Responsiveness of self-reported and objective measures of disease severity in carpal tunnel syndrome

Responsiveness, the ability to detect meaningful clinical change, is a critical attribute of instruments used to evaluate outcomes of treatments. The authors hypothesized that self-administered symptom severity and functional status questionnaires are more responsive to clinical improvement after carpal tunnel release than traditional physical examination measures of strength and sensibility. Data were obtained from a randomized clinical trial of endoscopic versus open carpal tunnel release conducted in four university medical centers. Patients were evaluated before surgery and 3 months after surgery. Seventy-four patients indicating that they were more than 80% satisfied with the results of surgery were assumed to have clinically meaningful improvement and were the focus of the analysis. Evaluations included questionnaires assessing symptom severity, functional status, and activities of daily living as well as measurement of grip, pinch, and abductor pollicus brevis strength, and 2-point discrimination and Semmes-Weinstein pressure sensibility. Responsiveness was calculated with the standardized response mean (mean change/standard deviation of change) as well as the effect size (mean change/standard deviation of baseline values). The symptom severity scale was four times as responsive, and the functional status and activities of daily living scales were twice as responsive, as the measures of strength and sensibility. Self-administered symptom severity and functional status scales are much more responsive to clinical improvement than measures of neuromuscular impairment and should severe as primary outcomes in clinical studies of therapy for carpal tunnel syndrome.     

Differential c-fos expression in the nucleus of the solitary tract and spinal cord following noxious gastric distention in the rat

c-Fos has been used as a marker for activity in the spinal cord following noxious somatic or visceral stimulation. Although the viscera receive dual afferent innervation, distention of hollow organs (i.e. esophagus, stomach, descending colon and rectum) induces significantly more c-Fos in second order neurons in the nucleus of the solitary tract and lumbosacral spinal cord, which receive parasympathetic afferent input (vagus, pelvic nerves), than the thoracolumbar spinal cord, which receives sympathetic afferent input (splanchnic nerves). The purpose of this study was to determine the contribution of sympathetic and parasympathetic afferent input to c-Fos expression in the nucleus of the solitary tract and spinal cord, and the influence of supraspinal pathways on Fos induction in the thoracolumbar spinal cord. Noxious gastric distention to 80 mmHg (gastric distension/80) was produced by repetitive inflation of a chronically implanted gastric balloon. Gastric distension/80 induced c-Fos throughout the nucleus of the solitary tract, with the densest labeling observed within 300 microns of the rostral pole of the area postrema. This area was analysed quantitatively following several manipulations. Gastric distension/80 induced a mean of 724 c-Fos-immunoreactive nuclei per section. Following subdiaphragmatic vagotomy plus distention (vagotomy/80), the induction of c-Fos-immunoreactive nuclei was reduced to 293 per section, while spinal transection at T2 plus distention (spinal transection/80) induced a mean of 581 nuclei per nucleus of the solitary tract section. Gastric distension/80 and vagotomy/80 induced minimal c-Fos in the T8-T10 spinal cord (50 nuclei/section), but spinal transection/80 induced 200 nuclei per section. Repetitive bolus injections of norepinephrine produced transient pressor responses mimicking the pressor response produced by gastric distension/80. This manipulation induced minimal c-Fos in the nucleus of the solitary tract and none in the spinal cord. It is concluded that noxious visceral input via parasympathetic vagal afferents, and to a lesser extent sympathetic afferents and the spinosolitary tract, contribute to gastric distention-induced c-Fos in the nucleus of the solitary tract. The induction of c-Fos in the nucleus of the solitary tract is significantly greater than in the viscerotopic segments of the spinal cord, which is partially under tonic descending inhibition, but is not subject to modulation by vagal gastric afferents. Distention pressures produced by noxious gastric distention are much greater than those produced during feeding, suggesting that c-Fos induction in the nucleus of the solitary tract to noxious distention is not associated with physiological mechanisms of feeding and satiety. The large vagal nerve-mediated induction of c-Fos in the nucleus of the solitary tract following gastric distension suggests that parasympathetic afferents contribute to the processing of noxious visceral stimuli, perhaps by contributing to the affective-emotional component of visceral pain.     

Effect of hemofiltration on hemodynamics and systemic concentrations of anaphylatoxins and cytokines in human sepsis

OBJECTIVE: To determine whether hemofiltration (HF) can eliminate cytokines and complement components and alter systemic hemodynamics in patients with severe sepsis. DESIGN: Prospective observation study. SETTING: Surgical intensive care unit of a university hospital. PATIENTS: 16 patients with severe sepsis. INTERVENTIONS: Continuous zero-balanced HF without dialysis (ultrafiltrate rate 2 l/h) was performed in addition to pulmonary artery catheterization, arterial cannulation, and standard intensive care treatment. MEASUREMENTS AND MAIN RESULTS: Plasma and ultrafiltrate concentrations of cytokines (the interleukins IL-1 beta, IL-6, IL-8, and tumor necrosis factor alpha) and of complement components (C3adesArg, C5adesArg) were measured after starting HF (t0) and 4 h (t4) and 12 h later (t12). Hemodynamic variables including mean arterial pressure (MAP), mean central venous pressure, mean pulmonary artery pressure, pulmonary capillary wedge pressure, and cardiac output were serially determined. During HF, cytokine plasma concentrations remained constant. However, C3adesArg and C5adesArg plasma concentrations showed a significant decline during 12-h HF (C3adesArg: t0 = 676.9 +/- 99.7 ng/ml vs t12 = 467.8 +/- 71, p < 0.01; C5adesArg: 26.6 +/- 4.7 ng/ml vs 17.6 +/- 6.2, p < 0.01). HF resulted in a significant increase over time in systemic vascular resistance (SVR) and MAP (SVR at t0: 669 +/- 85 dyne.s/cm5 vs SVR at t12: 864 +/- 75, p < 0.01; MAP at t0: 69.9 +/- 3.5 mmHg vs MAP at t12: 82.2 +/- 3.7, p < 0.01). CONCLUSIONS: HF effectively eliminated the anaphylatoxins C3adesArg and C5adesArg during sepsis. There was also a significant rise in SVR and MAP during high volume HF. Therefore, HF may represent a new modality for removal of anaphylatoxins and may, thereby, deserve clinical testing in patients with severe sepsis.     

