bluuebunny/crossref_metadata_2025_split huggingface dataset:
Medication-overuse headache and opioid-induced hyperalgesia: A review of mechanisms, a neuroimmune hypothesis and a novel approach to treatment
Authors: Johnson Jacinta L , Hutchinson Mark R , Williams Desmond B , Rolan Paul 
Published: November 2012

Introduction Patients with chronic headache who consume large amounts of analgesics are often encountered in clinical practice. Excessive intake of analgesics is now considered to be a cause, rather than simply a consequence, of frequent headaches, and as such the diagnosis “medication-overuse headache” (MOH) has been formulated. Despite the prevalence and clinical impact of MOH, the pathophysiology behind this disorder remains unclear and specific mechanism-based treatment options are lacking. Discussion Although most acute headache treatments have been alleged to cause MOH, here we conclude from the literature that opioids are a particularly problematic drug class consistently associated with worsening headache. MOH may not be a single entity, as each class of drug implicated may cause MOH via a different mechanism. Recent evidence indicates that chronic opioid administration may exacerbate pain in the long term by activating toll-like receptor-4 on glial cells, resulting in a pro-inflammatory state that manifests clinically as increased pain. Thus, from the available evidence it seems opioid-overuse headache is a phenomenon similar to opioid-induced hyperalgesia, which derives from a cumulative interaction between central sensitisation, due to repeated activation of nociceptive pathways by recurrent headaches, and pain facilitation due to glial activation. Conclusion Treatment strategies directed at inhibiting glial activation may be of benefit alongside medication withdrawal in the management of MOH.
The Effect of Initial Graft Tension After Anterior Cruciate Ligament Reconstruction
Authors: Fleming Braden C. , Fadale Paul D. , Hulstyn Michael J. , Shalvoy Robert M. , Oksendahl Heidi L. , Badger Gary J. , Tung Glenn A. 
Published: November 2012

Background: The initial graft tension applied at the time of anterior cruciate ligament (ACL) reconstruction alters joint contact and may influence cartilage health. The objective was to compare outcomes between 2 commonly used “laxity-based” initial graft tension protocols. Hypotheses: (1) The high-tension group would have less knee laxity, improved clinical and patient-oriented outcomes, and less cartilage damage than would the low-tension group after 36 months of healing. (2) The outcomes of the high-tension group would be equivalent to those of a matched control group. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Ninety patients with isolated unilateral ACL injuries were randomized to undergo ACL reconstruction using 1 of 2 initial graft tension protocols: (1) autografts tensioned to restore normal anterior-posterior (AP) laxity at the time of surgery (ie, low tension; n = 46) and (2) autografts tensioned to overconstrain AP laxity by 2 mm (ie, high tension; n = 44). Sixty matched healthy patients formed the control group. Outcomes were assessed preoperatively, intraoperatively, and at 6, 12, and 36 months after surgery. Results: No significant differences were found between the 2 initial graft tension protocols for any of the outcome measures at 36 months. However, there were differences when comparing the 2 treatment groups to the control group. On average, AP laxity was 2 mm greater in the ACL-reconstructed groups than in the control group ( P < .007). International Knee Documentation Committee (IKDC) knee evaluation scores, peak isokinetic knee extension torques, and 4 of 5 Knee Osteoarthritis Outcome Scores (KOOS) were significantly worse than the control group ( P < .001, P < .027, and P < .05, respectively). Short Form–36 Health Survey (SF-36) scores and reinjury rates were similar between groups at 36 months. Although there were significant changes in radiography and magnetic resonance imaging present in the ACL-reconstructed knees of both treatment groups, the magnitude was relatively small and likely clinically insignificant at 36 months. Conclusion: Both laxity-based initial graft tension protocols produced similar outcomes without fully restoring joint function or patient-oriented outcomes (KOOS) when compared with the control group. There was minimal evidence of cartilage damage 36 months after surgery.
Radiographic Landmarks for Tunnel Positioning in Posterior Cruciate Ligament Reconstructions
Authors: Johannsen Adam M. , Anderson Colin J. , Wijdicks Coen A. , Engebretsen Lars , LaPrade Robert F. 
Published: November 2012

