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Biomedical subjects

P Woo

Publications and source records attributed to P Woo.

At least 55 records · Page 3Linked to original sources

Amelioration of established collagen induced arthritis by systemic IL-10 gene delivery.

A novel formulation of cationic liposomes containing the novel cytofectin ACHx was used for delivery of an anti-inflammatory cytokine gene, IL-10, to mice with established collagen induced arthritis. A single intraperitoneal injection of human IL-10 expression plasmid complexed with liposomes 2 to 4 days after the onset of arthritis was sufficient to give significant and prolonged amelioration of arthritis for 30 days. Preliminary experiments suggested that the therapeutic effect was IL-10 dose-dependent. The distribution of the human IL-10 DNA after injection was widespread, including the inflamed paws. Human IL-10 mRNA was also detected in the paws 24 h after injection. IL-10 protein was below the level of detection in paws and serum but was detected in some tissues up to 10 days after injection. The target cell of transfection was demonstrated to be the macrophage. These results suggest that systemic therapy with plasmid DNA complexed with cationic liposomes merits further development as an alternative method for anti-inflammatory treatment of arthritis.

Animals↗

Tumour necrosis factor alpha and its soluble receptors in juvenile chronic arthritis.

OBJECTIVE: To identify possible imbalance of tumour necrosis factor alpha (TNFalpha) and its soluble receptors in the different subgroups of juvenile chronic arthritis (JCA). METHODS: Serum and synovial fluid samples from 45 children were examined, 25 pauciarticular JCA, 13 polyarticular JCA and seven spondyloarthropathy. TNFalpha, sTNFRI and sTNFRII levels were measured by EASIA and enzyme-linked immunosorbent assay (ELISA). Analysis of the results was carried out using non-parametric tests: Kruskal-Wallis one-way analysis of variance was used to compare the three clinical subgroups; the Mann-Whitney U-test was used to compare group medians. RESULTS: Thirty-three serum samples were assayed for TNFalpha. There was no significant difference between the three groups using the Kruskal-Wallis analysis of variance. Analysis of synovial fluid TNF levels showed significantly lower levels in the spondyloarthropathy group compared with the pauciarticular JCA (P = 0.01) and the polyarticular group (P = 0.002). Significantly higher levels of sTNFRI were observed in the synovial fluid of the polyarticular JCA group compared with the pauciarticular JCA group (P = 0.004) and similarly for sTNFRII (P = 0.03). Molar ratios were calculated for TNF vs sTNFRI. The sTNFRI/TNFalpha ratio was significantly higher in the spondyloarthropathy group compared with the pauci- (P 0.003) and the polyarticular JCA subgroups (P = 0.003). The combined soluble receptor levels expressed as molar ratio to TNF again showed a significantly higher ratio in the spondyloarthropathy group compared with the pauciarticular group (P = 0.01) and compared with the polyarticular group (P = 0.05). CONCLUSION: These results suggest that the increased joint destruction observed in polyarticular disease compared with the other two subtypes may be related to the lower sTNFR/TNFalpha ratios observed.

Adolescent↗

Fat augmentation for glottic insufficiency.

OBJECTIVES: Fat lipoinjection augmentation for glottic insufficiency has been used in patients with vocal fold paralysis. Relatively little information is available on the effectiveness of fat injection in patients with vocal atrophy, intubation trauma, and post-hemilaryngectomy defects. STUDY DESIGN: This paper retrospectively compares the efficiency of fat injection in patients with vocal cord paralysis (n = 9), vocal scar (n = 13), and vocal atrophy (n = 11). METHODS: The perceptual acoustic, phonatory function, and videolaryngostroboscopic data were evaluated before and after fat augmentation in 33 patients. RESULTS: Mean follow-up time was 9.7 months. Nineteen patients had excellent results. Three patients had no change. Five patients had late failure. Six patients were lost to follow-up. Phonatory function showed significant improvement in jitter, shimmer, noise-to-harmonic ratio, maximal phonation time, grade, asthenia, and breathiness (P < .05). Videolaryngostroboscopic rating showed significant improvement in right linearity of the vocal fold edge, amplitude of vocal fold vibration, excursion of the mucosal wave, vibratory behavior, and phase symmetry (P < .05). Anterior defects did better than posterior defects. Small vocal fold defects did better than large defects. CONCLUSIONS: Fat injection is a good autogenous implant and may be considered as an option in management of patients with vocal fold scar, defect, or atrophy. Reabsorption of fat is a problem, but the procedure may be repeated.

Adipose Tissue↗

Glottal area waveform analysis of benign vocal fold lesions before and after surgery.

Glottal area waveform (GAW) is the plot of relative glottal area versus time through 1 representative glottal cycle. It is derived from the quantitative analysis of the videostroboscopic image. A GAW analysis was performed on 24 patients before and after microlaryngeal phonosurgery. Patients with vocal fold polyps, polypoid degeneration, cysts, sulcus vocalis, and Reinke's edema were included. From each GAW, 5 parameters were determined and compared: maximum normalized glottal area, maximum opening rate, maximum closing rate, percent open time at 50% glottal opening, and glottal gap size. Statistically significant differences in postoperative states included an increased maximum glottal area, an increased maximum opening rate, and an increased maximum closing rate. Glottal opening and closing rate are objective measures of vocal fold pliability that have clinical relevance. The GAW may be used to quantitate vocal fold vibratory capability.