Flash photolysis of the carbon monoxide compounds of wild-type and mutant variants of cytochrome bo from Escherichia coli

The carbon monoxide compounds of the fully reduced and mixed valence forms of cytochrome bo from Escherichia coli were laser photolysed under anaerobic conditions at room temperature. The carbon monoxide recombined with characteristic rate constants of 50 s-1 or 35 s-1 in the fully reduced and mixed valence forms, respectively. Rates of CO recombination with the fully reduced enzyme were examined in a variety of mutant forms of cytochrome bo, produced by site-directed mutagenesis. A method was developed to deconvolute cytochromes bo and bd, leading to some reassessment of histidine ligands to the metals. Significant changes in the rate constant of recombination of carbon monoxide occurred in many of these mutants and these results could be rationalised generally in terms of our current working model of the folding structure of subunit I. In the mixed valence form of the enzyme the transient photolysis spectra in the visible region are consistent with a rapid electron redistribution from the binuclear centre to the low-spin haem. This electron transfer is biphasic, with rate constants of around 10(5) and 8000 s-1. The process was also examined in the His-333-Leu mutant, in which a putative histidine ligand to CuB is replaced by leucine, and which results in the loss of the CuB. It appeared that rapid haem-haem electron transfer could still occur. The observation that CuB is apparently not required for rapid haem-haem electron transfer is consistent with the recently proposed model in which the two haems are positioned on opposite sides of transmembrane helix X in subunit I of the oxidase.     

George Martin Haslerud (1906–1990): Obituary.

Commemorates G. M. Haslerud, who died suddenly on April 10, 1990. In his doctoral dissertation (1934) he addressed free and prescribed maze patterns in rats, pointing to a lifetime interest in creative transfer. In 1972 he completed his magnum opus, Transfer, Memory, and Creativity: After-Learning as Perceptual Process, which reflects continuing conversations with his mentor, Robert Yerkes. Haslerud is remembered as a co-founder of the New Hampshire Psychological Association. (0 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Intermodality, retrospective image registration in the thorax

The purpose of this study was to develop an accurate, retrospectively applicable procedure for registering thoracic studies from different modalities in a short amount of time and with minimal operator intervention. METHODS: CT and PET studies were acquired from six patients. The pleural surfaces in both image sets were determined by segmenting based on 50% of the maximum soft-tissue value in the study. These surfaces were converted into three-dimensional volumes and used to register the CT and PET studies in three dimensions using a sum of least squares fitting approach. The registered PET study was then displayed in a hot metal scale overlayed on top of the gray scale CT study. The accuracy of the fit was evaluated through a phantom study and preliminary clinical evaluation. RESULTS: A phantom study was performed to determine the limits of this technique. The accuracy was determined to be less than 2.3 mm in the x and y direction and 3 mm in the z direction. Preliminary clinical evaluation was also performed with encouraging results. CONCLUSION: This technique accurately registers PET and CT images of the thorax, retrospectively, without the need for external fiducial markers or other a priori action.     

Dietary fibre of coconuts from a pacific atoll: Soluble and insoluble components in relation to maturity

Polysaccharide fractions were measured in coconuts at three stages of maturity, which corresponded to dietary usage in the Tokelau Islands of the South Pacific. Kernel was sequentially extracted with cold water (CW), hot water (HW) hot 0.5% ammonium oxalate (HOX), 1M H² SO⁴ and 72% H² SO⁴, and the monosaccharide compositions of the fractions determined. Total readily soluble fractions (CW+HW+HOX) were predominantly galactomannan, and decreased from 77% of the polysaccharide in the immature kernel to 8.8% of that in the mature kernel. Insoluble mannan increased during maturation to be the major polysaccharide component in mature kernel. This indicates that marked differences exist between the three stages of maturity examined, in the properties of their dietary fibre. The results suggest that in studies of diets in which coconut is a staple part, there is a need for careful definition of the coconut component with respect to maturity. Furthermore, they show the importance of using dietary fibre methods which are appropriate to the solubility characteristics of the indigestible polysaccharide.     

Evaluation of the proline-rich antigen of Coccidioides immitis as a vaccine candidate in mice

We have expressed the proline-rich antigen (PRA) from Coccidioides immitis in Escherichia coli and evaluated its potential as a vaccine candidate. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of the recombinant protein (rPRA) revealed two bands, which exhibited virtually identical primary amino acid sequences. T cells from rPRA-immunized BALB/c mice showed a significant in vitro proliferative response to rPRA. A small but statistically significant proliferative response was also induced by rPRA in T cells from mice immunized with whole-cell coccidioidal vaccines. BALB/c mice immunized with rPRA and challenged intraperitoneally with virulent C. immitis had a greatly reduced fungal burden in their lungs and spleens compared to unvaccinated mice. The number of organisms in the lungs was reduced 500-fold, and similar reductions were observed in the spleens of immunized mice. These studies support the continued development of rPRA as a candidate vaccine for prevention of coccidioidomycosis.