Ambulatory transcutaneous carbon dioxide monitoring for children with neuromuscular disease.

OBJECTIVE: Early screening and diagnosis of nocturnal hypoventilation can slow progression to diurnal hypercapnia and mortality in children with neuromuscular disease (NMD). However, gold standard, laboratory-based polysomnography (PSG) testing is a limited resource. Therefore, we evaluated the diagnostic accuracy of ambulatory transcutaneous carbon dioxide (tcCO2) monitoring used in the home compared to PSG in children with NMD. METHODS: Prospective, cross-sectional study in children 0-18 years old with a confirmed diagnosis of NMD and a clinically indicated need for PSG. Ambulatory tcCO2 was assessed by a respiratory therapist in participant's homes. Demographics, and PSG (including tcCO2). RESULTS: We enrolled 39 children with NMD; 3 had unusable ambulatory tcCO2 data because of failure of drift correction on the machine (n = 2) or an air bubble (n = 1). The remaining 36 patients aged 11 months to 16 years (median (IQR) 12.5 years (6.0-15.8)) had ambulatory tcCO2 and outpatient level 1 PSG data. Ambulatory tcCO2 monitoring had a sensitivity of 20.0% (95% confidence interval [CI] 0.5-71.6%) and a specificity of 93.5% (95% CI 78.6-99.2%). Almost all children and/or parents (34/36, 94%) preferred ambulatory monitoring over in-hospital PSG. CONCLUSIONS: Ambulatory transcutaneous carbon dioxide monitoring was not sufficiently accurate as a clinical tool for the diagnosis of nocturnal hypoventilation our cohort of children with neuromuscular disease despite being preferred over PSG by both children and parents.

White Matter Biomarkers Associated with Motor Change in Individuals with Stroke: A Continuous Theta Burst Stimulation Study.

Continuous theta burst stimulation (cTBS) is a form of noninvasive repetitive brain stimulation that, when delivered over the contralesional hemisphere, can influence the excitability of the ipsilesional hemisphere in individuals with stroke. cTBS applied prior to skilled motor practice interventions may augment motor learning; however, there is a high degree of variability in individual response to this intervention. The main objective of the present study was to assess white matter biomarkers of response to cTBS paired with skilled motor practice in individuals with chronic stroke. We tested the effects of stimulation of the contralesional hemisphere at the site of the primary motor cortex (M1c) or primary somatosensory cortex (S1c) and a third group who received sham stimulation. Within each stimulation group, individuals were categorized into responders or nonresponders based on their capacity for motor skill change. Baseline diffusion tensor imaging (DTI) indexed the underlying white matter microstructure of a previously known motor learning network, named the constrained motor connectome (CMC), as well as the corticospinal tract (CST) of lesioned and nonlesioned hemispheres. Across practice, there were no differential group effects. However, when categorized as responders vs. nonresponders using change in motor behaviour, we demonstrated a significant difference in CMC microstructural properties (as measured by fractional anisotropy (FA)) for individuals in M1c and S1c groups. There were no significant differences between responders and nonresponders in clinical baseline measures or microstructural properties (FA) in the CST. The present study identifies a white matter biomarker, which extends beyond the CST, advancing our understanding of the importance of white matter networks for motor after stroke.

An Acute Bout of Barefoot Running Alters Lower-limb Muscle Activation for Minimalist Shoe Users.

Despite the abundance of barefoot running-related research, there have been no electromyography studies evaluating the effects of this mode of exercise on habitual users of minimalist footwear. The present study investigated differences in muscle activation during acute bouts of barefoot and shod running, in minimalist shoe users. 8 male participants ran on a motorized treadmill for 10 min under both conditions, at 70% maximal aerobic speed. Electromyographic data were sampled from the biceps femoris, gluteus maximus, gastrocnemius medialis, tibialis anterior, and vastus lateralis during both swing and stance. Root-mean-square analysis of electromyographic data was conducted to compare muscle activation between conditions. During stance, barefoot running resulted in greater muscle activity in gastrocnemius medialis and gluteus maximus, and lower muscle activity in tibialis anterior. During swing, barefoot running resulted in increased muscle activity in vastus lateralis and gastrocnemius medialus. These results indicate that, for minimalist shoe users, an acute bout of barefoot running results in significantly different lower-limb muscle activity. Increased activation in the above muscles presents a possible mechanism for injury, which should be considered during exercise prescription.

