Extracranial meningioma of the parapharyngeal space: report of a case and review of the literature

Parapharyngeal tumours are frequently encountered in clinical practice and are often difficult to diagnose upon clinical examination due to the anatomic complexity of the region. We report a rare case of extracranial meningioma of the parapharyngeal space in a patient with no history of von Recklinghausen's disease, family history of meningioma or central neurofibromatosis (NF-2). The purpose of this report is to reiterate and emphasize the role of CT and MRI in the diagnosis of parapharyngeal masses, and to describe the characteristic radiological features of extracranial meningiomas.     

Cardiac CT angiography (CTA) and nuclear myocardial perfusion imaging (MPI)-a comparison in detecting significant coronary artery disease

RATIONALE AND OBJECTIVES: Endowed with sufficient diagnostic accuracy, electron beam computed tomography angiography (CTA) is being increasingly used to evaluate coronary arteries. However, data on direct comparisons with nuclear myocardial perfusion studies are limited. In this study, we sought to compare the accuracies of CTA and myocardial perfusion imaging (MPI) for identifying symptomatic patients with hemodynamically significant obstructive coronary artery disease (CAD). MATERIALS AND METHODS: In a single-center study, symptomatic outpatients who were scheduled for cardiac catheterization were prospectively enrolled. Only patients with exertional angina or dyspnea were included. After fulfilling the inclusion criteria, 30 patients were enrolled in the study (mean age 54 +/- 9 years and 70% males). Patients underwent MPI, CTA including coronary artery calcification (CAC) measure, and invasive coronary angiography for evaluation of obstructive coronary artery disease. Significant CAD was defined as >50% left main artery stenosis or >70% stenosis of any other epicardial vessel by invasive angiography. The sensitivities, specificities and predictive values of MPI, CAC, and CTA were analyzed per patient RESULTS: CTA demonstrated significant higher sensitivity than MPI (95% vs. 81%, P < .05). CTA demonstrated significantly higher specificity than both MPI (89% versus 78%, P = .04) and CAC (56%, P = .002). CTA also performed better in a per-vessel analysis (sensitivity 94%, specificity 96%) than both nuclear and CAC. There were no significant differences between the sensitivities and specificities of MPI and CAC. CONCLUSION: CTA accurately detects obstructive CAD in symptomatic patients and may be more accurate than MPI or CAC assessment. Larger studies in a more diverse population are needed.     

Stability-indicating HPTLC method for simultaneous determination of nateglinide and metformin hydrochloride in pharmaceutical dosage form

A stability indicating high performance thin layer chromatography (HPTLC) method was developed and validated for determination of two anti-diabetic drugs, nateglinide and metformin hydrochloride in co-formulations. Study was performed on pre-coated silica gel HPTLC plates using chloroform:ethyl acetate:acetic acid (4:6:0.1 v/v/v) as the mobile phase. A TLC scanner set at 216 nm was used for direct evaluation of the chromatograms in the reflectance/absorbance mode. Method was validated according to ICH guidelines. The correlation coefficients of calibration curves were found to be 0.996 and 0.995 in the concentration range of 200–2400 and 500–3000 ng band⁻¹ for nateglinide and metformin, respectively. The method had an accuracy of 99.72% for nateglinide and 100.08% for metformin hydrochloride. The method had the potential to determine these drugs simultaneously from dosage forms without any interference of the tablets excipients. Nateglinide and metformin hydrochloride were also subjected to acid, base, oxidation, wet, heat and photo-degradation studies. The degradation products obtained were well resolved from the pure drugs with significantly different R_f values. As the method could effectively separate the drugs from its degradation products, it can be used for stability-indicating analysis.     

Selection of replicon variants resistant to ACH-806, a novel hepatitis C virus inhibitor with no cross-resistance to NS3 protease and NS5B polymerase inhibitors

We have discovered a novel class of compounds active against hepatitis C virus (HCV), using a surrogate cellular system, HCV replicon cells. The leading compound in the series, ACH-806 (GS-9132), is a potent and specific inhibitor of HCV. The selection of resistance replicon variants against ACH-806 was performed to map the mutations conferring resistance to ACH-806 and to determine cross-resistance profiles with other classes of HCV inhibitors. Several clones emerged after the addition of ACH-806 to HCV replicon cells at frequencies and durations similar to that observed with NS3 protease inhibitors and NS5B polymerase inhibitors. Phenotypic analyses of these clones revealed that they are resistant to ACH-806 but remain sensitive to other classes of HCV inhibitors. Moreover, no significant change in the susceptibility to ACH-806 was found when the replicon cellular clones resistant to NS3 protease inhibitors and NS5B polymerase inhibitors were examined. Sequencing of the entire coding region of ACH-806-resistant replicon variants yielded several consensus mutations. Reverse genetics identified two single mutations in NS3, a cysteine-to-serine mutation at amino acid 16 and an alanine-to-valine mutation at amino acid 39, that are responsible for the resistance of the replicon variants to ACH-806. Both mutations are located at the N terminus of NS3 where extensive interactions with the central hydrophobic region of NS4A exist. These data provide evidence that ACH-806 inhibits HCV replication by a novel mechanism.     

