tbuckley/cabot-search huggingface dataset:
Medicine vs Madison Avenue
Authors: Alan Blum
Journal: JAMA (1980)

ALL PHYSICIANS—and increasing numbers of the general public—recognize the link between cigarette smoking and emphysema, squamous cell carcinoma of the lung, chronic bronchitis, cardiovascular problems, low birth weight, and other disabilities. However, few people realize that the tobacco industry has always tried to associate cigarette smoking with<i>good</i>health. And those who look on cigarette smoking as an inalienable right find it hard to believe that it is not even a time-honored tradition. Even well into the 1920s, cigarette smoking still had little appeal—and definitely not to women—but through advertising, the tobacco companies thought they would be among the very first to give women one version of equal rights: "To keep a slender figure, no one can deny... Reach for a Lucky instead of a sweet." A well-promoted aura of romance and sophistication made smoking Camels synonymous with being "a social success," and dozens of movie stars were used as
In Vivo Quantitative Measurement of Intact Fibrous Cap and Lipid-Rich Necrotic Core Size in Atherosclerotic Carotid Plaque
Authors: Jianming Cai, Thomas S. Hatsukami, Marina S. Ferguson, William S. Kerwin, Tobias Saam, Baocheng Chu, Norihide Takaya, Nayak L. Polissar, Chun Yuan
Journal: Circulation (2005)

Background— Previous studies with contrast-enhanced magnetic resonance imaging (CEMRI) have shown that the fibrous cap (FC) in atherosclerotic carotid plaques enhances with gadolinium-based contrast agents. Conversely, the lipid-rich necrotic core (LR-NC), lacking both vasculature and matrix, shows no or only slight enhancement. The goal of this study was to assess whether CEMRI can be used to accurately measure the dimensions of the intact FC and LR-NC. Methods and Results— Twenty-one patients scheduled for carotid endarterectomy were imaged with a 1.5-T scanner. Precontrast images and CEMRI were obtained. One hundred eight locations with an intact FC were matched between MRI and the excised histology specimens. Quantitative measurements of FC length along the lumen circumference, FC area, and LR-NC area were collected from CEMRI images and histology sections. Blinded comparison of corresponding MR images and histology slices showed moderate to good correlation for length ( r =0.73, P &lt;0.001) and area ( r =0.80, P &lt;0.001) of the intact FC. The mean percentage LR-NC areas (LR-NC area/wall area) measured by CEMRI and histology were 30.1% and 32.7%, respectively, and were strongly correlated across locations ( r =0.87, P &lt;0.001). Conclusions— In vivo high-resolution CEMRI is capable of quantitatively measuring the dimensions of the intact FC and LR-NC. These new parameters may be useful to evaluate plaque vulnerability and provide continuous variables for characterizing the intact FC and LR-NC in progression and regression studies.
Abstract 1611: Hepatocellular carcinoma xenograft models and biomarkers are powerful tools for the evaluation of the new drugs targeting HCC
Authors: Yanmei Sun, Juan Zhang, Nan Li, Xiaoming Song, Jie Cai, Taiping Chen, Jean-Pierre Wery, Yiyou Chen
Journal: Cancer Research (2011)