Comparing a diffusion tensor and non-tensor approach to white matter fiber tractography in chronic stroke.

Diffusion tensor imaging (DTI)-based tractography has been used to demonstrate functionally relevant differences in white matter pathway status after stroke. However, it is now known that the tensor model is insensitive to the complex fiber architectures found in the vast majority of voxels in the human brain. The inability to resolve intra-voxel fiber orientations may have important implications for the utility of standard DTI-based tract reconstruction methods. Intra-voxel fiber orientations can now be identified using novel, tensor-free approaches. Constrained spherical deconvolution (CSD) is one approach to characterize intra-voxel diffusion behavior. In the current study, we performed DTI- and CSD-based tract reconstruction of the corticospinal tract (CST) and corpus callosum (CC) to test the hypothesis that characterization of complex fiber orientations may improve the robustness of fiber tract reconstruction and increase the sensitivity to identify functionally relevant white matter abnormalities in individuals with chronic stroke. Diffusion weighted magnetic resonance imaging was performed in 27 chronic post-stroke participants and 12 healthy controls. Transcallosal pathways and the CST bilaterally were reconstructed using DTI- and CSD-based tractography. Mean fractional anisotropy (FA), apparent diffusion coefficient (ADC), axial diffusivity (AD), and radial diffusivity (RD) were calculated across the tracts of interest. The total number and volume of reconstructed tracts was also determined. Diffusion measures were compared between groups (Stroke, Control) and methods (CSD, DTI). The relationship between post-stroke motor behavior and diffusion measures was evaluated. Overall, CSD methods identified more tracts than the DTI-based approach for both CC and CST pathways. Mean FA, ADC, and RD differed between DTI and CSD for CC-mediated tracts. In these tracts, we discovered a difference in FA for the CC between stroke and healthy control groups using CSD but not DTI. CSD identified ipsilesional CST pathways in 9 stroke participants who did not have tracts identified with DTI. Additionally, CSD differentiated between stroke ipsilesional and healthy control non-dominant CST for several measures (number of tracts, tract volume, FA, ADC, and RD) whereas DTI only detected group differences for number of tracts. In the stroke group, motor behavior correlated with fewer diffusion metrics derived from the DTI as compared to CSD-reconstructed ipsilesional CST and CC. CSD is superior to DTI-based tractography in detecting differences in diffusion characteristics between the nondominant healthy control and ipsilesional CST. CSD measures of microstructure tissue properties related to more motor outcomes than DTI measures did. Our results suggest the potential utility and functional relevance of characterizing complex fiber organization using tensor-free diffusion modeling approaches to investigate white matter pathways in the brain after stroke.

Orexin-1 receptor antagonism fails to reduce anxiety-like behaviour in either plus-maze-naïve or plus-maze-experienced mice.

Although several lines of evidence have recently implicated orexins and their receptors in fear and anxiety, there is also a growing number of apparently inconsistent and/or negative findings. In the present study, we have used ethological methods to comprehensively profile the behavioural effects of the orexin-1 receptor antagonist SB-334867 (3-30 mg/kg) in mice exposed to the elevated plus-maze. Two experiments were performed, the first involving test-naïve animals and the second using prior undrugged experience of the maze to induce a qualitatively different emotional response to that seen on first exposure. In Experiment 1, a reference benzodiazepine (chlordiazepoxide, CDP, 15 mg/kg) produced a robust anxioselective profile comprising substantial increases in open arm exploration and reduced risk assessment without any signiifcant change in general activity levels. In contrast, SB-334867 failed to produce any behavioural effects over the dose range tested. In Experiment 2, 5 min undrugged experience of the maze 24h prior to testing increased open arm avoidance and abolished the anxiolytic efficacy of CDP. Despite this altered baseline, SB-334867 again failed to alter plus-maze behaviour. These findings agree with several recent reports that orexin receptor antagonists, such as SB-334867 and almorexant, do not alter basal anxiety levels in rats but markedly contrast with the anxiolytic-like effects of the same agents when anxiety levels have been exacerbated by fear conditioning, drug challenge or hypercapnia. This unique pattern of activity suggests that orexin receptor antagonists may have therapeutic value in those clinical anxiety disorders characterised by intense emotional arousal.

