Citations

ABSTRACTFibrosis of the subsynovial connective tissue (SSCT) is a predominant feature of carpal tunnel syndrome (CTS). While the nature of CTS has been extensively studied, little is known about the etiology of this disease. We investigated SSCT tissue from patients with CTS and control subjects using fibrosis arrays and cell culture analysis. Twofold changes in fibrotic gene expression were found in multiple genes from patient SSCT using fibrosis arrays. This data was confirmed via qRT‐PCR on a subset of genes; collagen I (Col1), collagen III (Col3), connective tissue growth factor (CTGF), transforming growth factor β (TGF‐β), and SMAD3 (P < 0.05) which significantly corroborate the fold changes found in the fibrosis arrays. To further explore the nature of SSCT fibrosis, cells were isolated from patient and control tissue. Col1, Col3, TGF‐β, and SMAD3 were highly expressed in patient SSCT fibroblasts as compared to control (P < 0.05). Further, fibrotic genes expression was decreased by inhibiting TGF‐β receptor I (TβRI) activity (P < 0.05). TGF‐β second messenger SMAD activity was significantly activated in SSCT fibroblasts from patients and this activation was abrogated by inhibiting TβRI signaling (P < 0.05). These findings suggest that blocking TGF‐β signaling may be an important therapeutic approach to treating the underlying fibrosis of SSCT in CTS patients. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1444–1450, 2014.

AbstractPurposeThe purpose of this study was to review the results of patellofemoral arthroplasty (PFA) performed by a single surgeon at a single institution in order to determine factors associated with clinical outcomes and progression of tibiofemoral degenerative joint disease.MethodsSixty‐one patients with isolated patellofemoral osteoarthritis were treated with a PFA by a single surgeon between 2003 and 2009. Fifty‐nine patients were available for analysis with a mean follow‐up of 4 years (range 2–6 years). Patients were evaluated by measuring range of motion and with the use of the Knee Society clinical rating system, the Tegner Activity Level Scale, and the UCLA Activity Score. In addition, preoperative radiographs were evaluated for patellofemoral and tibiofemoral compartment osteoarthritis and presence of trochlear dysplasia, and post‐operative radiographs were reviewed for progression of tibiofemoral degenerative arthritis. Furthermore, multivariate statistical methods were applied to study factors that had potential to influence the final outcome.ResultsThere was no statistically significant association between age, gender, history of prior knee surgery, patellar height, patellofemoral osteoarthritis severity, patellar and femoral component size, or performance of lateral release with patient pain and function (as measured by the Knee Society scores) or progression of tibiofemoral joint osteoarthritis at final follow‐up. Increased preoperative body mass index (BMI) was associated with lower post‐operative Knee Society function scores (p = 0.03). Patients with preoperative trochlear dysplasia had significantly less radiographic evidence of tibiofemoral joint osteoarthritis progression compared with patients without trochlear dysplasia at final follow‐up (p < 0.0001).ConclusionIn this study, patients with preoperative radiographic evidence of trochlear dysplasia experienced less progression of tibiofemoral degenerative joint disease than patients without trochlear dysplasia at a mean follow‐up of 4 years.Level of evidenceIV.

BackgroundVascular endothelial growth factor (VEGF) induces angiogenesis and osteogenesis in bone allotransplants. We aim to determine whether bone remodeling in VEGF‐treated bone allotransplants results from repopulation with circulation‐derived autogenous cells or survival of allogenic transplant‐derived cells.MethodsVascularized femoral bone transplants were transplanted from female Dark Agouti rats (DA;RT1a) to male Piebald Viral Glaxo (PVG;RT1c). Arteriovenous bundle implantation and short‐term immunosuppression were used to maintain cellular viability. VEGF was encapsulated in biodegradable microspheres and delivered intramedullary in the experimental group (n = 22). In the control group (n = 22), no VEGF was delivered. Rats were sacrificed at 4 or 18 weeks. Laser capture microdissection of bone remodeling areas was performed at the inner and outer cortex. Sex‐mismatched genes were quantified with reverse transcription‐polymerase chain reaction to determine the amount of male cells to total cells, defined as the relative expression ratio (rER).ResultsAt 4 weeks, rER was significantly higher at the inner cortex in VEGF‐treated transplants as compared to untreated transplants (0.622 ± 0.225 vs. 0.362 ± 0.081, P = 0.043). At 4 weeks, the outer cortex in the control group had a significantly higher rER (P = 0.038), whereas in the VEGF group, the inner cortex had a higher rER (P = 0.015). Over time, in the outer cortex the rER significantly increased to 0.634 ± 0.106 at 18 weeks in VEGF‐treated rats (P = 0.049). At 18 weeks, the rER was >0.5 at all cortical areas in both groups.ConclusionsThese in vivo findings suggest a chemotactic effect of intramedullary applied VEGF on recipient‐derived bone and could imply that more rapid angiogenesis of vascularized allotransplants can be established with microencapsulated VEGF. © 2014 Wiley Periodicals, Inc. Microsurgery 35:45–51, 2015.

