tbuckley/cabot-search huggingface dataset:
New Pacific trade deal—good for pharma, bad for public health?
Authors: Jonathan Gornall
Journal: BMJ (2015)

Jonathan Gornall explains the debate about the Trans-Pacific Partnership

In his last term in office the US president, Barack Obama, is hoping that the vast trade deal known as the Trans-Pacific Partnership (TPP), will be “the most positive trade deal in history.” But opponents say the deal, being negotiated behind closed doors and to be signed by the end of the year, will be a shameful sell out that favours corporations over individuals and poses a grave threat to public health. 

Five years in the making, the TPP will bring together in a single trading block 12 nations that border the Pacific and which together account for almost 40% of global gross domestic product (GDP): Australia, Brunei, Canada, Chile, Japan, Malaysia, Mexico, New Zealand, Peru, Singapore, US, and Vietnam.1

The US government says the economic advantages are clear. Not only will the TPP boost US industries and jobs by wiping out the taxes imposed on American exports—one economic analysis says the TPP could be worth $78bn (£50bn; €70bn) a year for the US2—it will also serve America’s wider geopolitical agenda in the Asia-Pacific region.

“We have to make sure America writes the rules of the global economy,” Obama said in a speech in May. “Because if we don’t . . . China will.”3

Obama means well—he sees the TPP as an exercise in philanthropy as much as in job creation. The deal, says the White House, “reflects more than our interests . . . it reflects our values” and will impose “stronger, fully enforceable labor and environmental standards” on America’s trade partners. The White House says the deal puts in place, for the first time, labor standards, including a minimum wage, a ban on child labor, and the right to form …
Antenatal screening policies for Down's syndrome
Authors: N. J Wald
Journal: BMJ (2002)

Editor—Wellesley et al are unjustified in their view that serum screening for Down's syndrome is not worth while.1 They ignore evidence from previous studies that shows the substantial advantage of serum screening over screening based on maternal age alone.2–4 Their view is based on the results from two districts, the only two out of the eight where serum screening was routinely offered (using the Double test).

In these two districts only 24% of affected pregnancies (22 of the 91) were detected antenatally by using serum screening, though the Double test has a detection rate of 58% for a false positive rate of 5%.2 This could, at least in part, be due to a low screening uptake (in which case the focus should be on why this was so), but the uptake of screening cannot be determined from the paper. It could also be due to affected pregnancies that were positive on the serum test and positive on other tests being classified as positive under the other tests.

This problem arises because the detection rate used in this paper includes women who declined screening (the performance of screening tests, the uptake of screening, and the uptake of amniocentesis should all be reported separately). Methods of detection (serum screening, scan, maternal age, etc) were also tabulated in mutually exclusive categories, which cannot be correct because there will be pregnancies positive for Down's in two or more of these categories.

Wellesley et al compare screening results across different districts. In doing so they cannot (through lack of data) consider the substantial variations between districts in important factors that influence screening such as maternal age, uptake of screening, and use of ultrasonography. This problem is solved by comparing different screening methods in the same women—each woman acting as her own control. There is no better controlled study. Had they performed such an analysis, as we suggested in response to their earlier paper,5 they would have confirmed the substantial advantage of serum screening over age screening. Their call for controlled trials is unjustified.

Wellesley et al are incorrect in saying that the mathematical modelling carried out by others to estimate the effect of serum screening assumes that only 5% of pregnant women were aged over 35. Such modelling takes account of the maternal age distribution of the relevant population. The paper does not specify the performance of individual screening methods and does not assess the benefits of one over another. It is impossible to draw any valid conclusions about the different methods of screening for Down's syndrome from it.
Abstract 4192: Tissue ACE Inhibitors for Secondary Prevention of Adverse Cardiovascular Events in Patients with Preserved Left Ventricular Function: A Pooled Meta-Analysis
Authors: Sandeep A Saha, Janos Molnar, Rohit R Arora
Journal: Circulation (2006)

