tbuckley/cabot-search huggingface dataset:
The Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS)
Authors: Klaus Abt
Journal: JAMA (1997)

<h3>To the Editor.</h3> —The article by Dr Borhani et al<sup>1</sup>contains judgments of adverse event frequencies that call for some comments regarding the multiplicity<sup>2,3</sup>aspects of testing events (listed in their Table 4). Although the authors mention possible chance occurrences of significances, they suggest that the results are "of concern." Concentrating on the 6 "major vascular events" (ie, stroke, myocardial infarction, sudden death, congestive heart failure, angina pectoris, and other cardiovascular disease deaths) the problem of multiple testing may be circumvented. Although the authors state that only 1 major event was counted per patient (leading to 6 mutually independent groups of patients each with 1 major event), the total number of events is 28 and not 25 (as indicated in their Table 4). Ignoring this deviation as well as the fact that the 6 test results are based on randomized patients, the 6 tests may be considered as essentially independent of
Abstract 810: Dietary grape seed proanthocyanidins inhibit UV-induced immunosuppression through stimulation of CD8+ effector T cells and inactivation of regulatory CD4+ T cells
Authors: Mudit Vaid, Tripti Singh, Samriti Sharma, Anna Li, Craig A. Elmets, Hui Xu, Santosh K. Katiyar
Journal: Cancer Research (2011)

Abstract The immunosuppressive effects of solar ultraviolet (UV) radiation, particularly UVB (290-320 nm), are well recognized. Experimental evidence indicates that UV-induced immunosuppression is a risk factor for skin cancer development, including melanoma and non-melanoma, in mice and clinical evidence suggests that it is also a risk factor in humans. Conversely, animals with an enhanced immune response exhibit a lower risk of skin tumor development on chronic UV exposure. Dietary grape seed proanthocyanidins (GSPs) have been shown to inhibit UVB-induced immunosuppression in mice; however, the cellular and molecular mechanisms underlying this inhibitory effect of GSPs are not yet clearly understood. To characterize the cell population responsible for the GSPs-mediated inhibition of UVB-induced immunosuppression, we used an adoptive transfer approach. Splenocytes and draining lymph nodes were harvested from mice that had been administered dietary GSPs, exposed to UVB, and sensitized by topical application of 2,4-dinitorfluorobenzene (DNFB) onto the UVB-exposed skin. CD8+ and CD4+ T cells were positively selected and transferred into naïve mice that were subsequently challenged by application of DNFB on the ear skin. Naïve recipients that received CD8+ T cells from GSPs-treated, UVB-irradiated donors exhibited full contact hypersensitivity (CHS) response. CHS is considered to be a prototypic T-cell mediated immune response. Naïve mice that received CD4+ regulatory T cells from GSPs-treated, UVB-exposed mice were able to mount a CHS response after sensitization and subsequent challenge with DNFB. On culture, the CD8+ T cells from GSPs-treated, UVB-exposed mice secreted higher levels of Th1 cytokines (IL-2, IFNγ) than CD8+ T cells from UVB-irradiated mice not treated with GSPs. CD4+ T cells from GSPs-treated, UVB-exposed mice secreted significantly lower levels of Th2 cytokines (IL-4 and IL-10) than CD4+ T cells from UVB-exposed mice not treated with GSPs. These data suggest that dietary GSPs inhibit UVB-induced immunosuppression by stimulating CD8+ effector T cells and diminishing regulatory CD4+ T cells in mice. This property of GSPs can be used as an alternative strategy to augment the induction of CD8+ effector T cells and to diminish the development of CD4+ regulatory T cells and that may lead to the prevention of skin cancer risk in humans. 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 810. doi:10.1158/1538-7445.AM2011-810
The UGDP Study
Authors: Alexander G. Vongries
Journal: JAMA (1974)

<h3>To the Editor.—</h3> As support for the University Group Diabetes Program (UGDP), Dr. Clayman (228:1523, 1974) cited Soler et al,<sup>1</sup>although he acknowledges defects in their retrospective study. Soler et al reviewed the records of 184 diabetics with confirmed acute myocardial infarction admitted to a coronary care unit (CCU) in England from 1967 to 1973. Oral hypoglycemic therapy was discontinued on admission and, unless diabetic control was satisfactory on diet alone, insulin was used. Patients were grouped according to diabetic therapy at the time of myocardial infarction, and subsequent events were attributed to the effects of such treatment. The article discussed the incidence of primary ventricular fibrillation and fatalities while patients were still in the CCU, but did not provide the individual patient data necessary to make valid judgments about the effects of treatment. Eleven of the 15 patients who developed ventricular fibrillation while in the CCU did so within
Stem Cells Hold Vision for the Future
Authors: Rebecca Voelker
Journal: JAMA (1997)

AS AN OPHTHALMOLOGIC surgeon, Edward J. Holland, MD, tries to offer hope to hopeless eyes. One of his beneficiaries is 77-year-old Donald Smolley. The men met several years ago at the University of Minnesota Hospitals and Clinics in Minneapolis, where Holland directs the Corneal and External Disease Service. After a burning backsplash of drain-clearing liquid in 1968, Smolley was left legally blind in his right eye and with little vision in the left. A corneal transplant in Smolley's right eye shortly after the injury failed outright. Some sight returned to his left eye, and Smolley continued working as building superintendent at the Minneapolis public library. But eventually the left eye began to fail. Smolley took early retirement, and he and his wife moved to the small western Minnesota town of Montevideo. "I couldn't see to go across the street; I couldn't see what was on my plate at dinner," Smolley
Chemoembolization in Patients with Hepatocellular Carcinoma
Authors: Riccardo Lencioni
Journal: Liver Cancer (2012)

