Assessment and validation of a defined fluid restriction protocol in the use of subcutaneous desmopressin for children with inherited bleeding disorders.

INTRODUCTION: Despite the availability of subcutaneous desmopressin (1-deamino-8-d-arginine vasopressin, SC-DDAVP) as a haemostatic agent for children with mild bleeding disorders, few publications specifically address the safety or efficacy of this mode of administration. AIM: Our aim was to assess whether a defined fluid restriction protocol was effective in preventing hyponatremia in children receiving perioperative SC-DDAVP, and to document adequate biological and clinical response in this setting. METHODS: We retrospectively analysed a cohort of children with mild bleeding disorders prescribed SC-DDAVP over a 5-year period following institution of a 'two-thirds maintenance' fluid restriction protocol. RESULTS: Sixty-nine patients received SC-DDAVP following this protocol, including 15 with mild haemophilia A, 49 with von Willebrand disease (VWD) and five with platelet storage pool disorder. In patients who underwent formal preoperative assessment a complete or partial response was observed in 28/29 with type 1 VWD and 14/15 with mild haemophilia A. Perioperative SC-DDAVP provided excellent haemostasis in all patients, with no requirement for factor concentrate or blood products. Mild asymptomatic hyponatremia was detected in seven children who received multiple doses of DDAVP (lowest sodium 129 mmol L(-1) ); however, adherence to the prescribed fluid restriction protocol was questionable in six of these cases. Symptomatic hyponatremia was not observed. CONCLUSION: Subcutaneous desmopressin was well-tolerated, with no serious side-effects observed, and good biological responses in preoperative trials. A two-thirds maintenance fluid regimen was effective at preventing symptomatic hyponatremia in our cohort, and is now the standard protocol for fluid restriction post-DDAVP administration in our centre.

Single and multi-gene phylogeny of Hepatospora (Microsporidia) - a generalist pathogen of farmed and wild crustacean hosts.

Almost half of all known microsporidian taxa infect aquatic animals. Of these, many cause disease in arthropods. Hepatospora, a recently erected genus, infects epithelial cells of the hepatopancreas of wild and farmed decapod crustaceans. We isolated Hepatospora spp. from three different crustacean hosts, inhabiting different habitats and niches; marine edible crab (Cancer pagurus), estuarine and freshwater Chinese mitten crab (Eriocheir sinensis) and the marine mussel symbiont pea crab (Pinnotheres pisum). Isolates were initially compared using histology and electron microscopy revealing variation in size, polar filament arrangement and nuclear development. However, sequence analysis of the partial SSU rDNA gene could not distinguish between the isolates (~99% similarity). In an attempt to resolve the relationship between Hepatospora isolated from E. sinensis and C. pagurus, six additional gene sequences were mined from on-going unpublished genome projects (RNA polymerase, arginyl tRNA synthetase, prolyl tRNA synthetase, chitin synthase, beta tubulin and heat shock protein 70). Primers were designed based on the above gene sequences to analyse Hepatospora isolated from pea crab. Despite application of gene sequences to concatenated phylogenies, we were unable to discriminate Hepatospora isolates obtained from these hosts and concluded that they likely represent a single species or, at least subspecies thereof. In this instance, concatenated phylogenetic analysis supported the SSU-based phylogeny, and further, demonstrated that microsporidian taxonomies based upon morphology alone are unreliable, even at the level of the species. Our data, together with description of H. eriocheir in Asian crab farms, reveal a preponderance for microvariants of this parasite to infect the gut of a wide array of decapods crustacean hosts and the potential for Hepatospora to exist as a cline across wide geographies and habitats.

Independent fermentation and metabolism of dietary polyphenols associated with a plant cell wall model.

Ingested polyphenols from plant-based foods are in part carried to the large intestine and metabolised by resident microbiota. This work investigated the release and microbial transformation of polyphenols adsorbed individually or in combination to apple cell walls (ACW) and pure (bacterial) cellulose (BC). BC and ACW, representing poorly- and highly-fermentable fibre models respectively, were used to investigate influences of interactions with polyphenols (cyanidin-3-glucoside, (±)-catechin, ferulic acid), on the release and microbial metabolism of polyphenols during in vitro digestion and fermentation. Bound polyphenols were partially released (20-70%) during simulated digestion, depending on polyphenol molecular structure. All remaining bound polyphenols were completely released and metabolised after 6-9 h by porcine large intestine microbiota, with formation of a number of intermediates and end-products. The same pathways of polyphenol microbial metabolism were observed in the presence and absence of ACW/BC, suggesting that microbial metabolism of polyphenols and carbohydrate substrates seems likely independent. Some polyphenol metabolism products were produced faster in the presence of carbohydrate fermentation, particularly of ACW. Microbial metabolism pathways of model polyphenols by a porcine faecal inoculum are not affected by being associated with BC or ACW, but the rate of metabolism is modestly enhanced with concurrent carbohydrate fermentation.