Introduction: Although the role of angiotensin converting enzyme (ACE) inhibitors in patients with depressed left ventricular function is well established, their role in patients with preserved ventricular function is uncertain. We conducted a meta-analysis of recent clinical trials to evaluate the role of tissue ACE inhibitors in secondary prevention of cardiovascular disease in patients with preserved left ventricular function. Study Selection: Randomized placebo-controlled clinical trials of at least 12 months duration, conducted in patients who had experienced an acute cardiovascular event or were at high risk for cardiovascular events. Data Synthesis and Analysis: A total of 31,555 patients from 4 selected trials were analyzed. Relative risk estimations were made using pooled data from the 4 trials. Statistical significance was determined using the Chi-square test (two-sided alpha error &lt;0.05). Results: When compared to placebo, the use of tissue ACE inhibitors was associated with significant relative risk reductions in all-cause mortality (p&lt;0.001), cardiovascular mortality (p&lt;0.001), fatal &amp; non-fatal myocardial infarction (p&lt;0.001) and stroke (p&lt;0.001), as well as hospitalization for congestive heart failure (p=0.001) &amp; occurrence of new-onset diabetes mellitus (p&lt;0.001). The need for invasive coronary revascularization was also reduced (p&lt;0.03), but the risk of hospitalization for angina was not significantly affected. Conclusion: Tissue ACE inhibitors decrease mortality and cardiovascular morbidity in high risk patients with cardiovascular disease and preserved left ventricular function in randomized placebo-controlled clinical trials.
Abstract 14434: Impact of Linagliptin on Cardiovascular (CV) Risk in Type 2 Diabetes (T2D): Insights From a Pre-defined CV Meta-Analysis
Authors: Julio Rosenstock, Nikolaus Marx, Dietmar Neubacher, Thomas Seck, Sanjay Patel, Hans-Jurgen Worle, Odd Erik Johansen
Journal: Circulation (2013)

Incidence of CV events is increased in T2D but the potential for CV risk modulation with glucose-lowering agents is debated. Interestingly, several CV meta-analyses involving drugs from the class o...
Clinical Performance of Whole-Body 18F-FDG PET/Dixon-VIBE, T1-Weighted, and T2-Weighted MRI Protocol in Colorectal Cancer
Authors: Soo Jin Lee, Hyo Jung Seo, Keon Wook Kang, Seung-Yong Jeong, Nam-Joon Yi, Jeong Min Lee, June-Key Chung, E. Edmund Kim, Jin Chul Paeng, Gi Jeong Cheon, Dong Soo Lee
Journal: Clinical Nuclear Medicine (2015)

Purpose The aim of this study was to investigate the clinical performance of whole-body 18F-FDG PET/Dixon–volume-interpolated breath-hold examination (Dixon-VIBE), T1-weighted, and T2-weighted MRI protocol in patients with colorectal cancer. Patients and Methods A total of 59 patients with colorectal cancer were enrolled in this study. Each patient had one of the following clinical conditions: initial stage before therapy, stage after neoadjuvant therapy, suspicious colorectal liver metastases, and colorectal liver metastases after chemotherapy. Fourteen patients had primary colorectal cancer, whereas 38 patients had a total of 132 hepatic lesions, 53 lesions existed before chemotherapy, and 79 lesions appeared after chemotherapy. The primary stage and metastases images were obtained using our PET/Dixon-VIBE/T1/T2 MRI protocol and were analyzed by 2 nuclear medicine physicians. Diagnostic accuracy was compared with contrast-enhanced MRI images, which were based on surgical pathology results. Results The sensitivity of our imaging protocol for primary colorectal cancer was 100% (14/14). T and N stage both showed 92.9% (13/14) accuracy. Of all 132 hepatic lesions, 115 metastatic lesions were analyzed, and 17 benign lesions were excluded (6 were during pretreatment cases, and 11 were during posttreatment cases). In pretreatment metastatic lesions (n = 47), the sensitivities of our protocol and dedicated MRI were 95.7% (45/47) and 100% (47/47), respectively. In posttreatment lesions (n = 68), sensitivities of our protocol and dedicated MRI were 75% (51/68) and 91.2% (62/68), respectively. Conclusions Whole-body PET/Dixon-VIBE/T1/T2 MRI protocol is clinically useful for TNM staging and chemonaive hepatic metastasis in colorectal cancer.
Protease inhibitors in HIV infection
Authors: N. Buss, F. Duff, A. J Shaw, K. A McLean
Journal: BMJ (1999)

Editor—Berger’s article on HIV protease inhibitors and the putative increased risk of heart disease contains inaccuracies and could be unnecessarily alarming.1 Several recent reports describe one or more syndromes in HIV infected people known variously as buffalo hump, protease paunch, or lipodystrophy.2,3 The symptoms include fat accumulation associated with increased abdominal girth or abnormal dorsal cervical fat coupled with wasting in extremities. Some reports have also highlighted hypertriglyceridaemia, hypercholesterolaemia, and insulin resistance.2

Case reports on small numbers of patients have suggested that these symptoms are associated with protease inhibitors. However, similar symptoms occur in some HIV positive patients not receiving protease inhibitors.3,4 They may therefore be a characteristic of HIV infection, possibly unmasked by prolonged survival associated with treatment with protease inhibitors.

