smaller R/S enantiomeric ratio of mephenytoin. The two measures were discriminatory between the patient groups classified by either serum cholylglycine level or pathologic examination of biopsy specimens. Combination of the two measures of mephenytoin metabolism allowed the patients to be classified into three groups: normal hepatocyte function without portosystemic shunt, normal hepatocyte function with portosystemic shunt, and low hepatocyte function with or without portosystemic shunt. CONCLUSION: This study has shown the potential usefulness of mephenytoin metabolism as a sensitive indicator of hepatic pathologic condition with an ability to discriminate between contributory alternative mechanisms.

Regulation of cultured human chorion cell chemokine production by group B streptococci and purified bacterial products.

PROBLEM: To determine if different strains of group B streptococci (GBS) and purified bacterial products regulate chemokine production by cultured human chorion cells. METHOD OF STUDY: Primary cultures of human chorion cells were established from placentae isolated from normal women at term gestation having repeat cesarean section. Five different strains of heat-killed GBS were incubated with confluent chorion cells at 10(7) bacteria/ml for 16 hours at 37 degrees C. In separate experiments, lipoteichoic acid and sialic acid at various concentrations were incubated with chorion cells for 16 hours at 37 degrees C. Culture supernatants were collected and then assayed to determine concentrations of interleukin-8 (IL-8) and macrophage inflammatory protein-1 alpha (MIP-1 alpha) by ELISA. RESULTS: We found that GBS stimulated chorion cell production of MIP-1 alpha in a strain-specific fashion. We also found that both lipoteichoic acid and sialic acid stimulated concentration-dependent increases in chorion cell IL-8 production. Chorion cells, however, did not increase MIP-1 alpha production in response to either lipoteichoic acid or sialic acid. Two strains of GBS tested induced concentration-dependent increases in both IL-8 and MIP-1 alpha, but both stimulated IL-8 production to a greater extent. Similarly, IL-1 beta also caused chorion cells to produce more IL-8 than MIP-1 alpha. CONCLUSIONS: Our data are the first to show that GBS and purified bacterial products can stimulate chemokine production by fetal gestational tissues. We suggest that chorion cells may produce specific types of chemokines to attract different types of inflammatory cells and thus may participate in the pathophysiology of infection-mediated preterm labor by directing specific inflammatory responses.

Doramectin systemic activity against cattle grubs, Hypoderma lineatum and H. bovis (Diptera: Oestridae), and cattle lice, bovicola bovis (Mallophaga: Trichodectidae), Linognathus vituli and Solenopotes capillatus (Anoplura: Linognathidae), and Haematopinus eurysternus (Anoplura: Haematopinidae), in Wyoming.

Seven individual trials were conducted in Wyoming to evaluate the therapeutic efficacy of doramectin administered subcutaneously at a dosage of 200 micrograms kg-1 against multiple, natural infestations of cattle grubs or cattle lice. Insect species present and the number of trials that included each species were: Hypoderma lineatum, 2; Hypoderma bovis. 1; Bovicola bovis, 5; Haematopinus eurysternus, 1; Linognathus vituli, 5; and Solenopotes capillatus, 3. Examinations for lice were performed prior to treatment and either weekly or bi-weekly thereafter for 28 days. Examinations for cattle warbles were performed either weekly or every 4 to 5 weeks from time of first appearance through last appearance in the backs of the cattle. No H. lineatum, H. bovis, H. eurysternus, L. vituli, or S. capillatus were found on doramectin-treated animals at any time following treatment. By 28 days following treatment, the number of B. bovis was reduced between 58 and 98%. Treatments applied later in the season, i.e. in March, were more efficacious against B. bovis than those applied in January or February.

Factors that influence metaphor comprehension skills in adulthood.

We investigated differences between older and younger adults in interpreting metaphors describing emotions (e.g., "Joe was crashing thunder," meaning that he was angry). Subjects selected emotional interpretations and explained the basis of their selection for 12 metaphors. Twenty-four older and 24 younger adults read metaphors that described emotions. The group performed identically when selecting interpretations, but older adults were more likely to make up stories about the person named in the metaphor to explain the metaphor than were younger adults, who focused on attributes of the metaphoric terms. These findings suggest that observed adult age differences in metaphor comprehension reflect methodological factors and may reflect cognitive style differences.

Changes in "inflammatory" mediators and total body water during extra-corporeal membrane oxygenation (ECMO). A preliminary study.

We studied six patients (5 paediatric, 1 neonate) treated with ECMO to quantify changes in inflammatory mediators (neutrophil elastase (NE), free radical activity (FR), interleukin 8 (IL8)) and total body water (TBW). Blood samples were taken before instigation of ECMO, 4, 12, 24 hours post-ECMO and daily for six days. FR activity was quantified using the oxidised IgG FI/UV ration. NE and IL8 levels were measured by ELISA. TBW was assessed by electrical bioimpedance. Statistical analysis was made using repeated measures analysis of variance and modified t-test where appropriate. Results are presented as mean +/- standard error of the mean. FR activity increased 4 hours after instigation of ECMO (IgG FI/UV 32.1 +/- 3.2 from 24.1 +/- 3.0 p = 0.005) and remained elevated. NE also increased by 4 hours (94.8 micrograms/L +/- 8.9 to 678 micrograms/L +/- 153.4, p = 0.005) but returned to pre-ECMO values by day 6. IL8 levels rose after ECMO (from 98 pg/ml +/- 39, to 24 pg/ml +/- 117.4) although no statistical difference was noted over time due to the large variation between subjects (p = 0.009). TBW (% pre-ECMO body weight) fell by 24 hours (from 118.6 +/- 12.6 to 96.5 +/- 8.2 p = 0.0004). This study demonstrated that ECMO stimulates an 'inflammatory' response to extracorporeal perfusion (increased FR, NE) but despite this, results in a reduction in total body water. The complex relationship between the inflammatory response to prolonged extracorporeal perfusion and its effect on tissue oedema merits further investigation.

Hepatitis delta virus RNA in serum of patients with chronic delta hepatitis.

We studied 28 patients with chronic delta hepatitis for the presence of hepatitis delta virus (HDV) RNA in serum. The hot start polymerase chain reaction (PCR) method, in which the reaction begins at 60-80 degrees C, showed a higher sensitivity than conventional PCR reaction. Additionally, the presence of hepatitis B (HBV) and C virus (HCV) infections were determined by PCR. HDV RNA was detected in 26 patients (93%), HBV DNA in 22 (79%), and HCV RNA in only one. Detection of HDV RNA correlated very well with detection of hepatitis delta antigen by immunostaining in the liver. In six patients HDV RNA was detectable despite the absence of HBV DNA in serum, suggesting that high levels of HBV are not required for HDV replication. Of 29 control patients with chronic hepatitis B without antibody to HDV, none had detectable HDV RNA, while all had HBV DNA in serum. Detection of HDV RNA with PCR proved highly sensitive and specific, demonstrating that virtually all patients with chronic HDV infection had ongoing viral replication.