Anthropoid origins.

Recent fossil discoveries have greatly increased our knowledge of the morphology and diversity of early Anthropoidea, the suborder to which humans belong. Phylogenetic analysis of Recent and fossil taxa supports the hypotheses that a haplorhine-strepsirrhine dichotomy existed at least at the time of the earliest record of fossil primates (earliest Eocene) and that eosimiids (middle Eocene, China) are primitive anthropoids. Functional analysis suggests that stem haplorhines were small, nocturnal, arboreal, visually oriented insectivore-frugivores with a scurrying-leaping locomotion. A change from nocturnality to diurnality was the fundamental adaptive shift that occurred at the base of the tarsier-eosimiid-anthropoid clade. Stem anthropoids remained small diurnal arborealists but adopted locomotor patterns with more arboreal quadrupedalism and less leaping. A shift to a more herbivorous diet occurred in several anthropoid lineages.

Behavioral fever in newborn rabbits.

Rabbit pups, 12 to 72 hours old, did not develop a fever when injected intraperitoneally with a pyrogen and maintained at an ambient temperature of 32 degrees C for 2 hours. When placed in a thermally graded alleyway, animals injected with pyrogen selected gradient positions that represented significantly higher temperatures than controls injected with saline (40.4 degrees in contrast to 36.4 degrees C). Allowing the pups to remain at their selected positions for 5 minutes caused a significant increase in the rectal temperatures of the pyrogen-injected pups but not that of the controls. Thus, newborn rabbits will develop a fever by behavioral means after a single injection of an exogenous pyrogen.

Brain calcium: role in temperature regulation.

Perfusion of the preoptic-anterior hypothalamus with excess calcium ion in ground squirrels produces a drop in core temperature. The magnitude of the drop is directly dependent on ambient temperature. Respiration, heart rate, and oxygen consumption are also reduced during perfusion of calcium ion. It is concluded that the depression of body temperature during calcium ion perfusion is due to generalized depression of the neurons of the preoptic-anterior hypothalamus.

Interscalene block using ultrasound guidance: impact of experience on resident performance.

BACKGROUND: We evaluated the weekly progress of anesthesiology residents performing an interscalene block with ultrasound guidance (UG) for block success rates and for the specific time intervals: (i) time to image the brachial plexus and (ii) time from insertion of the block needle until motor stimulation occurred. Our primary objective was to characterize the influence of experience over the course of the regional anesthesia rotation on the performance of a UG interscalene block by anesthesiology residents. METHODS: Residents conducted an interscalene block with UG under the supervision of attending anesthesiologists experienced in this technique. Block efficacy, time intervals required to perform the block, and acute complications were recorded. We compared success rates over the course of the rotation, and analyzed process time data with respect to trainee level of experience, week of the trainee rotation, and patient body habitus. RESULTS: Twenty-one trainees conducted 222 blocks over a consecutive 7-month period. Block success rate was 97.3%, and did not change significantly over the course of the 4-week rotation. Total block time and imaging time significantly decreased over the 4-week rotation, while the needle insertion-to-stimulation time did not change. Slower imaging time was predicted by obesity. CONCLUSION: The success rates for a UG interscalene block provided by supervised residents were initially high, and remained so throughout the 4-week rotation. Trainees required less time to image the nerves and to perform the block over the course of the rotation.

Review: Effects of fibre, grain starch digestion rate and the ileal brake on voluntary feed intake in pigs.