Abstract Hepatocellular Carcinoma (HCC) is a major health problem, as the fifth most common cancer and the third most common cause of cancer death worldwide. Many pharmaceutical companies lead the effort to design new medicines on this cancer type. The overwhelming need to improve preclinical models of HCC requires robust models that closely mimic the disease population and therefore have the potential to better predict clinical outcome with novel therapies. Here we successfully validated subcutaneous and orthotopic xenograft models derived from HepG2, SK-HEP-1, Hep3B, PLC/PRF/5, HUH-1, HUH-7 and MHCC97H cell lines and also directly from HCC patient tumors (HuPrime®). Four HCC serum markers (AFP, α-fetoprotein; AFP-L3; DCP, Des-gamma-Carboxyprothrombin; GP73, Golgi Protein-73) have been used or will be potentially used clinically in detection of this disease. AFP is the most widely used biomarker in HCC, somehow it is not always correlated well with the liver cancer progress, even it gives false result, and some liver lesion or liver cirrhosis can also produce high level of AFP; while GP73 is reported a promising alternative as HCC serum marker. AFP and GP73 were tested at both mRNA level and protein level. They were also compared in the sensitivity and correlation with the tumor burden using the blood samples from the orthotopic xenograft models. Our results demonstrated that biomarkers released by the tumor models could well monitor the tumor take rate, growth and response to treatments. Furthermore, Sorafenib, one popular anti- HCC medicine, was tested, and the serum biomarkers could be utilized for confidence in evaluating the efficacy of Sorafenib. In conclusion, the use of HCC xenograft models combined with the biomarker strategies is helpful in maximizing the value of in vivo research and designing clinical trials Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1611. doi:10.1158/1538-7445.AM2011-1611
THE EVEREST II HIGH SURGICAL RISK COHORT: EFFECTIVENESS OF TRANSCATHETER REDUCTION OF SIGNIFICANT MITRAL REGURGITATION IN HIGH SURGICAL RISK PATIENTS
Authors: Scott Lim, Saibal Kar, Peter Fail, Brian Whisenant, William Gray, Tanvir Bajwa, Michael Rinaldi, Robert Kipperman, John Williams, Richard Smalling, James Hermiller, Paul Grayburn, Gorav Ailawadi, Neil Weissman, Elyse Foster, Donald Glower, Ted Feldman
Journal: Journal of the American College of Cardiology (2013)
Origin and Conduction of the Mitral Sound in the Heart
Authors: J. JAB FABER
Journal: Circulation Research (1964)

Mitral heart sounds were recorded by small microphones inserted in the heart muscles of dogs. Recordings showed that components having frequencies between 20 and 40 cycles/ sec originate at the base of the heart and travel from there to the apex. The velocity of conduction is in the order of 4 m/sec, so that the wavelengths can be calculated to be about 20 to 10 cm. At these frequencies the ventricle seems to vibrate as a whole. Components having frequencies higher than 40 cycles/sec could not be followed during their progression over the heart. In the range from 20 to 160 cycles/sec, the mitral sounds recorded above and below the mitral valve were of opposite phase so that the mitral valve is the main elastic element responsible for the mitral sound. The combined masses of the heart and the blood in it constitute the inertia of the cardiohemic system. In this range of frequencies oscillations in transmural pressure and circumferential tension of the heart were synchronous and of the same phase. The low velocity of conduction, the structural similarity between the heart and arteries, and the synchronism in the oscillations of transmural pressure and circumferential tension allow the conclusion that the mitral sound is conducted through the ventricle in the form of a transverse vibration, strictly analogous to the way pulse waves are conducted in arteries.
An Evaluation of Administrative Controls in Medical-Care Programs
Authors: Avedis Donabedian, Julia C. Attwood
Journal: New England Journal of Medicine (1963)

MEDICAL-care programs are set up to achieve fairly specific objectives through the use of finite, and sometimes severely limited, resources. The administering agency, whether private or public, is entrusted with the task of maintaining the program and realizing its purposes without overstepping its budgetary, jurisdictional or operational boundaries. To do this, the agency must exercise the necessary amount of administrative control.1 , 2 Control is direct and unequivocal in the few programs that employ full-time salaried personnel to operate facilities owned by the agency itself. But in many other programs, including health insurance and public-welfare medical care, the administering agency has only . . .
JNK, essential for anticancer therapy-induced apoptosis, promotes breast cancer progression.
Authors: J Wang, I Kuiatse, AJ Casa, AV Lee, X Cui
Journal: Cancer Research (2009)

