Tendon repair through stem cell intervention: Cellular and molecular approaches

Tendon injuries are common in either the workplace or sport activities, with some 3 to 5 million tendon and ligament injuries occurring annually worldwide. Management of tendon injury currently follows two routes: Conservative (rehabilitation and pain relief), or surgical. Irrespective of which of these primary treatment routes are followed, even if healing does occur, it may not result in a full gain of function. The inability of the tendon to self-repair and the relative inefficiency of current treatment regimens suggest that identifying alternative strategies is a priority. One such alternative is the use of stem cells to repair damage, either through direct application or in conjunction with scaffolding. We describe the current state of the art in terms of: (i) Molecular markers of tendon development, (ii) stem cell applicability to human tendon repair, (iii) scaffolding for in vitro tendon generation, and (iv) chemical/molecular approaches to both induce stem cell differentiation into tenocytes and maintain their proliferation in vitro.     

Rapid Selection of Plasmodium falciparum Chloroquine Resistance Transporter Gene and Multidrug Resistance Gene-1 Haplotypes Associated with Past Chloroquine and Present Artemether-Lumefantrine Use in Inhambane District,Southern Mozambique

Chloroquine (CQ) use in Mozambique was stopped in 2002 and artemether-lumefantrine (AL) was implemented in 2008. In light of no use of CQ and extensive use of AL, we determined the frequency of molecular markers of Plasmodium falciparum drug resistance/tolerance to CQ and AL in persons living in Linga-Linga, an isolated peninsula and in Furvela village, which is located 8 km inland. The P. falciparum chloroquine resistance transporter gene CVMNK wild type increased in frequency from 43.9% in 2009 to 66.4% in 2010 (P ≤ 0.001), and combined P. falciparum multidrug resistance gene 1 N86-184F-D1246 haplotype increased significantly between years (P = 0.039). The combination of P. falciparum chloroquine resistance transporter gene CVMNK and P. falciparum multidrug resistance gene NFD increased from 24.3% (2009) to 45.3% in (2010, P = 0.017). The rapid changes observed may largely be caused by decreased use of CQ and large-scale use of AL. In the absence of a clear AL-resistance marker and the (almost) continent-wide use of AL in sub-Saharan Africa, and when considering CQ reintroduction, continued monitoring of these markers is needed.     

Functional urinary and fecal incontinence in neurologically normal children: symptoms of one 'functional elimination disorder'?

OBJECTIVE: To clarify the relationship between disordered defecation and non-neuropathic bladder-sphincter dysfunction (NNBSD) by comparing the prevalence of symptoms of disordered defecation in children with NNBSD before and after treatment for urinary incontinence (UI), and assessing the effect of such symptoms on the cure rate for UI. PATIENTS AND METHODS: In the European Bladder Dysfunction Study, a prospective multicentre study comparing treatment plans for children with NNBSD, 202 children completed questionnaires on voiding and on defecation, at entry and after treatment for UI. Four symptoms of disordered defecation were evaluated; low defecation frequency, painful defecation, fecal soiling, and encopresis. RESULTS: At entry, 17 of the 179 children with complete data sets had low defecation frequency and/or painful defecation (9%), classified as functional constipation (FC). Of the 179 children, 57 had either isolated fecal soiling or soiling with encopresis (32%), classified as functional fecal incontinence (FFI). After treatment for UI, FFI decreased to 38/179 (21%) (statistically significant, P = 0.035); for FC there were too few children for analysis. After treatment for UI, 19 of the 179 children (11%) reported de novo FFI. Symptoms of disordered defecation did not influence the cure rate of treatment for UI. CONCLUSIONS: FFI improved significantly after treatment for UI only, but not in relation to the outcome of such treatment. FFI did not influence the cure rate for UI. There was little to support a causal relation between disordered defecation and NNBDS ('functional elimination syndrome').     

Outcome of a 4-step treatment algorithm for depressed inpatients

OBJECTIVE: The aim of this study was to examine the efficacy and the feasibility of a 4-step treatment algorithm for inpatients with major depressive disorder. METHOD: Depressed inpatients, meeting DSM-IV criteria for major depressive disorder, were enrolled in the algorithm that consisted of sequential treatment steps (washout period, anti-depressant monotherapy, lithium addition, treatment with a nonselective monoamine oxidase inhibitor, electroconvulsive therapy). Definition of nonresponse and progression through the steps of the algorithm was dependent on the score on the 17-item Hamilton Rating Scale for Depression (HAM-D) at predefined evaluation times. Patients were admitted from April 1997 through July 2001. RESULTS: Of the 203 patients studied, 149 were treated according to the full algorithm, and 54 patients were immediately entered into step 3. Of the 203 patients, 165 (81%) achieved response (> or = 50% reduction in HAM-D score) and 101 (50%) remitted (final HAM-D score < or = 7). Of the 149 patients treated according to the full algorithm, 129 (87%) responded and 89 (60%) remitted. Twenty-four patients (16%) dropped out from the algorithm. CONCLUSION: Although response with antidepressant monotherapy was less than 50%, successive treatment according to the 4-step algorithm was very effective in a sample of depressed inpatients. The adherence to the algorithm was good as shown by a low dropout rate. This study emphasizes the importance of persisting with standardized antidepressant treatment in patients who are initially nonresponders to the first antidepressant. By the end of the study, more than 80% of the patients responded and 50% achieved full remission.     

