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Biomedical subjects

T W Wright

Publications and source records attributed to T W Wright.

44 records · Page 3Linked to original sources

Functional outcome comparison of semiconstrained and unconstrained total elbow arthroplasties.

Twenty-six patients, each of whom had undergone either a semiconstrained (linked) or an unconstrained (unlinked) total elbow arthroplasty, were examined specifically to evaluate the restoration of function with respect to activities of daily living. The functional outcomes of these 2 groups were then compared to identify any significant differences. All of the unlinked/unconstrained prostheses were Ewald total elbow arthroplasties; the linked/semiconstrained prostheses, all of which were performed by a single surgeon, were Mayo-Coonrad prostheses. Follow-up radiographs, taken to rule out loosening or failure of the prosthesis as a cause for functional deficits, were available for review for 25 elbows. There were 14 elbows in 13 patients who had semiconstrained prostheses and 12 elbows in 10 patients who had unconstrained total prostheses. Average age at the time of elbow replacement surgery was 62.8 years (range, 47-75 years) for the semiconstrained group and 63.1 years (range, 54-74 years) for the unconstrained group. The semiconstrained group consisted of 8 female and 6 male elbows; the unconstrained group consisted of 10 female and 2 male elbows. Follow-up averaged 35.5 months (range, 24-73 months) in the semiconstrained group and 73 months (range, 27-110 months) in the unconstrained group. Twenty-two operations were performed for rheumatoid arthritis, 3 for posttraumatic humeral nonunion, and 1 for posttraumatic degenerative arthritis. Two elbows required revision, one (in the semiconstrained group) for aseptic loosening and the other (in the unconstrained group) for metal synovitis and pain from a chronically dislocated prosthesis; both of these elbows were considered failures and excluded from the functional comparison. No significant differences in functional performance were found, and no elbows demonstrated progressive radiolucencies suggestive of loosening. With the exception of 1 patient (in addition to the patients who had revisions) with a dislocated unconstrained prosthesis, all patients were satisfied with the procedure. It appears that when it is properly performed, total elbow arthroplasty with either type of prosthesis yields satisfactory functional results.

Activities of Daily Living↗

Comparison of adult and newborn pulmonary cytokine mRNA expression after hyperoxia.

Neonatal animals of several species are more tolerant of hyperoxic exposure than are adults. However, the mechanisms of increased neonatal tolerance are unknown, as are the cell types that contribute to oxygen resistance. This study examined hyperoxic lung injury in neonatal and adult C57BL/6 mice. Adults and neonatal mice were exposed to > 95% oxygen for 78 h and 10 days, respectively. Lung mRNAs were assayed by RNase protection assay. After 72 h of exposure, the messages encoding tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta and 6 (IL-1 beta, IL-6) were increased 2-fold in adult lungs. However, at this time point these mice are near or at lethality. No alterations in neonatal lung mRNAs were detected until 7 days of oxygen exposure. At that time neonatal mice demonstrated increases in lung mRNAs encoding TNF-alpha, IL-1 beta, and IL-6 of 3-, 5-, and 8-fold, respectively. Acute alveolitis and slight edema were detected, but lethality wasn't observed until 10 days of exposure. In situ hybridization in neonatal mice suggests accumulation of TNF-alpha and IL-1 beta transcripts in pulmonary interstitial macrophages and in a subset of neutrophils after 7 days of exposure. Messages encoding IL-1 alpha, IL-2, IL-3, IL-4, IL-5,IL-10 interferon-gamma (IFN-gamma), and TNF-beta were not altered from controls in either adult or neonatal mice at any time point examined. In conclusion, adult mice demonstrate little change in cytokine mRNA until lethality is imminent, whereas newborn mice demonstrate an acute induction of TNF-alpha, IL-1 beta, and IL-6 early in the development of hyperoxic injury, which suggests that a rapid cytokine response early in the development of hyperoxic injury may play an important role in the adaptation of neonatal lungs to toxicity from prolonged oxygen exposure.

Aging↗

Alterations in the expression of chemokine mRNA levels in fibrosis-resistant and -sensitive mice after thoracic irradiation.

