IS THE END-TIDAL PARTIAL PRESSURE OF ISOFLURANE A GOOD PREDICTOR OF ITS ARTERIAL PARTIAL PRESSURE?

End-tidal partial pressure of isoflurane (PE′iso) may be used as a measure of anaesthetic depth. During uptake, an arterial partial pressure (Paiso) which is considerably less than PE′iso(Paiso/PE′iso<<1) leads to underestimation of depth of anaesthesia and, during elimination, PE′iso/Paiso<<1 will lead to an overestimation of anaesthetic depth. We measured Paiso/PE′iso during a 60-min uptake period of 1% isoflurane and PE′iso/Paiso during the subsequent 60-min elimination period in 26 patients (age 13-88 yr, ASA I-III) undergoing various surgical procedures. After 15 min of isoflurane uptake, Paiso/PE′iso of 26 patients was mean 0.78 (SD 0.10) and this increased only marginally at 60 min (0.79 (0.09)), whereas during elimination, PE′iso/Paiso was in the range 0.79 (0.14)-0.83 (0.11). Predictability of Paiso in a given patient is hindered by the high SD of Paiso/PE′iso and PE′iso/Paiso, but it may be improved by taking into account age, ASA physical status category, vital capacity, inspired minus end-tidal isoflurane partial pressure and arterial minus end-tidal carbon dioxide partial pressure during uptake; and obesity, end-tidal isoflurane partial pressure and arterial minus end-tidal carbon dioxide partial pressure during elimination. However, even with multiple regression analysis (to account for the various possible variables), clinically useful prediction of Paiso/PE′iso and PE′iso/Paiso in a particular patient is not possible (residual SD 0.084 and 0.113, respectively

Monitoring of immune activation using biochemical changes in a porcine model of cardiac arrest.

In animal models, immune activation is often difficult to assess because of the limited availability of specific assays to detect cytokine activities. In human monocytes/macrophages, interferon-gamma induces increased production of neopterin and an enhanced activity of indoleamine 2,3-dioxygenase, which degrades tryptophan via the kynurenine pathway. Therefore, monitoring of neopterin concentrations and of tryptophan degradation can serve to detect the extent of T helper cell 1-type immune activation during cellular immune response in humans. In a porcine model of cardiac arrest, we examined the potential use of neopterin measurements and determination of the tryptophan degradation rate as a means of estimating the extent of immune activation. Urinary neopterin concentrations were measured with high-performance liquid chromatography (HPLC) and radioimmunoassay (RIA) (BRAHMS Diagnostica, Berlin, Germany). Serum and plasma tryptophan and kynurenine concentrations were also determined using HPLC. Serum and urine neopterin concentrations were not detectable with HPLC in these specimens, whereas RIA gave weakly (presumably false) positive results. The mean serum tryptophan concentration was 39.0 +/- 6.2 micromol/l, and the mean kynurenine concentration was 0.85 +/- 0.33 micromol/l. The average kynurenine-per-tryptophan quotient in serum was 21.7 +/- 8.4 nmol/micromol, and that in plasma was 20.7 +/- 9.5 nmol/micromol (n = 7), which corresponds well to normal values in humans. This study provides preliminary data to support the monitoring of tryptophan degradation but not neopterin concentrations as a potential means of detecting immune activation in a porcine model. The kynurenine-per-tryptophan quotient may serve as a short-term measurement of immune activation and hence permit an estimate of the extent of immune activation

Heat transport in ordered harmonic lattices

We consider heat conduction across an ordered oscillator chain with harmonic interparticle interactions and also onsite harmonic potentials. The onsite spring constant is the same for all sites excepting the boundary sites. The chain is connected to Ohmic heat reservoirs at different temperatures. We use an approach following from a direct solution of the Langevin equations of motion. This works both in the classical and quantum regimes. In the classical case we obtain an exact formula for the heat current in the limit of system size N to infinity. In special cases this reduces to earlier results obtained by Rieder, Lebowitz and Lieb and by Nakazawa. We also obtain results for the quantum mechanical case where we study the temperature dependence of the heat current. We briefly discuss results in higher dimensions.Comment: 8 pages, 2 figures, published versio

Impact of quality improvement in tuberculosis laboratories in low- and lower-middle-income countries: a systematic review.