Background: Consistent radiographic guidelines for tunnel placement in single- or double-bundle posterior cruciate ligament (PCL) reconstructions are not well defined. Quantitative guidelines reporting the location of the individual PCL bundle attachments would aid in intraoperative tunnel placement and postoperative assessment of a PCL reconstruction. Hypothesis: Consistent and reproducible measurements in relation to radiographic landmarks for the entire PCL and its individual bundle attachments are achievable. Study Design: Controlled laboratory study. Methods: The femoral and tibial PCL bundle attachment centers of 20 nonpaired fresh-frozen cadaveric knees were labeled using radio-opaque spheres and the attachment areas were labeled using barium sulfate. Anteroposterior (AP) and lateral radiographs of the femur and tibia were obtained, and measurements of the distances between the PCL bundle centers and landmarks were acquired. Results: On the AP femur view, the anterolateral bundle (ALB) and posteromedial bundle (PMB) centers were 34.1 ± 3.0 mm and 29.2 ± 3.0 mm lateral to the most medial border of the medial femoral condyle, respectively. The lateral femur images revealed that the ALB center was 17.4 ± 1.7 mm and the PMB center was 23.9 ± 2.7 mm posteroproximal to a line perpendicular to the Blumensaat line that intersected the anterior margin of the medial femoral condyle cortex. Anteroposterior tibia images revealed that the ALB and PMB centers were located 0.2 ± 2.1 mm proximal and 4.9 ± 2.9 mm distal to the proximal joint line, respectively. The PCL attachment center was 1.6 ± 2.5 mm distal to the proximal joint line. On the lateral tibia view, the ALB center was 8.4 ± 1.8 mm, the PCL attachment center was 5.5 ± 1.7 mm, and the PMB center was 2.5 ± 1.5 mm superior to the champagne glass drop-off of the posterior tibia. Conclusion: Radiographic measurements from several clinically relevant views of the femur and tibia were reproducible with regard to the anatomic locations of the ALB and PMB centers. The measurements from the lateral femur and tibia views provided the most clinically pertinent radiographic measurements intraoperatively. Clinical Relevance: This study established a set of clinically relevant radiographic guidelines for anatomic reconstruction of the PCL. The parameters set forth in this study can be used in both the intraoperative and postoperative settings for both single- and double-bundle PCL reconstructions.
Anatomic Femoral Tunnels in Posterior Cruciate Ligament Reconstruction
Authors: Tompkins Marc , Keller Thomas C. , Milewski Matthew D. , Gaskin Cree M. , Brockmeier Stephen F. , Hart Joseph M. , Miller Mark D. 
Published: November 2012

Background: During posterior cruciate ligament (PCL) reconstruction, the placement and orientation of the femoral tunnel is critical to postoperative PCL function. Purpose: To compare the ability of outside-in (OI) versus inside-out (IO) femoral tunnel drilling in placing the femoral tunnel aperture within the anatomic femoral footprint of the PCL, and to evaluate the orientation of the tunnels within the medial femoral condyle. Study Design: Controlled laboratory study. Methods: Ten matched pairs of cadaver knees were randomized such that within each pair, 1 knee underwent arthroscopic OI drilling and the other underwent IO drilling. All knees underwent computed tomography (CT) both pre- and postoperatively with a technique optimized for ligament evaluation (80 keV with maximum mAs). Commercially available third-party software was used to fuse the pre- and postoperative CT scans, allowing comparison of the PCL footprint to the drilled tunnel. The percentage of tunnel aperture contained within the native footprint, as well as the distance from the center of the tunnel aperture to the center of the footprint, were measured. In addition, the orientation of the tunnels in the coronal and axial planes was evaluated. Results: The OI technique placed 70.4% ± 23.7% of the tunnel within the native femoral footprint compared with 79.8% ± 16.7% for the IO technique ( P = .32). The OI technique placed the center of the femoral tunnel 4.9 ± 2.2 mm from the center of the native footprint compared to 5.3 ± 2.0 mm for the IO technique ( P = .65). The femoral tunnel angle in the coronal plane was 21.0° ± 9.9° for the OI technique and 37.0° ± 10.3° for the IO technique ( P = .002). The tunnel angle in the axial plane was 27.3° ± 4.8° for the OI technique and 39.1° ± 11.5° for the IO technique ( P = .01). Conclusion: This study demonstrates no difference in the ability of the OI and IO techniques to place the femoral tunnel within the PCL femoral footprint during PCL reconstruction. With the technique parameters used in this study, the IO technique created femoral tunnels with a more vertical and anterior orientation than the OI technique. Clinical Relevance: Either technique can be used to place the femoral tunnel within the anatomic footprint. Consideration should be given to tunnel orientation following each technique, and what effect it has on graft bending angles, as these characteristics may affect graft strain and, ultimately, graft failure. In this regard, the IO technique likely produces gentler graft bending angles.
Sensitivity and Specificity of the Online Version of ImPACT in High School and Collegiate Athletes
Authors: Schatz Philip , Sandel Natalie 
Published: November 2012