Female↗

Polymorphic haplotypes of the interleukin-10 5' flanking region determine variable interleukin-10 transcription and are associated with particular phenotypes of juvenile rheumatoid arthritis.

OBJECTIVE: To determine the distribution of the interleukin-10 (IL-10) 5' flanking region haplotypes in children with arthritis and in controls, and to investigate the functional significance of each haplotype. METHODS: Sequence-specific oligonucleotide probing was used to determine haplotype frequency. Transient transfection studies were used to investigate the transcription of reporter genes driven by each haplotype. Whole blood cultures were performed to assess IL-10 production by each genotype. RESULTS: Patients with arthritis involving >4 joints were more likely to have a genotype with an ATA haplotype than those whose arthritis remained restricted to <4 joints. This ATA haplotype was associated with lower transcriptional activity than the GCC haplotype (P = 0.02), and the ATA/ATA genotype was associated with lower IL-10 production under lipopolysaccharide stimulation than other genotypes (P < 0.02). CONCLUSION: The results of this study demonstrate the functional significance of the ATA haplotype and reveal a significant association of genotypes containing this haplotype with extended oligoarthritis.

Arthritis, Juvenile↗

Preliminary study on the ability of trained singers to control the intrinsic and extrinsic laryngeal musculature.

Little literature is available on professional musical theater female singers, a population that regularly uses a wide variety of vocal qualities. This study tested the hypothesis that different vocal qualities cause observable specific configurations of muscular movements and structural changes of the larynx, hypopharynx, oral pharynx, and oral cavity for individual singers. Fiberoptic rigid and flexible endoscopic observation were used to determine visual analysis of such configurations. This study documents observable physiologic changes that were made by professional musical theater female singers in specific vocal qualities.

Adult↗

Molecular fingerprinting reveals non-overlapping T cell oligoclonality between an inflamed site and peripheral blood.

We have demonstrated a stable expansion of CD8+ T cells in the peripheral blood of a child with chronic arthritis. The expanded TCRBV family (TCRBV14) was enriched for CD57hiCD28- T cells. Sequencing of the TCRBV14 amplification products showed a TCR sequence which contributed 32% of the total TCR in the CD8+TCRBV14 population. Using the modified heteroduplex technique, the CD8+TCRBV14 cells showed a clonal pattern and these bands were restricted to the CD28- population. This method also detected multiple other clones within the CD8+ population but few in the CD4+ cells. The dominant TCRBV14+ clone was not detectable in synovial fluid T cells from two inflamed joints by CDR3 length analysis or heteroduplex probing, suggesting that this long-lived clone is excluded from inflammatory sites. Synovial fluid T cells showed an unexpected discordance of the CD28 and CD57 phenotype compared to peripheral blood mononuclear cells. T cells from both inflamed joints both showed marked oligoclonality in all TCR families and had almost identical heteroduplex patterns. Taken together these data suggest that some clones are actively excluded from inflamed sites in juvenile chronic arthritis, yet the pattern of restricted T cell expansion is shared between sites of inflammation.

Arthritis, Juvenile↗

Upper aerodigestive tract liposarcoma: report on four cases and literature review.

OBJECTIVE: To report on the clinical behavior, histopathology, treatment, and prognosis of laryngeal, hypopharyngeal, and cervical esophageal liposarcomas. STUDY DESIGN: Retrospective reviews of pathology files and hospital records at a tertiary care hospital and a retrospective search of the English-language literature. METHODS: Cases of upper aerodigestive tract (UADT) liposarcoma with adequate histopathologic documentation and clinical information were included for review. RESULTS: Four cases of UADT liposarcomas were identified. The literature review revealed 26 cases of laryngeal liposarcomas, 7 cases of hypopharyngeal liposarcomas, and 6 cases of esophageal liposarcomas: the mean age at presentation was 55.8 years, the male:female ratio was 5:1, and 60% of the patients presented with dysphagia. Eighty-six percent of tumors had low-grade histologic findings. The recurrence rate after primary resection was 50%. Recurrence correlated with surgical procedure rather than with histologic subtype; 94.7% of recurrences happened after simple excision. Distant metastases occurred in three patients; two of them died of the disease. CONCLUSIONS: The literature supports that UADT liposarcomas are rare and usually of low-grade histologic type. The rate of metastatic disease and tumor-related mortality is low. However, high recurrence rates have been noted, particularly when less radical surgery is employed.

Adult↗

Fat implantation into Reinke's space: a histologic and stroboscopic study in the canine.

