bluuebunny/crossref_metadata_2025 huggingface dataset:
Isolation and screening of fungi to determine potential for ammonia nitrogen treatment in wastewater
Authors: Guest R K , Smith D W
Published: May 2007

Twenty-two fungi were studied to determine the potential for development of fungal nitrogen treatment (FNT) technology for municipal wastewater. Fungal nitrogen treatment has been hypothesized to have several significant advantages over bacterial nitrification–denitrification systems. The fungi were isolated from the biological nutrient reactor at the Gold Bar Wastewater Treatment Plant in Edmonton, Alberta, Canada. Fungi were screen for nitrogen treatment potential using an aerobic 3 day ammonium concentration decrease test. Seven fungi were found to have potential for nitrogen or phosphorus treatment. The highest average ammonium decreased was 59% with an average initial concentration of 22 mg N L–1. Fungal nitrogen treatment was also characterized by a lack of production of nitrate or nitrite under aerobic conditions. Data analysis indicated, the ammonium decrease was not consistent with nitrogen assimilation.Key words: fungi, biological nutrient removal, ammonium, nitrification, denitrification.
Validation of UV coiled tube reactor for fresh juices
Authors: Koutchma Tatiana , Parisi Brian , Patazca Eduardo
Published: May 2007

The objective of this study was to validate the performance of a coiled ultraviolet (UV) module with 24 lamps for fresh juice pasteurization. Escherichia coli K12 at an inoculation level of 106 cfu mL–1 was chosen as a target microorganism for biodosimetry. All tested fruit juices highly absorbed UV light, with absorption coefficients ranging from 11 cm–1 to 78 cm–1 for lillikoi and pineapple juice, respectively. Of the juices examined, pineapple juice appeared to be the worst case scenario in terms of UV absorptivity and high viscosity. A caramel model solution was developed to mimic juice absorption properties and was used for inoculation studies. The 5-log10 reduction standard under turbulent flow required by the FDA was achievable in Newtonian liquids with absorption coefficient less than 15 cm–1 after one pass. Turbulent flow was not developed in more viscous orange and pineapple juices at the flow rates tested. A biodosimetry technique that utilizes E. coli as a tracer showed no distribution of UV dose in liquids with absorption coefficient lower than 26 cm–1. The proposed technique may assist in validating the performance of UV reactors and improve efficiency of UV pasteurization. Key words: coiled ultraviolet module, fruit juices, caramel model, E. coli K12, biodosimetry.
Activation and inactivation of the volume-sensitive taurine leak pathway in NIH3T3 fibroblasts and Ehrlich Lettre ascites cells
Authors: Lambert Ian Henry
Published: May 2007

Hypotonic exposure provokes the mobilization of arachidonic acid, production of ROS, and a transient increase in taurine release in Ehrlich Lettre cells. The taurine release is potentiated by H2O2and the tyrosine phosphatase inhibitor vanadate and reduced by the phospholipase A2(PLA2) inhibitors bromoenol lactone (BEL) and manoalide, the 5-lipoxygenase (5-LO) inhibitor ETH-615139, the NADPH oxidase inhibitor diphenyl iodonium (DPI), and antioxidants. Thus, swelling-induced taurine efflux in Ehrlich Lettre cells involves Ca2+-independent (iPLA2)/secretory PLA2(sPLA2) plus 5-LO activity and modulation by ROS. Vanadate and H2O2stimulate arachidonic acid mobilization and vanadate potentiates ROS production in Ehrlich Lettre cells and NIH3T3 fibroblasts under hypotonic conditions. However, vanadate-induced potentiation of the volume-sensitive taurine efflux is, in both cell types, impaired in the presence of BEL and DPI and following restoration of the cell volume. Thus, potentiation of the volume-sensitive taurine efflux pathway following inhibition of tyrosine phosphatase activity reflects increased arachidonic acid mobilization and ROS production for downstream signaling. Vanadate delays the inactivation of volume-sensitive taurine efflux in NIH3T3 cells, and this delay is impaired in the presence of DPI. Vanadate has no effect on the inactivation of swelling-induced taurine efflux in Ehrlich Lettre cells. It is suggested that increased tyrosine phosphorylation of regulatory components of NADPH oxidase leads to increased ROS production and a subsequent delay in inactivation of the volume-sensitive taurine efflux pathway and that NADPH oxidase or antioxidative capacity differ between NIH3T3 and Ehrlich Lettre cells.
Vascular bed-specific endothelium-dependent vasomomotor relaxation in the hagfish,Myxine glutinosa
Authors: Feng Jun , Yano Kiichiro , Monahan-Earley Rita , Morgan Ellen S. , Dvorak Ann M. , Sellke Frank W. , Aird William C.
Published: May 2007

