tbuckley/cabot-search huggingface dataset:
Association of Hypoglycemic Treatment Regimens With Cardiovascular Outcomes in Overweight and Obese Subjects With Type 2 Diabetes
Authors: Adam Ali Ghotbi, Lars Køber, Nick Finer, W. Philip T. James, Arya M. Sharma, Ian Caterson, Walmir Coutinho, Luc F. Van Gaal, Christian Torp-Pedersen, Charlotte Andersson
Journal: Diabetes Care (2013)

To assess the association of hypoglycemic treatment regimens with cardiovascular adverse events and mortality in a large population of type 2 diabetic patients at increased cardiovascular risk.This analysis included 8,192 overweight patients with type 2 diabetes from the Sibutramine Cardiovascular Outcomes (SCOUT) trial randomized to lifestyle intervention with or without sibutramine for up to 6 years. Patients were grouped according to hypoglycemic treatment at baseline. The primary end point was the time from randomization to the first occurrence of a primary outcome event (POE), nonfatal myocardial infarction, nonfatal stroke, resuscitation after cardiac arrest, or cardiovascular death. Multivariable Cox proportional hazards regression models were used to assess the impact of antiglycemic treatment on POE and all-cause mortality.Treatments for type 2 diabetes were as follows: diet alone (n = 1,394 subjects), metformin monotherapy (n = 1,631), insulin monotherapy (n = 1,116), sulfonylurea monotherapy (n = 1,083), metformin plus sulfonylurea (n = 1,565), and metformin plus insulin (n = 1,000); 905 subjects experienced a POE and 708 died. Metformin monotherapy was associated with lower risk of POE than insulin (hazard ratio [HR], 0.74; 95% CI, 0.57-0.95; P = 0.02). Diet alone also was associated with lower risk of POE (HR, 0.65; 95% CI, 0.48-0.87; P = 0.004). Metformin monotherapy also was associated with lower mortality (HR, 0.73; 95% CI, 0.54-0.99; P < 0.05), whereas no other monotherapies or combination therapies were significantly associated with POE or all-cause mortality compared with insulin as monotherapy.In obese patients with type 2 diabetes and high risk of cardiovascular disease, monotherapy with metformin or diet-only treatment was associated with lower risk of cardiovascular events than treatment with insulin.
THE STABILITY OF THE ACID-BASE EQUILIBRIUM OF THE BLOOD IN NATURALLY NEPHROPATHIC ANIMALS AND THE EFFECT ON RENAL FUNCTION OF CHANGES IN THIS EQUILIBRIUM
Authors: William deB. MacNider
Journal: The Journal of Experimental Medicine (1918)

1. The naturally acquired chronic glomerulonephropathies of the dog are not due to an acid intoxication. 2. Such an injury renders the acid-base equilibrium of the animal unstable and susceptible to an agent such as an anesthetic which tends to induce an acid intoxication. 3. When naturally nephropathic animals are anesthetized by Grehant's anesthetic, the principal anesthetic ingredient of which is chloroform, the animals develop an acid intoxication, and become anuric and non-responsive to diuretic substances. 4. The development of the anuria has been constantly associated with swelling, vacuolation, and necrosis of the convoluted tubule epithelium. 5. In the kidneys of these animals there occurs an accumulation of fat which is largely confined to the ascending limbs of Henle's loops and which shows a quantitative relation with the degree of acid intoxication.
A recurrent 16p12.1 microdeletion supports a two-hit model for severe developmental delay
Authors: Santhosh Girirajan, Jill A Rosenfeld, Gregory M Cooper, Francesca Antonacci, Priscillia Siswara, Andy Itsara, Laura Vives, Tom Walsh, Shane E McCarthy, Carl Baker, Heather C Mefford, Jeffrey M Kidd, Sharon R Browning, Brian L Browning, Diane E Dickel, Deborah L Levy, Blake C Ballif, Kathryn Platky, Darren M Farber, Gordon C Gowans, Jessica J Wetherbee, Alexander Asamoah, David D Weaver, Paul R Mark, Jennifer Dickerson, Bhuwan P Garg, Sara A Ellingwood, Rosemarie Smith, Valerie C Banks, Wendy Smith, Marie T McDonald, Joe J Hoo, Beatrice N French, Cindy Hudson, John P Johnson, Jillian R Ozmore, John B Moeschler, Urvashi Surti, Luis F Escobar, Dima El-Khechen, Jerome L Gorski, Jennifer Kussmann, Bonnie Salbert, Yves Lacassie, Alisha Biser, Donna M McDonald-McGinn, Elaine H Zackai, Matthew A Deardorff, Tamim H Shaikh, Eric Haan, Kathryn L Friend, Marco Fichera, Corrado Romano, Jozef Gécz, Lynn E DeLisi, Jonathan Sebat, Mary-Claire King, Lisa G Shaffer, Evan E Eichler
Journal: Nature Genetics (2010)
Immune-Mediated Inhibition of Metastases after Treatment with Local Radiation and CTLA-4 Blockade in a Mouse Model of Breast Cancer
Authors: Sandra Demaria, Noriko Kawashima, Anne Marie Yang, Mary Louise Devitt, James S. Babb, James P. Allison, Silvia C. Formenti
Journal: Clinical Cancer Research (2005)

