Effectiveness of Balloon Angioplasty in Children With Recurrent Aortic Coarctation Depends on the Type of Aortic Arch Pathology.

OBJECTIVES: The aim of this study was to evaluate the effectiveness of balloon angioplasty (BAP) for recurrent aortic coarctation (ReCoA) in infants comparing simple and complex type of aortic arch pathology (Norwood I procedure). BACKGROUND: ReCoA is a known complication after cardiovascular surgery for coarctation of the aortic arch. METHODS AND RESULTS: In a single center case study, we analyzed 20 infants undergoing BAP for ReCoA comparing simple (n = 10) and complex type of aortic arch pathology (n = 10). At catherization diameter of ReCoA stenosis was 3.2 ± 0.7 mm (mean ± SD) with short localized (11/20) or long hypoplastic stenosis (9/20) before and 4.8 ± 1.2 mm after BAP (P < 0.001). Invasive systolic pressure gradient was reduced from 27.5 ± 16.2 mmHg before to 5.1 ± 6.6 mmHg after BAP (P < 0.001), comparable in simple and complex type of ReCoA. At day 1 after catherization noninvasive systolic arterial blood pressure gradient was reduced from 20.2 ± 23.1 to 6.7 ± 9.9 mmHg (P < 0.001), respectively, calculated continuous wave Doppler echo gradient from 36.3 ± 22 to 16.8 ± 9.6 mmHg (P < 0.01). Complications were aortic arch dissection (1/20), discrete aortic arch aneurysm formation (1/20), pericardial effusion (1/20), and peripheral arterial thrombosis (4/20). At a mid-term follow up of 9.5 months (1-40) after BAP, 3 infants needed early surgical reintervention due to secondary ReCoA, all with long hypoplastic aortic arch segments, but simple type of aortic arch pathology. CONCLUSIONS: At mid-term follow up, BAP remains an effective catheter intervention for ReCoA for infants with localized ReCoA, but not with long hypoplastic aortic arch segments, even in simple type of aortic arch pathology.

Immunohistochemical Expression of E-Cadherin in Atypical Parathyroid Adenoma.

BACKGROUND: Atypical parathyroid adenoma (APA) is a rare entity, sharing clinical symptoms like solid palpable mass in the neck, laboratory changes with very high serum calcium and parathyroid hormone levels, and some histopathological features with parathyroid carcinomas (PC). However, clinical behavior of APA seems to comply with benign parathyroid tumors (PA). There is some evidence that loss of the membranous staining pattern of E-Cadherin (E-Cad) suggests a key role of epithelial mesenchymal transition in the tumorigenesis of PC. Thus, the aim of this study was to compare clinical and surgical characteristics and immunohistochemical expression of E-Cad in APA, PC, and PA. METHODS: Data of patients who underwent surgery for primary hyperparathyroidism (pHPT) between 1985 and 2010 were retrospectively evaluated. All data were analyzed with special regard to distinctive criteria of APA, including trabecular growth, broad fibrous bands, nuclear atypia, mitosis, pseudocapsular invasion or strong adherence to the surrounding tissue, and potential invasive growth of a grossly altered and enlarged parathyroid gland. In addition, laboratory and clinical data were evaluated and additional immunohistochemical staining with E-Cad was performed in suspicious APA patients with available tissue. RESULTS: In 68 patients (39 female, 29 male), the parathyroid tumor was suspicious for APA. In 46 patients, a bilateral cervical exploration was performed. 15 patients underwent an en bloc resection including a hemithyroidectomy and lymphonodular dissection of the ipsilateral central compartment due to the malignant macroscopic aspect of the parathyroid. In seven patients, a focused parathyroid resection was done. The available parathyroid tissue of 38 APA patients was immunopositive for membranous E-Cad staining. During follow-up, only one patient with a successful initial surgery suffered from recurrent pHPT due to another solitary PA 10 years after initial surgery but without evidence of malignancy. CONCLUSIONS: In contrast to PC, parathyroid tumors suspicious for APA are characterized by a strong membranous E-Cad staining and, like PA, by a benign clinical course.

Characteristics of poorly controlled Type 2 diabetes patients in Swiss primary care.

BACKGROUND: Although a variety of treatment guidelines for Type 2 diabetes patients are available, a majority of patients does not achieve recommended targets. We aimed to characterise Type 2 diabetes patients from Swiss primary care who miss HbA1c treatment goals and to reveal factors associated with the poorly controlled HbA1c level. METHODS: Cross-sectional study nested within the cluster randomised controlled Chronic Care for Diabetes study. Type 2 diabetes patients with at least one HbA1c measurement ≥ 7.0 % during the last year were recruited from Swiss primary care. Data assessment included diabetes specific and general clinical measures, treatment factors and patient reported outcomes. RESULTS: 326 Type 2 diabetes patients from 30 primary care practices with a mean age 67.1 ± 10.6 years participated in the study. The patients' findings for HbA1c were 7.7 ± 1.3 %, for systolic blood pressure 139.1 ± 17.6 mmHg, for diastolic blood pressure 80.9 ± 10.5 mmHg and for low density lipoprotein 2.7 ± 1.1. 93.3 % of the patients suffered from at least one comorbidity and were treated with 4.8 ± 2.1 different drugs. No determining factor was significantly related to HbA1c in the multiple analysis, but a significant clustering effect of GPs on HbA1c could be found. CONCLUSIONS: Within our sample of patients with poorly controlled Type 2 diabetes, no "bullet points" could be pointed out which can be addressed easily by some kind of intervention. Especially within this subgroup of diabetes patients who would benefit the most from appropriate interventions to improve diabetes control, a complex interaction between diabetes control, comorbidities, GPs' treatment and patients' health behaviour seems to exist. So far this interaction is only poorly described and understood.