Quality of motion considerations in numerical analysis of motion restoring implants of the spine

BACKGROUND: Motion restoring implants function in a dynamic environment that encompasses the full range of spinal kinematics. Accurate assessment of the in situ performance of these devices using numerical techniques requires model verification and validation against the well-established nonlinear quality of motion of the spine, as opposed to the previous norm of matching kinematic endpoint metrics such as range of motion and intervertebral disc pressure measurements at a single kinematic reference point. METHODS: Experimental data was obtained during cadaveric testing of nine three-functional spinal unit (L3-S1) lumbar spine segments. Each specimen was tested from 8 Nm of applied flexion moment to 6 Nm of applied extension moment with an applied 400 N compressive follower preload. A nonlinear kinematic curve representing the spinal quality of motion (applied moment versus angular rotation) for the index finite element model was constructed and compared to the kinematic responses of the experimental specimens. The effect of spinal soft tissue structure mechanical behaviors on the fidelity of the model's quality of motion to experimental data was assessed by iteratively modifying the material representations of annulus fibrosus, nucleus pulposus, and ligaments. FINDINGS: The present work demonstrated that for this model, the annulus fibrosus played a small role in the nonlinear quality of motion of the model, whereas changes in ligament representations had a large effect, as validated against the full kinematic range of motion. An anisotropic continuum representation of the annulus fibrosus was used, along with nonlinear fabric representations of the ligaments and a hyperelastic representation of the nucleus pulposus. INTERPRETATION: Our results suggest that improvements in current methodologies broadly used in numerical simulations of the lumbar spine are needed to fully describe the highly nonlinear motion of the spine.     

An open-label pilot study of naltrexone in childhood-onset trichotillomania

OBJECTIVE: This pilot open study evaluates the safety and efficacy of naltrexone in the management of patients with childhood onset trichotillomania (TTM). METHODS: A total of 14 patients with childhood-onset TTM were treated with naltrexone (25-100 mg/day) and were assessed at each visit for frequency of hair pulling, urge to pull hair, and symptom severity. Liver function was monitored during the treatment. The duration of the study was 10 months. RESULTS: A mean dose of 66.07 +/- 22.23 mg/day naltrexone was well tolerated and 11 out of 14 subjects showed a positive response. The mean age of the children was 9 +/- 1.88 years. The mean age of onset of symptoms in the group was 7.07 +/- 0.91 years. No abnormality in liver function was noted in the study. No adverse effects were reported by the children. CONCLUSIONS: This encouraging pilot open study has promising findings suggesting the use of naltrexone in childhood-onset TTM. However, results are needed from larger and more definitive trials before any conclusions are made.     

Comparison of a novel FiberWire-button construct versus metallic screw fixation in a syndesmotic injury model

BACKGROUND: There is minimal experience with less rigid syndesmotic fixation devices which may approximate the normal distal tibio-fibular mechanics during healing. This study evaluates the ability of a FiberWire-button implant (Arthrex, Naples, FL) to maintain syndesmotic reduction as compared with a metallic screw. METHODS: Ten matched fresh-frozen cadaveric ankle pairs with intact ligaments were tested (12.5 Nm external rotation force) to establish physiologic syndesmotic diastasis. The same force was applied to the ankles after sectioning of the syndesmotic and deltoid ligaments. Within the pairs, each limb was randomized to receive a FiberWire-button implant or a metallic screw (Synthes, Paoli, PA); the ankles were tested for syndesmotic diastasis with progressive external rotation force, from 2.5 Nm to 25 Nm (or failure). RESULTS: There was no significant difference in diastasis amongst pairs with intact or sectioned syndesmosis (p=0.64 and p=0.80, respectively). There was a significantly greater diastasis in the FiberWire-button group at all external rotation loads (p<0.0001). Nine of the ten pairs failed (all through fracture of the distal fibula). There were no hardware failures. The metallic screw group failed at a lower load (mean 15 Nm) compared to the FiberWire-button group (mean 18 Nm, p=0.0004). The metallic screw group maintained syndesmotic reduction up to 5 Nm of force. CONCLUSIONS: The FiberWire-button was unable to maintain syndesmotic reduction of the ankles at any of the forces applied. The ankles fixed with the FiberWire-button demonstrated significantly greater widening of the syndesmosis compared to the screw, at all loads. CLINICAL RELEVANCE: The FiberWire-button implant may not maintain adequate ankle syndesmotic reduction in the immediate post-operative period relative to a metallic screw.