Tendinosis develops from age- and oxygen tension-dependent modulation of Rac1 activity.

Age-related tendon degeneration (tendinosis) is characterized by a phenotypic change in which tenocytes display characteristics of fibrochondrocytes and mineralized fibrochondrocytes. As tendon degeneration has been noted in vivo in areas of decreased tendon vascularity, we hypothesized that hypoxia is responsible for the development of the tendinosis phenotype, and that these effects are more pronounced in aged tenocytes. Hypoxic (1% O2 ) culture of aged, tendinotic, and young human tenocytes resulted in a mineralized fibrochondrocyte phenotype in aged tenocytes, and a fibrochondrocyte phenotype in young and tendinotic tenocytes. Investigation of the molecular mechanism responsible for this phenotype change revealed that the fibrochondrocyte phenotype in aged tenocytes occurs with decreased Rac1 activity in response to hypoxia. In young hypoxic tenocytes, however, the fibrochondrocyte phenotype occurs with concomitant decreased Rac1 activity coupled with increased RhoA activity. Using pharmacologic and adenoviral manipulation, we confirmed that these hypoxic effects on the tenocyte phenotype are linked directly to the activity of RhoA/Rac1 GTPase in in vitro human cell culture and tendon explants. These results demonstrate that hypoxia drives tenocyte phenotypic changes, and provide a molecular insight into the development of human tendinosis that occurs with aging

Predictors of perioperative blood loss in total joint arthroplasty.

UNLABELLED: UPDATE The print version of this article has errors that have been corrected in the online version of this article. In the Materials and Methods section, the sentence that reads as During the study period, our institution offered preoperative autologous blood donation to all patients who were scheduling for total joint arthroplasty with a hemoglobin level of no less than 11 mg/dL or a hematocrit level of at least 33%. in the print version now reads as During the study period, our institution offered preoperative autologous blood donation to all patients who were scheduling for total joint arthroplasty with a hemoglobin level of no less than 11 g/dL or a hematocrit level of at least 33%. in the online version. In Table III, the footnote that reads as The values are given as the estimate and the standard error in milligrams per deciliter. in the print version now reads as The values are given as the estimate and the standard error in grams per deciliter. in the online version. BACKGROUND: Despite advances in surgical and anesthetic techniques, lower-extremity total joint arthroplasty is associated with considerable perioperative blood loss. As predictors of perioperative blood loss and allogenic blood transfusion have not yet been well defined, the purpose of this study was to identify clinical predictors for perioperative blood loss and allogenic blood transfusion in patients undergoing total joint arthroplasty. METHODS: From 2000 to 2008, all patients undergoing unilateral primary total hip or knee arthroplasty who met the inclusion criteria were enrolled in the study. Perioperative blood loss was calculated with use of a previously validated formula. The predictors of perioperative blood loss and allogenic blood transfusion were identified in a multivariate analysis. RESULTS: Eleven thousand three hundred and seventy-three patients who underwent total joint arthroplasty, including 4769 patients who underwent total knee arthroplasty and 6604 patients who underwent total hip arthroplasty, were evaluated. Multivariate analysis indicated that an increase in blood loss was associated with being male (263.59 mL in male patients who had undergone total hip arthroplasty and 233.60 mL in male patients who had undergone total knee arthroplasty), a Charlson Comorbidity Index of \u3e3 (293.99 mL in patients who had undergone total hip arthroplasty and 167.96 mL in patients who had undergone total knee arthroplasty), and preoperative autologous blood donation (593.51 mL in patients who had undergone total hip arthroplasty and 592.30 mL in patients who had undergone total knee arthroplasty). In patients who underwent total hip arthroplasty, regional anesthesia compared with general anesthesia reduced the amount of blood loss. The risk of allogenic blood transfusion increased with the amount of blood loss in the patients who underwent total hip arthroplasty (odds ratio, 1.43 [95% confidence interval, 1.40 to 1.46]) and the patients who underwent total knee arthroplasty (odds ratio, 1.47 [95% confidence interval, 1.42 to 1.51]), but the risk of blood transfusion increased with the Charlson Comorbidity Index only in patients who underwent total knee arthroplasty (odds ratio, 3.2 [95% confidence interval, 1.99 to 5.15]). The risk of allogenic blood transfusion decreased with preoperative autologous blood donation in patients who underwent total hip arthroplasty (odds ratio, 0.01 [95% confidence interval, 0.01 to 0.02]) and patients who underwent total knee arthroplasty (odds ratio, 0.02 [95% confidence interval, 0.01 to 0.03]). CONCLUSIONS: This study identified some clinical predictors for blood loss in patients undergoing total joint arthroplasty that we believe can be used for implementing more effective blood conservation strategies. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence

Republication of “Open Repair of Acute Achilles Tendon Ruptures: Is the Incidence of Clinically Significant Wound Complications Overestimated?”