In the cases that are associated with protease inhibitors differences are emerging between the various types of drug. One cross sectional analysis of 116 patients receiving one or more protease inhibitor in combination with nucleoside reverse transcriptase inhibitors found that symptoms of lipodystrophy developed more rapidly in patients receiving ritonavir–saquinavir than in those receiving indinavir,2 while in two other studies high relative risks occurred with ritonavir or indinavir. Carr and colleagues recently suggested that the differences between protease inhibitors may at least partly relate to variable degrees of inhibition of the cytochrome P-450 3A enzyme.5 This is consistent with a high risk being associated with ritonavir, the most potent inhibitor of this enzyme currently available.

Roche is performing exploratory analyses of over 500 patients participating in three ongoing clinical trials of combination therapy with saquinavir either alone or in combination with nelfinavir or ritonavir. Preliminary data suggest that mild increases in triglyceride and cholesterol concentrations occur in some patients with long term treatment, and these rises seem greatest in patients receiving ritonavir plus saquinavir. When saquinavir is the only protease inhibitor, very little lipid disturbance is seen; in one study of saquinavir with two nucleotide reverse transcriptase inhibitors large increases in triglyceride concentrations occurred in only 2% of 90 patients at 48 weeks.

Protease inhibitors have been clearly shown to prolong life and reduce opportunistic infections in HIV, not only in clinical trials but in practice. More research is needed to assess the potential long term effects of these drugs on lipid metabolism. In the meantime, however, their clinical benefits should not be overlooked.
Mononuclear Cell Transfer Is Associated with Superior Cardiac Recovery and Neovascularization as Compared to Non modified Mesenchymal Stem Cell Therapy in Chronic Myocardial Infarction
Authors: Myrielle Mathieu, Bachar Ghassan El Oumeiri, Karim Touihri, Philippe Thoma, Thierry Metens, Ielham Hadad, Lynn Ray, Naima Mazouz, Aurore De Lavareille, P. Willemsen, Robert Naeije, Guy Heyndrickx, Jozef Bartunek, Kathleen McEntee
Journal: Circulation (2008)
Abstract P4-06-02: Insulin receptor targeting in breast cancer through yeast surface display
Authors: Jie Ying Chan, Benjamin Hackel, Douglas Yee
Journal: Cancer Research (2015)

Abstract Selective estrogen receptor modulators (SERMs) such as tamoxifen have been a conventional therapy for breast cancer patients expressing estrogen receptor, representing the most common breast cancer type. The development of secondary resistance to SERM is an unsolved clinical dilemma, leading to the exploration of more targeted therapies. The insulin-like growth factor (IGF) system is well documented and is implicated as a contributor to endocrine resistance. Unfortunately, antibodies directed against type I IGF receptor (IGF1R) failed to demonstrate efficacy in endocrine resistant breast cancer. We have previously shown that tamoxifen resistant (TamR) breast cancer cells lose IGF1R yet retain expression of insulin receptor (InsR), a closely related receptor to IGF1R. Thus, we hypothesized that InsR may serve as a compensatory pathway to the loss of IGF1R in TamR cells and InsR may be a target in the therapy of endocrine resistant breast cancer. Indeed, our preliminary results show that TamR breast cancer cells were more sensitive to insulin stimulation. As compared to the parental cells, TamR cells showed stronger PI3K/AKT and MAPK/ERK activation, greater MTT proliferation growth and anchorage-independent growth upon insulin treatment. Knocking down InsR in TamR cells with shRNA was able to attenuate their sensitivity towards insulin-mediated PI3K/MAPK activation and growth, suggesting InsR targeting may be necessary in endocrine resistant breast cancer. To develop new agents to target InsR, we used yeast surface display to develop an InsR-selective protein scaffold – the 10th type III domain of human fibronectin (Fn3). This technique has arisen as an alternative method for the development of specific binders of cell surface proteins. Compared to antibodies, the Fn3 proteins are smaller (∼10kDa), thermally more stable, lack disulfide bonds and have the ability to bind a large variety of proteins. Using error-prone polymerase mutagenesis, we identified improved Fn3 proteins with increased InsR affinity, specificity, and stability. Our current results show that InsR is an important target in endocrine resistant breast cancer cells. Development of engineered Fn3 peptides with increased InsR binding specificity and affinity for InsR compared to IGF1R could be used to disrupt signaling through this pathway. Engineered Fn3 will further be evaluated as a potential imaging and therapeutic tool. Citation Format: Jie Ying Chan, Benjamin Hackel, Douglas Yee. Insulin receptor targeting in breast cancer through yeast surface display [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-06-02.
Detection of serum anti-endothelial cell antibodies (AECA) in COPD rats
Authors: Yong Lin, Qiang Zhang, Xue-Feng Ling, Si-Qing Sun
Journal: European Respiratory Journal (2011)