The last common ancestor of hagfish and gnathostomes was also the last common ancestor of all extant vertebrates that lived some time more than 500 million years ago. Features that are shared between hagfish and gnathostomes can be inferred to have already been present in this ancestral vertebrate. We recently reported that hagfish endothelium displays phenotypic heterogeneity in ultrastructure, lectin binding, and mechanisms of leukocyte adhesion. Thus, phenotypic cell heterogeneity evolved as an early feature of the endothelium. In the present study, we wanted to extend these observations by determining whether hagfish endothelium plays a role in mediating vasomotor tone. Response of mesenteric and skeletal muscle arteries to a variety of mediators was assayed by videomicroscopy. Phenylephrine and acetylcholine induced vasoconstriction of mesenteric and skeletal muscle arteries. Bradykinin (BK) and ADP promoted vasorelaxation in precontracted mesenteric arteries but not those from skeletal muscle. BK- and ADP-mediated vasorelaxation of the mesenteric artery was abrogated by mechanical denudation of the endothelium but was unaffected by NG-nitro-l-arginine methyl ester. Indomethacin significantly inhibited the vasodilatory response to ADP but not BK. The nitric oxide donor sodium nitroprusside resulted in endothelium-independent relaxation of both mesenteric and skeletal muscle arteries. Together, these data suggest that site-specific endothelium-dependent vasorelaxation is an evolutionarily conserved property of this cell lineage.
Effects of dexamethasone exposure on rat metanephric development: in vitro and in vivo studies
Authors: Singh Reetu R. , Moritz Karen M. , Bertram John F. , Cullen-McEwen Luise A.
Published: May 2007

Maternal administration of dexamethasone (DEX) for 48 h early in rat kidney development results in offspring with a reduced nephron endowment. However, the mechanism through which DEX inhibits nephrogenesis is unknown. In this study, we hypothesized that DEX may indirectly inhibit nephrogenesis by inhibiting ureteric branching morphogenesis. Whole metanephroi from embryonic day 14.5 ( E14.5) rat embryos were cultured in the presence of DEX. DEX (10−5M) exposure for 2 days significantly inhibited ureteric branching compared with metanephroi grown in control media or DEX (10−7M). Culturing metanephroi for a further 3 days (in control media only) reduced total glomerular number in metanephroi previously exposed to DEX (10−5M) or (10−7M) compared with control cultures. Expression of genes known to regulate ureteric branching morphogenesis was determined by real-time PCR in metanephroi after 2 days in culture. DEX exposure in vitro decreased expression of glial cell line-derived neurotrophic factor (GDNF) and increased expression of bone morphogenetic protein-4 (BMP-4) and transforming growth factor-β1 (TGF-β1). Similar gene expression changes were found in E16.5 metanephroi in which the dam had been exposed to 2 days of DEX (0.2 mg·kg−1·day−1) at E14.5/15.5 in vivo. However, in kidneys collected at E20.5 after in vivo exposure for 2 days, GDNF expression was increased and BMP-4 and TGF-β1 expression decreased suggesting a biphasic response in gene expression to DEX exposure. These results show for the first time that inhibition of ureteric branching morphogenesis may be a key mechanism through which DEX exposure results in a reduced nephron endowment.
Testosterone regulation of renal cystathionine β-synthase: implications for sex-dependent differences in plasma homocysteine levels
Authors: Vitvitsky Victor , Prudova Anna , Stabler Sally , Dayal Sanjana , Lentz Steven R. , Banerjee Ruma
Published: May 2007

Elevated plasma total homocysteine (tHcy) is an independent risk factor for ischemic heart disease and stroke. Epidemiological studies reveal that men have higher tHcy levels than women, but the mechanism underlying this sex-dependent difference is unknown. One route for intracellular disposal of homocysteine is catalyzed by cystathionine β-synthase (CBS). Renal function is known to be an important determinant of tHcy, and, in this study, we demonstrate that renal CBS expression and activity in mice diminished approximately twofold after castration, whereas ovariectomization was without effect. The higher renal CBS activity in males (22.7 ± 3.1 mmol cystathionine·h−1·kg kidney−1) vs. females (8.4 ± 3.4 mmol cystathionine·h−1·kg kidney−1, P ≤ 10−6) in C57Bl/6J mice was associated with lower plasma tHcy levels in males vs. females, and this difference was exacerbated in Cbs+/− mice (7.7 ± 1.9 μmol/l in males vs. 13.8 ± 6.4 μmol/l in females, P = 0.005). Surprisingly, mammals exhibit a diversity of regulatory patterns for kidney CBS, with females exhibiting lower CBS activity in mice, higher in rats and humans, and being indistinguishable from males in rabbit, hamster, and guinea pig. Our data suggest that testosterone-dependent regulation of human CBS in kidney may contribute to sex-dependent differences in homocysteine transsulfuration.
Role of Sustained Excitability of the Leg Motor Cortex After Transcranial Magnetic Stimulation in Associative Plasticity
Authors: Roy François D. , Norton Jonathan A. , Gorassini Monica A.
Published: May 2007

Changes in the strength of corticospinal projections to muscles in the upper and lower limbs are induced in conscious humans after paired associative stimulation (PAS) to the motor cortex. We tested whether an intervention of PAS consisting of 90 low-frequency (0.1-Hz) stimuli to the common peroneal nerve combined with suprathreshold transcranial magnetic stimulation (TMS) produces specific changes to the motor-evoked potentials (MEPs) in lower leg muscles if the afferent volley from peripheral stimulation is timed to arrive at the motor cortex after TMS-induced firing of corticospinal neurons. Unlike PAS in the hand, MEP facilitation in the leg was produced when sensory inputs were estimated to arrive at the motor cortex over a range of 15 to 90 ms after cortical stimulation. We examined whether this broad range of facilitation occurred as a result of prolonged subthreshold excitability of the motor cortex after a single pulse of suprathreshold TMS so that coincident excitation from sensory inputs arriving many milliseconds after TMS can occur. We found that significant facilitation of MEP responses (>200%) occurred when the motor cortex was conditioned with suprathreshold TMS tens of milliseconds earlier. Likewise, it was possible to induce strong MEP facilitation (85% at 60 min) when afferent inputs were directly paired with subthreshold TMS. We argue that in the leg motor cortex, facilitation of MEP responses from PAS occurred over a large range of interstimulus intervals as a result of the paired activation of sensory inputs with sustained, subthreshold activity of cortical neurons that follow a pulse of suprathreshold TMS.
Cortical and Collicular Inputs to Cells in the Rat Paralaminar Thalamic Nuclei Adjacent to the Medial Geniculate Body
Authors: Smith Philip H. , Bartlett Edward L. , Kowalkowski Anna
Published: May 2007

