tbuckley/cabot-search huggingface dataset:
Contemporary Management of Chronic Obstructive Pulmonary Disease
Authors: Don D. Sin, Finlay A. McAlister, S. F. Paul Man, Nick R. Anthonisen
Journal: JAMA (2003)

<h3>Context</h3> The care of patients with chronic obstructive pulmonary disease (COPD) has changed radically over the past 2 decades, and novel therapies can not only improve the health status of patients with COPD but also modify its natural course. <h3>Objective</h3> To systematically review the impact of long-acting bronchodilators, inhaled corticosteroids, nocturnal noninvasive mechanical ventilation, pulmonary rehabilitation, domiciliary oxygen therapy, and disease management programs on clinical outcomes in patients with COPD. <h3>Data Sources</h3> MEDLINE and Cochrane databases were searched to identify all randomized controlled trials and systematic reviews from 1980 to May 2002 evaluating interventions in patients with COPD. We also hand searched bibliographies of relevant articles and contacted experts in the field. <h3>Study Selection and Data Extraction</h3> We included randomized controlled trials that had follow-up of at least 3 months and contained data on at least 1 of these clinical outcomes: health-related quality of life, exacerbations associated with COPD, or death. For pulmonary rehabilitation, we included studies that had a follow-up of at least 6 weeks. Using standard meta-analytic techniques, the effects of interventions were compared with placebo or with usual care. In secondary analyses, the effects of interventions were compared against each other, where possible. <h3>Data Synthesis</h3> Long-acting β<sub>2</sub>-agonists and anticholinergics (tiotropium) reduced exacerbation rates by approximately 20% to 25% (relative risk [RR] for long-acting β<sub>2</sub>-agonists, 0.79; 95% CI, 0.69-0.90; RR for tiotropium, 0.74; 95% CI, 0.62-0.89) in patients with moderate to severe COPD. Inhaled corticosteroids also reduced exacerbation rates by a similar amount (RR, 0.76; 95% CI, 0.72-0.80). The beneficial effects were most pronounced in trials enrolling patients with FEV<sub>1</sub>between 1 L and 2 L. Combining a long-acting β<sub>2</sub>-agonist with an inhaled corticosteroid resulted in an approximate 30% (RR, 0.70; 95% CI, 0.62-0.78) reduction in exacerbations. Pulmonary rehabilitation improved the health status of patients with moderate to severe disease, but no material effect was observed on long-term survival or hospitalization rates. Domiciliary oxygen therapy improved survival by approximately 40% in patients with PaO<sub>2</sub>lower than 60 mm Hg, but not in those without hypoxia at rest. The data on disease management programs were heterogeneous, but overall no effect was observed on survival or risk of hospitalization. Noninvasive mechanical ventilation was not associated with improved outcomes. <h3>Conclusions</h3> A significant body of evidence supports the use of long-acting bronchodilators and inhaled corticosteroids in reducing exacerbations in patients with moderate to severe COPD. Domiciliary oxygen therapy is the only intervention that has been demonstrated to prolong survival, but only in patients with resting hypoxia.
An Atlas of Advanced Surgical Techniques
Authors: B. Eiseman
Journal: JAMA (1968)

There are plenty of atlases available describing how to perform common general surgical procedures. We are now in an era of secondgeneration atlases, where the newer, more difficult, and less common operations are being described. The new<i>Atlas of Advanced Surgical Techniques</i>is such a volume. It aims to provide the trained surgeon with a ready reminder of how he was taught to do a procedure that he probably seldom performs. The operations described are varied but in general are on the borders of general surgery. Of the 29 procedures, 7 are of the head and neck; 6 of the chest; and 12 of the abdomen and pelvis. Many are procedures usually performed by the specialist but which the general surgeon occasionally finds within his practice. There are a few old friends, such as total colectomy and abdominal perineal resection, but the majority are nodding acquaintances, such as ileal conduits,
Inducing Tumor Immunity through the Selective Engagement of Activating Fcγ Receptors on Dendritic Cells
Authors: Alexis M. Kalergis, Jeffrey V. Ravetch
Journal: The Journal of Experimental Medicine (2002)