Pancreatobiliary tract carcinoma is a lethal disease with low survival rates and limited treatment options. Diagnosis is complicated by benign conditions that can mimic malignancy on radiological studies (e.g. primary sclerosing cholangitis or PSC) and the suboptimal sensitivity of endoscopic biopsy/brushings obtained by endoscopic retrograde cholangiopancreatography (ERCP). The detection of multiple chromosomal gains by fluorescence in situ hybridization (FISH), referred to as polysomy, has demonstrated improved sensitivity over routine cytological evaluation. The evaluation of brushings by both routine cytology and FISH in our cytopathology laboratory has been in clinical practice since 2003. Strong morphological and screening skills enable cytotechnologists to become proficient in the assessment of FISH slides, which translates into cost and time savings. Multiple reports from various institutions have demonstrated the utility of FISH for patients with and without PSC. The incorporation of routine cytology and FISH results into the management algorithm for patients under suspicion for pancreatobiliary malignancy is a testament to the clinical success of these cytological assays.

Controlling meal-related glucose excursions continues to be a therapeutic challenge in diabetes mellitus. Mechanistic reasons for this need to be understood better to develop appropriate therapies. To investigate delayed gastric emptying effects on postprandial glucose turnover, insulin sensitivity, and β-cell responsivity and function, as a feasibility study prior to studying patients with type 1 diabetes, we used the triple tracer technique C-peptide and oral minimal model approach in healthy subjects. A single dose of 30 μg of pramlintide administered at the start of a mixed meal was used to delay gastric emptying rates. With delayed gastric emptying rates, peak rate of meal glucose appearance was delayed, and rate of endogenous glucose production (EGP) was lower. C-peptide and oral minimal models enabled the assessments of β-cell function, insulin sensitivity, and β-cell responsivity simultaneously. Delayed gastric emptying induced by pramlintide improved total insulin sensitivity and decreased total β-cell responsivity. However, β-cell function as measured by total disposition index did not change. The improved whole body insulin sensitivity coupled with lower rate of appearance of EGP with delayed gastric emptying provides experimental proof of the importance of evaluating pramlintide in artificial endocrine pancreas approaches to reduce postprandial blood glucose variability in patients with type 1 diabetes.

AbstractBackgroundHeme oxygenase 1 (HO‐1) degrades heme and protects against oxidative stress. In vitro and animal models suggest that HO‐1 is beneficial in several diseases (e.g., postoperative ileus, gastroparesis, acute pancreatitis, and colitis). However, the only drugs (i.e., hemin and heme arginate) which pharmacologically upregulate HO‐1 in humans are expensive and can only be administered intravenously. Our aims were to compare the effects of placebo, aspirin, and simvastatin alone, and with α‐lipoic acid, on HO‐1 protein concentration and activity in humans.MethodsThis randomized, double‐blind, placebo‐controlled study compared the effects of three oral regimens administered for 7 days, i.e., placebo; aspirin (325 mg twice daily) and simvastatin (40 mg twice daily); aspirin, simvastatin, and the sodium salt of R‐ α‐lipoic acid (NaRLA, 600 mg three times daily) on markers of HO‐1 activation (i.e., plasma HO‐1 protein concentration and venous monocyte HO‐1 protein activity) in 18 healthy subjects (14 females). Markers of HO‐1 activation were evaluated at baseline, days 2, and 7.Key ResultsBaseline HO‐1 protein concentrations and activity were similar among the three groups. Compared to placebo, aspirin and simvastatin combined, or together with NaRLA did not affect HO‐1 protein concentration or activity at 2 or 7 days. HO‐1 protein concentrations and activity were correlated on day 7 (r = 0.75, p = 0.0004) but not at baseline and on day 2.Conclusions & InferencesAt therapeutic doses, aspirin, simvastatin, and α‐lipoic acid do not increase plasma HO‐1 protein concentration or venous monocyte HO‐1 activity in healthy humans.

This is a study of a 20-year-old girl who developed mild, breathy dysphonia which, because of its nonspecificity, had been previously diagnosed as psychogenic; in actuality her voice change was a sign of early myasthenia gravis. The case is presented to alert the clinician to the fact that voice changes can be one of the first and only signs of early neurologic disease. Differential diagnosis requires careful laryngologic, psychiatric, speech, and neurologic examinations. In this instance, the laryngologic and psychiatric examinations were nonproductive, but the speech examination elicited a marked increase in breathiness, hypernasality, and articulatory imprecision as the consequence of prolonged, effortful speaking. This finding, along with the neurologist’s demonstration of an increase in muscular strength by means of injecting edrophonium chloride (Tensilon) led to the diagnosis of myasthenia gravis. A summary of the incidence, clinical features, methods of examination, and treatment of this disease follow the case presentation.