Grains rich in starch constitute the primary source of energy for both pigs and humans, but there is incomplete understanding of physiological mechanisms that determine the extent of digestion of grain starch in monogastric animals including pigs and humans. Slow digestion of starch to produce glucose in the small intestine (SI) leads to undigested starch escaping to the large intestine where it is fermented to produce short-chain fatty acids. Glucose generated from starch provides more energy than short-chain fatty acids for normal metabolism and growth in monogastrics. While incomplete digestion of starch leads to underutilised feed in pigs and economic losses, it is desirable in human nutrition to maintain consistent body weight in adults. Undigested nutrients reaching the ileum may trigger the ileal brake, and fermentation of undigested nutrients or fibre in the large intestine triggers the colonic brake. These intestinal brakes reduce the passage rate in an attempt to maximise nutrient utilisation, and lead to increased satiety that may reduce feed intake. The three physiological mechanisms that control grain digestion and feed intake are: (1) gastric emptying rate; (2) interplay of grain digestion and passage rate in the SI controlling the activation of the ileal brake; and (3) fermentation of undigested nutrients or fibre in the large intestine activating the colonic brake. Fibre plays an important role in influencing these mechanisms and the extent of their effects. In this review, an account of the physiological mechanisms controlling the passage rate, feed intake and enzymatic digestion of grains is presented: (1) to evaluate the merits of recently developed methods of grain/starch digestion for application purposes; and (2) to identify opportunities for future research to advance our understanding of how the combination of controlled grain digestion and fibre content can be manipulated to physiologically influence satiety and food intake.

Buckling down on torus fractures: has evolving evidence affected practice?

PURPOSE: The purpose of this study was to evaluate the management of paediatric torus fractures of the distal forearm in current practice in light of growing evidence supporting a 'minimalist' approach with splint immobilization and limited follow-up. We hypothesized that 'traditional' cast-based management has persisted despite alternative evidence. METHODS: A retrospective review was performed of a consecutive series of paediatric patients diagnosed with torus fractures of the distal forearm between 2011 and 2014. Records were reviewed to abstract the type of immobilization (splint versus cast) prescribed at each visit, number of radiographic exams, duration of immobilization, number of clinical visits and complications. The primary outcome was the proportion of patients exclusively managed in splints. Injuries were grouped based on treatment into a cast group (CG) and a splint group (SG) for statistical analyses. Additionally, injuries were grouped by epoch of time to determine if immobilization usage patterns evolved. RESULTS: A total of 240 forty injuries met criteria for inclusion. Of these, 16 (6.7%) were exclusively splinted (SG). Relative to the CG, the SG had fewer clinical visits (p < 0.001), fewer radiographic exams (p < 0.001) and a shorter total encounter time (p = 0.015). No change in immobilization use occurred over the study period. In all, 21 (9.4%) of the CG experienced complications. No clinically significant displacements occurred in either group. CONCLUSION: Cast utilization and frequent radiographic follow-up remain prevalent at our institution in the management of paediatric torus fractures. Splint-only management was associated with fewer clinical visits, fewer radiographic exams and a shorter total encounter time. LEVEL OF EVIDENCE LEVEL III: Therapeutic retrospective cohort study.

A new simplified immediate prognostic risk score for patients with acute myocardial infarction.

BACKGROUND: Immediate risk stratification of patients with myocardial infarction in the emergency department (ED) at the time of initial presentation is important for their optimal emergency treatment. Current risk scores for predicting mortality following acute myocardial infarction (AMI) are potentially flawed, having been derived from clinical trials with highly selective patient enrollment and requiring data not readily available in the ED. These scores may not accurately represent the spectrum of patients in clinical practice and may lead to inappropriate decision making. METHODS: This study cohort included 1212 consecutive patients with AMI who were admitted to the Mayo Clinic coronary care unit between 1988 and 2000. A risk score model was developed for predicting 30 day mortality using parameters available at initial hospital presentation in the ED. The model was developed on patients from the first era (training set--before 1997) and validated on patients in the second era (validation set-during or after 1997). RESULTS: The risk score included age, sex, systolic blood pressure, admission serum creatinine, extent of ST segment depression, QRS duration, Killip class, and infarct location. The predictive ability of the model in the validation set was strong (c = 0.78). CONCLUSION: The Mayo risk score for 30 day mortality showed excellent predictive capacity in a population based cohort of patients with a wide range of risk profiles. The present results suggest that even amidst changing patient profiles, treatment, and disease definitions, the Mayo model is useful for 30 day risk assessment following AMI.

Glial cell-specific differences in repair of O6-methylguanine.