Induction of tumor-specific immunity requires that dendritic cells (DCs) efficiently capture and present tumor antigens to result in the expansion and activation of tumor-specific cytotoxic T cells. The transition from antigen capture to T cell stimulation requires a maturation signal; in its absence tolerance, rather than immunity may develop. While immune complexes (ICs) are able to enhance antigen capture, they can be poor at inducing DC maturation, naive T cell activation and protective immunity. We now demonstrate that interfering with the inhibitory signal delivered by FcgammaRIIB on DCs converts ICs to potent maturation agents and results in T cell activation. Applying this approach to immunization with DCs pulsed ex-vivo with ICs, we have generated antigen-specific CD8+ T cells in vivo and achieved efficient protective immunity in a murine melanoma model. These data imply that ICs may normally function to maintain tolerance through the binding to inhibitory FcgammaRs on DCs, but they can be converted to potent immunogenic stimuli by selective engagement of activating FcgammaRs. This mechanism suggests a novel approach to the development of tumor vaccines.
Sacked cardiologist takes former employer to High Court
Authors: C. Dyer
Journal: BMJ (2011)

A former consultant cardiologist who was sacked nearly nine years after he was first suspended has taken his former employers to the high court in London, claiming that his dismissal was unlawful and therefore void.

Raj Mattu was suspended by University Hospitals Coventry and Warwickshire NHS Trust in February 2002 on allegations of bullying, five months after he spoke to the BBC about the deaths of two patients in overcrowded bays at Walsall Hospital in Coventry.

He was reinstated in …
Pediatric Oncology as the Next Global Child Health Priority: The Need for National Childhood Cancer Strategies in Low- and Middle-Income Countries
Authors: Sumit Gupta, Roberto Rivera-Luna, Raul C. Ribeiro, Scott C. Howard
Journal: PLoS Medicine (2014)

N As is already the case in high-income countries, cancer represents the leading cause of non-accidental death among children in a growing number of middleincome countries N Meaningful declines in global childhood cancer mortality will require moving beyond the current situation through the establishment of national childhood cancer strategies N Key components of such strategies include financial coverage, accreditation of childhood cancer centers, mandatory childhood cancer reporting and registration, development of national standards of care, and the creation of national childhood cancer governing bodies N Challenges to implementing such strategies include a paucity of implementa- tion research, formal policy evaluation, and costing data N The ideal structure of such strategies in low-income countries is currently unknown, given severe resource constraints, deficits in infrastructure, and competing health needs
Why do posh people ignore poverty on their own doorstep?
Authors: Deborah Cohen
Journal: BMJ (2007)

Background: Nogo-B receptor (NgBR) has been shown to be involved in endothelial cell chemotaxis and morphogenesis. However, few studies analyzing its expression in cancer cells have been performed. Materials and Methods: We examined NgBR expression in 233 patients with invasive ductal breast carcinoma (IDC) and corresponding non-malignant breast tissues (NMBT) on mRNA (real-time polymerase chain reaction) and protein levels (immunohistochemistry; IHC and western-blot analysis). NgBR expression was found also analyzed in breast cancer cell lines of varying invasiveness. Results: NgBR expression was increased in IDC compared to NMBT on the mRNA (p=0.0007) and protein level (p=0.018). NgBR expression decreased significantly with IDC malignancy grade and correlated negatively with the Ki-67 antigen expression (r=−0.18; p=0.0005). High NgBR mRNA expression was associated with estrogen receptor negativity (p=0.0023) and the triple-negative phenotype of the tumors (p=0.0129). Conclusion: NgBR may be involved in IDC development, however, its role in its progression requires further research.
Reflection as a cause of mid-systolic deceleration of pulmonary flow wave in dogs with acute pulmonary hypertension: comparison of pulmonary artery constriction with pulmonary embolisation
Authors: Y. Furuno, Y. Nagamoto, M. Fujita, T. Kaku, S. Sakurai, A. Kuroiwa
Journal: Cardiovascular Research (1991)