Background: Conflicting evidence exists regarding the optimal management of acute Achilles tendon ruptures. Operative repair is thought to afford patients a lower risk of rerupture, albeit at a higher overall risk of wound complications. Methods: A retrospective chart review of 369 consecutive patients undergoing open repair of acute Achilles tendon ruptures performed by a single foot and ankle fellowship-trained orthopedic surgeon was undertaken. Healing was classified as no complications, complications without prolonging treatment, complications requiring prolonged local treatment, and complications requiring operative intervention. A statistical analysis comparing the rates of complications in this cohort to that reported in the literature was conducted. Results: There were a total of 33 (8.94%) wound complications. Compared to the rates reported in the literature, no significant difference was detected (P = .3943; CI 6.24-12.33). However, when the complications not requiring additional treatment or prolonged care were excluded, only 9 wound complications (2.44%) were identified—a significantly lower complication rate than that reported in the literature (P \u3c .0001; CI 1.12-4.58). There were only 2 (0.54%) major complications requiring operative intervention, also a significantly lower rate than in the literature (P \u3c .0001; CI 0.067-1.94). Conclusion: In the past, wound-healing complications have been cited as a concern when treating patients operatively. We found that when solely looking at healing complications prolonging the patients’ overall recovery, a significantly lower rate of complications existed compared to that reported in the literature. Level of Evidence: Level IV

Traumatic thoracic ASIA A examinations and potential for clinical trials

Study Design: Retrospective review of prospective database Objectives: To define the variability of neurologic examination and recovery after non-penetrating complete thoracic spinal cord injuries (ASIA A). Background Data: Neurologic examinations after SCI can be difficult and inconsistent. Unlike cervical SCI patients, alterations in thoracic (below T1) complete SCI (ASIA A – based on the ASIA Impairment Scale [AIS]) patients’ exams are based only on sensory testing, thus changes in the neurological level (NL) are determined only by sensory changes. Methods: A retrospective review of the placebo control patients in a multicenter prospective database utilized for the pharmacologic trial of Sygen. Patients were included if they had a complete thoracic SCI on initial evaluation, with completed ASIA examinations at follow-up weeks 4, 8, 16, 26 and 52. Specifically, pin prick (PP) and light touch (LT) were assessed and the absolute change was calculated as the number of spinal levels at a given observation time. Results 3165 patients were initially screened for the Sygen clinical trial, of which 57 were the control placebo patients used in this analysis. Alterations from the baseline exam (PP and LT) were fairly consistent and the median change/recovery in neurologic examination was one spinal level. Across all observations post-baseline, the average change for PP was 1.48 +/- 0.13 (mean +/- SE), and for LT, 1.40 +/-0.13. There were equal proportions of directional changes (none, improved, lost). Conclusions: Changes in a thoracic complete (ASIA A) SCI patient ASIA examination as measured through sensory modalities (PP/LT) are fairly uncommon. The overall examination had only 1-2 level variability across patients, indicating minimal change in the sensory exam over the follow-up period. Stability in the ASIA examination as measured through sensory modalities has thus been demonstrated over time, making it an excellent tool to monitor changes in neurologic function

Neurologic improvement after thoracic, thoracolumbar, and lumbar spinal cord (conus medullaris) injuries