Background:  Chronic obstructive pulmonary disease (COPD) may be a systemic disease of autoimmune abnormality. Alveoli disorganization in COPD includes micro-vascular destruction. Anti-endothelial cell antibodies (AECA) are a type of circulating antibodies which bind to endothelial antigens and induce endothelial cell damage. It is unclear whether the AECA play a role in COPD mechanisms.   Objective:  To detect the serum level of anti-endothelial cell antibody in adult rats of COPD in order to investigate the significance of AECA in COPD mechanism.   Methods:  Replicated COPD rat models with passive-smoking and lipopolysaccharide trachea injections. The expression of AECA was examined by ELIZA.   Results:  In smoking rats with simple airway inflammation, the alveolar septum thickened but was not destroyed, AECA149.48±7.47 ng/L. COPD rats had airway inflammation and emphysema, AECA138.46±7.85 ng/L. Compared with the normal control group (62.89±10.68 ng/L), AECA levels in the two test groups were much higher.   Conclusion:  Autoimmunity constituents which induce endothelial cell lesions may participate in the pathogenesis of COPD; detection of serum AECA levels in COPD may have some clinical significance.
PFEIFFER BACILLUS MENINGITIS; THE CURE OF A CASE WITH SULFAPYRIDINE
Authors: C. C. Mclean, Arthur W. Woods, H. H. Henderson
Journal: Annals of Internal Medicine (1940)

Case Reports1 August 1940PFEIFFER BACILLUS MENINGITIS; THE CURE OF A CASE WITH SULFAPYRIDINEC. C. MCLEAN, M.D., F.A.C.P., ARTHUR W. WOODS, M.D., H. H. HENDERSON, M.D.C. C. MCLEAN, M.D., F.A.C.P.Search for more papers by this author, ARTHUR W. WOODS, M.D.Search for more papers by this author, H. H. HENDERSON, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-14-2-331 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptDue to the fact that the results in this particular patient were so spectacular, and that the dosage of the drug given was somewhat larger than is generally recommended, it was thought that a report of this case might be of interest.CASE REPORTL. H., colored male, 30 months of age, weight 32½ pounds, was admitted to Hillman Hospital at 9:45 p.m., February 4, 1939, with a history of fever, vomiting, and headache of five days' duration. Entrance examination revealed a rectal temperature of 102° F., positive Kernig and Brudzinski signs, increased tendon reflexes, and a stuporous mental condition.... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Birmingham, Alabama*Received for publication April 24, 1939. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAdvances in the chemotherapy of influenzal meningitis 1 August 1940Volume 14, Issue 2Page: 331-333KeywordsBacillusDrugsFeversHeadachesMeningitisReflexesTemperatureTendonsVomiting ePublished: 1 December 2008 Issue Published: 1 August 1940 PDF downloadLoading ...
Correlation between histological examination of bronchi from resected lung specimens and preoperative evaluation with fluorescence bronchoscopy (FB)
Authors: Caroline Roufosse, Philippe Vermylen, Thierry Bosschaerts, P. Pierard, Michel Richez, Thierry Berghmans, Alain Verhest, Jean-Paul Sculier, Vincent Ninane
Journal: European Respiratory Journal (1999)
Cerebral Vasculopathy in Sickle Cell Anemia: Diagnostic Contribution of Positron Emission Tomography
Authors: Darleen R. Powars, Peter S. Conti, Wing-Yen Wong, Paula Groncy, Carol Hyman, Elaine Smith, Nadia Ewing, Robert N. Keenan, Chi-Shing Zee, Yvonne Harold, Alan L. Hiti, Evelyn L. Teng, Linda S. Chan
Journal: Blood (1999)
Abstract 20604: Nyha Classification, Creatinine and Oral Anticoagulation Are Independent Risk Factors for Adverse Outcome in Patients With Eisenmenger Syndrome.
Authors: Alexander Van De Bruaene, Marion Delcroix, Agnes Pasquet, Julie De Backer, Michel De Pauw, Robert Naeije, Jean-Luc Vachiery, Bernard Paelinck, Marielle Morissens, Werner Budts
Journal: Circulation (2010)