Study objective – The aim was to examine whether mid-systolic deceleration of the pulmonary flow wave occurred in acute pulmonary hypertension due to pulmonary artery constriction and pulmonary embolisation, and if so whether it was related to reflection. Design – Various degrees of pulmonary hypertension were induced by both pulmonary artery constriction and pulmonary embolisation in dogs. During control periods and during pulmonary artery constriction and pulmonary embolisation, pulmonary flow and pulmonary artery pressure were recorded, and the forward and backward (reflected) flow waves were separated from the measured pulmonary flow wave by the method of Westerhof et al. Materials – 20 adult mongrel dogs were used and 10 dogs qualified for analysis. The other 10 dogs, which died before both interventions were completed, were excluded. Measurements and main results – During pulmonary artery constriction, a distinct mid-systolic deceleration of the pulmonary flow wave was observed in five of the 10 dogs, while during pulmonary embolisation, no mid-systolic deceleration was found in these five dogs. The distinct deceleration of the pulmonary flow wave was related to a steep fall and early negative peak in the backward flow wave. Conclusion – Mid-systolic deceleration of pulmonary flow wave is likely to be related to reflection.
Pentoxifylline prevents fibrosis in an animal model and inhibits platelet-derived growth factor–driven proliferation of fibroblasts
Authors: Theresa C. Peterson
Journal: Hepatology (1993)

Liver fibrosis is a complex process characterized by two major events: fibroproliferation and increased collagen synthesis. The exact role of cytokines in the pathogenesis of hepatic fibrosis remains to be established, but platelet-derived growth factor clearly stimulates proliferation of fibroblasts and increases collagen synthesis. In in vitro studies, pentoxifylline, a methylxanthine, significantly reduced platelet-derived growth factor-driven proliferation of fibroblasts. Platelet-derived growth factor has also been identified as a fibroproliferative factor produced spontaneously by monocytes obtained from patients with liver disease. Long-term administration of pentoxifylline (16 mg/kg orally, 5 days/wk for 12 wk) in an animal model of liver fibrosis prevented elevations in gamma-glutamyl transpeptidase and alkaline phosphatase levels and prevented the reduction in serum albumin level normally observed in this animal model of liver disease. The animal model used was a long-term, low-dose yellow phosphorus--induced model in pigs that reproducibly results in extensive fibrosis after 10 to 12 wk of treatment. Long-term administration of pentoxifylline also prevented the histological changes characteristic of fibrosis in this animal model. Collagen concentration was significantly elevated in liver sections obtained from animals receiving yellow phosphorus, compared with controls. Long-term pentoxifylline treatment resulted in significantly lower collagen concentrations in liver sections from animals receiving yellow phosphorus than in sections from animals receiving yellow phosphorus alone; this was supported by histological observation. Therefore administration of pentoxifylline prevented the biochemical and histological changes associated with an animal model of liver disease. Pentoxifylline will likely have an important therapeutic role in liver fibrosis.
Cutaneous T cell lymphomas: mycosis fungoides, Sezary syndrome and HTLV-I-associated adult T cell leukemia (ATL) in Mali, West Africa: a clinical, pathological and immunovirological study of 14 cases and a review of the African ATL cases
Authors: N Fouchard, A Mahe, M Huerre, S Fraitag, F Valensi, E Macintyre, F Sanou, G de The, A Gessain
Journal: Leukemia (1998)
Induction of SOS functions in Escherichia coli and biosynthesis of nitrosamine in rabbits by nitrogen dioxide.
Authors: H Kosaka, M Uozumi, T Nakajima
Journal: Environmental Health Perspectives (1987)

Nitrogen dioxide induced SOS functions in Salmonella typhimurium and Escherichia coli K-12 and was mutagenic in Escherichia coli WP2. When a rabbit was administered aminopyrine intravenously and administered nitrogen dioxide by inhalation, N-nitrosodimethylamine was detected in its blood. Analysis was conducted with 15N-nitrosodimethylamine as an internal standard by a combination of capillary gas chromatography and mass spectrometry. Accompanying administration of cystamine increased the blood concentration of N-nitrosodimethylamine in the rabbit, suggesting inhibition of its metabolism. Concurrent sulfur trioxide inhalation increased N-nitrosodimethylamine formation in the rabbit.
Treatment of hepatocellular carcinoma with octreotide: a randomised controlled study
Authors: E Kouroumalis, P Skordilis, K Thermos, A Vasilaki, J Moschandrea, O N Manousos
Journal: Gut (1998)

