Delayed onset of malignant hyperthermia induced by isoflurane and desflurane compared with halothane in susceptible swine

BACKGROUND: Desflurane (difluoromethyl 1-fluoro 2,2,2-trifluoroethyl ether) is a new inhalational anesthetic currently under investigation for use in humans. Recently, the authors showed that desflurane is a trigger of malignant hyperthermia (MH) in susceptible swine. To date, there has been no in vivo comparison of the relative ability of inhalational anesthetics to trigger MH. The effects of desflurane, isoflurane, and halothane on six MH-susceptible purebred and six MH-susceptible mixed-bred Pietrain swine were examined. METHODS: The animals were exposed to 1 MAC and 2 MAC (if MH was not triggered after 1 MAC hour) doses of each of the three volatile anesthetics in random sequence at 7-10-day intervals and changes in end-tidal CO2, arterial blood gases, serum lactate, core and muscle temperature, blood pressure, and heart rate were measured. RESULTS: There was a statistical difference between anesthetics in the time required to trigger MH; halothane exposure resulted in the fastest onset of an MH episode (20 +/- 5 min), compared with isoflurane (48 +/- 24 min) and desflurane (65 +/- 28 min), both of which required significantly longer exposures. There was no statistical difference between the MH purebred and mixed-bred swine in the time required to trigger MH (defined as a PaCO2 of 70 mmHg) with a given agent, and time to triggering was also independent of the order of exposure to the three anesthetics. Malignant hyperthermia susceptibility was confirmed in ten surviving animals, by both in vivo succinylcholine challenge and in vitro contracture testing. CONCLUSIONS: Although all three volatile anesthetics triggered MH, exposure to halothane resulted in significantly shorter times to MH triggering when compared with desflurane and isoflurane.     

Intrinsic Motivation Systems for Autonomous Mental Development

Exploratory activities seem to be intrinsically rewarding for children and crucial for their cognitive development. Can a machine be endowed with such an intrinsic motivation system? This is the question we study in this paper, presenting a number of computational systems that try to capture this drive towards novel or curious situations. After discussing related research coming from developmental psychology, neuroscience, developmental robotics, and active learning, this paper presents the mechanism of Intelligent Adaptive Curiosity, an intrinsic motivation system which pushes a robot towards situations in which it maximizes its learning progress. This drive makes the robot focus on situations which are neither too predictable nor too unpredictable, thus permitting autonomous mental development. The complexity of the robot's activities autonomously increases and complex developmental sequences self-organize without being constructed in a supervised manner. Two experiments are presented illustrating the stage-like organization emerging with this mechanism. In one of them, a physical robot is placed on a baby play mat with objects that it can learn to manipulate. Experimental results show that the robot first spends time in situations which are easy to learn, then shifts its attention progressively to situations of increasing difficulty, avoiding situations in which nothing can be learned. Finally, these various results are discussed in relation to more complex forms of behavioral organization and data coming from developmental psychology     

Microstructure of aragonite grown at an air–liquid interface

Aragonite particles dispersed in a bioresorbable polymer matrix are considered to be a good candidate for bone prosthesis materials. It is important to characterize the microstructure of synthetic aragonite used for biomedical applications, since the microstructure may influence its integration, resorption and replacement by bone. We studied late stages of aragonite growth, at an air–liquid interface, from a solution not doped with additives. Comparison was made between the types of synthetic aragonite microstructure and that of aragonite which is found in nature (mollusc shells, gallstones, Earth's crust). The microstructure of natural aragonite is unique to certain classes of living organisms and the understanding of its structure/function relationships may help to select the types of synthetic aragonite for specific biomedical applications. Three types of synthetic aragonite were observed based on grain size and grain morphology. This revised version was published online in November 2006 with corrections to the Cover Date.     

Strains of Synechocystis sp. PCC 6803 with altered PsaC. II. EPR and optical spectroscopic properties of FA and FB in aspartate, serine, and alanine replacements of cysteines 14 and 51

A psaC deletion mutant of the unicellular cyanobacterium Synechocystis sp. PCC 6803 was utilized to incorporate site-specific amino acid substitutions in the cysteine residues that ligate the FA and FB iron-sulfur clusters in Photosystem I (PS I). Cysteines 14 and 51 of PsaC were changed to aspartic acid (C14DPsaC, C51DPsaC, C14D/C51DPsaC), serine (C14SPsaC, C51SPsaC), and alanine (C14APsaC, C51APsaC), and the properties of FA and FB were characterized by electron paramagnetic resonance spectroscopy and time-resolved optical spectroscopy. The C14DPsaC-PS I and C14SPsaC-PS I complexes showed high levels of photoreduction of FA with g values of 2.045, 1. 944, and 1.852 after illumination at 15 K, but there was no evidence of reduced FB in the g = 2 region. The C51DPsaC-PS I and C51SPsaC-PS I complexes showed low levels of photoreduction of FB with g values of 2.067, 1.931, and 1.881 after illumination at 15 K, but there was no evidence of reduced FA in the g = 2 region. The presence of FB was inferred in C14DPsaC-PS I and C14SPsaC-PS I, and the presence of FA was inferred in C51DPsaC-PS I and C51SPsaC-PS I by magnetic interaction in the photoaccumulated spectra and by the equal spin concentration of the irreversible P700(+) cation generated by illumination at 77 K. Flash-induced optical absorbance changes at 298 K in the presence of a fast electron donor indicate that two electron acceptors function after FX in the four mutant PS I complexes at room temperature. These data suggest that a mixed-ligand [4Fe-4S] cluster is present in the mutant sites of C14X-PS I and C51X-PS I (where X = D or S), but that the proposed spin state of S = 3/2 renders the resonances undetectable in the g = 2 region. The C14APsaC-PS I, C51APsaC-PS I and C14D/C51DPsaC-PS I complexes show only the photoreduction of FX, consistent with the absence of PsaC. These results show that only those PsaC proteins that contain two [4Fe-4S] clusters are capable of assembling onto PS I cores in vivo.     