Ionizing radiation therapy (RT) is an important component in the management of breast cancer. Although the primary tumor can be successfully treated by surgery and RT, metastatic breast cancer remains a therapeutic challenge. Here we tested the hypothesis that the combination of RT to the primary tumor with CTLA-4 blockade can elicit antitumor immunity inhibiting the metastases.The poorly immunogenic metastatic mouse mammary carcinoma 4T1 was used as a model. Mice were injected s.c. with 4T1 cells, and treatment was started 13 days later when the primary tumors measured 5 mm in average diameter. Mice were randomly assigned to four treatment groups receiving: (1) control IgG (IgG), (2) RT + IgG, (3) 9H10 monoclonal antibody against CTLA-4, (4) RT + 9H10. RT was delivered to the primary tumor by one or two fractions of 12 Gy. 9H10 and IgG were given i.p. thrice after RT.Consistent with the fact that 4T1 is poorly immunogenic, 9H10 alone did not have any effect on primary tumor growth or survival. RT was able to delay the growth of the primary irradiated tumor, but in the absence of 9H10 survival was similar to that of control mice. In contrast, mice treated with RT + 9H10 had a statistically significant survival advantage. The increased survival correlated with inhibition of lung metastases formation and required CD8+ but not CD4+ T cells.The combination of local RT with CTLA-4 blockade is a promising new immunotherapeutic strategy against poorly immunogenic metastatic cancers.
Management of occluded biliary Wallstents
Authors: T C K Tham, D L Carr-Locke, J Vandervoort, R C K Wong, D R Lichtenstein, J Van Dam, F Ruymann, S Chow, J J Bosco, T Qaseem, D Howell, D Pleskow, W Vannerman, E D Libby
Journal: Gut (1998)

Background— Wallstents (Schneider Stent, Inc., USA) used for the palliation of malignant biliary strictures, although associated with prolonged patency, can occlude. There is no consensus regarding the optimal management of Wallstent occlusion. Aims —To evaluate the efficacy of different endoscopic methods for managing biliary Wallstent occlusion. Methods —A multicentre retrospective study of patients managed for a biliary Wallstent occlusion. Results —Data were available for 38 patients with 44 Wallstent occlusions, all of which had initial endoscopic management. Twenty four patients had died and 14 were alive after a median follow up of 231 (30–1095) days following Wallstent occlusion. Occlusions were managed by insertion of another Wallstent in 19, insertion of a plastic stent in 20, and mechanical cleaning in five. Endoscopic management was successful in 43 (98%). Following management of the occlusion, bilirubin decreased from 6.0 (0.5–34.3) to 2.1 (0.2–27.7) mg/100 ml (p&lt;0.05). No complications occurred. The median duration of second stent patency was 75 days (95% confidence interval 43 to 107) after insertion of another Wallstent, 90 days (71 to 109) after insertion of a plastic stent, and 34 days (30 to 38) after mechanical cleaning (NS). The respective median survivals were 70 days (22–118), 98 days (54–142), and 34 days (30–380) (NS). Incremental cost effective analysis showed that plastic stent insertion is the most cost effective option. Conclusion —Although all three methods are equally effective in managing an occluded Wallstent, the most cost effective method appears to be plastic stent insertion.
Penetrating missile pulmonary embolisation
Authors: C. S. H. Ng, M. W. T. Kwok, R. H. L. Wong
Journal: European Respiratory Journal (2009)