The paralaminar nuclei, including the medial division of the medial geniculate nucleus, surround the auditory thalamus medially and ventrally. This multimodal area receives convergent inputs from auditory, visual, and somatosensory structures and sends divergent outputs to cortical layer 1, amygdala, basal ganglia, and elsewhere. Studies implicate this region in the modulation of cortical 40-Hz oscillations, cortical information binding, and the conditioned fear response. We recently showed that the basic anatomy and intrinsic physiology of paralaminar cells are unlike that of neurons elsewhere in sensory thalamus. Here we evaluate the synaptic inputs to paralaminar cells from the inferior and superior colliculi and the cortex. Combined physiological and anatomical evidence indicates that paralaminar cells receive both excitatory and inhibitory inputs from both colliculi and excitatory cortical inputs. Excitatory inputs from all three sources typically generate small summating EPSPs composed of AMPA and NMDA components and terminate primarily on smaller dendrites and occasionally on dendritic spines. The cortical input shows strong paired-pulse facilitation (PPF), whereas both collicular inputs show weak PPF or paired-pulse depression (PPD). EPSPs of cells with no low-threshold calcium conductance do not evoke a burst response when the cell is hyperpolarized. Longer-latency EPSPs were seen and our evidence indicates that these arise from axon collateral inputs of other synaptically activated paralaminar cells. The inhibitory collicular inputs are GABAergic, activate GABAA receptors, and terminate on dendrites. Their activation can greatly alter EPSP-generated spike number and timing.
Complex Cells Increase Their Phase Sensitivity at Low Contrasts and Following Adaptation
Authors: Crowder N. A. , van Kleef J. , Dreher B. , Ibbotson M. R.
Published: May 2007

One of the best-known dichotomies in neuroscience is the division of neurons in the mammalian primary visual cortex into simple and complex cells. Simple cells have receptive fields with separate on and off subregions and give phase-sensitive responses to moving gratings, whereas complex cells have uniform receptive fields and are phase invariant. The phase sensitivity of a cell is calculated as the ratio of the first Fourier coefficient ( F1) to the mean time-average ( F0) of the response to moving sinusoidal gratings at 100% contrast. Cells are then classified as simple ( F1/ F0>1) or complex ( F1/ F0<1). We manipulated cell responses by changing the stimulus contrast or through adaptation. The F1/ F0ratios of cells defined as complex at 100% contrast increased at low contrasts and following adaptation. Conversely, the F1/ F0ratios remained constant for cells defined as simple at 100% contrast. The latter cell type was primarily located in thalamorecipient layers 4 and 6. Many cells initially classified as complex exhibit F1/ F0>1 at low contrasts and after adaptation (particularly in layer 4). The results are consistent with the spike-threshold hypothesis, which suggests that the division of cells into two types arises from the nonlinear interaction of spike threshold with membrane potential responses.
Piezoelectric Actuators as Synthetic Jets: Cavity Dimension Effects
Authors: Mane Poorna , Mossi Karla , Rostami Ali , Bryant Robert , Castro Nicolas
Published: May 2007

Effects of dimensional cavity parameters, height, and orifice diameter, on synthetic jet peak velocities are investigated numerically and experimentally, utilizing two piezoelectric composite diaphragms, Bimorph and Thunder ®. The system is modeled using a RNG κ—ε model with a mesh generated using a tri-pave unstructured scheme and the diaphragms are modeled as moving boundaries. The model compares within 15% for a Bimorph but underpredicts the results for Thunder® by more than 30%. For a Bimorph, both cavity parameters are relevant with the orifice diameter having a higher effect. For Thunder® however, only orifice diameter is found to be statistically significant.
Performance of MRE-based Vibration Absorbers
Authors: Lerner A. Albanese , Cunefare K.A.
Published: May 2007

The purpose of this work is to use magnetorheological elastomers (MREs) as field-dependent springs within three vibration absorber configurations, and to determine their vibration absorption characteristics. Magnetorheological elastomers are fabricated from silicone gel and iron microparticles, and implemented as tunable springs in three vibration absorber configurations, which excited the MREs in shear, squeeze mode, and compression. Each vibration absorber configuration exploits different magneto-mechanical properties, achieving very different results. The MRE iron concentration is varied to find the largest natural frequency shift for the squeeze-mode absorber due to an applied magnetic field. Absorbers with MREs containing 35% iron by volume exhibits the largest natural frequency shift, 507%. MREs containing 35% iron are placed into shear and longitudinal mode vibration absorber devices, which exhibit 470% and 180% frequency increases, respectively.
Multimodal Vibration Control of a Flexible Structure using Piezoceramic Sensor and Actuator
Authors: Sethi Vineet , Gangbing Song
Published: May 2007