Abstract Abstract #5075 The c-Jun N-terminal kinase (JNK) is a critical mediator of stress-induced apoptosis and is required for the cytotoxic effect of anticancer therapies. Interestingly, recent clinical studies showed that high JNK activity is associated with poor prognosis in human breast cancer. The molecular basis of this potential dual function of JNK in breast cancer is poorly understood. Here we report that overexpression of a constitutively active JNK in breast cancer cells increased cell migration and invasion. In agreement with this, fibroblast-specific markers like the intermediate filament vimentin and the extracellular matrix protein fibronectin were up-regulated. AP-1 transcription factor, which induces expression of these two proteins, was markedly increased by JNK overexpression. In addition, hyperactive JNK reduced Akt1 activation but enhanced Erk activation in breast cancer cells. In relevance, we also found that JNK levels are significantly higher in invasive breast cancers including those with distant metastases (n = 235, p &amp;lt; 0.0001, Wilcoxon rank sum test) than in normal breast tissues (n = 69). Most surprisingly, an increase of JNK attenuated the apoptosis of breast cancer cells treated with chemotherapy drugs doxorubicin and taxol. This suggests that the role of JNK changes when its activity/expression increases above the basal levels associated with apoptosis. Our data, together with a recent finding that cells undergoing cytotoxic agent-induced apoptosis can induce compensatory hyper-proliferation of proximal cancer cells, suggest a novel mechanism of breast cancer therapeutic resistance. Therapy-elicited apoptosis of tumor cells with basal JNK activity may release mitogens that induce hyperactive JNK in neighboring cells to promote growth and invasion. Thus JNK activation may serve as a marker of breast cancer progression. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5075.
Let's open whole process of cost effective modelling
Authors: Jack Dowie
Journal: BMJ (2007)

The National Institute for Health and Clinical Excellence (NICE) needs to go much further than allowing access to its modelling data.1 The whole cost effectiveness modelling process needs to be opened up to involvement by all stakeholders, and inspection by the public, as it happens.The independent group should be contracted to develop the one and only model that NICE will consider in its appraisal, and it should do so in full and continuous collaboration with all registered stakeholders and interested parties who sign up to the NICE guidelines.The model will be run with any alternative parameters suggested by various parties and the alternative results (along with their evidential basis) submitted to the appraisal committee in a single report.No subsequent questioning of, or submissions regarding, the model structure, the results, or the underlying principles would be accepted in the context of any particular case.
Royal Society: March 2, 1843. On the Special Function of the Skin
Authors: R. Willis
Journal: BMJ (1843)

2. That the mortality from phthisis amongst the English soldiers in the West Indies is small, and one- fourth less amongst Europeans than black or colored people.3. It has not been proved that pulmonary consumption is frequent in Martinique, Senegal, Cayenne, or Italy; on the contrary, the imperfect statistics which we posse seem to show the contrary.
Thrombolytic Therapy for Inferior Vena Cava Thrombosis in Paroxysmal Nocturnal Hemoglobinuria
Authors: PAM W. SHOLAR
Journal: Annals of Internal Medicine (1985)

Two patients with paroxysmal nocturnal hemoglobinuria had increasing abdominal girth and ascites. The Budd-Chiari syndrome or inferior vena cava thrombosis was shown by angiography. After thrombolytic therapy, both patients improved, and thrombolysis was shown by radiography. Neither patient had induction of hemolysis secondary to these agents. These studies suggest that both streptokinase and urokinase are safe and effective in the treatment of intra-abdominal venous thromboses associated with paroxysmal nocturnal hemoglobinuria.
Proctosigmoidoscopy in Periodic Health Examinations
Authors: Edgar L. Crumpacker
Journal: JAMA (1961)

IN MOST tumor registeries cancer of the colon and rectum ranks from first to third in frequency in men, excluding skin cancer. According to the National Health Education Committee, it is first by a wide margin. 1 When discovered in its early stages the prospect for cure is the best of all internal malignancies. The challenge to find and remove these tumors in their curable stages is the challenge to reduce the death rate from one type of cancer.  The Greenbrier Clinic is a diagnostic medical clinic. Approximately two-thirds of the male patients are examined under company sponsored executive health programs. This gives a cross-section with low selection in the 35 to 65 year age group. Most analyses of sigmoidoscopic studies of statistical importance have been from cancer detection centers, where, it has been shown, some patients are motivated to undergo examinations because of symptoms which they sometimes conceal.  From
Common Gene Rearrangements in Prostate Cancer
Authors: Mark A. Rubin, Christopher A. Maher, Arul M. Chinnaiyan
Journal: Journal of Clinical Oncology (2011)

