Compromised axon initial segment integrity in EAE is preceded by microglial reactivity and contact

Axonal pathology is a key contributor to long‐term disability in multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system (CNS), but the mechanisms that underlie axonal pathology in MS remain elusive. Evidence suggests that axonal pathology is a direct consequence of demyelination, as we and others have shown that the node of Ranvier disassembles following loss of myelin. In contrast to the node of Ranvier, we now show that the axon initial segment (AIS), the axonal domain responsible for action potential initiation, remains intact following cuprizone‐induced cortical demyelination. Instead, we find that the AIS is disrupted in the neocortex of mice that develop experimental autoimmune encephalomyelitis (EAE) independent of local demyelination. EAE‐induced mice demonstrate profound compromise of AIS integrity with a progressive disruption that corresponds to EAE clinical disease severity and duration, in addition to cortical microglial reactivity. Furthermore, treatment with the drug didox results in attenuation of AIS pathology concomitantly with microglial reversion to a less reactive state. Together, our findings suggest that inflammation, but not demyelination, disrupts AIS integrity and that therapeutic intervention may protect and reverse this pathology. GLIA 2016;64:1190–1209     

Primary aneurysmal bone cyst of patella

Of all the aneurysmal bone cysts (ABC) occurring in the body, less than 1% are seen in the patella. We report here, a 27-year-old woman with Stage III ABC of patella. Curettage, chemical and thermal cautery of the bed followed by autogenous bone grafting of the defect was done. At two-year follow up, there was a suspicion of lucency in the middle of the patella. However a repeat curettage revealed only fibrous tissue. Now at four years of follow up, the bone graft remained well incorporated. Patient has mild anterior knee pain on stair climbing but regained normal knee function.     

Is Head and Neck Melanoma Different from Trunk and Extremity Melanomas with Respect to Sentinel Lymph Node Status and Clinical Outcome?

Background

Previous studies showed conflicting and inconsistent results regarding the effect of anatomic location of the melanoma on sentinel lymph node (SLN) positivity and/or survival. This study was conducted to evaluate and compare the effect of the anatomic locations of primary melanoma on long-term clinical outcomes.

Methods

All consecutive cutaneous melanoma patients (n = 2,079) who underwent selective SLN dissection (SLND) from 1993 to 2009 in a single academic tertiary-care medical center were included. SLN positive rate, disease-free survival (DFS), and overall survival (OS) were determined. Kaplan-Meier survival, univariate, and multivariate analyses were performed to determine predictive factors for SLN status, DFS, and OS.

Results

Head and neck melanoma (HNM) had the lowest SLN-positive rate at 10.8 % (16.8 % for extremity and 19.3 % for trunk; P = 0.002) but had the worst 5-year DFS (P < 0.0001) and 5-year OS (P < 0.0001) compared with other sites. Tumor thickness (P < 0.001), ulceration (P < 0.001), HNM location (P = 0.001), mitotic rate (P < 0.001), and decreasing age (P < 0.001) were independent predictive factors for SLN-positivity. HNM with T3 or T4 thickness had significantly lower SLN positive rate compared with other locations (P ≤ 0.05). Also, on multivariate analysis, HNM location versus other anatomic sites was independently predictive of decreased DFS and OS (P < 0.001). By Kaplan-Meier analysis, HNM was associated significantly with the worst DFS and OS.

Conclusions

Primary melanoma anatomic location is an independent predictor of SLN status and survival. Although HNM has a decreased SLN-positivity rate, it shows a significantly increased risk of recurrence and death as compared with other sites.     

Treatment of Budd-Chiari syndrome with inferior vena caval occlusion by mesoatrial shunt.

OBJECTIVE: To report the effectiveness of a mesoatrial shunt in the treatment of Budd-Chiari syndrome caused by combined hepatic vein and inferior vena caval block. DESIGN: Retrospective study. SETTING: Tertiary care hospital, India. PATIENTS: 10 patients (4 men and 6 women; mean age 28, range 18-45) who had operations for Budd-Chiari syndrome between 1994 and 2000. INTERVENTION: Mesoatrial shunt. MAIN OUTCOME MEASURES: Graft patency, survival, liver function and symptoms. RESULTS: One patient died. All grafts were patent over a mean follow up period of 40 months (range 6-71). All survivors have normal liver function and were symptom free at the time of writing. CONCLUSION: Mesoatrial shunt is effective in the treatment of Budd-Chiari syndrome caused by combined hepatic vein and vena caval occlusion.     

