The development of balance control in children: comparisons of EMG and kinetic variables and chronological and developmental groupings

This cross-sectional study examined electromyographic (EMG) and kinetic variables during reactive balance responses in children grouped according to developmental level as compared with chronological age. Purposes were to explore relationships between the two types of variables and the effectiveness of the two grouping methods. Forty-four children between 9 months and 10 years old were tested for reactive balance control on a moveable platform. Surface electrodes measured EMG activity in the gastrocnemius (GA), hamstrings (HA), paraspinals (PS), tibialis anterior (TA), quadriceps (QA), and abdominal (AB) muscles. Timing and distance of center-of-pressure (COP) movements and peak muscle torques at the ankle, knee, and hip were also examined. Significant relationships and group differences were found between postural muscle activity and both the torque generated in the lower limbs and the timing and distance of COP adjustments employed to restabilize balance. As postural muscle activity increased and became more coordinated in timing, peak torque at the ankle and hip also increased, while the distance of and time to complete COP readjustments decreased. Children in younger/developmentally lower groups had smaller-magnitude and less-synergic muscle activity, lower peak torques, longer times to restabilize the COP, and greater COP paths than older/higher developmental groupings. Grouping by developmental level produced more statistical differences than did grouping by age. The correspondence of GA, HA, and PS muscle activity with COP measures and joint peak torques confirms that these muscles are key contributors to the balance synergy correcting for induced forward sway. Additionally, developmental level appears to be a much better predictor of balance improvement than chronological age.     

The value of routine chest radiographs in a paediatric intensive care unit: a prospective study

Background. In many paediatric intensive care units (PICUs) chest X-ray films (CXRs) are required as part of the daily examination or after completion of invasive procedures. Objective. First, to evaluate if the American College of Radiology (ACR) guidelines for adult patients are appropriate for paediatric pa- tients. Second, to assess the diagnostic efficacy of the CXRs. Materials and methods. One-hundred-seventy-four CXRs acquired in 74 patients, either routinely or after invasive procedures, were analysed. The indication of the obtained CXRs, or the absence of indication in patients in whom no CXRs was taken, was compared with ACR guidelines. The position of medical devices was evaluated. Changes in cardiopulmonary status were noted. Results. Sixty-seven percent of the CXRs were in accordance with the ACR guidelines, and in 74 % of pa- tients in whom no CXRs were taken this was also in accordance with these guidelines. Sixteen percent of the endotracheal tubes, 23 % of central venous lines and 15 % of nasogastric tubes were malpositioned. Changes in cardiopulmonary status, after the initial film, were noted in 63 %. Conclusions. The indications for the majority of CXRs in our PICU appeared to be in accordance with ACR guidelines. The high percentage of malpositioned tubes and lines and the number of cardiopulmonary changes on CXRs in a PICU underline the value of these films. Adjustments of the ACR guidelines for particular groups of paediatric patients may limit the number of CXRs taken and may further increase diagnostic efficacy. Received: 16 May 2000 Accepted: 15 October 2000     

Reemergence of sexual dysfunction in patients with major depressive disorder: double-blind comparison of nefazodone and sertraline

