KCNE2 protein is expressed in ventricles of different species, and changes in its expression contribute to electrical remodeling in diseased hearts.

BACKGROUND: Mutations in KCNE2 have been linked to long-QT syndrome (LQT6), yet KCNE2 protein expression in the ventricle and its functional role in native channels are not clear. METHODS AND RESULTS: We detected KCNE2 protein in human, dog, and rat ventricles in Western blot experiments. Immunocytochemistry confirmed KCNE2 protein expression in ventricular myocytes. To explore the functional role of KCNE2, we studied how its expression was altered in 2 models of cardiac pathology and whether these alterations could help explain observed changes in the function of native channels, for which KCNE2 is a putative auxiliary (beta) subunit. In canine ventricle injured by coronary microembolizations, the rapid delayed rectifier current (I(Kr)) density was increased. Although the protein level of ERG (I(Kr) pore-forming, alpha, subunit) was not altered, the KCNE2 protein level was markedly reduced. These data are consistent with the effect of heterologously expressed KCNE2 on ERG and suggest that in canine ventricle, KCNE2 may associate with ERG and suppress its current amplitude. In aging rat ventricle, the pacemaker current (I(f)) density was increased. There was a significant increase in the KCNE2 protein level, whereas changes in the alpha-subunit (HCN2) were not significant. These data are consistent with the effect of heterologously expressed KCNE2 on HCN2 and suggest that in aging rat ventricle, KCNE2 may associate with HCN2 and enhance its current amplitude. CONCLUSIONS: KCNE2 protein is expressed in ventricles, and it can play diverse roles in ventricular electrical activity under (patho)physiological conditions.

Warm ischemia lung protection with pinacidil: an ATP regulated potassium channel opener.

BACKGROUND: Ischemia/reperfusion injury remains a limiting factor in lung transplantation. Traditional hyperkalemic preservation solutions are associated with a host of metabolic derangements. ATP-regulated potassium channel openers (PCOs) may provide an attractive alternative to traditional solutions by utilizing inherent mechanisms of ischemic preconditioning. The purpose of this study was to assess warm ischemia graft protection with pinacidil, a nonspecific PCO. METHODS: An isolated recirculating blood perfused ventilated rabbit lung model was used (n = 15). No ischemia control lungs underwent immediate reperfusion (n = 5). Warm ischemia control lungs were flushed with lactated Ringers (LR), stored at 37 degrees C for 2.5 hours and then reperfused for 2 hours (n = 5). PCO protected lungs were flushed with LR + 100 micromol/L pinacidil, stored, and then reperfused (n = 5). Intermittent blood gases were taken from the pulmonary artery and left atria. Every 30 minutes, graft function was assessed with a 10-minute 100% fractional inspired oxygen concentration challenge to measure maximal gas exchange. Lung samples were graded for histologic injury and assayed for myeloperoxidase activity. RESULTS: A mixed-models repeated measures ANOVA demonstrated a significant difference between groups. Tukey's honestly significant difference multiple comparison test demonstrated significantly improved graft function and reduced histologic injury with pinacidil protection compared with the warm ischemia controls. There was no significant difference in graft function or pathology grade between the pinacidil protected lungs and the no ischemia controls. A similar trend, although not significant, was seen in myeloperoxdiase activity. CONCLUSIONS: Potassium channel openers with pinacidil can provide pulmonary protection against warm ischemia reperfusion injury.

Sentinel lymph node biopsy in patients with multicentric/multifocal breast cancer: low false-negative rate and lack of axillary recurrence.

BACKGROUND: Accuracy of sentinel lymph node biopsy (SLNB) and rate of axillary recurrence in multicentric/multifocal (MC/MF) breast cancer are reported. METHODS: From 1999 to 2006, 93 patients with MC/MF breast cancer underwent SLNB; 41 underwent axillary lymph node dissection regardless of SLN pathology (group 1), and 52 underwent axillary lymph node dissection only if an SLN was positive (group 2). Patient demographics, SLN techniques, and pathology were recorded. RESULTS: There were no differences between the 2 groups with respect to patient age; tumor size, grade, stage, and histology; or method of SLN detection. The incidence of axillary metastasis was greater in group 1 patients (68%) compared with group 2 patients (12%) (P < .01). In group 1, the sensitivity and specificity of SLNB were 93% and 100%, respectively, with a false-negative rate of 7%. None of the 52 patients in group 2 experienced axillary recurrence (median follow-up 4.8 years). CONCLUSIONS: The accuracy of SLNB in MC/MF breast cancer is comparable with that observed in unifocal breast cancer. Despite a lower rate of SLN positivity in patients undergoing SLNB only, axillary recurrence was not observed.

Scientific Presentation Award: The combination of axillary ultrasound and ultrasound-guided biopsy is an accurate predictor of axillary stage in clinically node-negative breast cancer patients.

BACKGROUND: The study aim was to determine the accuracy of axillary ultrasound (AUS) and fine-needle aspiration biopsy (FNAB)/needle core biopsy in axillary breast cancer staging. METHODS: We reviewed 256 patients with clinically node-negative breast cancer who underwent AUS +/- FNAB/needle core biopsy. AUS-guided FNAB/needle core biopsy was compared with histopathology to determine sensitivity, specificity, negative predictive value, and positive predictive value. RESULTS: AUS-guided FNAB/needle core biopsy and final pathology were positive in 72 of 256 patients (28%). In 125 of 256 cases (49%), the AUS and final pathology were negative. Two of 110 patients had a false-positive FNAB (1.8%); both received neoadjuvant chemotherapy. Nine patients (8%) had a false-negative FNAB/needle core biopsy; the median size of lymph node metastasis was 3 mm. The sensitivity and specificity of AUS-guided FNAB/needle core biopsy was 71% and 99%, respectively, with a negative predictive value of 84% and a positive predictive value of 97%. CONCLUSIONS: AUS-guided FNAB/needle core biopsy is accurate in predicting the status of the axilla in 70% of clinically node-negative breast cancer patients. This technique is minimally invasive with a low complication rate and can obviate the need for staged lymph node procedures.

Case report of an 11-year-old child with a nonfunctional malignant pheochromocytoma.

Pheochromocytoma is an unusual cause of surgical hypertension and is extremely rare in the pediatric population. We present a case of a hypertension-producing malignant pheochromocytoma in an 11-year-old, which was initially unresectable. The tumor responded partially to aggressive chemotherapy and was completely resected. This approach highlights the importance of multidisciplinary care for patients with large pheochromocytomas.