Background: The utility of postconcussion neurocognitive testing versus symptom data has been debated. The sensitivity of the desktop version of the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) tool has been documented, but psychometric properties of the recently released online version of ImPACT have yet to be fully established. Purpose: To document the sensitivity of the online ImPACT version in samples of (1) symptomatic concussed (high school and collegiate) athletes, and (2) asymptomatic concussed (high school and collegiate) athletes suspected of hiding their concussions. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 81 athletes observed to sustain a concussion by a certified athletic trainer or team physician, a finding that was confirmed with reported postconcussion symptoms, completed the ImPACT test within 3 days of injury. Data were compared with an independent sample of 81 athletes who completed preseason baseline cognitive assessments using ImPACT and who were matched (with concussed athletes) on the basis of sex, age, sport, concussion history, and absence of attention deficit hyperactivity disorder and learning disability. An independent group of 37 athletes who were also observed to sustain a concussion completed ImPACT within 3 days of injury. These athletes reported no postconcussion symptoms but were noted for suspected invalid response patterns on ImPACT (Impulse Control index >30 and Verbal Memory index <69%). The subscale data from the assessments (excluding those contributing to the aforementioned indices) were compared with a matched sample of 37 athletes who completed preseason baseline cognitive assessments in ImPACT (using the same criteria described above). Results: Data from the ImPACT online version yielded 91.4% sensitivity and 69.1% specificity. For asymptomatic athletes suspected of hiding their concussion, data from ImPACT yielded 94.6% sensitivity and 97.3% specificity. Conclusion: The online version of the ImPACT tool is a valid measure of neurocognitive performance at the acute stages of concussion, with high levels of sensitivity and specificity, even when athletes appear to be denying postconcussion symptoms.
Protective Effect of K201 on Isoproterenol-Induced and Ischemic–Reperfusion-Induced Ventricular Arrhythmias in the Rat
Authors: Otani Naoyuki , Matsuda Ryuko , Oda Kazuhiko , Nishino Setsu , Inoue Teruo , Kaneko Noboru 
Published: November 2012

Aim: Ventricular arrhythmia (VA) is a risk for sudden death. Polymorphic ventricular tachycardia (VT) degenerating to ventricular fibrillation occurs subsequent to the prolongation of the QT interval following administration of catecholamines under Ca2+ loading. Fatal VA also occurs in ischemia and ischemic–reperfusion. We compared the suppressive effect of K201 (JTV519), a multiple-channel blocker and cardiac ryanodine receptor-calcium release channel (RyR2) stabilizer, with that of diltiazem, a Ca2+ channel blocker, in 2 studies of isoproterenol-induced (n = 30) and ischemic–reperfusion-induced VAs (n = 38) in rats. Methods: Adult male Wistar rats were administered 12 mg/kg/min calcium chloride (CaCl2) for 20 minutes and then 6 μg/kg/min isoproterenol was infused with CaCl2 for a further 20 minutes. In other rats, the left coronary artery was ligated for 5 minutes followed by reperfusion for 20 minutes. K201 or diltiazem (both 1 mg/kg) was administered before infusion of the isoproterenol or induction of ischemia. Results: After administration of isoproterenol under Ca2+ loading, fatal VA frequently occurred in the vehicle (9 of 10 animals, 90%) and diltiazem (8 of 10, 80%) groups, and K201 significantly suppressed the incidences of arrhythmia and mortality (2 of 10, 20%). In the reperfusion study, the incidence and the time until occurrence of reperfusion-induced VA and mortality were significantly suppressed in the K201 (2 of 15 animals, 13%) and diltiazem (1 of 9 animals, 11%) groups compared to the vehicle group (8 of 14 animals, 57%). Significance: Induction of VA in an experimental model was achieved with a low dose of isoproterenol under Ca2+ loading. K201 markedly suppressed both the isoproterenol-induced and the reperfusion-induced VAs, whereas diltiazem did not suppress the isoproterenol-induced VA. The results suggest that both VAs are related to early after depolarization (EAD) and indicate that K201 has the potential to suppress EAD by stabilizing RyR2 to mediate Ca2+ release from the sarcoplasmic reticulum and acting as a multiple-channel blocker.
Association of all-trans retinoic acid treatment with the renin-angiotensin aldosterone system expression in glomerulosclerosis rats
Authors: Zhou Tian-Biao , Wu Wei-Feng , Qin Yuan-Han , Yin Sheng-Sheng 
Published: November 2012