Genitourinary trauma in the pediatric patient

Trauma is the major source of mortality in the pediatric population. A retrospective review was performed on patients admitted to the Children's Hospital and Health Center Trauma Program, San Diego, California, from August 1984 to May 1990. The purpose of this review was to evaluate pediatric trauma and to determine the best treatment and evaluation for genitourinary injuries. Blunt trauma was responsible for 98 percent of the injuries, with renal injuries being the most common. Bladder (7) and male urethral (2) injuries, and vaginal lacerations (8) also occurred. The most severe renal injuries (70%) and all significant bladder and urethral injuries were associated with gross hematuria. Hypotension was present in 31 percent of patients but rarely required surgical exploration for correction. Eighty-six patients underwent radiographic imaging. Computerized tomography (CT) scans demonstrated the most information about intra-abdominal solid organ injuries but was inaccurate in detecting bladder or urethral injuries. Genitourinary injury is common in children but rarely requires surgical management. CT scan is the best study to determine extent of solid-organ injury but is inferior to cystourethrography to diagnose bladder or urethral injuries.     

Slipped capital femoral epiphysis associated with radiation therapy

We reviewed 32 children with 41 radiation-therapy associated slipped capital femoral epiphyses (RTASCFE). Ten were from the authors' institutions and 22 from the literature. Gender distribution was equal. The age at diagnosis of the malignancy was 4.3 +/- 3.1 years; the amount of radiation was 4,240 +/- 1,445 rads. Children with RTASCFE presented younger (10.4 +/- 3.2 years) than a routine SCFE. The average symptom duration was 5 +/- 6 months. Children with RTASCFE are usually thin (median weight, 10th percentile) in contrast to children with typical SCFE, who are usually obese (<95th percentile). The majority (82%) of the slips were mild, compared to routine SCFEs (approximately 50%); 28% were bilateral. There was a positive linear relationship between the age at presentation of the SCFE and the age at diagnosis of the malignancy; there was a negative linear relationship between the age at presentation of the SCFE and the amount of radiation therapy.     

Efficacy of monensin for the prevention of subclinical ketosis in lactating dairy cows

A total of 1010 dry cows and pregnant heifers was randomly selected from 25 dairy farms near Guelph, Ontario, Canada to receive either a controlled-release capsule of monensin or a placebo at 3 wk prior to expected calving. Serum samples were obtained at the time of treatment administration, and both serum and milk samples were collected at wk 1, 2, 3, 6, and 9 postcalving. The threshold used to define subclinical ketosis was selected a priori at a concentration of > or = 1200 mumol/L of beta-hydroxybutyrate. Using this threshold, the prevalence and incidence of subclinical ketosis were significantly reduced (50%) by monensin treatment. The duration of subclinical ketosis for cows that had been treated with monensin was also shorter than that for cows treated with the placebo. Monensin treatment significantly reduced the incidence of subclinical ketosis when the threshold was defined using higher concentrations of serum beta-hydroxybutyrate (1400 and 2000 mumol/L). In addition, monensin significantly reduced the prevalence of positive milk ketone tests.     

Structure of d(GT)n.d(GA)n sequences: formation of parallel stranded duplex DNA

Alternating polypurine sequences exhibit remarkable polymorphism. In this study, we report that dGA.dGT sequences form parallel stranded duplex DNA at neutral pH. Using two model hairpins, 3'-d(GT)3-5'5'-T4(AG)3-3' (I) and 3'-d(GT)4-5'5'-T4(AG)4-3' (II), containing 5'5' linkages which direct parallel strand formation, we systematically explored the spectroscopic and thermodynamic properties of parallel stranded d(GA)n.d(GT)n. The parallel stranded hairpins are remarkably stable structures with TM's of 41.5 and 47.5 degreesC (in 0.4 M NaCl) for the shorter and longer hairpins, respectively. The van't Hoff enthalpies of 80.7 and 114 kJ mol-1 are relatively low but are comparable to a parallel stranded d(GA)n duplex. On the basis of the spectroscopic and electrophoretic characteristics, we conclude that parallel strand formation is not restricted to hairpin systems, but also readily occurs in unconstrained dimeric duplexes with the appropriate sequence homologies. Both melting curves and electrophoretic analyses of parallel stranded heteroduplexes in which the sequence enforces specific base pairing demonstrate that G-G and A-T base pairs are formed in d(GA)n.d(GT)n segments.