Prostate cancer is a common heterogeneous disease, and most patients diagnosed in the post prostate-specific antigen (PSA) era present with clinically localized disease, the majority of which do well regardless of treatment regimen undertaken. Overall, those with advanced prostate cancer at time of diagnosis do poorly after androgen withdrawal therapy. Understanding the biologic underpinning of prostate cancer is necessary to best determine the risk of disease progression and would be advantageous for the development of novel therapeutic approaches to impede or prevent disease. This review focuses on the recently identified common ETS and non-ETS gene rearrangements in prostate cancer. Although multiple molecular alterations have been detected in prostate cancer, a detailed understanding of gene fusion prostate cancer should help explain the clinical and biologic diversity, providing a rationale for a molecular subclassification of the disease.
The use of cationic microbubbles to improve ultrasound-targeted gene delivery to the ischemic myocardium
Authors: Lu Sun, Chia-Wen Huang, Jun Wu, Ko-Jie Chen, Shu-Hong Li, Richard D. Weisel, Harry Rakowski, Hsing-Wen Sung, Ren-Ke Li
Journal: Biomaterials (2012)
Toxic Effect of Proguanil
Authors: P. Abbott
Journal: BMJ (1951)

<h3>Abstract</h3> <h3>Background</h3> Neuroimaging studies have just begun to explore the acute effects of psychedelics on large-scale brain networks’ functional organization. Even less is known on the neural correlates of subacute effects taking place days after the psychedelic experience. This study explores the subacute changes of primary sensory brain networks and networks supporting higher-order affective and self-referential functions 24h after a single session with the psychedelic ayahuasca. <h3>Methods</h3> We leveraged task-free functional magnetic resonance imaging data one day before and one day after a randomized placebo-controlled trial exploring the effects of ayahuasca in naïve healthy participants (21 placebo/22 ayahuasca). We derived intra- and inter-network functional connectivity of the salience, default mode, visual, and sensorimotor networks, and assessed post-session connectivity changes between the ayahuasca and placebo groups. Connectivity changes were associated with Hallucinogen Rating Scale scores assessed during the acute effects. <h3>Results</h3> Our findings revealed increased anterior cingulate cortex connectivity within the salience network, decreased posterior cingulate cortex connectivity within the default mode network, and increased connectivity between the salience and default mode networks one day after the session in the ayahuasca group compared to placebo. Connectivity of primary sensory networks did not differ between-groups. Salience network connectivity increases correlated with altered somesthesia scores, decreased default mode network connectivity correlated with altered volition scores, and increased salience-default mode network connectivity correlated with altered affect scores. <h3>Conclusion</h3> These findings provide preliminary evidence for subacute functional changes induced by the psychedelic ayahuasca on higher-order cognitive brain networks that support interoceptive, affective, and self-referential functions.
Plasma cell tumour-formation and antigen-binding myeloma proteins in mice.
Authors: M Potter
Journal: BMJ (1971)

Plasmacytoma can be induced in the inbred BALB/c mouse by the injection of mineral oil or implants of solid plastics. This induction depends on three factors: firstly, an abnormal peritoneal granulomatous tissue; secondly, genetically determined factors in the strain BALB/c genotype; and, thirdly, the presence of a gastrointestinal and respiratory microbial flora. The incidence of plasmacytomas following three injections of mineral oils or purified isoparaffins ranges from 40 to 600'. The tumours develop in the peritoneal oil granuloma and often remain localized in the peritoneal connective tissues. In several series of myeloma proteins in this strain of mice the IgA class predominates; 60-66%/' of all tumours that produce a detectable heavy chain class myeloma protein produce an IgA class protein. This finding strongly implies that a portion of the total immunocyte population is more prone to neoplastic transformation. Because IgA myeloma proteins in BALB/c mice are usually polymeric molecules, these proteins can be tested for their ability to bind polyvalent antigens by precipitin reactions. Using this method myeloma proteins with antigenbinding activity have been found to several different antigens. The chemical determinants have been identified for many and include: nitrophenyl compounds, al --3 dextrose (nigerotriose), methyl a-D-galactoside, methyl f3-D-galactoside (probably more specifically to p 1 -6 linked galactose), N-acetyl glucosamine in P1-+3 linkages, N-acetyl D-mannosamine, phosphoryl choline, choline, and a trypsin-sensitive determinant common to antigenic substances produced by salmonella. Other myeloma proteins have been found to precipitate with antigens of bacterial origin. The chemical determinants for these have not yet been established. The actual incidence of active M-components in a series of tumours ranges from 5 to 10% when test antigens containing the determinants mentioned above are used. Many of the antigens can be shown to be produced by organisms in the gastrointestinal and respiratory microbial flora. The chemical determinants, however, to which the myeloma proteins are directed may be found in some cases on autogenous macromolecules. Nevertheless, bacterial antigens containing these determinants are probably highly immunogenic and the precursors of the tumour cells were probably responding to these antigens before neoplastic transformation. The finding of several plasmacytomas of independent origin that produce myeloma proteins which identify the same antigen or chemical antigenic determinant supports this suggestion.
Dysfunction of the heme recycling system in heme oxygenase 1–deficient mice: effects on macrophage viability and tissue iron distribution
Authors: Gennadiy Kovtunovych, Michael A. Eckhaus, Manik C. Ghosh, Hayden Ollivierre-Wilson, Tracey A. Rouault
Journal: Blood (2010)

