Predictors of Patient-Reported Outcomes of Total Joint Arthroplasty in a Developing Country.

BACKGROUND: In response to the growing burden of joint disease, developing countries are starting to create their own total joint arthroplasty (TJA) programs. To date, there has been limited research on predictors of TJA outcomes in a developing country. This investigation uses patient-reported outcome measures collected by a medical mission to assess predictors of TJA outcomes in the Dominican Republic. METHODS: Baseline and postoperative information from 156 of the mission's recipients of hip and knee TJA was used. Demographics were abstracted from clinical notes, and self-reported pain and functional status were assessed using Western Ontario and McMaster University Osteoarthritis Index and Short-Form 36 measures. Bivariate analysis identified variables to include in multivariable regression models of factors associated with function and pain outcomes and improvement in these domains 1 or 2 years postoperatively. RESULTS: The cohort had a mean age of 61.3 years, 82% were female, 79% had total knee arthroplasty, and 42% of the procedures were bilateral. In multivariate analyses, at P < .05, male sex, better preoperative function, and use of bilateral procedure were associated with better functional outcome. Male sex and worse preoperative pain were associated with better pain outcome. Worse preoperative pain and function, as well as bilateral surgery were associated with greater improvement in function. Additionally, a greater number of bothersome joints was associated with greater pain reduction. CONCLUSION: Our findings of better follow-up pain scores among patients with worse pain preoperatively and better functional improvement among those undergoing bilateral replacements contrast with study results from developed countries. The explanations for these observations merit further study.

The cationic host defense peptide rCRAMP promotes gastric ulcer healing in rats.

Cathelicidin, a cationic host defense peptide, has been shown to promote cutaneous wound repair and reaches high levels in the gastric mucosa during infection and inflammation. Therefore, we investigated whether this peptide contributes to gastric ulcer healing in rats. Ulcer induction increased the expression of rat cathelicidin rCRAMP in the gastric mucosa. Further increase in expression of rCRAMP by local injection of rCRAMP-encoding plasmid promoted ulcer healing by enhancing cell proliferation and angiogenesis. rCRAMP directly stimulated proliferation of cultured rat gastric epithelial cells (RGM-1), which was abolished by inhibitors of matrix metalloproteinase (MMP), epidermal growth factor receptors (EGFR) tyrosine kinase, or mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase. rCRAMP also increased EGFR and ERK1/2 phosphorylation via an MMP-dependent mechanism. Knockdown of transforming growth factor alpha (TGFalpha), which is a ligand of EGFR, by small interfering RNA completely nullified the mitogenic signals evoked by rCRAMP in RGM-1 cells. These findings suggest that rCRAMP exhibits prohealing activity in stomachs through TGFalpha-dependent transactivation of EGFR and its related signaling pathway to induce proliferation of gastric epithelial cells.

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone from cigarette smoke stimulates colon cancer growth via beta-adrenoceptors.

Cigarette smoking is a risk factor for colorectal cancer. It is suggested that 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a tobacco-specific nitrosamine, mediates the carcinogenic action of cigarette smoking by promoting cancer growth. In the present study, the proliferative response of a cultured colon cancer cell line HT-29 to NNK was determined. It was found that NNK dose-dependently stimulated HT-29 cell proliferation. In this regard, the stimulatory action of NNK was abolished by atenolol and ICI 118,551, a beta1- and beta2-selective antagonist, respectively. In addition, cell growth was stimulated by the nonselective adrenergic agonist, noradrenaline, and more effectively by the beta-selective agonist, isoproterenol. The second message cyclic AMP level for beta-adrenoceptor activation was elevated by isoproterenol and NNK treatment. These agents also up-regulated cyclooxygenase-2 expression, cytosolic phospholipase A2 expression, and prostaglandin E2 release. Beta2-adrenoceptor blockade with ICI 118,551, in contrast, significantly decreased cyclooxygenase-2 expression, cytosolic phospholipase A2 expression and prostaglandin E2 release induced by NNK and isoproterenol. To conclude, it is proposed that NNK stimulates HT-29 cell proliferation through beta-adrenoceptors, preferentially beta2 receptors. Activation of the beta-adrenoceptors, and the consequent cyclic AMP elevation coupled with the downstream arachidonic acid pathway, is perhaps an important mechanistic cascade in the promotion of colon cancer growth. These findings partly elucidate the carcinogenic actions of cigarette smoke and shed new light on the novel modulatory role of beta-adrenoceptors in the development of colon cancer.