Background —Standard treatment of inoperable hepatocellular carcinoma has not been established. Somatostatin has been shown to possess antimitotic activity against a variety of non-endocrine tumours. Aims —To assess the presence of somatostatin receptors in human liver and to treat advanced hepatocellular carcinoma with the somatostatin analogue, octreotide. Methods —Somatostatin receptors were measured in liver tissue homogenates from patients with acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Fifty eight patients with advanced hepatocellular carcinoma were randomised to receive either subcutaneous octreotide 250 μg twice daily, or no treatment. Groups were comparable with respect to age, sex, Okuda classification, presence of cirrhosis, and liver biochemistry and virology. Results —Various amounts of somatostatin receptors were identified in liver tissue of all patients including those with hepatocellular carcinoma. Treated patients had an increased median survival (13 months versus four months, p=0.002, log rank test) and an increased cumulative survival rate at six and 12 months (75% versus 37%, and 56% versus 13% respectively). Octreotide administration significantly reduced α fetoprotein levels at six months. When a multivariable Cox’s proportional hazards model was fitted, variables associated with increased survival were: treatment administration, absence of cirrhosis, increased serum albumin, and small tumours. Treated patients clearly had a lower hazard (0.383) in the multivariate analysis. Conclusions —Octreotide administration significantly improves survival and is a valuable alternative in the treatment of inoperable hepatocellular carcinoma.
Abstract 3226: GALNT6 stabilizes GRP78 protein by O-type glycosylation
Authors: Jae-Hyun Park, Suyoun Chung, Jiaying Lin, Koji Ueda, Toyomasa Katagiri, Yusuke Nakamura
Journal: Cancer Research (2014)

Abstract Aberrant O-type glycosylation is predominantly detected in breast cancer and plays diverse roles in cancer cell proliferation, metastasis, and drug resistance. GALNT (polypeptide N-acetylgalactosaminyl transferase) family initiates the O-type glycosylation and its high activity accounts for aberrant O-type glycosylation in breast cancer. We previously suggested that GALNT6 is a promising molecular target in breast cancer and involved in O-type glycosylation of Mucin 1 and fibronectin. To further investigate the molecular function of GALNT6, we performed pull down assay using VVA (Vicia Villosa agglutinin) lectin and identified several O-glycosylated proteins specifically in GALNT6-positive stable cells. After in vitro and in vivo O-glycosylation assays, we confirmed GRP78 (glucose related protein 78) as a physiological substrate of GALNT6 and identified 5 O-glycosylation sites in GRP78 by mass spectrometry. GRP78 is a molecular chaperone that facilitates proper protein folding under cellular stress. Interestingly, accumulating evidences have indicated that GRP78 plays anti-apoptotic roles in cancer cells against chemotherapy. Exogenous induction of GALNT6 increased the amount of GRP78 protein without any changes in its transcriptional level. Concordantly, knockdown of GALNT6 significantly reduced the GRP78 protein. Collectively, our findings imply that GALNT6 stabilizes GRP78 via O-glycosylation and GALNT6 inhibitor will be able to sensitize breast cancer cells to chemotherapy. Citation Format: Jae-Hyun Park, Suyoun Chung, Jiaying Lin, Koji Ueda, Toyomasa Katagiri, Yusuke Nakamura. GALNT6 stabilizes GRP78 protein by O-type glycosylation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3226. doi:10.1158/1538-7445.AM2014-3226
The fibrodysplasia ossificans progressiva R206H ACVR1 mutation activates BMP-independent chondrogenesis and zebrafish embryo ventralization
Authors: Qi Shen, Shawn C. Little, Meiqi Xu, Julia Haupt, Cindy Ast, Takenobu Katagiri, Stefan Mundlos, Petra Seemann, Frederick S. Kaplan, Mary C. Mullins, Eileen M. Shore
Journal: Journal of Clinical Investigation (2009)