This study presents results of multimodal vibration suppression of a smart flexible cantilever beam with piezoceramic actuator and sensor by using a pole placement controller. Piezoceramic PZT (lead zirconate titanate) patches are surface-bonded on the beam and function as actuator and sensor. Nonparametric identification for the dynamics of the first three modes is carried out. From the nonparametric model, a parametric model is identified to assist the control system design. The identified model is used for state estimation and development of control algorithm. A linear pole placement controller is designed and simulated using the identified model. Experimental results demonstrate the effectiveness of observer-based multimodal active vibration control of the structure using piezoceramic smart materials.
p52Shc is required for CXCR4-dependent signaling and chemotaxis in T cells
Authors: Patrussi Laura , Ulivieri Cristina , Lucherini Orso Maria , Paccani Silvia Rossi , Gamberucci Alessandra , Lanfrancone Luisa , Pelicci Pier Giuseppe , Baldari Cosima T.
Published: May 2007

ShcA is an important mediator of Ras/MAPK activation in PTK-regulated pathways triggered by surface receptors. This function is subserved by the constitutively expressed p52-kDa isoform. Besides activating Ras, p52Shc couples the TCR to Rho GTPases, and thereby participates in actin cytoskeleton remodeling in T cells. Here we have addressed the potential involvement of p52Shc in T-cell chemotaxis and the role of the phosphorylatable tyrosine residues, YY239/240 and Y317, in this process. We show that CXCR4 engagement by the homeostatic chemokine, SDF-1α, results in p52Shc phosphorylation and its assembly into a complex that includes Lck, ZAP-70, and Vav. This process was found to be both Lck and Gi dependent. Expression of p52Shc mutants lacking YY239/240 or Y317, or p52Shc deficiency, resulted in a profound impairment in CXCR4 signaling and SDF-1α–dependent chemotaxis, underscoring a crucial role of p52Shc as an early component of the CXCR4 signaling cascade. p52Shc was also found to be required for ligand-dependent CXCR4 internalization independently of tyrosine phosphorylation. Remarkably, CXCR4 engagement promoted phosphorylation of the ζ chain of the TCR/CD3 complex, which was found to be essential for CXCR4 signaling, as well as for SDF-1α–dependent receptor endocytosis and chemotaxis, indicating that CXCR4 signals by transactivating the TCR.
Pharmacologic inhibition of CDK4/6: mechanistic evidence for selective activity or acquired resistance in acute myeloid leukemia
Authors: Wang Lisheng , Wang Jie , Blaser Bradley W. , Duchemin Anne-Marie , Kusewitt Donna F. , Liu Tom , Caligiuri Michael A. , Briesewitz Roger
Published: May 2007

Entry into the cell cycle is mediated by cyclin-dependent kinase 4/6 (CDK4/6) activation, followed by CDK2 activation. We found that pharmacologic inhibition of the Flt3 internal tandem duplication (ITD), a mutated receptor tyrosine kinase commonly found in patients with acute myelogenous leukemia (AML), led to the down-regulation of cyclin D2 and D3 followed by retinoblastoma protein (pRb) dephosphorylation and G1 cell-cycle arrest. This implicated the D-cyclin-CDK4/6 complex as a downstream effector of Flt3 ITD signaling. Indeed, single-agent PD0332991, a selective CDK4/6 inhibitor, caused sustained cell-cycle arrest in Flt3 ITD AML cell lines and prolonged survival in an in vivo model of Flt3 ITD AML. PD0332991 caused an initial cell-cycle arrest in well-established Flt3 wild-type (wt) AML cell lines, but this was overcome by down-regulation of p27Kip and reactivation of CDK2. This acquired resistance was not observed in a Flt3 ITD and a Flt3 wt sample from a patient with primary AML. In summary, the mechanism of cell-cycle arrest after treatment of Flt3 ITD AML with a Flt3 inhibitor involves down-regulation of cyclin D2 and D3. As such, CDK4/6 can be a therapeutic target in Flt3 ITD AML but also in primary Flt3 wt AML. Finally, acquired resistance to CDK4/6 inhibition can arise through activation CDK2.
The low-molecular-weight phosphotyrosine phosphatase is a negative regulator of FcγRIIA-mediated cell activation
Authors: Mancini Francesca , Rigacci Stefania , Berti Andrea , Balduini Cesare , Torti Mauro
Published: May 2007

Activation of human platelets by cross-linking of the low-affinity receptor for immunoglobulin G (FcγRIIA) is initiated by Src kinase–mediated phosphorylation of the immunoreceptor tyrosine–based activation motif (ITAM) within the receptor, but the identity of the enzyme responsible for its dephosphorylation and inactivation is unknown. Here we report that the 18-kDa low-molecular-weight phosphotyrosine phosphatase (LMW-PTP) is expressed in human platelets and undergoes subcellular redistribution upon FcγRIIA cross-linking. In vitro, LMW-PTP was found to efficiently dephosphorylate activated FcγRIIA and LAT, but not Syk or phospholipase Cγ2. In the megakaryocytic cell line DAMI, antibody-induced phosphorylation of FcγRIIA was rapid and transient. The late dephosphorylation of FcγRIIA was dramatically delayed upon reduction of LMW-PTP expression by siRNA. Strikingly, overexpression of LMW-PTP resulted in the inhibition of antibody-induced phosphorylation of FcγRIIA, and caused a more rapid dephosphorylation. In addition, overexpression of LMW-PTP inhibited activation of Syk downstream of FcγRIIA and reduced intracellular Ca2+ mobilization. These results demonstrate that LMW-PTP is responsible for FcγRIIA dephosphorylation, and is implicated in the down-regulation of cell activation mediated by this ITAM-bearing immunoreceptor.
Molecular evidence for the role of mycobacteria in sarcoidosis: a meta-analysis
Authors: Gupta D. , Agarwal R. , Aggarwal A. N. , Jindal S. K.
Published: May 2007

The aetiology of sarcoidosis is currently unknown. Due to the clinical and histological similarities between sarcoidosis and tuberculosis, the role of mycobacteria has been repeatedly investigated as an aetiological agent for sarcoidosis. The current meta-analysis aimed to evaluate the available molecular evidence on the possible role of mycobacteria in the development of sarcoidosis.

