Search PubMed⌕ Search

Biomedical subjects

P Woo

Publications and source records attributed to P Woo.

At least 73 records · Page 4Linked to original sources

A possible role for soluble IL-6 receptor in the pathogenesis of systemic onset juvenile chronic arthritis.

Investigation of the agonist and two antagonists to interleukin 6 (IL-6) and their possible role in the pathogenesis of different sub-groups of juvenile chronic arthritis (JCA). Sera of 54 patients and 10 age-matched controls were tested: 20 with pauci-articular JCA, 12 with polyarticular JCA, and 22 systemic JCA. Interleukin 6, soluble interleukin 6 receptor (agonist), soluble gp130 and autoantibodies to IL-6 (antagonist to IL-6) were measured, as well as C-reactive protein as an indicator of disease activity. In addition, during fever two systemic JCA patients were analysed longitudinally for these parameters. There was a significant increase in soluble IL-6 receptor (sIL-6R) concentrations. No difference in the levels of soluble gp130 and autoantibodies to IL-6 in the systemic JCA group was found. In two patients the fever curves corresponded to the IL-6 levels measured. sIL-6R serum concentrations also showed a tendency to follow the fever. The authors have shown that in systemic JCA, the levels of sIL-6R, agonist of IL-6, were increased significantly compared to the other groups, while levels of antagonists to IL-6 were not changed in the face of increased levels of IL-6 in systemic JCA. These results suggest an imbalance of IL-6 homeostasis.

Arthritis, Juvenile↗

Biomechanics of combined arytenoid adduction and medialization laryngoplasty in an ex vivo canine model.

Arytenoid adduction (AA) and medialization laryngoplasty (ML) are being performed concurrently in patients with unilateral vocal fold paralysis with a large posterior glottal gap. The biomechanical effects of this combined procedure on the larynx have not been studied. An excised canine larynx model was used to study the effects of AA, ML, and combined AA and ML (AA-ML) on vocal fold configuration (length and degree of medialization) and tension. AA-ML lengthens the affected vocal fold relative to the opposite vocal fold, although both were slightly shortened compared with the control state (nonsignificant trends). AA-ML medializes the entire length of the vocal fold more effectively than AA or ML alone. Midmembranous vocal fold tension did not increase with AA-ML. With AA-ML, the vocal process resisted significantly greater lateralizing forces than with the control state or ML. We conclude that in an excised canine model, AA-ML combines the biomechanical properties of AA and ML. The larynx appears to be divided into 2 biomechanical subunits: membranous vocal fold (anterior) and arytenoid cartilage (posterior). When surgical rehabilitation of both laryngeal subunits is required, AA-ML appears to be a better choice than AA or ML alone.

Animals↗

The biomechanics of the medialization laryngoplasty (thyroplasty type 1) in an ex vivo canine model.

The biomechanics of medialization laryngoplasty are not well understood. An excised canine larynx model was used to test the effects of various sized silicon implants. The vocal fold length, position, and tension were measured. Medialization laryngoplasty did not affect vocal fold length. At the mid-membranous vocal fold, larger shims resulted in greater medialization and tension. Medialization laryngoplasty neither medialized nor stiffened the vocal process to resist lateralizing forces. We conclude that medialization laryngoplasty provides bulk and support for defects of the membranous region of the vocal fold, but does not appear to close a posterior glottal gap. The selection of a surgical procedure to treat glottal incompetence should take into account the unique biomechanical properties of the anterior (membranous vocal folds) and posterior (cartilaginous portion) glottis.

Animals↗

Voice disorders in patients with suspected laryngo-pharyngeal reflux disease.

Many symptoms have been recognized in association with laryngo-pharyngeal reflux disease (LPRD), but reports of perceptual voice disorders in this condition have been lacking to date. Forty-nine patients with suspected LPRD were studied for five specific perceptual voice characteristics, and these characteristics were compared to the same characteristics in individuals who had never seen an Otolaryngologist for a voice disorder or throat problem (controls). Sixteen of the suspected LPRD patients also underwent 24-hour pH probe studies. All patients with suspected LPRD had significantly increased abnormal perceptual voice characteristics (musculoskeletal tension, hard glottal attack, glottal fry, restricted tone placement, and hoarseness) compared to the controls. Statistical objective differences between the two groups was demonstrated by the presence of increased shimmer in patients with suspected LPRD compared to controls. The differential diagnosis between functional voice disorders and LPRD may be complex, and perceptual parameters may overlap. Interdisciplinary evaluation is advocated.

