Evaluating rotational kinematics of the knee in ACL reconstructed patients using 3.0 Tesla magnetic resonance imaging

IntroductionInjury to the anterior cruciate ligament (ACL) is common. While prior studies have shown that surgical reconstruction of the ACL can restore anterior–posterior kinematics, ACL-injured and reconstructed knees have been shown to have significant differences in tibial rotation when compared to uninjured knees. Our laboratory has developed an MR compatible rotational loading device to objectively quantify rotational stability of the knee following ACL injuries and reconstructions. Previous work from our group demonstrated a significant increase in total tibial rotation following ACL injuries. The current study is a prospective study on the same cohort of patients who have now undergone ACL reconstruction. We hypothesize that ACL reconstructed knees will have less tibial rotation relative to the pre-operative ACL deficient condition. We also hypothesize that ACL reconstructed knees will have greater rotational laxity when compared to healthy contralateral knees.MethodsPatients. Six of the ACL injured patients from our initial study who had subsequently undergone ACL reconstruction were evaluated 8.1 ± 2.9  months after surgery. All patients underwent single-bundle ACL reconstruction using anteromedial portal drilling of the femoral tunnel with identical post-operative regimens.Magnetic Resonance (MR) Imaging. Patients were placed in a supine position in the MR scanner on a custom-built loading device. Once secured in the scanner bore, an internal/external torque was applied to the foot. The tibiae were semi-automatically segmented with in-house software. Tibial rotation comparisons were made within subjects (i.e. side-to-side comparison between reconstructed and contralateral knees) and differences were explored using paired sample t-tests with significance set at p = 0.05.ResultsRegarding tibial rotation, in the ACL deficient state, these patients experienced an average of 5.9 ± 4.1° difference in tibial rotation between their ACL deficient and contralateral knees. However, there was a ?0.2 ± 6.1° difference in tibial rotation of the ACL reconstructed knee when compared to the contralateral uninjured knee. Regarding tibial translation, ACL deficient patients showed a difference of 0.75 ± 1.4mm of anterior tibial translation between injured and healthy knees. After ACL reconstruction, there was a 0.2 ± 1.1mm difference in coupled anterior tibial translation of the ACL reconstructed knee compared to the contralateral knee. No significant differences in contact area between the two time points could be discerned.DiscussionThe objective of our study was to assess the rotational laxity present in ACL reconstructed knees using a previously validated MRI-compatible rotational loading device. Our study demonstrated that ACL reconstruction can restore rotational laxity under load. This may speak to the benefit of an anteromedial drilling technique, which allows for a more horizontal and anatomically appropriate graft position.     

Comparative evaluation of torasemide and furosemide on rats with streptozotocin-induced diabetic nephropathy

Nephropathy is one of the complications of diabetes mellitus in human and experimental animals. There are various pathological renal remodeling processes leading to diabetic nephropathy because of the chronic hyperglycemia during diabetes mellitus. Various reports suggest the involvement of oxidative stress, inflammation and fibrosis during this progression. As antihypertensive drugs are reported to provide renoprotection in various animal models and clinical studies, we have carried out this study to identify the effect of torasemide, a loop diuretic, against streptozotocin-induced diabetic nephropathy and compare with furosemide. Here we have performed the measurement of blood and urine parameters and renal protein expression levels for measuring the disease severity in streptozotocin-induced diabetic rats treated torasemide or furosemide and compared with the vehicle treated rats. Furosemide treatment significantly increased the urinary protein excretion when compared with the normal rats. Torasemide treatment has reduced the expression of mineralocorticoid receptor and oxidative stress marker p67phox levels with improved mRNA levels of heme oxygenase-1 in the kidneys. In addition, torasemide treated diabetic rats showed significantly reduced expression of renal fibrosis related proteins when compared with the vehicle treated diabetic rats. Although furosemide treatment has produced improvement, its effects are comparably less than that of torasemide. Thus with the present results, we can suggest that torasemide treatment can improve the diabetic kidney disease in this rat model and which is superior to furosemide against renal fibrotic remodeling.     

A regio- and stereoselective 1,3-dipolar cycloaddition for the synthesis of novel spiro-pyrrolothiazolyloxindoles and their antitubercular evaluation

The 1,3-dipolar cycloaddition of azomethine ylides derived from substituted isatins and 1,3-thiazolane-4-carboxylic acid to a series of 2-(arylmethylene)-2,3-dihydro-1H-inden-1-ones afforded twenty nine novel spiro-pyrrolothiazolyloxindoles regio- and stereoselectively in moderate yields. These compounds were screened for their in vitro activity against Mycobacterium tuberculosis H37Rv (MTB) using agar dilution method. Among 29 compounds screened, spiro[5.3']-5'-nitrooxindole-spiro-[6.3″]-2,3-dihydro-1H-inden-1″-one-7-(2,3-dichlorophenyl)tetrahydro-1H-pyrrolo[1,2-c][1,3]thiazole, was found to be the most active compound with MIC of 2.8?μM against MTB, being 1.67 and 2.70 times more active than ciprofloxacin and ethambutol respectively.     