Novel techniques for enhancing sensitivity in static headspace extraction-gas chromatography.

Static headspace extraction-gas chromatography (SHE-GC) is one of the most commonly used techniques for the analysis of volatile compounds. It is considered by most to be a mature technique and to an extent this is true: there are many users from outside the traditional chromatography research community developing and publishing SHE-GC methods and there are numerous instruments and devices for SHE-GC commercially available. However, research on new SHE-GC methods continues. In this review, several interesting new developments in SHE-GC are described using examples from the past three years' literature. First, the fundamental theory of SHE-GC is reviewed to provide a basis and common theme for the discussion of new methods. Next, several areas of SHE-GC research are explored: new sampling configurations, analyte derivatization and ionic liquids as solvents. These are all means for enhancing partitioning of the analyte into the vapor phase, thus improving analytical sensitivity of the overall SHE-GC method. Ideally, partitioning of analytes into the vapor phase is increased while partitioning of matrix components is not, or is decreased. There are many aspects of the seemingly straightforward process in SHE-GC that require further fundamental research to extend the application range of SHE-GC and to make method development more systematic.

Community treatment orders: the ethical balancing act in community mental health.

Community treatment orders (CTOs) are legal mechanisms by which an individual with a mental illness and a history of non-compliance and potential for violence can be mandated (against their will) to undergo psychiatric treatment in an outpatient setting. Although CTOs are increasingly being adopted by governments as a means of protecting both mentally ill persons and society itself, their use continues to stimulate considerable debate. While there is some evidence of their potential benefits in promoting treatment compliance and reducing hospital stays, there is concern that they infringe on the mental health client's human rights and freedoms. Consideration of the ethical and practical implications of the use of CTOs must continue. In this paper, some of the most pressing issues are identified and discussed.

Adsorption behavior of hexafluorophosphate on selected bonded phases.

The adsorption behavior of ammonium hexafluorophosphate was studied on four HPLC columns packed with adsorbents of different ability for dispersive interactions using frontal chromatography with LC/MS detection in negative ESI mode. Hexafluorophosphate (PF(6)(-)) adsorption isotherms were measured from acetonitrile/water and methanol/water mixtures. Increased PF(6)(-) adsorption with increased acetonitrile content was found between 0 and 15% of acetonitrile in the eluent. Further increase of the acetonitrile concentration leads to an exponential decrease of PF(6)(-) adsorption. Methanol, on the other hand, causes a steady decrease of PF(6)(-) adsorption with increased organic concentration in the mobile phase.

Replacement of degenerated mitral and aortic bioprostheses without explantation.

BACKGROUND: The most common indication for reoperation in patients with a bioprosthetic valve is primary tissue failure. Explantation of the bioprosthesis is time consuming, and for a mitral valve, may be complicated by cardiac rupture at the atrioventricular junction or the posterior left ventricular wall where a strut is imbedded, injury to the circumflex artery, and late perivalvular leak; for an aortic valve, annular disruption and perivalvular leak may complicate explantation. A new approach to simplify these procedures and avoid these complications, by excising only the bioprosthetic tissue and attaching a bileaflet mechanical valve to the intact stent, was developed in 1991 and was evaluated over a 9-year period in 50 patients who had had one (34), two (10), three (4), or four (2) previous open cardiac operations. METHODS: Since 1991, we have replaced degenerated mitral bioprostheses in 34 patients (25 to 84 years of age; 12 male, 22 female) by preserving the stent and suturing a St. Jude or Carbomedics bileaflet valve to the atrial side of the bioprosthetic cuff; the mitral valve was exposed through a median sternotomy in 21 patients and through a right anterolateral thoracotomy in 13. Using a similar approach, starting in 1995, 16 additional patients (55 to 73 years of age; 11 male, 5 female) with degenerated aortic bioprostheses had the aortic valve replaced by excising the bioprosthetic tissue and amputating the struts, then suturing a Carbomedics valve to the aortic side of the bioprosthetic cuff. This allows the use of a bileaflet valve similar in size to the bioprosthesis with exact matching of the orifices. RESULTS: Bypass time averaged 61 +/- 14 minutes and aortic cross-clamp time 43 +/- 12 minutes. There has been no operative mortality. Three late deaths occurred at 9, 37, and 58 months, and were not valve related. No gradients of hemodynamic significance have been detected on transesophageal echocardiographic follow-up. CONCLUSIONS: Leaving the bioprosthetic cuff intact eliminates the need for extensive dissection, thus shortening and simplifying the procedure and diminishing its attendant mortality and morbidity. This valve-on-valve approach also allows replacement of a degenerated bioprosthesis with a bileaflet valve of comparable size rather than a smaller one jammed into the orifice of the bioprosthetic stent, thus avoiding undue trauma to the bileaflet valve and maintaining excellent hemodynamic function.