The predictive value of the pediatric symptom checklist in 5-year-old Austrian children.

UNLABELLED: In this investigation the predictive value of the pediatric symptom checklist (PSC) in relation to the child behaviour checklist (CBCL) was studied in preschool children. Thirty nursery schools in the city and province of Salzburg participated in the study and a total of 179 correctly completed questionnaires (82 male and 97 female children) were analysed. Questionnaires were completed by the parents. Data were analysed using descriptive statistics (SPSS 11.0). Predictive validity was determined by non-parametric correlations and calculations of sensitivity and specificity, as well as an ROC analysis. The mean PSC at 10.74 +/- 6.8 was found to be below both international and Austrian values for this age group and was also found to differ significantly between girls (9.33 +/- 6.2) and boys (12.4 +/- 7.1; p < 0.01). The recommended international cut-off point at 24 is too high. CBCL analysis resulted in 12.6% impaired (T value between 60 and 64) and 8.2% pathological children (T value > 64). PSC sensitivity in relation to the CBCL total score was 15.7% and specificity 98.5%. The cut-off was optimized with the help of ROC analysis and optimum specificity (80.2%) and sensitivity (81.1%) were obtained at a cut-off value of 15.5. This cut-off would allow 24.6% to be detected as impaired, which is somewhat above the frequency (20.2%) found by CBCL. CONCLUSION: To summarize, the PSC is a valid psychosocial screening instrument, at least for this age group, and thus applicable for German-speaking countries.

Activated protein C protects against diabetic nephropathy by inhibiting endothelial and podocyte apoptosis.

Data providing direct evidence for a causative link between endothelial dysfunction, microvascular disease and diabetic end-organ damage are scarce. Here we show that activated protein C (APC) formation, which is regulated by endothelial thrombomodulin, is reduced in diabetic mice and causally linked to nephropathy. Thrombomodulin-dependent APC formation mediates cytoprotection in diabetic nephropathy by inhibiting glomerular apoptosis. APC prevents glucose-induced apoptosis in endothelial cells and podocytes, the cellular components of the glomerular filtration barrier. APC modulates the mitochondrial apoptosis pathway via the protease-activated receptor PAR-1 and the endothelial protein C receptor EPCR in glucose-stressed cells. These experiments establish a new pathway, in which hyperglycemia impairs endothelial thrombomodulin-dependent APC formation. Loss of thrombomodulin-dependent APC formation interrupts cross-talk between the vascular compartment and podocytes, causing glomerular apoptosis and diabetic nephropathy. Conversely, maintaining high APC levels during long-term diabetes protects against diabetic nephropathy.

The role of junctional adhesion molecule-C (JAM-C) in oxidized LDL-mediated leukocyte recruitment.

The junctional adhesion molecule-C (JAM-C) was recently shown to be a counter receptor for the leukocyte beta2-integrin Mac-1 (CD11b/CD18), thereby mediating interactions between vascular cells, particularly in inflammatory cell recruitment. Here, we investigated the role of JAM-C in oxidized low-density lipoprotein (LDL)-mediated leukocyte recruitment. As compared with normal arteries, immunostaining of atherosclerotic vessels revealed a high expression of JAM-C in association with neointimal smooth muscle cells and the endothelium. Moreover, JAM-C was strongly up-regulated in the spontaneous early lesions in ApoE -/- mice. In vitro, cultured human arterial smooth muscle cells (HASMC) were found to express JAM-C, and oxLDL, as well as enzymatically modified LDL (eLDL) significantly up-regulated JAM-C on both HASMC and endothelial cells in a time- and dose-dependent manner. Although under quiescent conditions, JAM-C predominantly localized to interendothelial cell-cell contacts in close proximity to zonula occludens-1 (ZO-1), oxLDL treatment induced a disorganization of JAM-C localization that was no more restricted to the interendothelial junctions. JAM-C thereby mediated both leukocyte adhesion and leukocyte transendothelial migration upon oxLDL treatment of endothelial cells, whereas JAM-C on quiescent endothelial cells only mediates leukocyte transmigration. Thus, upon oxLDL stimulation endothelial JAM-C functions as both an adhesion, as well as a transmigration receptor for leukocytes. Taken together, JAM-C is up-regulated by oxLDL and may thereby contribute to increased inflammatory cell recruitment during atherosclerosis. JAM-C may therefore provide a novel molecular target for antagonizing interactions between vascular cells in atherosclerosis.