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Biomedical subjects

B J Wong

Publications and source records attributed to B J Wong.

36 records · Page 2Linked to original sources

Reproducibility of allergen-induced early and late asthmatic responses.

BACKGROUND: Constant-dose allergen inhalation challenges are frequently used to examine the effect of antiasthma drugs on the allergen-induced early and late asthmatic responses. The end-point measurements in such studies are the maximal early and late percent decreases in the forced expiratory volume in 1 second (FEV1). OBJECTIVE: Our purpose was to observe the reproducibility and to determine the sample sizes required for such studies. METHODS: Twenty-eight subjects with allergen-induced early and late responses were studied with two constant-dose allergen challenges separated by 2 to 12 weeks. The early response was measured as the maximum percent decrease in FEV1 during the first 2 hours and the late response as the maximum percent decrease in FEV1 between 3 to 7 hours. RESULTS: The mean +/- SEM early responses were 23.1% +/- 1.0% and 24.7% +/- 2.0%, whereas the mean late responses were 23.3% +/- 2.0% and 24.5% +/- 2.2%. Reproducibility of measurements were such that fewer than eight subjects are required, to show 50% attenuation of either the early or late response (with 90% power). CONCLUSIONS: The method of constant-dose allergen challenge is a sensitive tool for detecting changes in early and late asthmatic responses after the use of antiasthma medication.

Administration, Inhalation↗

Metastatic small cell carcinoma to the masseter muscle originating from the uterine cervix.

Metastatic tumors to the head from infraclavicular primaries are relatively uncommon. The vast majority of primary tumors that metastasize to the head originate from the lung and breast. Tumors metastatic to the masseter are exceedingly rare with only one other case being reported in the literature. The case of a 34-year-old woman with a history of surgically-treated small cell carcinoma of the uterine cervix is presented. This case and our review of the literature illustrates the unusual nature of metastatic patterns in the head and their diagnostic complexity. Masses localized to the buccomasseteric region are usually considered to be of parotid origin. The differential diagnosis for masses in this area is generally limited to cogenital, inflammatory, or neoplastic lesions. Though uncommon, metastatic tumors from non-head and neck primary malignancies should be considered in the diagnosis as they may herald the onset of a new disease or the recurrence of cancer.

Adult↗

Nerve wound healing. An overview.

This article describes the mechanisms of peripheral nerve healing and the efforts to achieve an optimal healing outcome. The mainstay of treatment has been adherence to good surgical technique and the use of microsurgical equipment. Despite advances in microsurgery, complete structural and functional recovery is uncommon. Research focused on adjunctive methods for nerve repair is also reviewed in this article.

Anastomosis, Surgical↗

Noninvasive methods to examine the anti-inflammatory effects of drugs.

The anti-inflammatory effects of drugs can be studied non invasively using sputum which has either been produced spontaneously or induced with hypertonic saline. We have developed an efficient semi-automated method to examine sputum which should be widely applicable. This approach is recommended to provide a direct sampling of the airway secretions to study the inflammatory process and to demonstrate drug effects. We have validated a method to prospectively induce a mild exacerbation of airway inflammation by controlled reduction of inhaled steroid in steroid-dependent asthmatics. This can be used to examine the ability of drugs to prevent or reverse airway inflammation.

Anti-Inflammatory Agents↗

Intraepithelial mast cells in allergic and nonallergic asthma. Assessment using bronchial brushings.

Mast cell mediators are known to contribute to the pathogenesis of asthma. There is some disagreement concerning the numbers of mast cells in asthmatic mucosa. In this study a standardized bronchial brush technique was developed and used to assess intraepithelial mast cells and other inflammatory cells in allergic and nonallergic asthmatic and nonasthmatic subjects. A total of 10 nonasthmatic (5 allergic) and 13 asthmatic (8 allergic) subjects with stable controlled asthma treated with beta-agonist only were assessed by history, spirometry, allergy prick tests, and methacholine airway responsiveness. During fiberoptic bronchoscopy, bronchoalveolar lavage (BAL) was performed from the middle lobe and standardized bronchial brushings were taken from the lingula and left lower lobe bronchi. Quantitative cell counts were performed blind to the clinical characteristics of the subjects. The average total cell recovery from the brushings was 1.04 (SEM 0.09) x 10(6) ml, with a cell viability of 64% (5.3%). Reproducible total cell and mast cell counts were obtained from brushings taken from two lobar bronchi (ICC 0.86). Mast cells were significantly elevated in asthmatic compared with nonasthmatic subjects (1.5 +/- 0.34 versus 0.15 +/- 0.06%). Allergic asthmatic subjects had the greatest numbers of mast cells (1.86 +/- 0.48%); however, the numbers present in brushings from nonallergic asthmatic subjects were also increased (1.03 +/- 0.45%). The mast cells had the staining characteristics of mucosal mast cells, with formalin-blockable metachromatic staining and positive staining for tryptase. Both asthmatic groups also had elevated BAL eosinophils, and neutrophils were elevated in nonallergic asthmatic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

An approach to preventing methotrexate prescribing errors in rheumatoid arthritis.