To better understand the tissue iron overload and anemia previously reported in a human patient and mice that lack heme oxygenase-1 (HO-1), we studied iron distribution and pathology in HO-1(Hmox1)(-/-) mice. We found that resident splenic and liver macrophages were mostly absent in HO-1(-/-) mice. Erythrophagocytosis caused the death of HO-1(-/-) macrophages in in vitro experiments, supporting the hypothesis that HO-1(-/-) macrophages died of exposure to heme released on erythrophagocytosis. Rupture of HO-1(-/-) macrophages in vivo and release of nonmetabolized heme probably caused tissue inflammation. In the spleen, initial splenic enlargement progressed to red pulp fibrosis, atrophy, and functional hyposplenism in older mice, recapitulating the asplenia of an HO-1-deficient patient. We postulate that the failure of tissue macrophages to remove senescent erythrocytes led to intravascular hemolysis and increased expression of the heme and hemoglobin scavenger proteins, hemopexin and haptoglobin. Lack of macrophages expressing the haptoglobin receptor, CD163, diminished the ability of haptoglobin to neutralize circulating hemoglobin, and iron overload occurred in kidney proximal tubules, which were able to catabolize heme with HO-2. Thus, in HO-1(-/-) mammals, the reduced function and viability of erythrophagocytosing macrophages are the main causes of tissue damage and iron redistribution.
Blockade of Endogenous Cytokines Mitigates Neointimal Formation in Obese Zucker Rats
Authors: Ryo Takeda, Etsu Suzuki, Hiroshi Satonaka, Shigeyoshi Oba, Hiroaki Nishimatsu, Masao Omata, Toshiro Fujita, Ryozo Nagai, Yasunobu Hirata
Journal: Circulation (2005)

Background— It is well known that diabetes mellitus is a major risk factor for vascular diseases such as atherosclerosis and restenosis after angioplasty. It has become clear that advanced glycation end products (AGE) and their receptor (RAGE) are implicated in vascular diseases, especially in diabetes mellitus. Nevertheless, the mechanisms by which diabetes mellitus is often associated with vascular diseases remain unclear. Methods and Results— To study the role of endogenous cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 in the development of vascular diseases and in the expression of RAGE, we used semapimod, a pharmacological inhibitor of cytokine production, and examined its effect on neointimal formation in the femoral artery of obese Zucker (OZ) rats. We also used an adenovirus construct expressing a dominant negative mutant of the receptor for TNF-α (AdTNFRΔC) to block the action of endogenous TNF-α. Semapimod significantly suppressed neointimal formation and RAGE expression in OZ rats compared with untreated OZ rats. This inhibitory effect of semapimod on neointimal formation was overcome by infection of an adenovirus expressing RAGE into the femoral artery of OZ rats. Furthermore, AdTNFRΔC infection significantly suppressed neointimal formation and RAGE expression in the femoral artery of OZ rats. Conclusions— These results suggest that endogenous cytokines, especially TNF-α, were implicated in neointimal formation in OZ rats and that RAGE was a mediator of the effect of these cytokines on neointimal formation.