To the Editors: 

We read with interest the review by Jorens et al. 1 highlighting the causes, diagnosis and treatment of nonthrombotic pulmonary embolism. Certainly, particulate material embolisation, especially from an iatrogenic source, is becoming more common. In fact, another well recognised source of embolisation of cyanoacrylate glue and lipiodol is following endoscopic injection …
A Notch1 Ectodomain Construct Inhibits Endothelial Notch Signaling, Tumor Growth, and Angiogenesis
Authors: Yasuhiro Funahashi, Sonia L. Hernandez, Indranil Das, Audrey Ahn, Jianzhong Huang, Marina Vorontchikhina, Anshula Sharma, Emi Kanamaru, Valeriya Borisenko, Dinuka M. DeSilva, Akihiko Suzuki, Xing Wang, Carrie J. Shawber, Jessica J. Kandel, Darrell J. Yamashiro, Jan Kitajewski
Journal: Cancer Research (2008)

Abstract Notch signaling is required for vascular development and tumor angiogenesis. Although inhibition of the Notch ligand Delta-like 4 can restrict tumor growth and disrupt neovasculature, the effect of inhibiting Notch receptor function on angiogenesis has yet to be defined. In this study, we generated a soluble form of the Notch1 receptor (Notch1 decoy) and assessed its effect on angiogenesis in vitro and in vivo. Notch1 decoy expression reduced signaling stimulated by the binding of three distinct Notch ligands to Notch1 and inhibited morphogenesis of endothelial cells overexpressing Notch4. Thus, Notch1 decoy functioned as an antagonist of ligand-dependent Notch signaling. In mice, Notch1 decoy also inhibited vascular endothelial growth factor–induced angiogenesis in skin, establishing a role for Notch receptor function in this process. We tested the effects of Notch1 decoy on tumor angiogenesis using two models: mouse mammary Mm5MT cells overexpressing fibroblast growth factor 4 (Mm5MT-FGF4) and NGP human neuroblastoma cells. Exogenously expressed FGF4 induced Notch ligand expression in Mm5MT cells and xenografts. Notch1 decoy expression did not affect tumorigenicity of Mm5MT-FGF4 cells in vitro but restricted Mm5MT-FGF4 xenograft growth in mice while markedly impairing neoangiogenesis. Similarly, Notch1 decoy expression did not affect NGP cells in vitro but disrupted vessels and decreased tumor viability in vivo. These results strongly suggest that Notch receptor signaling is required for tumor neoangiogenesis and provides a new target for tumor therapy. [Cancer Res 2008;68(12):4727–35]
TRPV2 Is a Component of Osmotically Sensitive Cation Channels in Murine Aortic Myocytes
Authors: Katsuhiko Muraki, Yuko Iwata, Yuki Katanosaka, Tomohiro Ito, Susumu Ohya, Munekazu Shigekawa, Yuji Imaizumi
Journal: Circulation Research (2003)