Normal and malignant cells of the oligodendrocyte lineage show increased sensitivity to alkylating agents compared to astrocytes. One of the most mutagenic DNA lesions formed following exposure to alkylating agents is O6-alkylguanine. To determine whether the increased sensitivity to nitrosoureas seen in oligodendrocytes is due to decreased repair capacity for O6-alkylguanine, removal of this lesion from DNA was assessed in primary cultures of rat oligodendrocytes, astrocytes, and microglia. Glial cells were exposed to 1 mM N-methyl-N-nitrosourea for 1 h and allowed 8 or 24 h for repair. Repair was evaluated using an immunoslot blot technique and a monoclonal antibody which recognizes O6-methylguanine (O6MeGua). Astrocytes removed O6MeGua more efficiently (approximately 80% in 24 h) than either oligodendrocytes (approximately 20%) or microglia (approximately 4%). Determination of O6-alkylguanine-DNA-alkyltransferase (AT) activity revealed that astrocytes contain 0.4 pmol/mg protein, which is average by comparison to other cell types. Both oligodendrocytes and microglia exhibited very low levels of AT (oligodendrocytes, 0.08; microglia, 0.01 pmol/mg protein). These data are the first to show that within different populations of glial cells, O6MeGua adduct removal is substantially reduced in both oligodendrocytes and microglia. Rapid removal of O6MeGua in astrocytes coupled with persistence of this mutagenic lesion in oligodendrocytes following exposure of the developing central nervous system to nitrosoureas could contribute to the observed formation of oligodendrogliomas. Inefficient removal of O6MeGua in oligodendrogliomas might also account for their response to chemotherapeutic regimens involving alkylating agents such as procarbazine, lomustine, and carmustine. The lack of repair of O6MeGua in microglia suggests that primary lymphomas of the central nervous system might be sensitive to treatment with alkylating drugs whose toxicity depends on repair of this adduct.

The effect of replacing lactose by starch on protein and fat digestion in milk-fed veal calves.

Replacing dairy components from milk replacer (MR) with vegetable products has been previously associated with decreased protein and fat digestibility in milk-fed calves resulting in lower live weight gain. In this experiment, the major carbohydrate source in MR, lactose, was partly replaced with gelatinized corn starch (GCS) to determine the effect on protein and fat digestibility in milk-fed calves. In total, 16 male Holstein-Friesian calves received either MR with lactose as the carbohydrate source (control) or 18% GCS at the expense of lactose. In the adaptation period, calves were exposed to an increasing dose of GCS for 14 weeks. The indigestible marker cobalt ethylenediaminetetraacetic acid was incorporated into the MR for calculating apparent nutrient digestibility, whereas a pulse dose of chromium (Cr) chloride was fed with the last MR meal 4 h before slaughter as an indicator of passage rates. The calves were anesthetized and exsanguinated at 30 weeks of age. The small intestine was divided in three; small intestine 1 and 2 (SI1 and SI2, respectively) and the terminal ileum (last ~100 cm of small intestine) and samples of digesta were collected. Small intestinal digesta was analysed for α-amylase, lipase and trypsin activity. Digestibility of protein was determined for SI1, SI2, ileum and total tract, whereas digestibility of fat was determined for SI1, SI2 and total tract. Apparent protein digestibility in the small intestine did not differ between treatments but was higher in control calves at total tract level. Apparent crude fat digestibility tended to be increased in SI1 and SI2 for GCS calves, but no difference was found at total tract level. Activity of α-amylase in SI2 and lipase in both SI1 and SI2 was higher in GCS calves. Activity of trypsin tended to be higher in control calves and was higher in SI1 compared with SI2. A lower recovery of Cr in SI2 and a higher recovery of Cr in the large intestine suggest an increased rate of passage for GCS calves. Including 18% of GCS in a milk replacer at the expense of lactose increased passage rate and decreased apparent total tract protein digestibility. In the small intestine, protein digestion did not decrease when feeding GCS and fat digestion even tended to increase. Overall, effects on digestion might be levelled when partially replacing lactose with GCS, because starch digestion is lower than that of lactose but fat digestion may be slightly increased when feeding GCS.

Microsporidia - Emergent Pathogens in the Global Food Chain.

Intensification of food production has the potential to drive increased disease prevalence in food plants and animals. Microsporidia are diversely distributed, opportunistic, and density-dependent parasites infecting hosts from almost all known animal taxa. They are frequent in highly managed aquatic and terrestrial hosts, many of which are vulnerable to epizootics, and all of which are crucial for the stability of the animal-human food chain. Mass rearing and changes in global climate may exacerbate disease and more efficient transmission of parasites in stressed or immune-deficient hosts. Further, human microsporidiosis appears to be adventitious and primarily associated with an increasing community of immune-deficient individuals. Taken together, strong evidence exists for an increasing prevalence of microsporidiosis in animals and humans, and for sharing of pathogens across hosts and biomes.

