Orbital tuberculosis manifesting with enophthalmos and causing a diagnostic dilemma

A 60-year-old woman with no known systemic disease was referred with a hard mass in the left orbit and enophthalmos of two months duration. Differential diagnoses of metastasis from an undetected scirrhous carcinoma and sclerosing nonspecific orbital inflammatory disease were considered and a biopsy was performed. Histopathology demonstrated granulomatous inflammation with fibrosis. Subsequent polymerase chain reaction was positive for Mycobacterium tuberculosis deoxyribonucleic acid. There was no evidence of systemic tuberculosis. The patient was treated with four-drug combination anti-tubercular therapy for 6 months. The mass regressed and there was no local recurrence at two years follow-up. Orbital tuberculosis generally manifests with proptosis or osteomyelitis. However, enophthalmos may be caused by the fibrosing variant. Biopsy with histopathologic and microbioloic evaluation is essential to distinguish it from other more common causes of an orbital mass with paradoxical enophthalmos such as metastatic scirrhous carcinoma and sclerosing nonspecific orbital inflammatory disease.     

The Middle-East connection of Wolman Disease

The clinical, laboratory and cytological features of 2 Bahraini infants with Wolman's disease are described. While one of the cases showed the classical diagnostic features, the other case exhibited a few atypical features such as lack of adrenal calcification and unusual morphology of vacuolated marrow macrophages. Literature review shows that this disorder may not be rare in this region.     

Bcl-2 family member Mcl-1 expression is reduced under hypoxia by the E3 ligase FBW7 contributing to BNIP3 induced cell death in glioma cells

Mcl-1 is an anti-apoptotic Bcl-2 family member that is often over-expressed in the malignant brain tumor glioblastoma (GBM). It has been previously shown that epidermal growth factor receptors up-regulate Mcl-1 contributing to a cell survival response. Hypoxia is a poor prognostic marker in glioblastoma despite the fact that hypoxic regions have areas of necrosis. Hypoxic regions of GBM also highly express the pro-cell death Bcl-2 family member BNIP3, yet when BNIP3 is overexpressed in glioma cells, it induces cell death. The reasons for this discrepancy are unclear. Herein we have found that Mcl-1 expression is reduced under hypoxia due to degradation by the E3 ligase FBW7 leading to increased hypoxia induced cell death. This cell death is reduced by EGFR activation leading to increased Mcl-1 expression under hypoxia. Conversely, BNIP3 is over-expressed in hypoxia at times when Mcl-1 expression is decreased. Knocking down BNIP3 expression reduces hypoxia cell death and Mcl-1 expression effectively blocks BNIP3 induced cell death. Of significance, BNIP3 and Mcl-1 are co-localized under hypoxia in glioma cells. These results suggest that Mcl-1 can block the ability of BNIP3 to induce cell death under hypoxia in GBM tumors.     

Acute clinical evaluation of a left ventricular automatic threshold determination algorithm based on evoked response sensing

Introduction: Automatic pacing threshold (AT) testing may simplify device follow‐up and improve device longevity. This study's objective was to evaluate the performance of a left ventricular (LV) evoked response sensing‐based AT algorithm, for cardiac resynchronization therapy (CRT) devices. Methods: Patients scheduled for CRT‐D/P implant were enrolled. A manual step‐down threshold test and a Left Ventricular Automatic Threshold (LVAT) test in each of four pacing vectors—LVTip→Can, LVTip→right ventricle (RV), = LVRing→Can, and LVRing→RV—were conducted. Patients were randomized to either 0.4‐ms or 1.0‐ms pacing pulse width and in the manual and LVAT test order. A blinded core lab electrophysiologist (EP) determined the threshold using the surface electrocardiogram (gold standard). Results: Data from 70 patients were analyzed. Bipolar LV leads from three major manufacturers were used. A total of 273 AT tests were performed; 12 AT tests did not result in a threshold due to improper testing conditions. Of 261 eligible tests, 234 AT tests (89.6%) returned a threshold measurement. Of the 234 tests, in 233 tests (99.5%) the algorithm‐determined threshold matched the EP‐determined threshold for that test. A total of 16,689 capture and 526 noncapture beats were collected and the accuracy for detecting capture and noncapture were 98.5% and 99.7% with a two‐sided 95% confidence level of (98.4%, 98.7%) and (99.4%, 100%), respectively. No AT threshold measurement was lower than the EP‐determined threshold. Conclusion: In this study, the results suggest that the LVAT algorithm is accurate at determining pacing thresholds in multiple pacing configurations and a wide range of LV leads in CRT‐D/P patients. (PACE 2011;1–5)     

Influence of the skeletal muscle activity on time and frequency domain properties of the body surface ECG during evolving ventricular fibrillation in the pig

AIM OF THE STUDY: To evaluate influence of the skeletal muscle activity (SMA) on time and frequency domain properties of ECG during VF. MATERIALS AND METHODS: We studied the first 9min of electrically induced VF (N=7). We recorded Lead II ECG, 247 unipolar epicardial ventricular electrograms (UEGs) and 3 bipolar skeletal electromyograms (EMGs) near the positions of the ECG electrodes (sampling rate, 500Hz). We reconstructed ECG (RECG) from UEGs using forward-solution transformation matrix. Spectral properties of ECG, RECG, UEGs and MEGs were assessed in the range 2-250Hz by the median frequency (MF) and the upper limit of frequency range containing 99% of spectral energy (Flim(99)). Scaling exponent of ECG, RECG and EMGs was calculated in the ranges of 1-8 and 5-20 sampling intervals (ScE1-8 and ScE5-20, respectively). RESULTS: We observed non-monotonic increases in MF and Flim(99) of the ECG, but not UEGs and RECG, at 1-5min of VF. Maximum values of MF and Flim(99) in ECG, UEGs and RECG were (in Hz): 32+/-29 and 166+/-67; 11+/-2 and 36+/-7; 10+/-2 and 32+/-6, respectively. The transient increases in the high-frequency content of the ECG were correlated with enhanced activity in EMGs, characterized by an almost uniform spectrum in the range 2-250Hz (MF=92+/-29; Flim(99)=245+/-4Hz). Peak values of ScE(1-8) were the highest in EMGs (1.95+/-0.04), intermediate in the ECG (1.59+/-0.26), and the lowest in RECG (1.088+/-0.007). CONCLUSION: SMA significantly contributes to ECG during VF and can bias metrics used for assessment of VF organization.