BACKGROUND: Several different classes of antidepressants have been associated with sexual adverse effects. This double-blind, randomized trial compared the effects of nefazodone and sertraline on reemergence of sexual dysfunction in depressed patients who had experienced sexual dysfunction as a result of sertraline treatment. Depressive symptoms were also monitored. METHOD: One hundred five patients with DSM-III-R major depressive episode who were experiencing sexual dysfunction attributable to sertraline (100 mg/day) were screened for entry. Eligible patients entered a 1-week washout period that was followed by a 7- to 10-day single-blind placebo phase. Patients without symptoms of sexual dysfunction at the end of the single-blind placebo phase were randomly assigned to receive double-blind treatment with either nefazodone (400 mg/day) or sertraline (100 mg/day) for 8 weeks. RESULTS: Nearly 3 times more sertraline-treated patients (76%; 25/33) experienced reemergence of sexual dysfunction (ejaculatory and/or orgasmic difficulty) than did nefazodone-treated patients (26%; 10/39) (p < .001). In addition, patients treated with nefazodone were more satisfied with their sexual functioning than were patients treated with sertraline. Both treatment groups demonstrated a similar and sustained improvement in depressive symptoms. Both drugs were well tolerated, and the overall incidence of adverse reactions was similar for both treatment groups; however, 9 sertraline-treated patients (26%) discontinued because of adverse events compared with 5 nefazodone-treated patients (12%). Of the patients discontinuing therapy for adverse events, 5 of the sertraline-treated patients did so because of sexual dysfunction reported as an adverse event, whereas only 1 of the nefazodone-treated patients discontinued therapy secondary to sexual dysfunction. CONCLUSION: In this sample of patients with major depression who had recovered from sexual dysfunction induced by treatment with sertraline, nefazodone treatment resulted in significantly less reemergence of sexual dysfunction than did renewed treatment with sertraline and provided continued antidepressant activity.     

LC/MS/MS structure elucidation of reaction intermediates formed during the TiO2 photocatalysis of microcystin-LR

Microcystin-LR (MC-LR), a cyanotoxin and emerging drinking water contaminant, was treated with TiO₂ photocatalysts immobilized on stainless steel plates as an alternative to nanoparticles in slurry. The reaction intermediates of MC-LR were identified with mass spectrometry (MS) at pH of Milli-Q water (pH_sq=5.7). Eleven new [M+H]⁺ were observed in the liquid chromatography mass spectrometry (LC/MS) chromatogram with some of them giving multiple peaks. Most of these reaction intermediates have not been reported from previous studies employing TiO₂ nanoparticles at acidic conditions (pH=4.0). Investigating the effects of pH (for 3.02 photocatalytic films showed that acidic conditions are preferable for the degradation. Combined with the limited surface area of the films and the absence of additional oxidants (i.e., H₂O₂) the degradation was slower and more intermediate steps were identified. Possible structures of the intermediates (formed at neutral pH) after analyzing the corresponding MS/MS spectra are reported. The collision-induced dissociation of the [M+H]⁺ of MC-LR and the intermediates 1011.5 and 1029.5 are discussed and possible fragmentation pathways and mechanisms are also proposed. Analysis of the MS/MS spectra indicates that the fragmentation of some amino acids is less favorable because of internal interaction with free groups of adjacent amino acids. The MS/MS spectra assisted in determining hydroxylation sites, by the formation or alteration of specific product ions such as m/z 599.     

Discontinuation of Anticytomegalovirus Therapy in Patients With HIV Infection and Cytomegalovirus Retinitis

Context  Persons with cytomegalovirus (CMV) retinitis and acquired immunodeficiency syndrome (AIDS) have required lifelong anti-CMV therapy to prevent the progression of retinal disease and subsequent loss of vision. Objective  To determine whether patients who were taking highly active antiretroviral therapy (HAART) and who had stable CMV retinitis could safely discontinue anti-CMV therapy without reactivation of their retinitis or increase in human immunodeficiency virus (HIV) viral load. Design  Prospective nonrandomized interventional trial performed from July 1997 to August 1999. Setting  Clinical Center of the National Institutes of Health, Bethesda, Md. Patients  Fourteen patients with stable CMV retinitis and HIV infection and CD4⁺ cell counts higher than 0.15 x 10⁹/L and being treated with systemic anti-CMV medications and HAART. Interventions  Discontinuation of specific anti-CMV therapy. Main Outcome Measures  Reactivation of CMV retinitis, development of extraocular CMV infection, detection of CMV in blood and urine, HIV burden, immunologic function, quality of life, morbidity, and mortality. Results  Twelve (89.7%) of 14 patients had evidence of immune recovery uveitis before anti-CMV drugs were discontinued. No patient had reactivation of CMV retinitis or development of extraocular CMV disease during mean follow-up of 16.4 months (range, 8.3-22.0 months) without anti-CMV therapy. Human immunodeficiency viral load remained stable following cessation of anti-CMV medications. Blood and urine assays for CMV were briefly positive in 9 patients but did not predict reactivation of CMV disease. Worsening immune recovery uveitis was associated with a substantial (>3 lines) vision loss in 3 patients. Conclusions  Maintenance anti-CMV medications were safely stopped in those patients who had stable CMV retinitis and elevated CD4⁺ cell counts and who were taking HAART. The study demonstrates that immune recovery following potent antiretroviral therapy is effective in controlling a major opportunistic infection, even in patients with a history of severe immunosuppression.      