Background: Pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD) usually results from a systemic-to-pulmonary shunt. Eisenmenger's syndrome (ES) is characterised by ...
Possible role of atrial natriuretic hormone in pituitary-adrenocortical unresponsiveness in lactate-induced panic
Authors: M Kellner, L Herzog, A Yassouridis, F Holsboer, K Wiedemann
Journal: American Journal of Psychiatry (1995)

This study investigated whether lactate-induced panic attacks in patients with panic disorder would activate atrial natriuretic hormone, which could explain the missing ACTH and cortisol response found in this kind of experimentally induced panic.Sodium lactate and placebo infusions were administered to 10 patients with panic disorder and to 10 healthy comparison subjects, and the atrial natriuretic hormone responses of the two groups were compared.During lactate infusion both the seven patients who had panic attacks and the eight comparison subjects who did not responded with increased plasma concentrations of atrial natriuretic hormone, but the patients had more pronounced surges of the hormone.Because atrial natriuretic hormone suppresses both pituitary ACTH and adrenal cortisol release, the authors suggest that the immediate rise of atrial natriuretic hormone explains the reported lack of pituitary-adrenocortical activation during lactate-induced panic.
Radiation Injury of Lungs and Heart
Authors: N. Ragner Johnson
Journal: Annals of Internal Medicine (1974)

Comments and Correction1 October 1974Radiation Injury of Lungs and HeartN. RAGNER JOHNSON, M.D.N. RAGNER JOHNSON, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-81-4-568_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The recent article "Latent Radiation Injury of Lungs or Heart Activated by Steroid Withdrawal" presented an interesting effect ( 1 ). The conclusion relating this to radiation injury is bothersome. Could not radiation have injured the lung in the past, to a mild but roentgenographically nondetectable level and the reactions discussed have been hypersensitivity to the MOPP*chemotherapy, especially the procarbazine? In other words, is this tissue affected by the radiation later more sensitive to a drug-induced immune response rather than showing just delayed radiation effect (2)? The delayed hypersensitivity might be more easily stimulated...References1. CASTELLINOGLATSTEINTURBOW REM: Latent radiation injury of lungs or heart activated by steroid withdrawal. Ann Intern Med 80:593-599, 1974 LinkGoogle Scholar2. ROSENOW E: The spectrum of drug-induced pulmonary disease. Ann Intern Med 77:977-991, 1972 LinkGoogle Scholar3. FLEMINGFILBEEWIERNIK JJG: Sequelae to radical irradiation in carcinoma of the breast. An inquiry into the incidence of certain radiation injuries. Br J Radiol 34:713-719, 1961 CrossrefMedlineGoogle Scholar4. TEATESCOOPER DG: Some consequences of pulmonary irradiation. A second long term report. Am J Roentgenol 96:612-619, 1966 CrossrefGoogle Scholar1. KAPLAN H: Hodgkin's Disease. Cambridge, Massachusetts, Harvard University Press, 1971, Figures 5-31, 10-46, and 10-47 Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Barlow Hospital for Respiratory Diseases Los Angeles, California 90026*Nitrogen mustard, vincristine sulfate (Oncovin®), procarbazine, and prednisone. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 October 1974Volume 81, Issue 4Page: 568-569KeywordsChemotherapyDrugsHeartHypersensitivityImmune responseLungsProcarbazineSulfates ePublished: 1 December 2008 Issue Published: 1 October 1974 PDF downloadLoading ...