Fibrosis, characterized by the accumulation of collagen, is a consequence of a chronic inflammatory response. The purpose of this study was to determine if the mRNA expression of the chemokines, lymphotactin (Ltn), RANTES, eotaxin, macrophage inflammatory protein (MIP)-1 alpha, -1 beta, and -2, interferon-inducible protein 10 (IP-10), and monocyte chemotactic protein-1 (MCP-1), are altered during the development of radiation-induced pneumonitis and fibrosis. Further, we wished to determine if these changes differ between two strains of mice that vary in their sensitivity to radiation fibrosis. Fibrosis-sensitive (C57BL/6) and fibrosis-resistant (C3H/HeJ) mice were irradiated with a single dose of 12.5 Gy to the thorax. Total lung RNA was prepared and hybridized utilizing RNase protection assays. Data were quantified by phosphorimaging and results normalized to a constituitively expressed mRNA L32. 8 weeks post-irradiation most chemokines measured were elevated to varying degrees. The degree of elevation of each chemokine was identical in both strains. This suggested that chemotactic activity for neutrophils, macrophages, and lymphocytes were occurring during pneumonitis. By 26 weeks post-irradiation, messages encoding Ltn, RANTES, IP-10, and MCP-1 were elevated only in fibrosis sensitive (C57BL/6) mice. In situ hybridization demonstrated that MCP-1 and RANTES transcripts were produced predominantly from macrophages and lymphocytes. These studies suggest that lymphocytic recruitment and activation are key components of radiation-induced fibrosis.

Animals↗

Inflammatory and epithelial responses in mouse strains that differ in sensitivity to hyperoxic injury.

The pulmonary response to various toxicants including bleomycin, ozone, ionizing radiation, and hyperoxia is highly variable among mouse strains. The current study tests the hypothesis that at a similar stage of injury, regardless of strain, expression of inflammatory cytokine and epithelial marker genes would be similar, indicating a common pathway of injury progression. Three strains of mice, C57B1/6J, 129/J, and C3H/HeJ, ranging from sensitive to resistant, were exposed to > 95% O2 for varying times. Ribonuclease protection was used to quantify changes in cytokine mRNA. Despite differences in the kinetics, each strain demonstrated similar hyperoxia-induced changes in the abundance of interleukin (IL)-6, IL-1 beta, IL-3, and tumor neucrosis factor (TNF)-alpha. For each strain, death was accompanied by similar increases in cytokine mRNAs above steady-state control levels. Other inflammatory cytokines, including IL-1 alpha, IL-4, and interferon (IFN)-gamma, were unaltered in all strains at all times. In situ hybridization analysis of the epithelial markers, surfactant protein B (SPB), and clara cell secretory protein (CCSP) at the time of proinflammatory induction showed a similar pattern of expression in all strains. Increased SPB was detected in bronchiolar epithelium, while the number of type II cells expressing this message declined. Both the number of cells expressing CCSP as well as abundance per cell declined. These results suggest that although differences in acute sensitivity to hyperoxia exist between mouse strains, once initiated, acute epithelial cell injury and associated inflammatory changes follow the same pattern in all strains.

Animals↗

Chemokine mRNA alterations in newborn and adult mouse lung during acute hyperoxia.

Chemokines play a major role in the recruitment of inflammatory cells during acute lung injury. Adult and newborn C57BL/6 mice were exposed to > 95% oxygen for up to 72 hours and 7 days, respectively. Chemokine mRNA abundance was evaluated in whole lung RNA by ribonuclease protection assay and in tissue sections by in situ hybridization. Monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-2, and interferon gamma-induced protein (IP)-10 mRNAs were present in whole newborn lung by 4 days of hyperoxia and were markedly elevated by 7 days. Levels of mRNA for MCP-1, MIP-1 alpha, and MIP-2 were elevated to a lesser extent by 72 hours of hyperoxia in adults. MCP-1 mRNA abundance was moderately elevated in scattered areas of perivascular tissue, peribronchiolar tissue, and the alveolar interstitium in 4-day hyperoxic newborns and markedly upregulated diffusely throughout the peripheral airspaces in 7-day hyperoxic newborns. MCP-1 mRNA abundance was limited to scattered perivascular areas and airspaces in 72-hour hyperoxic adults. These differences in the intensity, timing, and distribution of chemokine mRNA abundance between adult and newborn mice may help to explain the marked differences in their susceptibility to oxygen injury.

Acute Disease↗