A Single Gradient Stability-Indicating Reversed-Phase LC Method for the Estimation of Impurities in Omeprazole and Domperidone Capsules

A gradient reversed-phase liquid chromatographic (RP-LC) method was developed for the quantitative estimation of impurities in the pharmaceutical dosage form of Omeprazole and Domperidone capsules. The developed method is a stability-indicating test method for the estimation of impurities generated during the formulation and storage of Omeprazole and Domperidone capsules. The chromatographic separation was achieved on a column packed with octadecyl silane, having a column length of 250 mm and diameter of 4.6 mm with a particle size of 5 μm, and by following a gradient program using a combination of a monobasic potassium phosphate buffer (0.05M) and acetonitrile. Since the spectral properties were similar, both compounds’ individual impurities were estimated at 285 nm. Forced degradation studies were performed on Omeprazole pellets (enteric coated) and Domperidone pellets (SR coated) encapsulated in size ‘1’ hard gelatin capsules. Omeprazole and Domperidone were degraded using acid hydrolysis (0.1 N hydrochloric acid), base (0.1 N sodium hydroxide), oxidation (50% hydrogen peroxide), heat (105 °C), and UV light (254 nm). The established method was validated and found to be linear, accurate, precise, specific, robust, and rugged.     

Simultaneous quantitative determination of metoprolol, atorvastatin and ramipril in capsules by a validated stability-indicating RP-UPLC method

A simple ultra performance liquid chromatographic (UPLC) method has been developed for the simultaneous estimation of Metoprolol (MT), Atorvastatin (AT) and Ramipril (RM) from capsule dosage form. The method was developed using Zorbax® XDB-C18 (4.6 mm × 50 mm, 1.8 μm) column with a mobile phase consisting of 0.06% ortho phosphoric acid in Milli Q® water having an ion pair reagent, 0.0045 M Sodium lauryl sulphate as buffer, at ratio of buffer: Acetonitrile (50:50 v/v), at 55°C column temperature with a flow rate of 1.0 ml/min. Detection was carried out with ultra-violet detection at 210 nm for RM, MT and AT respectively. The retention times were about 1.3, 2.1 and 2.6 min for MT, AT and RM respectively, the method was validated for linearity, accuracy, precision, specificity, robustness and ruggedness. The % mean recoveries are 101.9, 102.1 and 101.4 for MT, AT and RM respectively. The method was found to be rugged and robust and can be successfully used to determine the three drugs and its combinations.     

Current management of gall bladder perforations

BACKGROUND: Gall bladder perforation is a serious complication of acute cholecystitis. The purpose of the present study is to evaluate the presenting symptoms, diagnosis and management of patients with gall bladder perforations. METHODS: A retrospective study was undertaken of 31 consecutive patients with gall bladder perforation in a single unit of a tertiary referral hospital, between January 1996 and December 2001. RESULTS: The incidence of gall bladder perforation was 5.9% of all cases of acute cholecystitis. Associated comorbidity was quite common (58%). Ultrasound and computed tomography scans of the abdomen are sensitive investigations. Ultrasound guided percutaneous drainage helps in tiding over the emergency. The morbidity (35%) and mortality (9.6%) is considerable. CONCLUSION: The patterns of presentations, diagnosis and management of gall bladder perforation are changing. But there is scope for improvement.     

Vascular complications of drug abuse: an Indian experience

Background: Vascular complications resulting from i.v. drug abuse constitute a range of clinical problems from simple to serious. In addition, patients who present with these complications frequently have viral infections, which are a hazard to health care workers. Patients and Methods: The present study is a retrospective review of 46 male drug addicts with 52 vascular complications (45 arterial, seven venous). Pseudoaneurysm of the femoral artery was the most common complication (n = 35). Fourteen of these patients underwent ligation of the common, superficial and deep femoral arteries above and below the pseudoaneurysm. Twenty‐one underwent bipolar ligation of the common femoral artery after complete excision of the pseudoaneurysm. The decision to revascularize was based on the presence or absence of postligation Doppler signal. Arterial reconstruction was performed in five patients. All eight brachial artery pseudoaneurysms were ligated and excised, and deep vein thrombosis was managed with anticoagulation. Results: There was no mortality but three patients had to undergo late amputations of the lower limb after successful salvage following the initial surgery. The median postoperative ankle‐brachial indices, after bipolar and triple ligations were 0.51 and 0.46, respectively. Positive blood cultures were present in 30% of patients and tissue cultures were positive in 72%, the most common organism isolated was methicillin‐sensitive Staphylococcus aureus. Six patients were positive for viral markers. The median hospital stay was 43 days. Conclusion: Ligation and excision of pseudoaneurysms without revascularization is safe for drug addicts provided it is based on the presence of a postligation Doppler signal.