Association of serum levels of aggrecan ARGS,NITEGE fragments and radiologic knee osteoarthritis in Tunisian patients

ObjectivesProteolytic degradation of aggrecan is a hallmark of the pathology of osteoarthritis. The aim of this study was to develop enzyme-linked immunosorbent assay (ELISA) to quantify the serum levels of specific aggrecan fragments generated by aggrecanases-mediated cleavage. We investigated the relationships between these two aggrecan degradations fragments and urinary CTX-II levels.MethodsThe competitive ELISAs employ a polyclonal antibody raised against the aggrecan fragments containing two neoepitopes NITEGE³⁷³ and ³⁷⁴ARGSVI. We measured serum levels of ARGSV and NITEGE in 125 women with knee osteoarthritis (mean ± SD age of 53.6 ± 7.6 years, mean ± SD disease duration of 3.6 ± 3.8 years), and 57 women age-matched controls.ResultsAggrecan neoepitopes assays showed an intra- and inter-assay imprecision (CV) lower than 20% for both tests and good linearity. Median serum ARGSVI (by 18%; P = 0.002), and NITEGE (36.4%; P < 0.001) levels were significantly decreased in patients with knee osteoarthritis compared with controls. Minimal joint space width was negatively correlated with ARGSVI (r = –0.368, P = 0.04) and NITEGE (r = –0.274, P = 0.038) in knee osteoarthritis patients. Median urinary CTX-II levels were significantly increased by 39.5% (P = 0.001) in knee OA patients compared with controls.ConclusionMarkers of degradation aggrecan were analyzed for the first time in an African osteoarthritis population. These markers can be used to monitor aggrecanase activity in human joint disease. Their combination with CTX-II can improve clinical investigation of patients with osteoarthritis patients.     

Positron-emission tomography imaging of early events after transplantation of islets of Langerhans

The aim of our study was to assess cell trafficking and early events after intraportal islet transplantation. Sprague-Dawley rat islets were incubated for various times, with various concentrations of 2-[F]fluoro-2deoxy-D-glucose (FDG), and in presence of various glucose concentrations. FDG-labeled syngeneic islets or FDG alone were injected in rats. Radioactivity was measured in the liver and in various organs by positron-emission tomography for 6 hours. FDG uptake increased with incubation time or FDG concentration and decreased in presence of glucose. In vivo, all islets implanted in the liver, with an uptake 4.4 times higher than controls (44.2% vs. 10.1%, P=0.02). Radioactivity in the liver decreased at the same rate after injection of labeled-islets and FDG alone. Ex vivo labeling of islets and imaging of posttransplant early events were feasible. Islets engrafted exclusively in the liver. No islet loss could be demonstrated 6 hours after transplantation.     

Rotational instability of the knee: internal tibial rotation under a simulated pivot shift test

Introduction  Recently, several publications investigated the rotational instability of the human knee joint under pivot shift examinations and reported the internal tibial rotation as measurement for instrumented knee laxity measurements. We hypothesize that ACL deficiency leads to increased internal tibial rotation under a simulated pivot shift test. Furthermore, it was hypothesized that anatomic single bundle ACL reconstruction significantly reduces the internal tibial rotation under a simulated pivot shift test when compared to the ACL-deficient knee. Methods  In seven human cadaveric knees, the kinematics of the intact knee, ACL-deficient knee, and anatomic single bundle ACL reconstructed knee were determined in response to a 134 N anterior tibial load and a combined rotatory load of 10 N m valgus and 4 N m internal tibial rotation using a robotic/UFS testing system. Statistical analyses were performed using a two-way ANOVA test. Results  Single bundle ACL reconstruction reduced the anterior tibial translation under a simulated KT-1000 test significantly compared to the ACL-deficient knee (P < 0.05). After reconstruction, there was a statistical significant difference to the intact knee at 30° of knee flexion. Under a simulated pivot shift test, anatomic single bundle ACL reconstruction could restore the intact knee kinematics. Internal tibial rotation under a simulated pivot shift showed no significant difference in the ACL-intact, ACL-deficient and ACL-reconstructed knee. Conclusion  In conclusion, ACL deficiency does not increase the internal tibial rotation under a simulated pivot shift test. For objective measurements of the rotational instability of the knee using instrumented knee laxity devices under pivot shift mechanisms, the anterior tibial translation should be rather evaluated than the internal tibial rotation. This study was supported in part by a grant of the German Speaking Association of Arthroscopy (AGA).     

Postoperative analgesia and functional recovery after total-knee replacement: comparison of a continuous posterior lumbar plexus (psoas compartment) block, a continuous femoral nerve block, and the combination of a continuous femoral and sciatic nerve block

BACKGROUND AND OBJECTIVES: Continuous femoral nerve block is a well-accepted technique for regional analgesia after total-knee replacement. However, many patients still experience considerable pain at the popliteal space and at the medial aspect of the knee. The goal of this study is to evaluate whether a psoas compartment catheter provides better postoperative analgesia than a femoral nerve catheter does and whether it is as effective as the combination of a femoral and a sciatic nerve catheter and, thus, improves functional outcome. METHODS: Ninety patients who underwent total-knee replacement under standardized general anesthesia participated in this prospective randomized study. Group FEM received a continuous femoral nerve block, group FEM/SCI received a combination of a femoral and a sciatic continuous nerve block, and group PSOAS received a continuous psoas compartment block. Patient-controlled analgesia with piritramide was available for 48 hours. Maximal bending and extending of the knee and walking distance was assessed during the first 7 days. A standardized telephone survey was conducted after 9 to 12 months to evaluate residual pain and functional outcome. RESULTS: Postoperative opioid consumption during 48 hours was significantly less in the FEM/SCI group (median: 18 mg; 25th/75th percentile: 6/40) compared with the FEM group (49 mg; 25/66) and the PSOAS group (44 mg; 30/62) (P =.002). Postoperative pain scores were not different, and no differences occurred with respect to short-term or long-term functional outcome. CONCLUSION: The FEM/SCI catheter is superior to FEM and PSOAS catheter with respect to reduced analgesic requirements after total-knee replacement, but functional outcome does not differ with those 3 continuous regional analgesia techniques.     