Duration of smoking abstinence as a predictor for non-small-cell lung cancer survival in women.

BACKGROUND: Previous studies have attempted to investigate the impact of smoking cessation on lung cancer survival but have been limited by small numbers of former smokers and incomplete data. METHODS: Over a six-year period, 5229 patients with non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) were enrolled in a prospective cohort of whom 2052 were former smokers. Patient's characteristics were obtained from medical records and a baseline interview. Vital status was determined through multiple sources. Cox proportional hazards models were used to estimate the effect of smoking abstinence on post-diagnosis mortality. RESULTS: For all patients with NSCLC, the median survival among never, former, and current smokers was 1.4 years, 1.3 years, and 1.1 years, respectively (P < 0.01). Female NSCLC patients had a significantly lower risk of mortality with a longer duration of smoking abstinence (RR per 10 years of smoking abstinence = 0.85; 95% CI: 0.75, 0.97). No effect of smoking abstinence on mortality was observed for women with SCLC or for men with either histologic group. CONCLUSIONS: The identification of smoking history as a prognostic factor in lung cancer survival supports previous research suggesting a direct biologic effect of smoking on survival. However, this effect may vary by sex and type of lung cancer.

Measurement of glucose and 2-deoxy-2-[18F]fluoro-D-glucose transport and phosphorylation rates in myocardium using dual-tracer kinetic experiments.

To examine the use of 2-deoxy-2-[18F]fluoro-D-glucose (2-FDG) as a glucose analog for measuring glucose utilization rate in myocardium, dual-tracer kinetic experiments with 2-FDG and 2-[3H]glucose were performed in the perfused, isolated rabbit interventricular septum to measure simultaneously the transport and phosphorylation rates of glucose and 2-FDG. Results of the present study indicated that, in the septum, the transport rate constants of 2-FDG and glucose were similar in magnitude, the phosphorylation rate constant for 2-FDG was about 60% of that of glucose, hypoxia caused an increase in phosphorylation rates of glucose and 2-FDG without affecting transport.

The role of probability of reinforcement in models of choice.

A general account of choice behavior in animals, the cumulative effects model, has been proposed by Davis, Staddon, Machado, and Palmer (1993). Its basic assumptions are that choice occurs in an all-or-none fashion for the response alternative with the highest probability of reinforcement and that the probability of reinforcement for each response alternative is calculated from the entire history of training (total number of reinforced responses/total number of reinforced and nonreinforced responses). The model's reliance on probability of reinforcement as the fundamental variable controlling choice behavior subjects the cumulative effects model to the same criticisms as have been directed toward other related models of choice, notably melioration theory. Several different data sets show that the relative value of a response alternative is not predicted by the obtained probability of reinforcement associated with that alternative. Alternative approaches to choice theory are considered.

Hyperthermic effects of centrally injected (D-ala2, N-Me-Phe4, Met-(O)5-ol)-enkephalin (FK 33-824) in rabbits and guinea-pigs.

Intracerebroventricular administration of (D-ala2, N-Me-Phe4, Met-(O)5-ol)-enkephalin (FK 33-824) induced dose-related hyperthermia in rabbits and guinea-pigs. Prostaglandins (PG) and norepinephrine (NE) were not involved in the hyperthermia induced by FK 33-824 because a cyclooxygenase inhibitor, indomethacin, and an alpha-adrenoceptor antagonist, phenoxybenzamine, had no antagonistic effects. Likewise, cAMP was not required since a phosphodiesterase inhibitor, theophylline, did not accentuate the hyperthermia due to FK 33-824. It is suggested that mu receptors were involved in the induction of hyperthermia by FK 33-824 in rabbits and guinea-pigs since naloxone attenuated it. These results indicate that FK 33-824-induced hyperthermia is not mediated by PG, NE and cAMP, but rather that mu receptors are involved in the induction of hyperthermia by FK 33-824.

Opposing actions of dibutyryl cyclic AMP and GMP on temperature in conscious guinea-pigs.