The MEDLINE, EMBASE, CINAHL, DARE and CENTRAL databases were searched for relevant studies published from 1980 to 2006, and studies evaluating the presence of mycobacteria using molecular techniques in biological samples of patients with sarcoidosis were included in the current analysis. The 95% confidence intervals (CI) were calculated for the expected proportion (of individual studies); the data was then pooled to obtain a summary success rate with 95% CI. The odds ratio (95% CI) was also calculated in order to assess the presence of mycobacteria in samples of patients with sarcoidosisversusthose from nonsarcoidosis control samples.

The database search yielded 31 studies. All studies used polymerase chain reaction for nucleic acid amplification followed by identification of nucleic acid sequences specific for different types of mycobacteria. Overall, 231 out of the 874 patients were positive for mycobacteria with a positive signal rate of 26.4 (23.6–29.5%), and the odds of finding mycobacteria in samples of patients with sarcoidosisversuscontrols were 9.67 (4.56–20.5%) using the random effects model and 19.49 (11.21–35.54%) using the exact method. There was methodological and statistical heterogeneity and evidence of publication bias.

The results of the current study illustrate a demonstrable mycobacterial presence in sarcoidosis lesions suggesting an association between mycobacteria and some cases of sarcoidosis. To avoid methodological diversity, larger multicentre trials with a central laboratory for sample testing should be designed.
Inhibition of allergen-induced airway remodelling by tiotropium and budesonide: a comparison
Authors: Bos I. S. T. , Gosens R. , Zuidhof A. B. , Schaafsma D. , Halayko A. J. , Meurs H. , Zaagsma J.
Published: May 2007

Chronic inflammation in asthma and chronic obstructive pulmonary disease drives pathological structural remodelling of the airways. Using tiotropium bromide, acetylcholine was recently identified as playing a major regulatory role in airway smooth muscle remodelling in a guinea pig model of ongoing allergic asthma. The aim of the present study was to investigate other aspects of airway remodelling and to compare the effectiveness of tiotropium to the glucocorticosteroid budesonide.

Ovalbumin-sensitised guinea pigs were challenged for 12 weeks with aerosolised ovalbumin.

The ovalbumin induced airway smooth muscle thickening, hypercontractility of tracheal smooth muscle, increased pulmonary contractile protein (smooth-muscle myosin) abundance, mucous gland hypertrophy, an increase in mucin 5 subtypes A and C (MUC5AC)-positive goblet cell numbers and eosinophilia. It was reported previously that treatment with tiotropium inhibits airway smooth muscle thickening and contractile protein expression, and prevents tracheal hypercontractility. This study demonstrates that tiotropium also fully prevented allergen-induced mucous gland hypertrophy, and partially reduced the increase in MUC5AC-positive goblet cell numbers and eosinophil infiltration. Treatment with budesonide also prevented airway smooth muscle thickening, contractile protein expression, tracheal hypercontractility and mucous gland hypertrophy, and partially reduced MUC5AC-positive goblet cell numbers and eosinophilia.

This study demonstrates that tiotropium and budesonide are similarly effective in inhibiting several aspects of airway remodelling, providing further evidence that the beneficial effects of tiotropium bromide might exceed those of bronchodilation.
Sepsis severity predicts outcome in community-acquired pneumococcal pneumonia
Authors: Schaaf B. , Kruse J. , Rupp J. , Reinert R. R. , Droemann D. , Zabel P. , Ewig S. , Dalhoff K.
Published: May 2007

Easily performed prognostic rules are helpful for guiding the intensity of monitoring and treatment of patients. The aim of the present study was to compare the predictive value of the sepsis score and the Confusion, Respiratory rate (≥30 breaths·min−1), Blood pressure (systolic value <90 mmHg or diastolic value ≤60 mmHg) and age ≥65 yrs (CRB-65) score in 105 patients with community-acquired pneumococcal pneumonia. In addition, the influence of timing of the antimicrobial treatment on outcome was investigated. The sepsis and the CRB-65 scores were used to allocate patients to subgroups with low, intermediate and high risk.

Comparable, highly predictive values for mortality were found for both scores (sepsis scoreversusCRB-65): 1) low-risk group, 0versus0%; 2) intermediate-risk group, 0versus8.6%; 3) high-risk group, 30.6versus40%, with an area under the curve of 0.867versus0.845. Patients with ambulatory antibiotic pre-treatment had less severe disease with a lower acute physiology score, lower white blood cell count and a faster decline of C-reactive protein levels. No pre-treated patient died.

In summary, both scores performed equally well in predicting mortality. The prediction of survival in the intermediate-risk group might be more accurate with the sepsis score. Pre-hospital antibiotic treatment was associated with less severe disease.
Quantitative scoring of an interferon-γ assay for differentiating active from latent tuberculosis
Authors: Janssens J-P. , Roux-Lombard P. , Perneger T. , Metzger M. , Vivien R. , Rochat T.
Published: May 2007

The aim of this study was to assess the contribution of an interferon-γ release assay (T-SPOT.TB) to the differentiation of active tuberculosis (TB) from latent TB infection by quantifying spot-forming units (sfu).