Regulators of human stem cell proliferation and engraftment

Transplantable human hematopoietic stem cells can be routinely detected by their ability to engraft sublethally irradiated immunodeficient mice with both lymphoid and myeloid progeny for periods of at least 6-8 weeks [1]. These cells include subsets with both short-term and longterm reconstituting activity, the former being responsible for most of the human cells seen in fully immunodeficient mice (eg, NOD/SCID-β2microglobulin^?/? mice) in the first 8 weeks and the latter being responsible for the lower levels of engraftment seen after the same period of time in less compromised (eg, NOD/SCID) mice [2]. Interestingly, human cells with short- and longterm hematopoietic reconstituting potential show further differences in the regulation of their ability to engraft when they are activated into cycle short-term reconstituting cells being unaffected whereas longterm reconstituting cells lose their transplantability when they transit S/G₂/M [2,3]. A closely related population of primitive human hematopoietic cells (referred to as longterm culture-initiating cells or LTC-ICs) are detected by virtue of their ability to generate intermediate types of progenitor cells for at least 5 weeks when co-cultured with stromal cell feeder layers, the intermediate progenitors being those that produce colonies of granulocytes and macrophages and/or erythroblasts in 2-week semi-solid cultures [4]. The proliferative status of these various stages of primitive human hematopoietic cells is regulated by their exposure to distinct types of both positively acting (mitogenic) and negatively acting (cytostatic) cytokines. We have recently discovered that stromal-derived growth factor 1 (SDF-1) belongs to a group of chemokines that act as inhibitors of primitive human progenitor cycling and is unique in its ability to force the entry of human LTC-ICs into G_o. SDF-1 can similarly act on proliferating human cells with longterm hematopoietic reconstituting ability in NOD/SCID mice. These cells can be shown to be actively proliferating at early times post-transplant in primary NOD/SCID mice by their high sensitivity to treatment with 5-fluorouracil in vivo or with high specific activity³H-thymidine in vitro as revealed when they are subsequently assayed in secondary NOD/SCID mice. Prior SDF-1 treatment in the primary mice abrogates this sensitivity. Importantly, this exposure to SDF-1 in vivo also causes a marked increase in the number of reconstituting cells that can be detected in the secondary mice even without exposure to a cycle-active drug - consistent with the restoration of engraftment potential by cycling longterm reconstituting stem cells forced to re-enter G_o. A similar, albeit less marked effect has also been achieved by SDF-1 treatment of human stem cells stimulated to proliferate in vitro. These findings demonstrate that cell cycle activation is a major but reversible constraint to the use of proliferating stem cells for transplantation therapies and suggest a novel approach to overcoming this limitation.     