Methotrexate is an effective treatment for rheumatoid arthritis and is fairly well tolerated by patients when used appropriately. However, errors do occur due to a lack of awareness of the normal dosage range and potentially serious dose related side effects of methotrexate among physicians, pharmacists, and nurses. The approach taken by one hospital to prevent methotrexate prescribing errors includes daily monitoring of methotrexate by a pharmacist, building caution flags in the order loading program of the pharmacy computer system, and educating healthcare professionals to heighten awareness when prescribing, dispensing, and administering methotrexate for rheumatoid arthritis. At the hospital, since the institution of these policies and education of pharmacists, nurses, and physicians, there have been no incidents of methotrexate prescribing errors.

Arthritis, Rheumatoid↗

A research method to induce and examine a mild exacerbation of asthma by withdrawal of inhaled corticosteroid.

This study evaluated a research method to examine an exacerbation of asthma induced by corticosteroid withdrawal. Ten non-smoking adult asthmatics who were stable on treatment with inhaled steroid underwent a graded reduction of the daily dose by 200 micrograms at weekly intervals until an exacerbation of symptoms occurred. A daily symptom, peak expiratory flow rate (PEF) and medication diary was kept. Weekly clinic visits were used to assess symptoms, spirometry, methacholine airway responsiveness (expressed as the provocative concentration to cause a fall in FEV1 of 20%, PC20), circulating eosinophils, basophils and their progenitors (Eo/B-CFU), and sputum inflammatory cells. The laboratory tests were performed blind to the clinical details. Each subject developed an exacerbation of symptoms, on average at 16 (7-26) days after the onset of steroid reduction. This was accompanied by a deterioration in each of the objective measures. There was a fall in FEV1 by 320 ml (s.e.m. 9.5) and in PC20 from 0.8 to 0.43 mg/ml. Circulating eosinophils rose from 114 (24) x 10(3)/ml to 227 (50) x 10(3)/ml and Eo/B-CFU rose from 31 (5.6) to 44 (11.3)/10(6) cells. Sputum developed in five subjects and contained 36 (5.2)% eosinophils and 1.98 (0.21)% metachromatic cells (mast cells or basophils). The symptom diary and weekly questionnaire were demonstrated to be valid and responsive to change. A deterioration indicated by the daily symptom score preceded changes in PEF. Treatment by an increase in steroid was followed by reversal of each of the changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

Formoterol compared with beclomethasone and placebo on allergen-induced asthmatic responses.

Formoterol is a new long-acting beta 2-agonist. We compared the protective effect of 24 micrograms formoterol with 200 micrograms beclomethasone and placebo on inhaled allergen-induced asthmatic responses in mild stable asthmatic subjects. We measured airflow rates, histamine airway responsiveness, cell counts from sputum and peripheral blood, and markers of lymphocyte and eosinophil activation. Adjustments were made for the confounding effect of bronchodilatation produced by formoterol in comparisons using a control inhalation of normal saline. Formoterol caused bronchodilation and inhibition of histamine airway responsiveness for at least 24 h. It completely inhibited the early asthmatic responses when beclomethasone had no effect. Control comparisons of the effect of formoterol and beclomethasone on the allergen-induced late asthmatic response and increase in histamine responsiveness showed each to be equally effective but not to inhibit the responses completely. Formoterol caused bronchodilation in addition to preventing bronchoconstriction. Both drugs inhibited the rise in serum eosinophil cationic protein 24 h after allergen, but neither inhibited the allergen-induced increases in sputum or blood eosinophils or CD25+ lymphocytes. These results suggest that formoterol modifies allergen-induced airway responses through functional antagonism rather than the inhibition of inflammatory cell infiltration.

Adult↗

Cathepsin-G and leukocyte elastase inactivate human tumor necrosis factor and lymphotoxin.

The addition of either cathepsin-G or leukocyte elastase to endotoxin-stimulated human peripheral blood monocytes decreased the immunoreactive tumor necrosis factor (TNF) detected in culture supernatants in a concentration-dependent manner. Both enzymes also induced a loss of supernatant cytolytic activity as determined on the WEHI-164 target cell line. Incubation of recombinant human TNF and lymphotoxin (LT) with either cathepsin-G or leukocyte elastase resulted in a loss of cytokine bioactivity. Examination of enzyme-treated recombinant cytokines by gel electrophoresis revealed that cathepsin-G cleaved LT into a 12.6-kDa fragment and leukocyte elastase fragmented LT into a 14.1-kDa product. On Western blots cathepsin-G and leukocyte elastase degraded TNF into 11- and 7.6-kDa fragments, respectively. Incubating leukocyte elastase with plasma elastase inhibitor alpha-1-antitrypsin prevented the loss of recombinant TNF bioactivity and blocked the degradation of this cytokine. This study suggests that two of the most abundant neutrophil proteases, cathepsin-G and leukocyte elastase, may be important regulators of TNF and LT bioactivity.

Adult↗

The effects of polyamines and polyamine inhibitors on rat sciatic and facial nerve regeneration.