Study Design. Retrospective. Objective. With approximately 10,000 new spinal cord injury (SCI) patients in the United States each year, predicting public health outcomes is an important public health concern. Combining all regions of the spine in SCI trials may be misleading if the lumbar and sacral regions (conus) have a neurologic improvement at different rates than the thoracic or thoracolumbar spinal cord. Summary of Background Data. Over a 10-year period between January 1995 to 2005, 1746 consecutive spinal injured patients were seen, evaluated, and treated through a level 1 trauma referral center. A retrospective analysis was performed on 150 patients meeting the criteria of T4 to S5 injury, excluding gunshot wounds. One-year follow-up data were available on 95 of these patients. Methods. Contingency table analyses (chi-squared statistics) and multivariate logistic regression. Variables of interest included level of injury, initial American Spinal Injury Association (ASIA), age, race, and etiology. Results. A total of 92.9% of lumbar (conus) patients neurologically improved one ASIA level or more compared with 22.4% of thoracic or thoracolumbar spinal cord-injured patients. Only 7.7% of ASIA A patients showed neurologic improvement, compared with 95.2% of ASIA D patients; ASIA B patients demonstrated a 66.7% improvement rate, whereas ASIA C had a 84.6% improvement rate. When the two effects were considered jointly in a multivariate analysis, ASIA A and thoracic/thoracolumbar patients had only a 4.1% rate of improvement, compared with 96% for lumbar (conus) and incomplete patients (ASIA B-D) and 66.7% to 72.2% for the rest of the patients. All of these relationships were significant to P \u3c 0.001 (chi-square test). There was no link to age or gender, and race and etiology were secondary to region and severity of injury. Conclusion. Thoracic (T4-T9) SCIs have the least potential for neurologic improvement. Thoracolumbar (T10-T12) and lumbar (conus) spinal cord have a greater neurologic improvement rate, which might be related to a greater proportion of lower motor neurons. Thus, defining the exact region of injury and potential for neurologic improvement should be considered in future clinical trial design. Combining all anatomic regions of the spine in SCI trials may be misleading if different regions have neurologic improvement at different rates. Over a ten-year period, 95 complete thoracic/thoracolumbar SCI patients had only a 4.1% rate of neurologic improvement, compared with 96.0% for incomplete lumbar (conus) patients and 66.7% to 72.2% for all others

Endovascular Neurosurgery: A History of Electricity, Balloons, Wires and Glue

Physicians may have first known what an aneurysm was as far back as the 14th Century BC in Egypt1, but by the early 19th century they were still trying to find satisfactory options for treating large or surgically inaccessible aneurysms.4,5 One of the techniques being considered was inserting a needle to provoke formation of a clot that would close off the aneurysm. The proof that this technique could work was discovered by C. H. Moore in 1864, during an autopsy of a gunshot victim. The bullet, lodged in the ascending aorta, was embedded in fibrin. Based on this, Moore speculated that a wire could be introduced into the body through a small wound, but then passed up to the aneurysm where it would coil and attract fibrin to block the aneurysm. Moore used 26 yards of coil to treat a thoracic aorta aneurysm; the patient died of sepsis, but the aneurysm had decreased in pulsation and size before that, and autopsy confirmed that the coils had promoted fibrin clotting as predicted. Later efforts trying a variety of materials, ranging from iron wire to gold-plated watch springs, also had poor outcomes. Attempts using electrical current to provoke clots during this period did not produce a consistent benefit either.5,

Jewell Osterholm: Sharing Fifty Years of Insight

Jewell L. Osterholm was appointed Professor and Chairman of the Department of Neurosurgery in 1974, and left the Chairmanship in 1994. Recently, he gave a series of workshops on performing neurological examinations. These workshops are being archived on DVD so future residents can benefit from Dr. Osterholm’s training. The emphasis is on interviewing and observing the patient; the only specialized devices used are the stethoscope and the reflex hamme

Estimation Of The Electrical Parameters Of Spinal Motoneurons Using Impedance Measurements

Electrical parameters of spinal motoneurons were estimated by optimizing the parameters of motoneuron models to match experimentally determined impedance functions with those of the models. The model was described by soma area, somatic and dendritic membrane resistivities, and the diameter of an equivalent dendritic cable having a standard profile. The impedance functions of motoneurons and optimized models usually differed (rms error) by \u3c2% of input resistance. Consistent estimates for most parameters were obtained from repeated impedance determinations in individual motoneurons; estimates of dendritic resistivity were most variable. The few cells that could not be fit well had reduced impedance phase lag consistent with dendritic penetrations. Most fits were improved by inclusion of a voltage-dependent conductance G v with time constant Ï„v. A uniformly distributed Gv with Ï„v \u3e5 ms provided a better fit for most cells. The magnitude of this conductance decreased with depolarization. Impedance functions of other cells were adequately fit by a passive model or by a model with a somatic Gv and \u3c5 ms. Most of these neurons (7/8) had resting potentials positive to -60 mV. The electrotonic parameters Ï, Ï„, and L, estimated from model parameters, were consistent with published distributions. Most motoneuron parameters obtained in somatic shunt and sigmoidal models were well correlated, and parameters were moderately affected by changes in dendritic profile. These results demonstrate the utility and limitations of impedance measurements for estimating motoneuron parameters and suggest that voltage-dependent conductances are a substantial component of resting electrical properties