The right paratracheal stripe (RPS) is seen on postero-anterior chest radiographs as a thin, water-density stripe between the air column of the trachea and the adjacent right lung. The range of width ...of the RPS in 1,259 normal subjects was 1 to 4 mm. An RPS width of 5 mm or more is reliable evidence of disease. The differential diagnosis of this finding is lengthy, and best divided into those diseases affecting the (a) trachea; (b) mediastinum; and (c) pleura.
This book moves scholarly debates beyond the old question of whether or not international institutions matter in order to examine how they matter, even in a world of power politics. Power politics ...and international institutions are often studied as two separate domains, but this is in need of rethinking because today most states strategically use institutions to further their interests. Anders Wivel, T.V. Paul, and the international group of contributing authors update our understanding of how institutions are viewed among the major theoretical paradigms in international relations, and they seek to bridge the divides. Empirical chapters examine specific institutions in practice, including the United Nations, International Atomic Energy Agency, and the European Union. The book also points the way to future research. International Institutions and Power Politics provides insights for both international relations theory and practical matters of foreign affairs, and it will be essential reading for all international relations scholars and advanced students.
Despite inhaled medications that decrease exacerbation risk, some COPD patients experience frequent exacerbations. We determined prospective risk factors for exacerbations among subjects in the ...COPDGene Study taking inhaled medications.
2113 COPD subjects were categorized into four medication use patterns: triple therapy with tiotropium (TIO) plus long-acting beta-agonist/inhaled-corticosteroid (ICS ± LABA), tiotropium alone, ICS ± LABA, and short-acting bronchodilators. Self-reported exacerbations were recorded in telephone and web-based longitudinal follow-up surveys. Associations with exacerbations were determined within each medication group using four separate logistic regression models. A head-to-head analysis compared exacerbation risk among subjects using tiotropium vs. ICS ± LABA.
In separate logistic regression models, the presence of gastroesophageal reflux, female gender, and higher scores on the St. George's Respiratory Questionnaire were significant predictors of exacerbator status within multiple medication groups (reflux: OR 1.62-2.75; female gender: OR 1.53 - OR 1.90; SGRQ: OR 1.02-1.03). Subjects taking either ICS ± LABA or tiotropium had similar baseline characteristics, allowing comparison between these two groups. In the head-to-head comparison, tiotropium users showed a trend towards lower rates of exacerbations (OR = 0.69 95 % CI 0.45, 1.06, p = 0.09) compared with ICS ± LABA users, especially in subjects without comorbid asthma (OR = 0.56 95% CI 0.31, 1.00, p = 0.05).
Each common COPD medication usage group showed unique risk factor patterns associated with increased risk of exacerbations, which may help clinicians identify subjects at risk. Compared to similar subjects using ICS ± LABA, those taking tiotropium showed a trend towards reduced exacerbation risk, especially in subjects without asthma.
ClinicalTrials.gov NCT00608764, first received 1/28/2008.
Purpose We assessed the ability of different classes of histone deacetylase inhibitors to target tumor and invasive suppressor genes in a panel of bladder carcinoma cell lines using reverse phase ...protein arrays. Materials and Methods Three poorly, moderately and highly invasive cell lines were exposed to histone deacetylase inhibitors, trichostatin A, apicidin, valproic acid (Sigma®) and MS-275 (AXXORA®) for 0 to 36 hours. Lysates were harvested and arrayed in a 10-fold dilution series in duplicate. Data points were collected and analyzed using a concentration interpolation methodology after normalization. Results Protein expression profiles revealed up-regulation of γ-catenin in highly invasive lines, and α-catenin in moderately and highly invasive lines after exposure to all histone deacetylase inhibitors, apicidin and MS-275, respectively. Gelsolin was up-regulated in poorly and moderately invasive lines after exposure to all histone deacetylase inhibitors. Desmoglein was down-regulated in poorly and moderately invasive cell lines by all 4 histone deacetylase inhibitors, in addition to decreased FAK (Transduction Laboratories™) expression in moderately and highly invasive lines exposed to valproic acid and MS-275. Conclusions Different histone deacetylase inhibitor classes have the potential to modulate tumor and invasive suppressor gene expression, identifying histone deacetylase inhibitors as potential therapeutic agents for bladder cancer. Reverse phase protein arrays enable high throughput screening of multiple compounds to assess the expression profile of specific protein groups targeted for therapy.
Preoperative mechanical bowel preparation (MBP) for elective intestinal operations has been a long accepted practice. However, MBP is often unpleasant and time-consuming for patients, and clinical ...trials in adults have not shown improved outcomes. We conducted this pilot study to test whether omitting MBP before elective intestinal operations in infants and children would increase the risk of infectious or anastomotic complications.