The investigation was a prospective study of contacts exposed to a case of contagious TB and cases of HIV-negative culture-proven TB referred over a 16-month period. Tuberculin skin tests (TSTs) and T-SPOT.TBwere performed in 310 contacts 8–12 weeks after exposure. In subjects with culture-proven TB, T-SPOT.TBwas performed within 2 weeks of initiation of treatment. The analysis included all contacts with a positive T-SPOT.TBresult and all subjects with TB.

TB contacts (n = 127) and cases (n = 58) were included. Mean±sdT-SPOT.TBresults were 107±56 (range 1–207) sfu for TB, 54±60 (7–239) sfu for contacts with positive T-SPOT.TBresults and a TST induration diameter of >5 mm, and 19±27 (7–143) sfu for contacts with positive T-SPOT.TBresults and a TST induration diameter of ≤5 mm. By receiver operating characteristic curve analysis, a threshold value of 49.5 sfu showed a sensitivity of 83% and specificity of 74% for distinguishing latent TB infection from TB.

Although T-SPOT.TBresults were significantly related to disease activity, the test cannot be recommended for the diagnosis of tuberculosis.
The need for macrolides in hospitalised community-acquired pneumonia: propensity analysis
Authors: Paul M. , Nielsen A. D. , Gafter-Gvili A. , Tacconelli E. , Andreassen S. , Almanasreh N. , Goldberg E. , Cauda R. , Frank U. , Leibovici L.
Published: May 2007

The present study compared β-lactam macrolide (“combination”) therapyversusβ-lactam alone (“monotherapy”) for hospitalised community-acquired pneumonia, using propensity scores to adjust for the differences between patients.

A prospective multinational observational study was carried out. Baseline patient and infection characteristics were used to develop a propensity score for combination therapy. Patients were matched by the propensity score (three decimal point precision) and compared with 30-day mortality and hospital stay. The propensity score was used as a covariate in a logistic model for mortality.

Patients treated with monotherapy (n = 169) were older (mean±sdage 70.6±17.3versus65.0±19.6 yrs), had a higher chronic diseases score and a different clinical presentation compared with patients treated with combination therapy (n = 282). Unadjusted mortality was significantly higher with monotherapy (37 (22%) out of 169versus21 (7%) out of 282). Only 27 patients in the monotherapy group could be matched to 27 patients in the combination group using the propensity score. The mortality in these groups was identical, with three (11%) demises each. The multivariable odds ratio for mortality associated with combination therapy, adjusted for the propensity score and the Pneumonia Severity Index, was 0.69 (95% confidence interval 0.32–1.48).

The benefit of combination therapyversusmonotherapy cannot be reliably assessed in observational studies, since the propensity to prescribe these regimens differs markedly.
Nocturnal melatonin plasma levels in patients with OSAS: the effect of CPAP
Authors: Hernández C. , Abreu J. , Abreu P. , Castro A. , Jiménez A.
Published: May 2007

Melatonin is a pineal hormone that regulates the human cycle of sleep and wakefulness. Plasma melatonin levels were investigated in patients with obstructive sleep apnoea syndrome (OSAS).

In total, 20 patients with OSAS and 11 healthy controls were studied. OSAS patients were tested twice: on the night of diagnostic polysomnography and the night of continuous positive airway pressure (CPAP) titration. Controls were tested on one occasion. Plasma melatonin levels were determined at 23:00 h (light period), at 02:00 h (dark period) and at 06:00 h (light period) in patients and control subjects using the radioimmunoassay method.

The control subjects showed a nocturnal melatonin peak value at 02:00 h (70.6±14 pg·mL−1). However, this nocturnal melatonin peak was absent in the OSAS patients. The highest melatonin value was found in OSAS patients on the night of diagnosis, at 06:00 h (49.3±36.8 pg·mL−1). It was found that the melatonin level in OSAS patients at 06:00 h was significantly lower in the night of titration (35.6±37.9 pg·mL−1) than in the diagnosis night. However, the melatonin levels at either 23:00 h or 02:00 h in OSAS patients did not differ significantly when comparing levels in the night of diagnostic polysomnography (23:00 h: 31.6±29.8 pg·mL−1; 02:00 h: 47.4±33.8 pg·mL−1) with levels in the night of CPAP titration (23:00 h: 20.2±10.3 pg·mL−1; 02:00 h: 37.7±27.5 pg·mL−1).

Patients with obstructive sleep apnoea syndrome have an abnormal melatonin secretion pattern. The absence of a nocturnal serum melatonin peak could be partially related to the difficulty that these patients have in achieving a normal sleep–wakefulness pattern.
Pharmacogenetics and asthma: false hope or new dawn?: Table 1—
Authors: Hall I. P. , Sayers I.
Published: May 2007

Pharmacogenetic approaches provide the opportunity to improve prescribing for asthmatic patients in order to optimise efficacy and prevent side-effects. Currently, there are comprehensive data available on the extent of genetic variation in the human genome that will further this area of research. However, less is known about the functional consequences of many of the identified polymorphisms in genes whose products may predict drug efficacy. In addition, there is a shortage of well-designed, adequately powered clinical studies in this area. This series summarises the current state of knowledge and identifies areas for further research.
Exacerbations of chronic obstructive pulmonary disease
Authors: Celli B. R. , Barnes P. J.
Published: May 2007

Exacerbations of chronic obstructive pulmonary disease are of major importance in terms of their prolonged detrimental effects on patients, the acceleration in disease progression and high healthcare costs.