Computer-aided methods for assessing lower limb deformities in orthopaedic surgery planning

Accurate, simple, and quick measurement of anatomical deformities at preoperative stage is clinically important for decision making in surgery planning. The deformities include excessive torsional, angular, and curvature deformation. This paper presents computer-aided methods for automatically measuring anatomical deformities of long bones of the lower limb. A three-dimensional bone model reconstructed from CT scan data of the patient is used as input. Anatomical landmarks on femur and tibia bone models are automatically identified using geometric algorithms. Medial axes of femur and tibia bones, and anatomical landmarks are used to generate functional and reference axes. These methods have been implemented in a software program and tested on a set of CT scan data. Overall, the performance of the computerized methodology was better or similar to the manual method and its results were reproducible.     

The tumor suppressor activity of SOCS-1

SOCS-1 is an inducible SH2-containing inhibitor of Jak kinases and as such can potently suppress cytokine signaling. SOCS-1 deficient mice die within the first three weeks of life from a myeloproliferative disorder driven by excessive interferon signaling. We report here that SOCS-1 inhibits proliferation signals induced by a variety of oncogenes active within the hematopoietic system. Ectopic expression of SOCS-1 abolished proliferation mediated by a constitutively active form of the KIT receptor, TEL-JAK2, and v-ABL, and reduced metastasis from BCR-ABL transformed cells. SOCS-1, however, did not interfere with v-SRC or RASV12 mediated cellular transformation. A mutant form of SOCS-1 unable to bind through its SH2 domain to tyrosine phosphorylated proteins could still inhibit KIT, but not TEL-JAK2, indicating multiple mechanisms for SOCS-1-mediated tumor suppression. We show that the steady state levels of TEL-JAK2 and to a greater extent v-ABL are diminished in the presence of SOCS-1. Lastly, we show that SOCS-1 -/- fibroblasts are more sensitive than wild type fibroblasts to either spontaneous or oncogene-induced transformation. These data suggest that loss-of-function of SOCS-1 may collaborate with a variety of hematopoietic oncogenes to facilitate tumor progression.     

Rapid development of auricular prosthesis using CAD and rapid prototyping technologies

External ear defects can be corrected by surgery, but this may not be feasible for personal or medical reasons. Reconstructive solutions are a good alternative, but rely on the artistry and availability of the anaplastologist. A semi-automated methodology using computer-aided design (CAD) and rapid prototyping (RP) technologies was developed for auricular prosthesis development, and demonstrated in a real-life case. The correct geometry and position of the prosthesis were ensured by stacking the computed tomography scan images of the contralateral normal ear in reverse order, and joining them using a medical modelling software program. The CAD model of the remnant portion of the defective ear was subtracted from the model of the mirrored contralateral ear, using a haptic CAD system, to obtain the final geometry of the prosthesis. Polymer models were fabricated in RP systems, and used for making a corresponding mould. Medical grade silicone rubber of the appropriate colour was packed into the mould to fabricate the final ear prosthesis and fitted to the deficient side of the patient using medical grade adhesive. The computer-aided methodology gave a high level of accuracy in terms of shape, size and position of the prosthesis, and a significantly shorter lead time compared to the conventional (manual) technique.     

Molecular mechanism of nitrogen mustard induced leukocyte(s) chemotaxis

Nitrogen mustard(s) (NM) are the primary chemotherapeutic agents (Chlorambucil, BSO) that are used in treating the B-cell chronic lymphocyte leukemia (B-CLL). It is known that NM imparts oxidative stress by inducing the reactive oxygen species (ROS) and reactive nitrogen species (RNS) production in B-lymphocytes of B-CLL. It is likely that these nitrogen mustards can cause the oxidative stress in the peripheral blood leukocytes (PBL) of B-CLL patients. It is possible that chronic exposure of PBL to NM would induce drug resistance in B-CLL patients. However, the precise molecular mechanism(s) by which NM affect the PBL are not known at present. Here, an effort is made to present plausible mechanisms by which chronic NM exposure could lead to increased PBL chemotaxis and vascular tissue damage in B-CLL patients The clinical implication of this phenomenon is most likely the unwanted organ dysfunction in B-CLL patients. Identification of viable therapeutic targets to attenuate the PBL activation during the NM therapy would be beneficial for the clinical remission of B-CLL.