Background and objective: All-trans retinoic acid (ATRA), a promising therapeutic agent, has been confirmed in animal experiments as playing a protective role against renal diseases. The renin-angiotensin aldosterone system (RAAS) plays a key role in the pathogenesis of renal diseases, and RAAS inhibitors can prevent the progression of kidney diseases. In our previous study, we found that ATRA could play a protective role against glomerulosclerosis (GS) lesions in rats, and its effect was similar to RAAS inhibitors. However, whether ATRA treatment was associated with RAAS expression was not clear. Methods: Six-week-old male Wistar rats were divided into three groups: sham operation group (SHO), glomerulosclerosis model group without treatment (GS) and GS model group treated with ATRA (GA). At the end of 13 weeks, the relevant samples were collected and analyzed. Results: The mRNA and protein expression of angiotensin-converting enzyme 1 (ACE1) in the GS group was notably higher when compared with the SHO group. However, mRNA and protein expression of ACE1 in the ATRA treatment group was markedly down-regulated when compared with the GS group. Angiotensin-converting enzyme 2 (ACE2) expression (mRNA or protein) in the GS group was reduced compared with that in the SHO group, and ATRA markedly increased the mRNA and protein expression of ACE2 compared with the GS group. The levels of protein expression of angiotensin I and angiotensin II were significantly up-regulated in the GS group compared with those in the SHO group, and ATRA reduced their expression in the GA group when compared with the GS group. Conclusion: ATRA is associated with RAAS expression in GS rats, but its detailed mechanism needs to be elucidated by further research.
CD59 deficiency is associated with chronic hemolysis and childhood relapsing immune-mediated polyneuropathy
Authors: Nevo Yoram , Ben-Zeev Bruria , Tabib Adi , Straussberg Rachel , Anikster Yair , Shorer Zamir , Fattal-Valevski Aviva , Ta-Shma Asaf , Aharoni Sharon , Rabie Malcolm , Zenvirt Shamir , Goldshmidt Hanoch , Fellig Yakov , Shaag Avraham , Mevorach Dror , Elpeleg Orly 
Published: November 2012

AbstractCD59 deficiency is a common finding in RBCs and WBCs in patients with chronic hemolysis suffering from paroxysmal nocturnal hemoglobinuria in which the acquired mutation in the PIGA gene leads to membrane loss of glycosylphosphatidylinositol-anchored membrane proteins, including CD59. The objective of the present study was to elucidate the molecular basis of childhood familial chronic Coombs-negative hemolysis and relapsing polyneuropathy presenting as chronic inflammatory demyelinating polyradiculoneuropathy in infants of North-African Jewish origin from 4 unrelated families. A founder mutation was searched for using homozygosity mapping followed by exome sequencing. The expression of CD59, CD55, and CD14 was examined in blood cells by flow cytometry followed by Western blot of the CD59 protein. A homozygous missense mutation, p.Cys89Tyr in CD59, was identified in all patients. The mutation segregated with the disease in the families and had a carrier rate of 1:66 among Jewish subjects of North-African origin. The mutated protein was present in the patients' cells in reduced amounts and was undetectable on the membrane surface. Based on the results of the present study, we conclude that the Cys89Tyr mutation in CD59 is associated with a failure of proper localization of the CD59 protein in the cell surface. This mutation is manifested clinically in infancy by chronic hemolysis and relapsing peripheral demyelinating disease.
Histone demethylase GASC1 - a potential prognostic and predictive marker in invasive breast cancer
Authors: Berdel Bozena , Nieminen Kaisa , Soini Ylermi , Tengström Maria , Malinen Marjo , Kosma Veli-Matti , Palvimo Jorma J , Mannermaa Arto 
Published: November 2012

