Faculty Bibliography

BACKGROUND: The electrocardiogram (ECG) is the most important diagnostic tool for acute myocardial infarction (AMI). T wave inversion (TWI) in lead aVL has not been emphasized or well recognized. OBJECTIVE: This study examined the relationship between the presence of TWI before the event and mid-segment left anterior descending (MLAD) artery lesion in patients with AMI. METHODS: Retrospective charts of patients with acute coronary syndrome between the months of January 2009 and December 2011 were reviewed. All patients with MLAD lesion were identified and their ECG reviewed for TWI in lead aVL. RESULTS: Coronary angiography was done on 431 patients. Of these, 125 (29%) had an MLAD lesion. One hundred and six patients (84.8%) had a lesion > 50% and 19 patients (15.2%) had a lesion < 50%. Of the 106 patients who had a MLAD lesion > 50%, 90 patients (84.9%) had TWI in lead aVL and one additional lead. Of the 19 patients who had an MLAD lesion < 50%, 8 patients (42.1%) had TWI in lead aVL and one additional lead. Isolated TWI in lead aVL had an overall sensitivity of 76.7% (95% confidence interval [CI] 0.65-0.86), a specificity of 71.4% (95% CI 0.45-0.88), a positive predictive value of 92%, a negative predictive value of 41.7%, a positive likelihood ratio of 2.7 (95% CI 1.16-6.22), and negative likelihood ratio of 0.32 (95% CI 0.19-0.58) for predicting a MLAD lesion of > 50% (p = 0.0011). CONCLUSIONS: TWI in lead aVL might signify a mid-segment LAD lesion. Recognition of this finding and early appropriate referral to a cardiologist might be beneficial. Additional studies are needed to validate this finding.

Subthreshold-activating A-type K(+) currents are essential for the proper functioning of the brain, where they act to delay excitation and regulate firing frequency. In CA1 hippocampal pyramidal neuron dendrites, the density of A-type K(+) current increases with distance from the soma, playing an important role in synaptic integration and plasticity. The mechanism underlying this gradient has, however, remained elusive. Here, dendritic recordings from mice lacking the Kv4 transmembrane auxiliary subunit DPP6 revealed that this protein is critical for generating the A-current gradient. Loss of DPP6 led to a decrease in A-type current, specifically in distal dendrites. Decreased current density was accompanied by a depolarizing shift in the voltage dependence of channel activation. Together these changes resulted in hyperexcitable dendrites with enhanced dendritic AP back-propagation, calcium electrogenesis, and induction of synaptic long-term potentiation. Despite enhanced dendritic excitability, firing behavior evoked by somatic current injection was mainly unaffected in DPP6-KO recordings, indicating compartmentalized regulation of neuronal excitability.

Endobronchial ultrasonography (EBUS) has emerged as a new diagnostic tool that allows the bronchoscopist to see beyond the airway, including pulmonary and mediastinal lesion. The real time EBUS-guided transbronchial needle aspiration (TBNA) has advanced the diagnostic yield in primary lung pathology and mediastinal lymph node staging of lung carcinoma. Sixty-four patients (36 males, 28 females, ages ranging from 16 to 86 years) with peribronchial lung lesions and mediastinal and/or hilar lymph node lesions underwent EBUS-TBNA. All patients had intraoperative cytological assessment by smears on aspiration samples or touch preparation on needle core biopsies.The cytological final diagnoses were categorized as negative, suspicious/positive, and non-diagnostic. Forty-nine samples were obtained from lymph node lesions and 15 samples were obtained from lung lesions. In cytology specimens, 32 patients had suspicious/positive diagnoses and 32 patients had negative diagnosis. In follow-up histology specimens, 35 patients had malignant diagnoses, including 18 adenocarcinomas, 8 small cell carcinomas, 6 squamous cell carcinomas, 1 metastatic hepatocellular carcinoma, 1 metastatic melanoma, and 1 lymphoma. Twenty-nine patients had negative diagnoses. Sensitivity and specificity were 88.9% and 96.4%, respectively. Positive and negative predictive values were 97.0% and 87.1%, respectively. Diagnostic accuracy was 92.2%. EBUS-TBNA is an efficient and effective technique for diagnosis of intrapulmonary and mediastinal/hilar lymph nodes. It becomes significantly invaluable on clinical management for staging in those patients with lung cancer of other metastatic malignancies. This technique enables us to obtain tissue samples for quick diagnoses beyond central airway with minimal complications. Diagn. Cytopathol. 2010. (c) 2009 Wiley-Liss, Inc

Tay-Sachs disease (TSD) carrier screening, initiated in the 1970s, has reduced the birth-rate of Ashkenazi Jews with TSD worldwide by 90%. Recently, several nationwide programs have been established that provide carrier screening for the updated panel of Jewish genetic diseases on college campuses and in Jewish community settings. The goals of this study were to determine the performance characteristics of clinical TSD testing in college- and community-based screening programs and to determine if molecular testing alone is adequate in those settings. Clinical data for TSD testing were retrospectively anonymized and subsequently analyzed for 1,036 individuals who participated in these programs. The performance characteristics of the serum and the platelet Hexosaminidase assays were compared, and also correlated with the results of targeted DNA analysis. The serum assay identified 29 carriers and the platelet assay identified 35 carriers for carrier rates of 1/36 and 1/29, respectively. One hundred sixty-nine samples (16.3%) were inconclusive by serum assay in marked contrast to four inconclusive samples (0.4%) by the platelet assay. Molecular analysis alone would have missed four of the 35 carriers detected by the platelet assay, yielding a false negative rate of 11.4% with a sensitivity of 88.6%. Based on the results of this study, platelet assay was superior to serum with a minimal inconclusive rate. Due to changing demographics of the Ashkenazi Jewish population, molecular testing alone in the setting of broad-based population screening programs is not sufficient, and biochemical analysis should be the assay of choice.