BACKGROUND: The effect of quality improvement measures on the performance of diagnostic tuberculosis (TB) laboratories in low- and lower-middle-income countries is not known, and is the subject of this review. METHODS: Three databases were searched for quality improvement studies presenting data on performance parameters before and after the implementation of quality improvement interventions. RESULTS: Twenty-one studies were included in this review. Quality improvement measures were most frequently implemented by an external organization; settings targeted ranged from microscopy centers, hospitals, districts, regional and national reference laboratories. Quality improvement interventions and outcome measurements were highly heterogeneous. Most studies investigated interventions aimed at improving smear microscopy (n = 17). Two studies evaluated comprehensive quality improvement measures (n = 2) and another three studies focused on mycobacterial culture and drug susceptibility testing. Most studies showed an improvement in outcomes measured on before-after or time trend analysis. CONCLUSION: Quality improvement measures implemented in TB laboratories showed a positive impact on various outcomes. Due to the high heterogeneity of outcome reporting and interventions and the low quality of the studies, the effect size was not clear. Identification of standardized quality indicators and their link to the quality of patient care would improve knowledge in this field

Kinetochore fiber formation in animal somatic cells : dueling mechanisms come to a draw

Author Posting. © The Author, 2005. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Chromosoma 114 (2005): 310-318, doi:10.1007/s00412-005-0028-2.The attachment to and movement of a chromosome on the mitotic spindle is mediated by the formation of a bundle of microtubules (MTs) that tethers the kinetochore on the chromosome to a spindle pole. The origin of these “kinetochore fibers” (K-fibers) has been investigated for over 125 years. As noted in 1944 by Schrader, there are only three possible ways to form a K-fiber: either it a) grows from the pole until it contacts the kinetochore; b) grows directly from the kinetochore; or c) it forms as a result of an interaction between the pole and the chromosome. Since Schrader’s time it has been firmly established that K-fibers in centrosome-containing animal somatic cells form as kinetochores capture MTs growing from the spindle pole (route a). It is now similarly clear that in cells lacking centrosomes, including plants and many animal oocytes, K-fibers “self-assemble” from MTs generated by the chromosomes (route b). Can animal somatic cells form K-fibers in the absence of centrosomes by the “self-assembly” pathway? In 2000 the answer to this question was shown to be a resounding “yes”. With this result, the next question became whether the presence of a centrosome normally suppresses K-fiber self-assembly, or if this route works concurrently with centrosome-mediated K-fiber formation. This question, too, has recently been answered: observations on untreated live animal cells expressing GFP-tagged tubulin clearly show that kinetochores can nucleate the formation of their associated MTs in the presence of functional centrosomes. The concurrent operation of these two “dueling” routes for forming K-fibers in animals helps explain why the attachment of kinetochores and the maturation of K-fibers occur as quickly as it does on all chromosomes within a cell.The work is sponsored by NIH grant GMS 40198

The selective phosphodiesterase 4 inhibitor roflumilast and phosphodiesterase 3/4 inhibitor pumafentrine reduce clinical score and TNF expression in experimental colitis in mice.