Modeling flavor release using inverse gas chromatography-mass spectrometry.

Inverse gas chromatography (IGC)-mass spectrometry was used to determine the extent of flavor release from a food matrix as a function of moisture uptake. At the surface of a solid, components with higher binding affinities can exchange with and replace components with lower binding affinities. As a low moisture baked product absorbs moisture from the air, flavor is lost from the matrix as water molecules exchange with the flavor molecules. The amount of flavor lost over time can be modeled using this approach to determine the onset of flavor release and total amount of flavor release as well as the identity of the released components and their relative order of exclusion from the matrix.

Determination of apparent association constants of steroid-cyclodextrin inclusion complexes using a modification of the Hummel-Dreyer method.

A modified Hummel-Dreyer method was used to calculate the apparent association constants of steroid-cyclodextrin inclusion complexes. An external calibration technique was employed, using the y-intercept from a plot of peak area versus concentration to correct for sample solvent effects. Mobile phase temperature and sample diluent organic content were found to be critical factors affecting the accuracy and reproducibility of the results. For four of six sets of data, the modified Hummel-Dreyer method yielded statistically equivalent results to another HPLC method for determining apparent association constants. Limitations of the modified Hummel-Dreyer method are discussed. In particular, the accuracy of the method is poor when measuring small apparent association constants.

Pulmonary venous drainage into the left atrial appendage facilitates transplantation of the left lung with difficult exposure.

Heterotopic implantation of the pulmonary venous confluence into the left atrial appendage during left lung transplantation is a reasonable alternative technique to reestablish venous drainage when exposure of the native left pulmonary veno-atrial connection may be problematic. We used this approach in a 39-year-old woman with chronic bronchiectasis who underwent bilateral sequential lung transplantation through a clam-shell approach. Dense hilar scarring and a small left atrial size made exposure of the native left pulmonary veno-atrial connection difficult.

A 32-year experience in 100 patients with giant paraesophageal hernia: the case for abdominal approach and selective antireflux repair.

BACKGROUND: Giant paraesophageal hiatal hernia (GPEH) presents a risk of catastrophic complications that include massive bleeding, strangulation, and perforation and should be repaired. Controversy persists as to the surgical approach and whether an antireflux repair is required. METHODS: This study reviews the experience with 100 patients with GPEH who underwent surgical repair between 1967 and 1999. Eighty patients underwent an elective operation, and 20 patients underwent an emergency procedure for complications of GPEH. The gastroesophageal junction was above the hiatus ("combined" hernia with sliding component) in 23 patients and in the abdomen in 77 patients, including 3 patients with a true parahiatal hernia. RESULTS: A thoracic approach was used in 18 patients, mostly early in our experience; postoperative gastric volvulus requiring transabdominal repair developed in 2 patients. The remaining 82 patients underwent an abdominal repair, with temporary gastrostomy to prevent gastric displacement in 75 patients; the hernial sac was resected, and the hiatus was reconstructed in all of the patients. Thirty-five patients with reflux on preoperative work up underwent a fundoplication, with gastroplasty in 2 patients because of a short esophagus. No patient has experienced hernia recurrence. Whereas symptomatic relief was excellent in all patients with elective repair, mild reflux was present in 2 patients after emergency operation. There were no deaths among the patients who underwent elective operation; there were 2 hospital deaths among those patients who underwent emergency operation (10%). CONCLUSIONS: GPEH should be repaired soon after recognition. Reflux should be evaluated before the operation, and if present, fundoplication should be part of the repair along with the reduction of the hernia, excision of the sac, gastropexy, and crural closure. These are best achieved with an abdominal approach.