Female↗

Cytokines in juvenile chronic arthritis.

Cytokines are important mediators of the immune response as well as the inflammatory response. Those concerned primarily with cell growth, differentiation and activation of cells within the immune system are called interleukins, of which there are now 18. Exposure to antigenic and environmental stimuli causes T cells to differentiate and polarise into Th1 or 2-like cells with different cytokine profiles, and requiring different cytokines for differentiation (IL-12 for Th1 and IL-4 for Th2). Homeostasis is usually restored as these cells are mutually inhibitory. Autoimmune diseases have been associated with a persistent imbalance with more Th1-like cells, which are thought to contribute to pathology. With regard to juvenile chronic arthritis (JCA), there is some preliminary evidence of this imbalance in the oligoarticular subgroup. Imbalance of pro-inflammatory cytokines, IL-1 and TNF with their natural inhibitors has also been shown to contribute to persistence of inflammation. In the case of JCA, there has been some evidence that these imbalances could account for some of the disease phenotypes. Furthermore, the tendency to imbalance is genetically determined.

Arthritis, Juvenile↗

Human serum amyloid A has cytokine-like properties.

Human serum amyloid A (SAA) proteins are a group of 12-14 kDa apolipoproteins found predominantly in the high-density lipoprotein (HDL) fraction of plasma. Several functions have been proposed for SAA, but its primary physiological function remains elusive. In this report, we used the monocytic cell line THP-1 to investigate whether recombinant SAA1 (rSAA) or the HDL-rSAA protein complex can affect the capacity of these cells to produce inflammatory cytokines in vitro. Incubation of rSAA, plasma HDL (which contains < or = 30 microg/ml of SAA) or HDL-rSAA complex with THP-1 cells induced synthesis of IL-1beta, IL-1ra and sTNFR-II protein and mRNA. The induction of cytokine synthesis was not due to endotoxin contamination since the effect was abrogated by protein denaturation. The rSAA and HDL-rSAA complex did not induce detectable levels of IL-6 or TNFalpha protein or mRNA. In contrast 10 microg/ml LPS stimulated secretion of the inflammatory cytokines, IL-1beta, IL-6 and TNFalpha, as well as IL-1ra and sTNFR-II from THP-1 cells. We confirmed that rSAA has chemoattractant properties in vivo, by subcutaneous injections into mice and examined the histology of the injection site at 72 h, however, the HDL-rSAA complex has a substantially reduced effect.

Animals↗

Atypical juvenile generalized scleroderma presenting as polyarthritis and failure to thrive.

In this Grand Round, two children are described with atypical generalized scleroderma and severe failure to thrive. Neither had Raynaud's phenomenon nor evidence of gastrointestinal (GI) disease. Treatment with non-steroidal anti-inflammatory drugs, prednisone, D-penicillamine, alpha and gamma interferon was unsuccessful in reversing the sclerodermatous changes and growth arrest. Dietary intake analysis and extensive GI investigation were performed in both. In one case, resting energy expenditure (Ee) was repeatedly measured. His intake did not meet requirements for growth. Supplemental tube feeding (900 kcal in 6 h) was commenced, causing an increase in weight from 11 to 16 kg. The other patient refused supplementary tube feeding and no weight gain has been observed for 5 yr. In conclusion, early-onset generalized scleroderma in the absence of visceral involvement, but with growth failure, may represent an atypical form of systemic sclerosis. The response of the two patients to conventional therapy was disappointing. However, the rapid catch-up growth induced by tube feeding observed in one patient underlines the importance of adequate dietary management.

Arthritis↗

Inflammatory cytokines and cytokine antagonists in whole blood cultures of patients with systemic juvenile chronic arthritis.

In the present study, we investigated the kinetics and the activation thresholds for the production of a number of pro-inflammatory cytokines and cytokine antagonists in Escherichia coli lipopolysaccharide (LPS) or phytohaemagglutinin (PHA) stimulated whole blood cultures of 13 patients with systemic juvenile chronic arthritis (SJCA) and 10 healthy children. In unstimulated cultures, the levels of interleukin (IL)-1beta, IL-6 and tumour necrosis factor alpha (TNF-alpha) were undetectable in both groups, suggesting that there was no spontaneous production of these cytokines by circulating leucocytes. The activation thresholds for the production of these cytokines, as well as the capacity for production, did not differ significantly between patients and controls. The level of interleukin-1 receptor antagonist (IL-1ra) in plasma of the patients was significantly elevated, while the in vitro production of IL-1ra was essentially normal and it did not correlate with plasma levels of IL-1ra. Supernatant levels of soluble TNF-alpha receptor (sTNF-R) I and II were both significantly elevated and correlated with the global activity score. In contrast, the supernatant levels of IL-10 were reduced in both PHA- and LPS-driven cultures. Although IL-10 levels did not correlate with laboratory or clinical indices of disease activity, the results suggest that reduced IL-10 production may play a pathogenetic role in SJCA.