The effects of exogenous polyamines and polyamine biosynthetic pathway inhibitors on regenerating nerves were examined in adult male rats following nerve transection and surgical repair. Several studies have demonstrated the efficacy of exogenous polyamines in promoting the functional recovery of peripheral nerves following crush or freeze injuries in the rat. In order to simulate clinical peripheral nerve surgery, we studied these effects after complete nerve transection and evaluated regeneration by counting axons. There was no statistical difference in axon number with and without polyamines and in the presence of inhibitors and inhibitors with end product addition. Our study suggests that the difference in recovery seen in previous studies is not mediated by a change in axon number.

Animals↗

Experimental nerve regeneration. A review.

The aim of peripheral nerve repair is to restore motor and sensory function, which requires more than just 10-0 sutures and a good microscope. The past decade has seen an explosion in the understanding of how nerves grow, and this information is being used to develop better treatments for nerve injuries. In the future, treatment will not be limited to the operating room, because postoperative adjuvant therapies will become increasingly more important in the management of nerve repairs. At the same time, advancement in manufacturing techniques, a better understanding of biomaterials, and the use of the laser will replace the time-honored techniques of surgical repair in many clinical settings.

Animals↗

Feedback-controlled laser-mediated cartilage reshaping.

OBJECTIVE: To demonstrate feedback-controlled laser-mediated cartilage reshaping using dynamic measurements of tissue optical properties and radiometric surface temperatures. DESIGN: Flat cartilage specimens were reshaped into curved configurations using a feedback-controlled laser device. MATERIALS: Fresh porcine nasal septum, stripped of perichondrium and cut into uniform strips (25 x 10 x 1.5-2.1 mm) with a custom guillotine microtome. INTERVENTIONS: Cartilage specimens secured in a cylindrical reshaping jig (2.5 cm in diameter) and irradiated with an Nd:YAG laser (lambda = 1.32 microns, 25 W/cm2, 50-Hz pulse repetition rate). During laser irradiation, radiometric surface temperature was measured along with changes in forward-scattered light from a diode probe laser (lambda = 650 nm, 5 mW), using a lock-in detection technique. Sequential irradiation of the specimen outer surface was made (3 laser passes). Characteristic changes in tissue temperature and light-scattering signals were used to terminate laser irradiation. RESULTS: Effective reshaping was accomplished for both thin (1.5-mm) and thick (2.1-mm) specimens. Following reshaping, specimens were stored in saline solution at 4 degrees C for 21 days. No return to the original flat configuration was noted during this period. CONCLUSIONS: The prototype device effectively reshapes flat native porcine cartilage into curve configurations. The use of optical and thermal signals provides effective feedback control for optimizing the reshaping process.

Animals↗

The porcine and lagomorph septal cartilages: models for tissue engineering and morphologic cartilage research.

Interest in reconstruction and modification of the facial cartilaginous frameworks using advanced technology and instrumentation is growing rapidly. Despite this maturing interest, no animal model has been established to provide morphologic cartilage tissue with similar characteristics to human septum in suitable quantities. The objective of this study was to characterize porcine and lagomorph (rabbit) nasal septal cartilage tissue. Both models share great similarity with their human counterpart and provide a low-cost, high-volume, and easily obtained source of bulk cartilage tissue. We present a technique for harvesting intact septal cartilages from these species, and characterize select cellular, metabolic, and physical properties using pulse-chase radiolabeling, flow cytometry, and mechanical analysis. Our selective evaluation of key tissue properties establishes these species as appropriate animal models for nasal septal cartilaginous surgery.

Animals↗

Angioresistance of thermally modified cartilage grafts in the chick chorioallantoic membrane model.

BACKGROUND: The chick chorioallantoic membrane (CAM) model allows direct observation of vascularization acutely in explanted or cultured tissues in an immunologically isolated environment. In vivo, angioinvasion of the tissue matrix does not occur in viable cartilage tissue, whereas denatured or nonviable grafts are readily vascularized and/or resorbed. OBJECTIVE: To determine, using the CAM model, whether angioinvasion of thermally altered cartilage explants occurs acutely. MATERIALS AND METHODS: Porcine septal cartilage specimens were removed from freshly killed animals and divided into 3 groups (n = 10): an untreated control group, a group in which cartilage was boiled in isotonic sodium chloride solution (normal saline) for 1 hour, and a laser-irradiated group (Nd:YAG, lambda = 1.32 microm, 30.8 W/cm2, irradiation time = 10 seconds). Tissue specimens were then washed in antibiotic solutions, cut into small cubes (approximately 1.5 mm3), placed on the surface of 30 CAMs (7 days after fertilization), and allowed to incubate for an additional 7 days. After incubation, the membranes and specimens were fixed in situ with formaldehyde and then photographed using a dissection microscope. RESULTS: Examination with a dissecting microscope showed no obvious vascular invasion of the cartilage or loss of gross tissue integrity in any of the 3 experimental groups, although all specimens were completely enveloped by the CAM vascular network. No vascular invasion of the tissue matrix was observed histologically. CONCLUSION: These experiments demonstrate that cartilage specimens remain acutely resistant to angioinvasion or metabolism by the immunologically immature CAM whether native unmodified tissue, completely denatured (boiled), or thermally modified following laser irradiation.

Allantois↗