Changes in membrane tension resulting from membrane stretch represent one of the key elements in blood flow regulation in vascular smooth muscle. However, the molecular mechanisms involved in the regulation of membrane stretch remain unclear. In this study, we provide evidence that a vanilloid receptor (TRPV) homologue, TRPV2 is expressed in vascular smooth muscle cells, and demonstrate that it can be activated by membrane stretch. Cell swelling caused by hypotonic solutions activated a nonselective cation channel current (NSCC) and elevated intracellular Ca 2+ ([Ca 2+ ] i ) in freshly isolated cells from mouse aorta. Both of these signals were blocked by ruthenium red, an effective blocker of TRPVs. The absence of external Ca 2+ abolished this increase in [Ca 2+ ] i caused by the hypotonic stimulation and reduced the activation of NSCC. Significant immunoreactivity to mouse TRPV2 protein was detected in single mouse aortic myocytes. Moreover, the expression of TRPV2 was found in mesenteric and basilar arterial myocytes. Treatment of mouse aorta with TRPV2 antisense oligonucleotides resulted in suppression of hypotonic stimulation-induced activation of NSCC and elevation of [Ca 2+ ] i as well as marked inhibition of TRPV2 protein expression. In Chinese hamster ovary K1 (CHO) cells transfected with TRPV2 cDNA (TRPV2-CHO), application of membrane stretch through the recording pipette and hypotonic stimulation consistently activated single NSCC. Moreover, stretch of TRPV2-CHO cells cultured on an elastic silicon membrane significantly elevated [Ca 2+ ] i . These results provide a strong basis for our purpose that endogenous TRPV2 in mouse vascular myocytes functions as a novel and important stretch sensor in vascular smooth muscles.
Bright/ARID3A contributes to chromatin accessibility of the immunoglobulin heavy chain enhancer
Authors: Danjuan Lin, Gregory C Ippolito, Rui-Ting Zong, James Bryant, Janet Koslovsky, Philip Tucker
Journal: Molecular Cancer (2007)

Abstract Bright/ARID3A is a nuclear matrix-associated transcription factor that stimulates immunoglobulin heavy chain (IgH) expression and Cyclin E1/E2F-dependent cell cycle progression. Bright positively activates IgH transcriptional initiation by binding to ATC-rich P sites within nuclear matrix attachment regions (MARs) flanking the IgH intronic enhancer (Eμ). Over-expression of Bright in cultured B cells was shown to correlate with DNase hypersensitivity of Eμ. We report here further efforts to analyze Bright-mediated Eμ enhancer activation within the physiological constraints of chromatin. A system was established in which VH promoter-driven in vitro transcription on chromatin- reconstituted templates was responsive to Eμ. Bright assisted in blocking the general repression caused by nucleosome assembly but was incapable of stimulating transcription from prebound nucleosome arrays. In vitro transcriptional derepression by Bright was enhanced on templates in which Eμ is flanked by MARs and was inhibited by competition with high affinity Bright binding (P2) sites. DNase hypersensitivity of chromatin-reconstituted Eμ was increased when prepackaged with B cell nuclear extract supplemented with Bright. These results identify Bright as a contributor to accessibility of the IgH enhancer.
Coupling of Ca <sup>2+</sup> to CREB Activation and Gene Expression in Intact Cerebral Arteries From Mouse
Authors: L. Cartin, K. M. Lounsbury, M. T. Nelson
Journal: Circulation Research (2000)

Abstract —Pathological changes of the vasculature are characterized by changes in Ca 2+ handling and alterations in gene expression. In neurons and other cell types, [Ca 2+ ] i often drives changes in gene expression. However, the relationship between Ca 2+ signaling and gene expression in vascular smooth muscle is not well understood. This study examines the ability of Ca 2+ influx through voltage-dependent, L-type Ca 2+ channels (VDCCs) and Ca 2+ release through ryanodine receptors (RyRs) to activate the transcription factor, cAMP-responsive element binding protein (CREB), and increase c- fos levels in intact cerebral arteries. Membrane depolarization increased the fraction of nuclei staining for phosphorylated CREB (P-CREB) and levels of c- fos mRNA in intact mouse cerebral arteries. Ryanodine, which inhibits RyRs, increased P-CREB staining and c- fos levels. Forskolin, an activator of adenylyl cyclase, and sodium nitroprusside, an NO donor, increased P-CREB and c- fos levels. Nisoldipine, an inhibitor of VDCCs, reversed the effects of depolarization and ryanodine on P-CREB and c- fos levels, but not the effects of forskolin or sodium nitroprusside. Inhibition of Ca 2+ /calmodulin-dependent protein kinase (CaM kinase) blocked increases in P-CREB and c- fos levels seen with membrane depolarization, suggesting that CaM kinase has an important role in the pathway leading from Ca 2+ influx to CREB-mediated changes in c- fos levels. Our data suggest that membrane depolarization increases [Ca 2+ ] i through activation of VDCCs, leading to increased P-CREB and c- fos , and that RyRs have a profound effect on this pathway by indirectly regulating Ca 2+ entry through VDCCs. These results provide the first evidence of Ca 2+ regulation of CREB and c- fos in arterial smooth muscle.
Morbidity and Mortality Following Elective Splenectomy for Benign and Malignant Hematologic Conditions
Authors: Naina Bagrodia, Anna M. Button, Philip M. Spanheimer, Mary E. Belding-Schmitt, Lori J. Rosenstein, James J. Mezhir
Journal: JAMA Surgery (2014)