The specific inhibition of phosphodiesterase (PDE)4 and dual inhibition of PDE3 and PDE4 has been shown to decrease inflammation by suppression of pro-inflammatory cytokine synthesis. We examined the effect of roflumilast, a selective PDE4 inhibitor marketed for severe COPD, and the investigational compound pumafentrine, a dual PDE3/PDE4 inhibitor, in the preventive dextran sodium sulfate (DSS)-induced colitis model. The clinical score, colon length, histologic score and colon cytokine production from mice with DSS-induced colitis (3.5% DSS in drinking water for 11 days) receiving either roflumilast (1 or 5 mg/kg body weight/d p.o.) or pumafentrine (1.5 or 5 mg/kg/d p.o.) were determined and compared to vehicle treated control mice. In the pumafentrine-treated animals, splenocytes were analyzed for interferon-γ (IFNγ) production and CD69 expression. Roflumilast treatment resulted in dose-dependent improvements of clinical score (weight loss, stool consistency and bleeding), colon length, and local tumor necrosis factor-α (TNFα) production in the colonic tissue. These findings, however, were not associated with an improvement of the histologic score. Administration of pumafentrine at 5 mg/kg/d alleviated the clinical score, the colon length shortening, and local TNFα production. In vitro stimulated splenocytes after in vivo treatment with pumafentrine showed a significantly lower state of activation and production of IFNγ compared to no treatment in vivo. These series of experiments document the ameliorating effect of roflumilast and pumafentrine on the clinical score and TNF expression of experimental colitis in mice

Global stabilization of feedforward systems under perturbations in sampling schedule

For nonlinear systems that are known to be globally asymptotically stabilizable, control over networks introduces a major challenge because of the asynchrony in the transmission schedule. Maintaining global asymptotic stabilization in sampled-data implementations with zero-order hold and with perturbations in the sampling schedule is not achievable in general but we show in this paper that it is achievable for the class of feedforward systems. We develop sampled-data feedback stabilizers which are not approximations of continuous-time designs but are discontinuous feedback laws that are specifically developed for maintaining global asymptotic stabilizability under any sequence of sampling periods that is uniformly bounded by a certain "maximum allowable sampling period".Comment: 27 pages, 5 figures, submitted for possible publication to SIAM Journal Control and Optimization. Second version with added remark

Quantum transport using the Ford-Kac-Mazur formalism

The Ford-Kac-Mazur formalism is used to study quantum transport in (1) electronic and (2) harmonic oscillator systems connected to general reservoirs. It is shown that for non-interacting systems the method is easy to implement and is used to obtain many exact results on electrical and thermal transport in one-dimensional disordered wires. Some of these have earlier been obtained using nonequilibrium Green function methods. We examine the role that reservoirs and contacts can have on determining the transport properties of a wire and find several interesting effects.Comment: 10 pages, 4 figure

Oppositional COMT Val158Met effects on resting state functional connectivity in adolescents and adults

© 2014, The Author(s).Prefrontal dopamine levels are relatively increased in adolescence compared to adulthood. Genetic variation of COMT (COMT Val158Met) results in lower enzymatic activity and higher dopamine availability in Met carriers. Given the dramatic changes of synaptic dopamine during adolescence, it has been suggested that effects of COMT Val158Met genotypes might have oppositional effects in adolescents and adults. The present study aims to identify such oppositional COMT Val158Met effects in adolescents and adults in prefrontal brain networks at rest. Resting state functional connectivity data were collected from cross-sectional and multicenter study sites involving 106 healthy young adults (mean age 24 ± 2.6 years), gender matched to 106 randomly chosen 14-year-olds. We selected the anterior medial prefrontal cortex (amPFC) as seed due to its important role as nexus of the executive control and default mode network. We observed a significant age-dependent reversal of COMT Val158Met effects on resting state functional connectivity between amPFC and ventrolateral as well as dorsolateral prefrontal cortex, and parahippocampal gyrus. Val homozygous adults exhibited increased and adolescents decreased connectivity compared to Met homozygotes for all reported regions. Network analyses underscored the importance of the parahippocampal gyrus as mediator of observed effects. Results of this study demonstrate that adolescent and adult resting state networks are dose-dependently and diametrically affected by COMT genotypes following a hypothetical model of dopamine function that follows an inverted U-shaped curve. This study might provide cues for the understanding of disease onset or dopaminergic treatment mechanisms in major neuropsychiatric disorders such as schizophrenia and attention deficit hyperactivity disorder