AbstractBackgroundThe histone demethylase GASC1 (JMJD2C) is an epigenetic factor suspected of involvement in development of different cancers, including breast cancer. It is thought to be overexpressed in the more aggressive breast cancer types based on mRNA expression studies on cell lines and meta analysis of human breast cancer sets. This study aimed to evaluate the prognostic and predictive value of GASC1 for women with invasive breast cancer.MethodsAll the 355 cases were selected from a cohort enrolled in the Kuopio Breast Cancer Project between April 1990 and December 1995. The expression of GASC1 was studied by immunohistochemistry (IHC) on tissue microarrays. Additionally relativeGASC1mRNA expression was measured from available 57 cases.ResultsIn our material, 56% of the cases were GASC1 negative and 44% positive in IHC staining. Women with GASC1 negative tumors had two years shorter breast cancer specific survival and time to relapse than the women with GASC1 positive tumors (p=0.017 and p=0.034 respectively). The majority of GASC1 negative tumors were ductal cases (72%) of higher histological grade (84% of grade II and III altogether). When we evaluated estrogen receptor negative and progesterone receptor negative cases separately, there was 2 times more GASC1 negative than GASC1 positive tumors in each group (chi2, p= 0.033 and 0.001 respectively). In the HER2 positive cases, there was 3 times more GASC1 negative cases than GASC1 positives (chi2, p= 0.029). Patients treated with radiotherapy (n=206) and hormonal treatment (n=62) had better breast cancer specific survival, when they were GASC1 positive (Cox regression: HR=0.49, p=0.007 and HR=0.33, p=0.015, respectively). The expression ofGASC1mRNA was in agreement with the protein analysis.ConclusionsThis study indicates that the GASC1 is both a prognostic and a predictive factor for women with invasive breast cancer. GASC1 negativity is associated with tumors of more aggressive histopathological types (ductal type, grade II and III, ER negative, PR negative). Patients with GASC1 positive tumors have better breast cancer specific survival and respond better to radiotherapy and hormonal treatment.
Total hip arthroplasty: leg length inequality impairs functional outcomes and patient satisfaction
Authors: Röder Christoph , Vogel Raphael , Burri Lukas , Dietrich Daniel , Staub Lukas P 
Published: November 2012

AbstractBackgroundLeg length inequality (LLI) was identified as a problem of total hip arthroplasty soon after its introduction. Leg lengthening is the most common form of LLI. Possible consequences are limping, neuronal dysfunction and aseptic component loosening. LLI can result in an increased strain both on the contralateral hip joint and on the abductor muscles. We assessed the influence of leg lengthening and shortening on walking capacity, hip pain, limping and patient satisfaction at 2-year follow-up.Methods478 cases with postoperative lengthening and 275 with shortening were identified, and matched with three controls each. Rigorous adjustment for potential differences in baseline patient characteristics was performed by propensity-score matching of covariates. The arbitrarily defined desired outcomes were a walking capacity >60 minutes, no hip pain, no limping, and excellent patient satisfaction. Differences in not achieving the desired outcomes between the groups were expressed as odds ratios.ResultsIn the lengthened case group, the odds ratio for not being able to walk for an hour was 1.70 (95% CI 1.28-2.26) for cases compared to controls, and the odds ratio for having hip pain at follow-up was 1.13 (95% CI 0.78-1.64). The odds ratio for limping was 2.08 (95% CI 1.55-2.80). The odds ratio for not achieving excellent patient satisfaction was 1.67 (95% CI 1.23-2.28). In the shortening case group, the odds ratio for not being able to walk for an hour was 1.23 (95% CI 0.84-1.81), and the odds ratio for having hip pain at follow-up was 1.60 (95% CI 1.05-2.44). The odds ratio for limping for cases was 2.61 (95% CI 1.78-3.21). The odds ratio for not achieving excellent patient satisfaction was 2.15 (95% CI 1.44-3.21).ConclusionsWalking capacity, limping and patient satisfaction were all significantly associated with leg lengthening, whereas pain alleviation was not. In contrast, hip pain, limping and patient satisfaction were all significantly associated with leg shortening, whereas walking capacity was not.