Intracerebroventricular administration of dibutyryl cyclic AMP (Db-cAMP), induced hyperthermia in guinea-pigs which was not mediated through prostaglandins (PG) or norepinephrine since a prostaglandin synthesis inhibitor, indomethacin, and an alpha-adrenergic receptor blocking agent, phenoxybenzamine did not antagonize the hyperthermia. In contrast, the hyperthermic response to dibutyryl cyclic AMP was attenuated by central administration of a beta-adrenergic receptor antagonist, sotalol, indicating that cyclic AMP may be involved, through beta-adrenergic receptors, in the central regulation of heat production/conservation. Central administration of dibutyryl cyclic GMP (Db-cGMP) produced hypothermia which was not mediated via histamine H1- or H2-receptors and serotonin since the H1-receptor antagonist, mepyramine, the H2-receptor antagonist, cimetidine, and the serotonin antagonist, methysergide, had no antagonistic effects. The antagonism of hypothermia induced by dibutyryl cyclic GMP and acetylcholine + physostigmine, by central administration of a cholinergic muscarinic receptor antagonist, atropine, and not by a cholinergic nicotinic receptor antagonist, d-tubocurarine, suggests that cholinoceptive neurons and endogenous cyclic GMP may regulate heat loss through cholinergic muscarinic receptors. These results support a regulatory role in thermoregulation provided by a balance between opposing actions of cyclic AMP and cyclic GMP in guinea-pigs.

Hypothermic and antipyretic effects of ACTH (1-24) and alpha-melanotropin in guinea-pigs.

Intracerebroventricular administration of adrenocorticotropin (ACTH 1-24) and alpha-melanotropin (alpha-MSH), peptides which occur naturally in brain induced dose-related hypothermia in guinea-pigs at room temperature (21 degrees C) and also produced greater hypothermia at low (10 degrees C) ambient temperature. However, when the experiments were repeated in a warm (30 degrees C) environment, no effect on body temperature was observed. These results indicate that the peptides did not reduce the central set-point of temperature control. The hypothermia induced by ACTH and alpha-MSH was not mediated via histamine H1- or H2-receptors and serotonin since the H1-receptor antagonist, mepyramine, the H2-receptor antagonist, cimetidine, and the serotonin antagonist, methysergide, had no antagonistic effects. The peptides were antipyretic since they reduced pyrogen-induced-fever and hyperthermia due to prostaglandin E2, norepinephrine and dibutyryl cAMP, at a dose which did not affect normal body temperature. The powerful central effects of these peptides on normal body temperature, fever and hyperthermia, together with their presence of the brain regions important to temperature control, suggest that they participate in thermoregulation.

Hyperthermic responses to central injections of some peptide and non-peptide opioids in the guinea-pig.

Intracerebroventricular administration of prototype non-peptide opioid receptor (mu, kappa, sigma) agonists, morphine, ketocyclazocine and N-allyl normetazocine (SKF 10,047) and an agonist at both kappa and sigma receptors, pentazocine, induced hyperthermia in guinea-pigs. Similar administration of peptide opioids like beta-endorphin (BE), methionine enkephalin (Met-E), leucine enkephalin (Leu-E) and their synthetic analogues D-ala2-methionine-enkephalinamide (D-ala2-Met-E) and D-ala2-leucine-enkephalinamide (D-ala2-Leu-E) also caused hyperthermia. Of the three anion transport systems (iodide, hippurate and liver-like) present in the choroid plexus, only the liver-like transport system seems to be important to central inactivation of beta-endorphin, D-ala2-Met-enkephalin and D-ala2-Leu-enkephalin since iodipamide (an inhibitor of the liver-like transport system) augmented the hyperthermia. Prostaglandins (PG) and norepinephrine (NE) were not involved in peptide- and non-peptide opioid-induced hyperthermia because a prostaglandin synthesis inhibitor, indomethacin, and an alpha-adrenergic receptor blocker, phenoxybenzamine, had no thermolytic effect. Likewise cAMP was not required since a phosphodiesterase inhibitor, theophylline, did not accentuate the hyperthermia due to administration of peptide and non-peptide opioids. Naloxone-sensitive receptors were involved in the induction of hyperthermia by morphine and beta-endorphin since naloxone attenuated the effect. In contrast, the hyperthermic responses to ketocyclazocine, SKF 10,047, pentazocine, Met-enkephalin, Leu-enkephalin, D-ala2-Met-enkephalin and D-ala2-Leu-enkephalin were not antagonized by naloxone. Lack of antagonism of naloxone on pyrogen, arachidonic acid, PGE2, dibutyryl cAMP and NE-induced hyperthermia indicates that endogenous opioid peptides are not likely to be central mediators of the hyperthermia induced by these agents.