Retrospective review was performed of 143 patients who had an elective colon or distal small bowel procedure performed at our children's hospital between 1990 and 2003.
Thirty-three patients (No PREP) were managed by a single surgeon who routinely omitted MBP, whereas another 110 patients (PREP) were prepared with enemas, laxatives, or both. Both groups received 24 hours of preoperative dietary restriction to clear liquids and perioperative parenteral antibiotics. The No PREP group had one anastomotic leak and no wound infections, whereas the PREP group had 2 anastomotic leaks and 1 wound infection (
P = .58). These results occurred despite greater duration of antibiotic therapy and incidence of delayed wound closures in the PREP group.
The results of this pilot study suggest that omitting MBP before elective intestinal operations in infants and children carries no increased risk of infectious or anastomotic complications. Eliminating MBP may reduce health care costs and inconvenience to patients. These findings warrant a large, prospective, randomized clinical trial to validate our findings and to investigate further the necessity of MBP in the pediatric population.
Eighteen radiologists failed to detect 27 potentially resectable bronchogenic carcinomas revealed retrospectively on serial chest radiographs. Most of the cancers were in an upper lobe (n = 22 81%), ...especially the right upper lobe (n = 15 56%). More of the cancers were in women (n = 18 67%) than in men (n = 9 33%). The mean diameter of the missed lesions was 1.6 cm +/- 0.8 (range, 0.6-3.4 cm). Only two lesions (7%) were well defined around their entire extent. A lateral radiograph (available for 23 patients) revealed the missed lesion better than the posteroanterior radiograph in four patients (17%). Six consultant radiologists, who were biased by knowledge that the cases were of missed bronchogenic carcinoma, were individually shown the radiographs in 22 of the cases. Each consultant missed a mean of 26% (5.8 +/- 1.7) of the lesions. At least one of the six consultants missed the lesion in 16 (73%) of the cases. The predominant characteristics of radiographically missed and potentially resectable bronchogenic carcinomas were difficulty in radiographic detection, female gender, and location in an upper lobe, especially on the right side.
Abstract only
9581
Background: AKT, a serine threonine protein kinase, is activated downstream of phosphatidylinositol 3-kinase (PI3K) which transmits signals from cytokines, growth factors and ...oncoproteins to multiple targets. Activated AKT regulates survival, proliferation, and growth. The PI3K/AKT pathway is downstream of most of the common growth factor tyrosine kinase receptors in cancer, e.g., EGFR, HER2, IGFR, etc., and is a driver of tumor progression in many cancers. AKT protein kinase is activated in many pediatric solid tumors, including glioblastoma, malignant rhabdoid tumors, neuroblastoma, synovial sarcoma, rhabdomyosarcoma and medulloblastoma. MK2206, an oral allosteric AKT1, 2,3 inhibitor, has demonstrated antitumor activity in in vitro and in vivo cancer models.A phase I trial evaluating MK2206 was conducted in children with refractory solid tumors. Methods: Using a rolling-6 design, MK2206 was administered either once every 7 days (schedule 1), or once every other day (schedule 2) in a 28-day cycle. Serial PK studies were obtained on day 1, cycle 1 and trough samples were obtained on days 7, 14, 21 and 28. Biological studies included analysis of PI3K/PTEN/AKT-cell signaling pathway in pre and post-therapy in PBMC and in tumors at diagnosis or recurrence. Results: Forty-five patients 23 males, median age 13.6 years (range 3.1-21.9) with malignant glioma (14), ependymoma (4), hepatocellular carcinoma (3), gliomatosis cereberi (2) or other tumors (22) were enrolled; 34 were fully evaluable for toxicity (schedule 1 n=17; schedule 2 n=17). Schedule 1 DLTs included: grade 3 dehydration in 1/6 patients at 28 mg/m
2
; grade 4 hyperglycemia and neutropenia in 1/6 patients at 45 mg/m
2
. There were no DLTs at 35 mg/m
2
and dose level 4 (58 mg/m
2
) is currently open for patient accrual with one enrollment. Schedule 2 DLTs included: grade 3 alkaline phosphatase in 1/6 patients at 90 mg/m
2
; grade 3 rash in 1/6 patients at 120 mg/m
2
), and grade 3 rash in 2/6 patients at 155 mg/m
2.
Conclusions: The recommended pediatric phase II dose of weekly MK2206 is 120 mg/m
2
and the last cohort of patients to the every other day dosing schedule of MMK206 is enrolling. PK and PD data are currently being analyzed and will be presented.
PDF
