Leonard, Jennifer

AbstractNasogastric/nasoenteric (NG/NE) feeding tube placements are associated with adverse events and, without proper training, can lead to devastating and significant patient harm related to misplacement. Safe feeding tube placement practices and verification are critical. There are many procedures and techniques for placement and verification; this paper provides an overview and update of techniques to guide practitioners in making clinical decisions. Regardless of placement technique and verification practices employed, it is essential that training and competency are maintained and documented for all clinicians placing NG/NE feeding tubes. This paper has been approved by the American Society for Parenteral and Enteral Nutrition (ASPEN) Board of Directors.

Abstract Lymphangioleiomyomatosis (LAM) and multifocal micronodular pneumocyte hyperplasia (MMPH) produce cystic and nodular disease, respectively, in the lungs of patients with tuberous sclerosis. The objective of this study was to prospectively characterize the prevalence, clinical presentation, and genetic basis of lung disease in TSC. We performed genotyping and computerized tomographic (CT) scanning of the chest on 23 asymptomatic women with tuberous sclerosis complex (TSC). Cystic pulmonary parenchymal changes consistent with LAM were found in nine patients (39%). These patients tended to be older than cyst-negative patients (31.9 ± 7.6 yr versus 24.8 ± 11.6 yr, p = 0.09). There was no correlation between presence of cysts and tobacco use, age at menarche, history of pregnancy, or estrogen-containing medications. Three of the cyst-positive patients had a prior history of pneumothorax. Pulmonary function studies revealed evidence of gas trapping but normal spirometric indices in the cyst-positive group. All nine cyst-positive patients had angiomyolipomas (AML), which were larger (p < 0.05) and more frequently required intervention (p = 0.08) than cyst-negative patients (8 of 14 with AMLs, p < 0.05). Ten patients (43%) had pulmonary parenchymal nodules. Pulmonary nodules were more common in women with cysts (78% versus 21%, p < 0.05), and 52% of all patients had either cystic or nodular changes. TSC2 mutations were identified in all cyst-positive patients who were tested (n = 8), whereas both TSC1 and TSC2 mutations were found in patients with nodular disease. Correlation of the mutational and radiographic data revealed one pair of sisters who were discordant for cystic disease, two mother– daughter pairs who were discordant for nodular disease, and no clear association between cyst development and a specific mutational type. This prospective analysis demonstrates that cystic and nodular pulmonary changes consistent with LAM and MMPH are common in women with TSC.

The Sonic Hedgehog (Shh) pathway plays important roles in embryogenesis, stem cell maintenance, tissue repair, and tumorigenesis. Haploinsufficiency of Patched-1, a gene that encodes a repressor of the Shh pathway, dysregulates the Shh pathway and increases genomic instability and the development of spontaneous and ionizing radiation (IR)–induced tumors by an unknown mechanism. Here we show that Ptc1+/− mice have a defect in the IR-induced activation of the ATR–Chk1 checkpoint signaling pathway. Likewise, transient expression of Gli1, a downstream target of Shh signaling, disrupts Chk1 activation in human cells by preventing the interaction of Chk1 with Claspin, a Chk1 adaptor protein that is required for Chk1 activation. These results suggest that inappropriate Shh pathway activation promotes tumorigenesis by disabling a key signaling pathway that helps maintain genomic stability and inhibits tumorigenesis.