There is still debate about how exacerbations should be defined and graded, and their mechanisms are poorly understood. The major causal agents are either bacteria or viral infections, or a combination of the two. Noninfective causes include air pollution and pulmonary embolus but, in some patients, no cause is identified.

Exacerbations represent an increase in the inflammation that is present in the stable state, with increased numbers of inflammatory cells (particularly neutrophils), cytokines, chemokines and proteases in the airways, and increased concentrations of certain cytokines and C-reactive protein in the blood. There are presently no reliable biomarkers with which to predict exacerbations.

Exacerbations have a long-lasting adverse influence on health status. High doses of bronchodilators are the mainstay of treatment and systemic corticosteroids have some benefit. The routine use of antibiotics remains controversial but they are of benefit with exacerbations of a bacterial origin. Noninvasive ventilation is beneficial in preventing the need for intubation and its important complications but it is not certain whether its use in stable patients prevents exacerbations. Although important advances have been made, more effective treatments are needed in the future for prevention and treatment of exacerbations.
Long-term asthma treatment guided by airway hyperresponsiveness in children: a randomised controlled trial
Authors: Nuijsink M. , Hop W. C. J. , Sterk P. J. , Duiverman E. J. , de Jongste J. C.
Published: May 2007

Management plans for childhood asthma show limited success in optimising asthma control. The aim of the present study was to assess whether a treatment strategy guided by airway hyperresponsiveness (AHR) increased the number of symptom-free days and improved lung function in asthmatic children, compared with a symptom-driven reference strategy.

In a multicentre, double-blind, parallel-group, randomised, 2-yr intervention trial, 210 children (aged 6–16 yrs) with moderate atopic asthma, selected on the basis of symptom scores and/or the presence of AHR, were studied. At 3-monthly visits, symptom scores, forced expiratory volume in one second (FEV1) and methacholine challenge results were obtained, and medication (five levels of fluticasone with or without salmeterol) adjusted according to algorithms based on symptom score (reference strategy, n = 104) or AHR and symptom score (AHR strategy, n = 102).

After 2 yrs, no difference was found in the percentage of symptom-free days between treatment strategies. Pre-bronchodilator FEV1was higher in the AHR strategy (2.3% predicted). This was entirely explained by a gradual worsening of FEV1in a subgroup of 91 hyperresponsive children enrolled with low symptom scores (final difference between study arms was 6%).

Asthma treatment guided by airway hyperresponsiveness showed no benefits in terms of number of symptom-free days, but produced a better outcome in terms of pre-bronchodilator forced expiratory volume in one second in allergic asthmatic children, especially those characterised by low symptom scores despite airway hyperresponsiveness.
New recommendations for duration of respiratory isolation based on time to detectMycobacterium tuberculosisin liquid culture
Authors: Ritchie S. R. , Harrison A. C. , Vaughan R. H. , Calder L. , Morris A. J.
Published: May 2007

It was hypothesised that the time to detectMycobacterium tuberculosisin liquid culture of sputum from patients with pulmonary tuberculosis may be a better indicator for the duration of respiratory isolation than sputum smear status.

Pre-treatment and during-treatment sputum acid-fast bacilli (AFB) smear and culture results were reviewed in 284 patients with pulmonary tuberculosis. The time to detectM. tuberculosisin liquid culture (TTD-TB) was the number of days from inoculation of the Mycobacterial Growth Indicator Tube to culture detection and visualisation of AFB.

The median (interquartile range) TTD-TB for smear group 0 (no bacilli seen) was 14 (12–20) days. This value was used as the standard at which release from isolation could be permitted. In smear group 4 (>9 AFB per high-power field (hpf) in sputum specimens before treatment) patients, the TTD-TB exceeded 14 days after a median of 25 days of treatment.

The current authors recommend that patients in smear groups 1 and 2 (1–9 AFB per 100 hpf and 1–9 AFB per 10 hpf in sputum specimens before treatment, respectively) receive treatment in respiratory isolation for 7 days, provided the risk of drug resistance is low. Smear group 3 (1–9 AFB per hpf) and 4 patients should receive treatment in respiratory isolation for 14 and 25 days, respectively. These criteria would have reduced the duration of respiratory isolation by 1,516 days in the 143 study participants with sputum smear-positive pulmonary tuberculosis.

Provided clinical and radiographical criteria are satisfactory, use of the time to detectMycobacterium tuberculosisin liquid culture could enable the duration of respiratory isolation to be predicted from the pre-treatment sputum smear grade. The recommendations enable isolation to end well before sputum becomes smear negative, with considerable benefits to patients and healthcare providers.
Influenza vaccination and mortality: prospective cohort study of the elderly in a large geographical area
Authors: Örtqvist Å. , Granath F. , Askling J. , Hedlund J.
Published: May 2007

The 50% reduced overall mortality previously associated with influenza vaccination among the elderly was based on studies neither fully taking into account systematic differences between individuals who accept or decline vaccination nor encompassing the entire general population.

A population-based prospective cohort study was performed in Stockholm County (Sweden), including all persons aged ≥65 yrs (n = ∼260,000), over three influenza seasons: 1998/1999, 1999/2000 and 2000/2001. The relative risks of mortality among vaccinatedversusunvaccinated individuals were estimated using Cox's proportional hazards regression adjusted for, and stratified by, demographic factors and comorbid conditions during the three seasons and the respective following off-seasons.

Influenza vaccination was associated with an unadjusted reduction in all-cause mortality during the three seasons of 50, 46 and 42%, respectively, which decreased to 14, 19 and 1%, respectively, following adjustment for confounders and differences in mortality between vaccinated and unvaccinated individuals following the influenza season. The numbers needed to treat to prevent one death, during the three seasons, were 297, 158 and 743, respectively.