Imipramine is effective in preventing relapse in electroconvulsive therapy-responsive depressed inpatients with prior pharmacotherapy treatment failure: a randomized, placebo-controlled trial

OBJECTIVE: To compare the efficacy of imipramine versus placebo in preventing relapse after successful electroconvulsive therapy (ECT) in depressive inpatients with pharmacotherapy treatment failure prior to ECT. METHOD: During a 6-month period, the incidence of relapse was assessed. Two centers, both inpatient units for treatment of depressed patients, participated in this trial. Patients with DSM-IV-diagnosed major depressive disorder resistant to an anti-depressant and subsequent lithium addition and/or a monoamine oxidase inhibitor were included. Patients were randomly assigned to double-blind treatment with imipramine with adequate plasma levels (N=12) or placebo (N=15) after successful ECT. The mean imipramine dosage was 209 mg/day (standard deviation: 91.7, range: 75-325 mg/day). The main outcome measure was relapse defined as at least "moderately worse" compared with baseline score on the Clinical Global Impressions-Improvement scale. Treatments were compared with survival analysis using the Cox proportional hazards model, including psychotic features and the score on the Hamilton Rating Scale for Depression (HAM-D) at baseline as prespecified covariables. Patients were enrolled in the study from April 1997 to July 2001. RESULTS: In the placebo group, 80% (12/15) of the patients relapsed compared with 18% (2/11) in the imipramine group. The Cox regression analysis showed a significant reduction in the risk of relapse of 85.6% with imipramine compared to placebo (p=.007; 95% confidence interval [CI]=24.6% to 97.2%) adjusted for the covariables. There was an 18% increase in the relapse rate (p=.032; 95% CI=2% to 36%) per unit increase in HAM-D score before the start of the trial; psychotic features had no significant effect (p=.794). CONCLUSIONS: Depressed patients with pharmacotherapy treatment failure may benefit from the prophylactic effect of the same class of drug during maintenance therapy after response to ECT.     

Does the severity of bilateral carpal tunnel syndrome influence the timing of staged bilateral release?

A retrospective chart analysis was performed of 66 patients with bilateral carpal tunnel syndrome (CTS) who underwent either single endoscopic carpal tunnel release (ECTR) or staged bilateral ECTR to determine the frequency and timing of contralateral surgery. Bilateral CTS patients with contralateral severe CTS underwent bilateral staged ECTR 86% of the time and the second operation was performed 6 ± 5 weeks after the initial ECTR. Patients with contralateral moderate CTS underwent bilateral staged ECTR 74% of the time with a mean of 11 ± 3 months between operations. Patients with contralateral mild CTS underwent bilateral staged ECTR 20% of the time and averaged 7 ± 3 years between procedures. For patients with bilateral CTS, the severity of CTS on the contralateral side to the initial release affects both the frequency and timing of the contralateral surgery. This information may be used to establish guidelines for treatment with bilateral simultaneous CTR.     

The dilated distal esophagus: a new entity that is the pathologic basis of early gastroesophageal reflux disease

Present management algorithms for patients with gastroesophageal reflux disease (GERD) limit endoscopy to patients with advanced disease. When endoscopy is performed, biopsy is limited to patients who have a visible columnar-lined esophagus. Biopsy is not recommended for patients whose endoscopy is normal. This algorithm results in the failure to evaluate patients with early stages of GERD at a pathologic level. We report 714 patients with normal endoscopic findings irrespective of symptoms who had adequate biopsies taken from the squamocolumnar junction and the area 1-cm distal to this from mucosa that had rugal folds. Concurrent biopsies were also taken from the gastric body and/or antrum. All patients had a gap between their esophageal squamous epithelium and gastric oxyntic mucosa in the junctional region composed of oxyntocardiac ± cardiac ± intestinal epithelia. A total of 643 (90.1%) patients had no significant pathology in the gastric antrum and/or body, indicating that the squamooxyntic gap was an isolated abnormality in this region in all but 71 (9.9%) patients. The gap contained only oxyntocardiac epithelium in 71 (9.9%) patients, cardiac mucosa without intestinal metaplasia in 482 (67.5%) patients, and intestinal metaplasia in 161 (22.6%) patients. The pathologic interpretation of biopsies taken from the gastroesophageal junction is confusing and has significant interobserver variation. This results from lack of agreement as to whether these biopsies originate in the proximal stomach ("gastric cardia") or in the esophagus. We provide evidence that the presence of oxyntocardiac ± cardiac ± intestinal epithelia in biopsies from patients who are endoscopically normal is diagnostic of a dilated GERD-damaged distal esophagus. The dilated distal esophagus is the pathologic manifestation of destruction of the abdominal segment of the lower esophageal sphincter. Its presence is the pathologic basis of early GERD, which is missed if patients who are endoscopically normal are not biopsied, as is the present recommendation. Its recognition allows for accurate and evidence-based interpretation of biopsies from this region and removes the present confusion and permits the development of a reproducible pathologic diagnostic method.     

Percutaneous K-wire fixation versus palmar plating with locking screws for Colles' fractures

Different methods exist to treat distal radius fractures. A prospective randomized study was conducted to establish whether palmar plate fixation with locking screws gave better results than percutaneous K-wire fixation in patients over 50 years of age. Only fractures with dorsal displacement after a simple fall were included in the study. Twenty wrists were treated with K-wires and 20 with a plate. Radiological parameters were measured on preoperative radiographs and at five weeks postoperatively. Clinical results and DASH scores were determined at three months postoperatively and at more than one year. No significant difference in radial inclination, palmar tilt, clinical outcome and DASH score was found between plating and K-wires, but the mean difference in ulnar variance between pre- and postoperative radiographs was significantly better with plates. It can be concluded that plates were superior to K-wires in restoring ulnar variance, but functional outcome was similar with both techniques.