Splenectomy is a commonly performed operation; however, data from large series regarding operative outcomes to help guide decision making and informed consent are lacking.To evaluate clinical and pathologic variables associated with morbidity and mortality following elective splenectomy for benign and malignant hematologic conditions in the United States.A review of the American College of Surgeons National Surgical Quality Improvement Program data for elective splenectomy between January 1, 2005, and December 31, 2011, was performed, and 1715 eligible individuals were identified.Elective splenectomy for hematologic conditions.Complications and operative mortality were evaluated for the entire cohort and compared between patients with benign vs malignant diseases. Multivariable logistic regression was used to evaluate factors predictive of operative complications and death.Splenectomy was performed in 1344 patients (78.4%) for benign disease and in 371 patients (21.6%) for malignant disease. Two hundred ninety-one patients (17.0%) had a complication, and operative mortality occurred in 27 patients (mortality rate, 1.6%). Patients treated for malignant disease had a higher rate of overall complications (27.2%) compared with patients treated for benign disease (14.1%) (P < .001). Several variables were independent predictors of complications, including malignant disease (vs benign) (Odds Ratio [OR], 1.86; 95% CI, 1.23-2.80; P = .003), independent performance status (vs dependent) (OR, 0.33; 95% CI, 0.07-1.52; P = .02), and increasing albumin level (OR, 0.75; 95% CI, 0.66-0.86; P < .001). Increasing age (OR, 1.03; 95% CI, 1.00-1.06; P = .05) was an independent predictor of mortality while increasing albumin level (OR, 0.63; 95% CI, 0.46-0.86; P = .003) predicted lower risk of operative death. From these data, a patient older than 60 years with a low preoperative albumin level has a predicted probability for operative death as high as 10.0%.Preoperative performance and nutritional status are significant risk factors for complications and mortality following elective splenectomy. Although operative mortality continues to decrease over time, specific preoperative variables may help with patient selection before elective splenectomy for certain patients.
Tamoxifen for 5 years reduced 16-year risk for breast cancer in women at increased risk
Authors: Heather Parsons, Vered Stearns
Journal: Annals of Internal Medicine (2015)

Source Citation Cuzick J, Sestak I, Cawthorn S, et al; IBIS-I Investigators. Tamoxifen for prevention of breast cancer: extended long-term follow-up of the IBIS-I breast cancer prevention trial. Lancet Oncol. 2015;16:67-75. 25497694
A diachronic-comparative analysis for the identification of the most powerful prognostic index for localized diffuse large B-cell lymphoma
Authors: M. Mian, L. Marcheselli, A. Rossi, C. Visco, A. Chiappella, S. Volpetti, F. Zaja, P. Mondello, M. Fiegl, A. Billio, M. Federico, S. Luminari, A. Rambaldi, S. Cortelazzo
Journal: Annals of Oncology (2014)
Metformin for Weight Loss and Metabolic Control in Overweight Outpatients With Schizophrenia and Schizoaffective Disorder
Authors: L. Fredrik Jarskog, Robert M. Hamer, Diane J. Catellier, Dawn D. Stewart, Lisa LaVange, Neepa Ray, Lauren H. Golden, Jeffrey A. Lieberman, T. Scott Stroup, Lawrence Adler, Glen Burnie, Michael Barber, Matthew Byerly, Jose M. Canive, Ira Glick, David C. Henderson, J. Steven Lamberti, Ahsan Khan, Joseph Patrick McEvoy, Herbert Meltzer, Alexander Miller, Del D. Miller, Henry A. Nasrallah, Stephen Olson, Jayendra K. Patel, Bruce L. Saltz
Journal: American Journal of Psychiatry (2013)