Adolescent↗

Jet ventilation in upper airway obstruction: description and model lung testing of a new jetting device.

UNLABELLED: Patients with critical upper airway stenosis require a tracheotomy for corrective surgery. We describe a new transtracheal device that permits safe ventilation of these patients without tracheotomy. It is based on a coaxial bicannular design that allows "push-pull" ventilation by jetting gas through the inner cannula and applying suction through the outer cannula. It further allows monitoring of airway pressure, tidal volume, and end-tidal CO2. The device was placed in the "trachea" of an artificial lung, and the preparation was made airtight by sealing the proximal end of the trachea. Tidal volumes and their associated pressures were measured simultaneously at different parts of the airway at several lung compliances and airway resistance settings while varying the jet and suction pressures. A large range of tidal volumes was achieved at safe airway pressures using clinically relevant airway resistance and lung compliance settings. Airway pressures measured through the device correlated well with pressures measured directly in the airways at the same time. Tidal volumes, measured through a Wright respirometer in the suction line, exceeded actual values at high suction settings and decreased below actual values at low suction settings. This new form of jet ventilation allowed efficient ventilation of the artificial lung with a totally occluded upper airway. IMPLICATIONS: Tracheotomy is required for surgery to relieve stridor because gas forced into the trachea at high pressures through a percutaneously placed needle (jetting) cannot be exhaled quickly enough for respiration. We describe a device that allows jetting in the stridorous patient by actively assisting expiration, thereby eliminating the tracheotomy requirement.

Airway Resistance↗

Biomechanics of arytenoid adduction surgery in an ex vivo canine model.

The biomechanics of arytenoid adduction surgery are not well understood. An excised canine larynx model was used to study the effects of variable suture tension on glottal configuration and on vocal fold tension (at the midfold and the vocal process). Arytenoid adduction both medializes the vocal fold and closes a posterior glottal chink. Vocal fold tension at the midfold did not vary significantly with suture tension. As suture tension increased to approximately 100 g, vocal fold tension at the vocal process also increased. Beyond 100 g of suture tension, vocal fold tension at the vocal process did not increase. We conclude that the effects of suture tension on the resistance to lateral movement are different at the midfold compared to the vocal process. Procedures for surgical rehabilitation of vocal fold paralysis should address the biomechanical subunits of the larynx individually in order to achieve optimum results.

Animals↗

Left ventricular size determined by electron beam computed tomography predicts significant coronary artery disease and events.

A novel method in the measurement of left ventricular (LV) area using noncontrast electron beam computed tomography (EBCT) was introduced and studied as a diagnostic and prognostic marker for coronary artery disease. Larger LV area measured by noncontrast EBCT was significantly associated with angiographic coronary disease and was a better predictor of coronary disease events than log calcium score.

Adult↗

The cytokine network in juvenile chronic arthritis.

This article is an overview of the cytokine network in patients with different types of juvenile chronic arthritis. The concept of the production of TH1-cell or TH2-cell differentiation as a result of cytokine production and the concept of the balance between proinflammatory and anti-inflammatory cytokines are explored. The balance of proinflammatory and anti-inflammatory cytokines could be altered as a result differences in the expression levels of a number of key cytokines and could be the critical events leading to chronic inflammation. Identifying molecular targets for intervention therapy to change the balance of the cytokine network is proposed.

Adolescent↗

Cross-talk between transcription factors NF-kappa B and C/EBP in the transcriptional regulation of genes.