The scarred vocal fold is a cause of persistent dysphonia after laryngeal trauma, microsurgery, and tumor resection. The loss of Reinke's space with scar and stiffness is the primary cause. This study explores the technical aspects of endoscopic implantation of fat as an autologous implant for restoring the bulk and pliability of the vocal folds. Fat from the buccal area was harvested and prepared in 6 dogs. A mucosal flap submucosal pocket was prepared by means of microlaryngoscopy instrumentation. The fat implant was placed into the submucosal pocket. The mucosal flap was sutured endoscopically. Six weeks later, the larynx was harvested and mounted, and vocal fold oscillation was studied while driven by a humidified flow source. The vibratory patterns were studied by stroboscopy. Histologic sections of the vocal folds were made in the coronal plane. All 6 specimens had histologic evidence of viable implanted fat and/or fibrous tissue at the implant site. The site of implantation was in the superior aspect of the vocal fold, but contributed to mass in vocal fold bulk. This increase in bulk histologically corresponded to stroboscopic evidence of increased mass. On stroboscopy, the implant side continued to demonstrate good vibratory function. The study shows that fat implantation can be carried out as an endoscopic procedure. Fat implantation may be useful as a surgical procedure for restoration of Reinke's space. It may be applicable in patients with scars, sulcus vocalis, or vocal fold atrophy.

Adipose Tissue↗

Videolaryngostroboscopy following vertical partial laryngectomy.

Phonation after partial laryngeal ablative surgery has not often been examined. Videolaryngostroboscopic recordings made after vertical partial laryngectomy (VPL) were retrospectively reviewed and correlated with patient historical and operative factors. Among VPL patients (n = 42), the most common site of vibration during phonation was the contralateral false vocal fold (17/42 patients or 40.5%), followed by the contralateral arytenoid mucosa (10/42 or 23.8%) and the contralateral true vocal fold (8/42 patients or 19.0%). There was no overall difference in vocal quality judgment with respect to site of vibration (ANOVA, p = .373). Vocal quality scores were similar with use of the pyriform mucosal flap versus other reconstructive methods (Student's t-test, p = .568). This study highlights the fact that reconstruction of a new vibratory source after VPL is important for voice production. Because VPL patients infrequently demonstrated true vocal fold vibration, alternative sites (ie, false vocal fold, arytenoid mucosa) must be considered as new phonatory sources after VPL.

Arytenoid Cartilage↗

Metabolism and excretion of atorvastatin in rats and dogs.

Atorvastatin (AT) is a second-generation potent inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase, clinically approved for lowering plasma cholesterol. Using a mixture of [D(5)/D(0)] AT and/or [(14)C]AT, the metabolic fate and excretion of AT were examined in rats and dogs following single and multiple oral doses. Limited biliary recycling was examined in one dog after a single dose of AT. AT-derived metabolites in bile samples were identified by metabolite screening of the [D(5)/D(0)] AT molecular clusters using tandem mass spectrometry. Bile was a major route of [(14)C] drug-derived excretion, accounting for 73 and 33% of the oral dose in the rat and dog, respectively. The remaining radioactivity was recovered in the feces; only trace amounts were excreted in urine. Radioactive components identified in rat and dog bile were the para- and ortho-hydroxy metabolites, a glucuronide conjugate of ortho-hydroxy AT, and unchanged AT. Two minor radioactive components were identified as beta-oxidation products of AT with one confirmed as a beta-oxidized AT derivative. The reappearance of AT and major metabolites in bile from a dog administered a sample of its previously excreted bile indicated biliary recycling is an important component in AT metabolism. Multiple dose administration in rats did not alter biliary metabolic profiles. Rat and dog plasma profiles after multiple dose administration were similar and showed no additional metabolites not found in bile. Examination of rat and dog bile and plasma indicates that AT primarily undergoes oxidative metabolism.

Animals↗

The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis.

During active disease, patients with systemic-onset juvenile chronic arthritis (S-JCA) demonstrate a rise and fall in serum interleukin-6 (IL-6) that parallels the classic quotidian fever. To investigate the possibility that this cytokine profile results from a difference in the control of IL-6 expression, we examined the 5' flanking region of the IL-6 gene for polymorphisms. A G/C polymorphism was detected at position -174. In a group of 383 healthy men and women from a general practice in North London, the frequency of the C allele was 0.403 (95% confidence interval 0.37-0.44). In comparison, 92 patients with S-JCA had a different overall genotype frequency, especially those with onset of disease at < 5 yr of age. This was mainly due to the statistically significant lower frequency of the CC genotype in this subgroup. When comparing constructs of the 5' flanking region (-550-+61 bp) in a luciferase reporter vector transiently transfected into HeLa cells, the -174C construct showed 0.624+/-0.15-fold lower expression than the -174G construct. After stimulation with LPS or IL-1, expression from the -174C construct did not significantly change after 24 h, whereas expression from the -174G construct increased by 2.35+/-0.10- and 3.60+/-0.26-fold, respectively, compared with the unstimulated level. Plasma levels of IL-6 were also measured in 102 of the healthy subjects, and the C allele was found to be associated with significantly lower levels of plasma IL-6. These results suggest that there is a genetically determined difference in the degree of the IL-6 response to stressful stimuli between individuals. The reduced frequency of the potentially protective CC genotype in young S-JCA patients may contribute to its pathogenesis. Similarly the individual's IL-6 genotype may be highly relevant in other conditions where IL-6 has been implicated, such as atherosclerosis.

Adolescent↗