Posttraumatic stress disorder symptoms among low-income, African American women with a history of intimate partner violence and suicidal behaviors: self-esteem, social support, and religious coping

There is a dearth of research on risk/protective factors for posttraumatic stress disorder (PTSD) among low-income African American women with a history of intimate partner violence (IPV), presenting for suicidal behavior or routine medical care in a large, urban hospital. We examined self-esteem, social support, and religious coping as mediators between experiences of child maltreatment (CM) and IPV and symptoms of PTSD in a sample (N = 134) of low-income African American women. Instruments used included the Index of Spouse Abuse, the Childhood Trauma Questionnaire, the Taylor Self-Esteem Inventory, the Multidimensional Profile of Social Support, the Brief Religious Coping Activities Scale, and the Davidson Trauma Scale. Both CM and IPV related positively to PTSD symptoms. Risk and resilience individual difference factors accounted for 18% of the variance in PTSD symptoms over and above IPV and CM, with self-esteem and negative religious coping making unique contributions. Both variables mediated the abuse-PTSD symptom link. In addition, we tested an alternate model in which PTSD symptoms mediated the relationship between abuse and both self-esteem and negative religious coping.     

Cardiac channelopathy causing sudden death as revealed by molecular autopsy

Background

Mutations in cardiac ion channel genes have been identified to cause sudden unexplained deaths (SUD), and polymorphisms have also been suggested to be risk factors. Therefore, postmortem genetic testing has become an important tool in elucidating the cause of death.

Methods and results

In a sudden death case, a LQT-3-associated mutation (Il768V) in the cardiac sodium channel gene SCN5A was detected beside the common polymorphism H558R which is known to mitigate the effect of mutations in the gene. Both sequence variations were heterozygous. Large number of intervening base pairs make it impossible to identify whether they were located in cis or trans. Functional consequences of both variants were characterized after expressing different cRNAs in Xenopus oocytes by voltage clamp measurements. Western blot analysis indicates that the cis configuration of both variants may lead to a null allele. Since the woman had received an injection of Ultracain®, the potential effect of this drug was tested. In a trans configuration of both variants, the mutant channel exhibited an increase susceptibility of at least 10% for blocking with the drug articaine. Another novel finding is that the midpoint of activation in the case of the mutant channel is leftward shifted of at least ?10 mV.

Conclusion

The results of the study suggest that postmortem molecular screening is an important tool to elucidate the cause of SUD and that the administration of a drug and a functional interaction between polymorphisms and ion channel mutations may trigger the risk for sudden death.     

Development of a computer assisted system aimed at RFA liver surgery

Radio frequency ablation (RFA) is a minimally invasive treatment for either hepatocellular carcinoma or metastasis liver carcinoma. In order to resect large lesions, the surgeon has to perform multiple time-consuming destruction cycles and reposition the RFA needle for each of them. The critical step in handling a successful ablation and preventing local recurrence is the correct positioning of the needle. For small tumors, the surgeon places the middle of the active needle tip in the center of the tumor under intra-operative ultrasound guidance. When one application is not enough to cover the entire tumor, the surgeon needs to repeat the treatment after repositioning of the needle, but US guidance is obstructed by the opacity stemming from the first RFA application. In this case the surgeon can only rely on anatomical knowledge and the repositioning of the RFA needle becomes a subjective task limiting the treatment accuracy. We have developed a computer assisted surgery guidance application for this repositioning procedure. Our software application handles the complete process from preoperative image analysis to tool tracking in the operating room. Our framework is mostly used for this RFA procedure, but is also suitable for any other medical or surgery application.     

Effect of apelin on glomerular hemodynamic function in the rat kidney

Apelin is a vasoactive peptide identified as the endogenous ligand of an orphan G protein-coupled receptor called APJ. Apelin and its receptor have been found in the brain and the cardiovascular system. Here we show that the apelin receptor mRNA is highly expressed in the glomeruli while its level of expression is lower in all nephron segments including collecting ducts that express vasopressin V2 receptors. Intravenous injection of apelin 17 into lactating rats induced a significant diuresis. Apelin receptor mRNA was also found in endothelial and vascular smooth muscle cells of glomerular arterioles. Apelin administration caused vasorelaxation of angiotensin II-preconstricted efferent and afferent arterioles as shown by an increase in their diameter. Activation of endothelial apelin receptors caused release of nitric oxide which inhibited angiotensin II-induced rise in intracellular calcium. In addition, it appears that apelin had a direct receptor-mediated vasoconstrictive effect on vascular smooth muscle. These results show that apelin has complex effects on the pre- and post glomerular microvasculature regulating renal hemodynamics. Its role on tubular function (if any) remains to be determined.