Patients with classic fibrodysplasia ossificans progressiva, a disorder characterized by extensive extraskeletal endochondral bone formation, share a recurrent mutation (R206H) within the glycine/serine-rich domain of ACVR1/ALK2, a bone morphogenetic protein type I receptor. Through a series of in vitro assays using several mammalian cell lines and chick limb bud micromass cultures, we determined that mutant R206H ACVR1 activated BMP signaling in the absence of BMP ligand and mediated BMP-independent chondrogenesis that was enhanced by BMP. We further investigated the interaction of mutant R206H ACVR1 with FKBP1A, a glycine/serine domain–binding protein that prevents leaky BMP type I receptor activation in the absence of ligand. The mutant protein exhibited reduced binding to FKBP1A in COS-7 simian kidney cell line assays, suggesting that increased BMP pathway activity in COS-7 cells with R206H ACVR1 is due, at least in part, to decreased binding of this inhibitory factor. Consistent with these findings, in vivo analyses of zebrafish embryos showed BMP-independent hyperactivation of BMP signaling in response to the R206H mutant, resulting in increased embryonic ventralization. These data support the conclusion that the mutant R206H ACVR1 receptor in FOP patients is an activating mutation that induces BMP signaling in a BMP-independent and BMP-responsive manner to promote chondrogenesis, consistent with the ectopic endochondral bone formation in these patients.
Danazol distribution in plasma and cell membranes as related to altered cell properties: Implications for mechanism
Authors: Lawrence L. Horstman, Wenche Jy, Manuel Arce, Yeon S. Ahn
Journal: American Journal of Hematology (1995)

Abstract Concentrations of danazol in patient plasma and red blood cells (RBC) were assayed over a 6‐month period in 75 patients on danazol therapy using a high‐pressure liquid chromatography (HPLC) method more reliable than previous radioimmunoassay (RIA) methods. It was found that plasma danazol rose regularly for 15 days after the beginning of treatment, reaching a steady state plateau of 175 ± 76 ng/ml in 20 patients on normal dose, and less for lower dose schedules. After stopping danazol, concentrations declined to near zero in a similar time frame. RBC concentrations on a packed volume basis were similar to plasma levels. However, the membrane ghosts of RBC contained about 50% of the total RBC danazol, implying about 100‐fold higher concentration in membranes than in plasma. Similar distributions were obtained in vitro with both RBC and platelets, and were confirmed by 14‐C‐labeled danazol. These findings tend to support the hypothesis that the benefits of danazol in immune disorders may be attributable in part to its intercalation in the lipid bilayer of the plasma membrane, altering antigen/receptor expression to modulate immune reactions. This hypothesis was first suggested when it was observed that the RBC of patients on danazol therapy showed morphological changes and increased resistance to osmotic lysis. It was later shown that danazol in vitro reduces binding of autoantibodies, and protects against complement‐mediated lysis, suggesting direct action of danazol on the membranes. This hypothesis is discussed, and danazol's effect in protecting against complement‐mediated lysis is described.
Conservative Treatment of Ureteropelvic Junction Obstruction in Children with Antenatal Diagnosis of Hydronephrosis: Lessons Learned after 16 Years of Follow-Up
Authors: Boris Chertin, Avner Pollack, Dmitry Koulikov, Ron Rabinowitz, Daniel Hain, Irit Hadas-Halpren, Amicur Farkas
Journal: European Urology (2006)
Medical Treatment Leads to Closure of Patent Ductus Arteriosus
Authors: Zenonas Danilevicius
Journal: JAMA (1977)

Elliott et al<sup>1</sup>were probably the first to indicate that prostaglandin E<sub>1</sub>infused into infants enlarged the patency of ductus arteriosus. Their findings also suggested that administration of a nonspecific antagonist of prostaglandin synthesis, such as indomethacin, was associated with a fall in arterial saturation. Cotton et al<sup>2</sup>showed that medical management of symptomatic ductus arteriosus shunts in small preterm infants is possible. They used digitalis, mechanical ventilation, and transfusions. Although the results of medical management indicated the effectiveness of conservative means, Cotton considered that surgical treatment may be unavoidable in life-threatening situations. Pharmacologic closure of patent ductus arteriosus using indomethacin was achieved by Friedman et al.<sup>3</sup>Within 24 hours, all the clinical symptoms and signs attributable to left-to-right shunting dramatically and permanently disappeared in infants receiving the drug. Heymann et al<sup>4</sup>reported their experience with 18 infants who had cardiac failure associated with persistent