Impaired postural stability as a marker of premanifest Huntington's disease

Subtle changes in fine motor control have been observed in individuals who carry the Huntington's disease (HD) mutation but have not yet manifested symptoms, referred to as premanifest HD (preHD). However, few studies have examined gross motor impairments in this population. This study sought to examine the role of sensory involvement in maintaining postural stability during the premanifest and manifest stages of HD using computerized dynamic posturography. Eleven HD participants, 22 preHD subdivided into “preHD Near” (<5 years from estimated clinical onset) and “preHD Far” (>5 years from estimated clinical onset), and 17 nongene carriers (NGC) completed a sensory organization test (SOT) to assess postural control when vestibular, visual, and somatosensory information was systematically degraded. The HD group demonstrated greater postural sway than the NGC and preHD Far groups on all conditions including baseline, and greater postural sway than the preHD Near group when sensory information was manipulated. The preHD Near group showed significantly greater postural sway than the preHD Far group when visual and somatosensory information was degraded and only vestibular information was available and reliable for maintaining postural stability. The results of this study highlight subtle postural deficits in the face of changing sensory conditions in preHD up to 5 years before estimated disease onset. The findings suggest that the SOT may be a highly sensitive indicator of early motor impairment and subsequent phenoconversion to manifest HD in preHD. © 2010 Movement Disorder Society     

High intraindividual variation of B-type natriuretic peptide (BNP) and amino-terminal proBNP in patients with stable chronic heart failure

BACKGROUND: Plasma B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are promising markers for heart failure diagnosis, prognosis, and treatment. Insufficient data on the intraindividual biological variation (CV(i)) of BNP and NT-proBNP hamper interpretation of changes in concentration on disease progression or treatment optimization. We therefore investigated CV(i) values in stable heart failure patients. METHODS: We recruited 43 patients with stable chronic heart failure living in Curacao (22 males, 21 females; median age, 63 years; range, 20-86 years; New York Heart Association classes I-III). Samples were collected for within-day CV(i) (n = 6; every 2 h starting at 0800), day-to-day CV(i) (n = 5; samples collected between 0800 and 1000 on 5 consecutive days), and week-to-week CV(i) (n = 6; samples collected between 0800 and 1000 on the same day of the week for 6 consecutive weeks). NT-proBNP (Roche) and BNP (Abbott) were measured by immunoassay. RESULTS: Median (range) concentrations were 134 (0-1630) ng/L (BNP) and 570 (17-5048) ng/L (NT-proBNP). Analytical variation, week-to-week CV(i), and reference change values were 8.4%, 40%, and 113% (BNP), and 3.0%, 35%, and 98% (NT-proBNP). Week-to week CV(i)s were inversely related to median BNP concentrations. Week-to week CV(i)s for BNP were 44% (BNP < or =350 ng/L) and 30% (BNP >350 ng/L). Both BNP and NT-proBNP increased between 0800 and 1000. Median NT-proBNP/BNP ratios were inversely related to median BNP concentrations. CONCLUSIONS: The high CV(i)s hamper interpretation of changes in BNP and NT-proBNP concentrations and may partly explain their poor diagnostic values in chronic heart failure. Easily modifiable determinants to lower CV(i) have not been identified. The value of BNP and NT-proBNP for chronic heart failure diagnosis, and especially for follow-up and treatment optimization of individuals, remains largely to be established.     

Optimisation of an in vitro procedure for the determination of the enzymatic inhibition potency of multifunctional polymers.

An in vitro procedure for the determination of the inhibition potency of multifunctional polymers towards the proteolytic enzyme trypsin was optimised. Carbopol((R)) 934P was used as the reference polymer. The enzymatic reaction was optimised and the HPLC method was validated. The optimal substrate concentration and enzymatic activity were determined aiming at extracting the linear or steady-state part of the metabolite concentration versus time curve of the enzymatic degradation reaction. A substrate concentration of 20 mmol/l N-alpha-benzoyl-L-arginine-ethylester and an enzymatic activity of 30 enzymatic units trypsin/ml were used. The degree of trypsin inhibition was expressed by the inhibition factor (IF), defined as the ratio of the enzymatic reaction rate without a polymer (control) to the reaction rate in the presence of a polymer. During the optimisation of the trypsin inhibition assay, formation of an ion complex between the substrate and the poly(acrylic acid) was observed. The complex formation was concentration dependent, but the influence on the enzymatic reaction was negligible as long as an excessive substrate concentration was present in the reaction medium. The optimised method allows to characterize, evaluate and compare the in vitro trypsin inhibition strength for most multifunctional polymers.