Vaccination remains the most important measure for prevention of influenza complications in elderly people, although the effectiveness in reducing all-cause mortality in elderly persons is lower than previously thought.
Hepatopulmonary syndrome following portopulmonary hypertension
Authors: Ioachimescu O. C. , Mehta A. C. , Stoller J. K.
Published: May 2007

Portopulmonary hypertension (PPHTN) and hepatopulmonary syndrome (HPS) are distinct clinical entities that may accompany liver disease.

While PPHTN and HPS have been infrequently described as occurring in the same patient, to the present authors’ knowledge, the order of occurrence has always been the initial onset of HPS, with pulmonary hypertension developing either concurrently or subsequently. In some instances, liver transplantation has been undertaken for HPS, followed by resolution of the HPS and subsequent development of pulmonary hypertension.

The current case study presents a patient with hepatitis C-related cirrhosis in whom PPTHN developed initially, followed 2 yrs later by the development of the HPS.

The current authors speculate that progressive imbalance in favour of endogenous vasodilators over vasoconstrictive factors led to normalisation of the pulmonary artery pressures.
First months of employment and new onset of rhinitis in adolescents
Authors: Riu E. , Dressel H. , Windstetter D. , Weinmayr G. , Weiland S. , Vogelberg C. , Leupold W. , von Mutius E. , Nowak D. , Radon K.
Published: May 2007

The aim of the present study was to investigate the incidence of rhinitis in adolescents, taking into account the duration and type of employment in holiday and vocational jobs, and to study latency until development of symptoms.

Participants of the International Study of Asthma and Allergies in Childhood (ISAAC)-II study in Munich and Dresden (Germany), who were enrolled in 1995, were re-contacted by a postal questionnaire in 2002 (aged 16–18 yrs). The questionnaire focused on allergic rhinitis, type and duration of all jobs, and potential confounders. All jobs held for ≥8 h·week−1and ≥1 month were coded and occupational exposure was assigned by a job-exposure matrix.

Out of the 3,785 participants, 964 reported an employment history. The median (25th–75th percentile) duration of employment was 10 (1–16) months. After adjusting for potential confounders, those working in high-risk occupations (odds ratio (OR) 1.4, 95% confidence interval (CI) 1.0–2.1) had an increased risk for new onset of rhinitis, especially those exposed to low molecular weight agents (OR 1.8, 95% CI 1.1–2.8). The incidence of rhinitis was highest among those currently employed in a high-risk job for <10 months.

Teenagers who start working in high-risk occupations have a higher incidence of rhinitis compared with those not working. This increased risk might occur early on during employment.
Dailyversusweekly azithromycin in cystic fibrosis patients
Authors: McCormack J. , Bell S. , Senini S. , Walmsley K. , Patel K. , Wainwright C. , Serisier D. , Harris M. , Bowler S.
Published: May 2007

Four randomised, placebo-controlled trials have previously documented the clinical benefits of azithromycin (AZM) in cystic fibrosis (CF) patients. The present study examined whether the beneficial effect of AZM is equivalent when administered daily or weekly.

A double-blind, randomised study was carried out in 208 CF patients aged 6–58 yrs who were assigned to AZM either 250 mg daily (n = 103) or 1,200 mg weekly (n = 105) for 6 months, with assessments at baseline and at 1, 3, 6 and 7 months. Patients were taken from five adult and children CF centres in South-east Queensland, Australia.

Equivalence was demonstrated between the two groups (dailyversusweekly) with respect to improvements in lung function (forced expiratory volume in one second and forced vital capacity), C-reactive protein, days spent in hospital, admission rates and nutrition (body mass index, z-scores) using 95% confidence intervals with a tolerance interval of ±10%.

In patients aged <18 yrs the daily group had significantly better improvements in z-scores for height and weight after 6 months. In children, a nutritional advantage for daily administration was found. Gastro-intestinal adverse effects were more common with weekly therapy. Apart from these findings, daily and weekly administered azithromycin demonstrated similar outcomes for cystic fibrosis patients.
Severe exacerbations predict excess lung function decline in asthma
Authors: Bai T. R. , Vonk J. M. , Postma D. S. , Boezen H. M.
Published: May 2007

Severe asthma exacerbations are periods of intense airway inflammation that have been hypothesised to contribute to structural changes in the airways. If so, accelerated lung function decline over time should be more prevalent in adult patients with asthma who have frequent exacerbations than those without, but to date this has not been demonstrated.

A cohort study was performed in order to investigate the effect of severe exacerbations on the progression of airway obstruction in 93 nonsmoking asthmatics with moderate-to-severe disease prior to treatment with inhaled corticosteroids. Subjects were followed for ≥5 yrs (median follow-up 11 yrs).

In total, 56 (60.2%) subjects experienced at least one severe exacerbation (median rate 0.10·yr−1). Oral corticosteroid use and more severe airway obstruction at baseline were associated with a higher exacerbation rate. Independent of these variables, asthma patients with frequent exacerbations had a significantly larger annual decline in forced expiratory volume in one second (FEV1; median difference (95% confidence interval) 16.9 (1.5–32.2) mL·yr−1). Exacerbation rate significantly predicted an excess decline in FEV1, such that one severe exacerbation per year was associated with a 30.2 mL greater annual decline in FEV1.

These data support the hypothesis that exacerbations, indicating intermittent periods of worsening airway inflammation, are associated with excess lung function decline in asthma.