Objective The purpose of this study was to determine whether metformin promotes weight loss in overweight outpatients with chronic schizophrenia or schizoaffective disorder. Method In a double-blind study, 148 clinically stable, overweight (body mass index [BMI] ≥27) outpatients with chronic schizophrenia or schizoaffective disorder were randomly assigned to receive 16 weeks of metformin or placebo. Metformin was titrated up to 1,000 mg twice daily, as tolerated. All patients continued to receive their prestudy medications, and all received weekly diet and exercise counseling. The primary outcome measure was change in body weight from baseline to week 16. Results Fifty-eight (77.3%) patients who received metformin and 58 (81.7%) who received placebo completed 16 weeks of treatment. Mean change in body weight was −3.0 kg (95% CI=−4.0 to −2.0) for the metformin group and −1.0 kg (95% CI=−2.0 to 0.0) for the placebo group, with a between-group difference of −2.0 kg (95% CI=−3.4 to −0.6). Metformin also demonstrated a significant between-group advantage for BMI (−0.7; 95% CI=−1.1 to −0.2), triglyceride level (−20.2 mg/dL; 95% CI=−39.2 to −1.3), and hemoglobin A1c level (−0.07%; 95% CI=−0.14 to −0.004). Metformin-associated side effects were mostly gastrointestinal and generally transient, and they rarely led to treatment discontinuation. Conclusions Metformin was modestly effective in reducing weight and other risk factors for cardiovascular disease in clinically stable, overweight outpatients with chronic schizophrenia or schizoaffective disorder over 16 weeks. A significant time-by-treatment interaction suggests that benefits of metformin may continue to accrue with longer treatment. Metformin may have an important role in diminishing the adverse consequences of obesity and metabolic impairments in patients with schizophrenia.
Guidelines for musculoskeletal ultrasound in rheumatology
Authors: M Backhaus
Journal: Annals of the Rheumatic Diseases (2001)

Within the past decade, musculoskeletal ultrasound (US) has become an established imaging technique for the diagnosis and follow up of patients with rheumatic diseases.1-5 This has been made possible through technological improvements, resulting in faster computers and higher frequency transducers. US is most commonly used in the assessment of soft tissue disease or detection of fluid collection and can also be used to visualise other structures, such as cartilage and bone surfaces.6 7 Owing to the better axial and lateral resolution of US, even minute bone surface abnormalities may be depicted. Thus destructive and/or reparative/hypertrophic changes on the bone surface may be seen before they are apparent on plain x rays or even magnetic resonance imaging.8 However, US wave frequencies cannot penetrate into bone, therefore imaging of intra-articular disease is usually not possible. The “real time” capability of US allows dynamic assessment of joint and tendon movements, which can often aid the detection of structural abnormalities. Advantages of US include its non-invasiveness, portability, relative inexpensiveness, lack of ionising radiation, and its ability to be repeated as often as necessary, making it particularly useful for the monitoring of treatment. US can also be used for guidance of aspiration, biopsy, and injection treatment.9 Most musculoskeletal work is performed using “grey scale”, which means images are produced in a black and white format; each white dot in the image represents a reflected sound wave. Sound waves travel in a similar way to light waves and therefore the denser a material is—for example, bone cortex, the more reflective it is and the whiter it appears on the screen. Water is the least reflective body material and therefore appears as black as the sound waves travel straight through it.

Newer US techniques, which are currently being evaluated, include colour and power …