Total intravenous anesthesia with a propofol-ketamine combination during coronary artery surgery.

OBJECTIVE: To evaluate the cardiovascular effects of a propofol-ketamine combination in patients undergoing coronary artery surgery. DESIGN: Prospective, randomized study. SETTING: Tertiary care teaching hospital, single center. PARTICIPANTS: Seventy-eight adult patients. INTERVENTIONS: Patients were randomly allocated to receive propofol-ketamine for induction and maintenance of anesthesia (n = 36) or fentanyl-enflurane (controls, n = 42). MEASUREMENTS AND MAIN RESULTS: Hemodynamics and other variables were recorded during and after surgery and for 24 hours in the intensive care unit. Before cardiopulmonary bypass (CPB), there was similar incidence of treatment for hypotension (42% of patients in both groups), tachycardia (propofol-ketamine, 6%; controls, 5%), and myocardial ischemia (propofol-ketamine, 3%; controls, 12%). In the propofol-ketamine group, there was a decreased requirement for inotropic agents after CPB (22% of patients) compared with controls (49% of patients; p = 0.02). There was a reduced incidence of myocardial infarctions (creatine kinase myocardial band >133 U/L) in the propofol-ketamine group compared with the control group (0% v 14%; p = 0.02; Fisher's exact test). Patients in the propofol-ketamine group were more likely to have their tracheas extubated within 8 hours of arrival in the intensive care unit compared with controls (33% v 7%; p = 0.01; Cochran-Mantel-Haenzel test). CONCLUSIONS: The propofol-ketamine combination was associated with a similar incidence of pre-CPB hypotension and ischemia, a decreased need for inotropes after CPB, an earlier time to tracheal extubation, and a reduced incidence of myocardial infarctions compared with controls.

Solid-phase micro-extraction of drugs from biological matrices.

Solid phase micro-extraction was originally designed as a technique for the solvent-free analysis of volatile organic contaminants in environmental samples. However, a wide variety of applications are now being pursued, including the analysis of drugs from a variety of matrices. In this review, the analysis of drugs by SPME from biological and related matrices, including water, urine, blood, hair and saliva, is discussed. A general overview of the special problems and techniques involved in SPME from biological matrices is presented, along with specific references and discussion of the analysis of many types of drugs and metabolites. It is seen that SPME is a highly versatile and flexible technique for these analyses.

Characterization of inclusion complexes of betamethasone-related steroids with cyclodextrins using high-performance liquid chromatography.

HPLC was used to study the inclusion complexes formed between various beta- and gamma-cyclodextrins and a series of corticosteroids related to betamethasone. Apparent association constants were measured in acetonitrile-water for a set of 13 steroids. An increase in the stability of the steroid-cyclodextrin complex is observed at lower concentrations of acetonitrile. The effects of the nature of the halide at the 9-position, the location of a double bond within the C-ring, substitution at the 9- and 11-positions, and modification of the D-ring of the steroid backbone were studied. The 11- and 17-positions were found to be critically involved in the inclusion process. Larger apparent association constants were obtained with gamma-cyclodextrin (gamma-CD) than with beta-cyclodextrin (beta-CD) due to the increased diameter of the gamma-CD cavity. Van't Hoff plots were constructed to examine the thermodynamic properties of the inclusion process. Plots constructed using retention factors were found to be nonlinear when gamma-CD was present in the mobile phase. This is due to an increase in the strength of the inclusion complex as temperature decreases. Plots constructed using apparent association constants were linear, indicating that the mechanism of inclusion does not change over the range of temperatures studied (10 to 80 degrees C). Enthalpy-entropy compensation was observed for 11 of the 13 steroids studied. The usefulness of cyclodextrins to achieve the separation of steroids in HPLC is discussed and a practical application for the analysis of a steroid and three potential impurities is described.