The study of the acute phase response has attracted substantial interest, not only for its medical implication, but also its provision as an excellent system with which to elucidate the molecular mechanisms involved in the modulation of gene expression. Our previous data suggest that the synergistic induction of the major acute phase reactant serum amyloid A2 (SAA2) expression by interleukin-1 (IL-1) and interleukin-6 (IL-6) is mediated by two families of transcription factors, namely NF-kappa B and C/EBP. To understand the molecular mechanisms of this synergy, we have undertaken a molecular dissection of the factors involved in the formation of the regulatory complex. Electrophoretic mobility shift analysis indicates that NF-kappa B p65 (RelA) and p50, but not p52 or c-Rel, bind specifically to the NF-kappa B site of the SAA2 promoter in response to IL-1 stimulation. In addition, C/EBP beta and C/EBP delta, but not C/EBP alpha, bind specifically to the C/EBP site of SAA2 in response to IL-6 stimulation. Transient co-transfection analysis indicates that co-operative association of NF-kappa B p65 with C/EBP beta and, in particular, with C/EBP delta, results in synergistic transcriptional activation of the SAA2 promoter. When incubated together, NF-kappa B p65 and C/EBP beta form a ternary complex by direct protein/protein interaction. Mutational analysis demonstrates that the C-terminus region of the Rel homology domain (RHD) and the C-terminus of the activation domain of p65 are important for its interaction with C/EBP beta. These results suggest the NF-kappa B and C/EBP may form a new complex of transcription factors that mediates the synergistic induction of SAA2 by IL-1 and IL-6.

Acute-Phase Reaction↗

Juvenile chronic arthritis: diagnosis and management of tibio-talar and sub-talar disease.

The aim of this study was to compare clinical evaluation of the site of hindfoot synovitis with contrast-enhanced magnetic resonance imaging (MRI) findings in children with juvenile chronic arthritis (JCA), and to evaluate the efficacy of selective guided intra-articular steroid injections. Thirteen symptomatic ankles of 11 consecutive JCA patients were examined clinically and with contrast-enhanced MRI. Pannus was demonstrated on MRI in both tibio-talar and sub-talar joints in 10 ankles, in the tibio-talar joint only in one ankle and in neither joint in two ankles. Correlation of clinical and MRI findings was good for the tibio-talar joint with concordance in 11/13 cases. Correlation was poor for the sub-talar joints. Of the 10 sub-talar joints shown to have pannus on MRI, only two were thought to have had definite clinical evidence of synovitis. Guided intra-articular steroid injection resulted in at least 6 months remission in 6/9 ankles compared with 1/10 ankles which had had previous unguided injections. We therefore recommend the use of image guidance for intra-articular triamcinolone hexacetonide injection in children with hindfoot synovitis.

Adolescent↗

School attendance and juvenile chronic arthritis.

We studied the school attendance of 113 children and adolescents (mean age 11 yr, S.D. 3.8, range 3-18 yr) with juvenile chronic arthritis (73 with pauci- and 40 with polyarthritis). The mean attendance rate for the group was 92% (equivalent to 15 absent days a year) with a median of 97%. Attendance was significantly lower in the more severely affected poly group (90% vs 98% in the pauci group; P = 0.03). We found associations of school absence (i) with decreased compliance with physical treatments (r = -0.35, P < 0.05 for compliance with physiotherapy) in the poly group and (ii) with child psychological deviance (r = 0.36 for parentally rated and r = 0.42 for teacher-rated psychological deviance; both P < 0.05) in the pauci group. We conclude that school attendance can be good in severely affected children. Severity of illness, treatment compliance and psychological problems in the child may affect school attendance.

Absenteeism↗

Suppression of fever and the acute-phase response in a patient with juvenile chronic arthritis treated with monoclonal antibody to tumour necrosis factor-alpha (cA2).

Juvenile chronic arthritis (JCA) is the commonest chronic rheumatic disorder of childhood. Although conventional therapy of JCA continues to improve, many patients experience long-term ill health as a result of their disease or treatment. In adult rheumatoid arthritis (RA), similar concerns have led to the development of therapies designed to interfere in key disease processes. One such therapy is cA2, a chimeric neutralizing monoclonal antibody to the inflammatory cytokine, tumour necrosis factor-alpha (TNF-alpha). The administration of cA2 in adult RA has led to impressive short-term suppression of disease, with a good safety profile. Here, we report the first use of cA2 in childhood arthritis, choosing a patient with severe systemic-onset JCA, resistant to conventional therapies. The patient received two i.v. infusions of cA2, each at a dose of 10 mg/kg, separated by 1 week. The treatment was well tolerated and induced rapid control of fever, anorexia and serositis, together with downregulation of interleukin (IL)-6, soluble TNF receptors (sTNFR) and IL-1ra, and the acute-phase proteins C-reactive protein (CRP) and serum amyloid A (SAA). In contrast, we saw no significant improvement in joint pain or tenderness. Our findings suggest that TNF-alpha is a mediator of fever and other systemic aspects of disease in systemic JCA. TNF-alpha blockade as a treatment modality in JCA deserves further study.

Acute-Phase Reaction↗