Transcatheter arterial chemoembolization (TACE) is the standard of care for nonsurgical patients with preserved liver function with large or multinodular noninvasive hepatocellular carcinoma (HCC) confined to the liver. The administration of an anticancer-in-oil emulsion followed by embolic agents is the most popular TACE technique; however, the introduction of embolic, drug-eluting beads (DEB) has provided an alternative to conventional regimens. Experimental studies have shown that DEB-TACE results in a safe pharmacokinetic profile and effective tumor killing in animal models. Clinical experiences have confirmed that DEB-TACE provides a combined ischemic and cytotoxic effect locally, with significantly reduced drug-related toxicity and liver toxicity compared with conventional TACE. The addition of molecular targeted drugs to the therapeutic armamentarium for HCC has prompted the design of clinical trials aimed at investigating the synergies between TACE and systemic treatments. Combining TACE with antiangiogenic agents represents a promising strategy because TACE is thought to cause local hypoxia, resulting in a temporary increase in levels of vascular endothelial growth factor. Recently, a large phase 2, randomized, double-blind, placebo-controlled trial (the SPACE study) indicated that the concurrent administration of DEB-TACE and sorafenib has a manageable safety profile and suggested that the time to progression (TTP) and time to vascular invasion or extrahepatic spread may be improved compared with DEB-TACE alone. These data support the further evaluation of molecular targeted, systemically active agents in combination with DEB-TACE in a phase 3 setting.
Blood Screening for Phenylketonuria
Authors: Robert Guthrie
Journal: JAMA (1961)

<h3>To the Editor:—</h3> Since the discovery by Fölling, in 1935, of phenylketonuria (PKU), the simple ferric chloride test of urine has been the universal method of detecting this disease in spite of serious limitations. These include (1) failure of young infants to produce a positive test until several weeks after birth, even though there is evidence that blood phenylalanine concentration increases rapidly in the first few days of life in this condition (Armstrong<i>et al., Proceedings of the Third International Neurochemical Symposium,</i>1958, to be published) and (2) failure of older PKU cases to produce a positive ferric chloride test if blood phenylalanine levels are below approximately 20 mg. per cent. Obviously a simple method of detecting elevated phenylalanine blood levels should overcome these limitations. Recently, with the cooperation of Dr. William Welch, Director of the Laboratory at Newark State School, Newark, N.Y., we have had the opportunity to develop
Select committee angry over absence of drug regulator from session
Authors: Lynn Eaton
Journal: BMJ (2005)

Members of the House of Commons select committee on health appeared angry that they were not able to question one of the employees of the United Kingdom's drug regulatory authority at a session last week looking into the influence of the drug industry.

Although several senior figures from the Medicines and Healthcare Products Regulatory Agency attended the session, the committee said that it would also have liked to have heard evidence from Ian Hudson. Dr Hudson is a member of the agency's executive board and was worldwide director of safety at SmithKline Beecham from 1999 to 2001, having worked forthe company since …
Stimulation of human neutrophil leukocyte aerobic glucose metabolism by purified chemotactic factors.
Authors: E J Goetzl, K F Austen
Journal: Journal of Clinical Investigation (1974)

The interaction of human neutrophils adherent to plastic petri dishes with the purified chemotactic factors C5a and kallikrein increased their rate of aerobic glycolysis 25-120% and the activity of their hexose monophosphate shunt (HMPS) 100-600%, reaching a plateau after 2 hr at 37 degrees C. The stimulation of either pathway required a chemotactically active stimulus since neither C5 nor prekallikrein or inactivated kallikrein could enhance metabolic activity. Marked suppression of the neutrophil chemotactic response by preincubation with a chemotactic factor to achieve deactivation, 5 x 10(-7) M diisopropyl fluorophosphate, or the neutrophil immobilizing factor (NIF) did not prevent the stimulation of HMPS activity or glycolysis by chemotactic factors. The metabolic inhibitors iodoacetate and 6-aminonicotinamide at concentrations which blocked enhancement of glycolysis or HMPS activity, respectively, partially suppressed the chemotactic response of neutrophils to the chemotactic factors. The capacity of a chemotactic factor to stimulate glucose metabolism of human neutrophils is associated with a maximal chemotactic response, but this stimulation is not alone sufficient for chemotaxis.
Neurofibroma of the Diaphragm
Authors: Richard H. Sweet, Thomas Gephart
Journal: New England Journal of Medicine (1953)

PRIMARY tumors of the diaphragm are rare, less than 40 cases having been reported in the literature. In 1949 Clagett and Johnson1 analyzed reports of 30 cases of diaphragmatic tumor and, when information was available, described the method of diagnosis. Sixteen of these cases were discovered at autopsy; 12 were diagnosed during life so that partial or complete surgical removal could be carried out, and no mention was made of the method of diagnosis in 2. In 1950 Samson and Childress2 reported 5 additional cases, making 35 in all, of which 17 were benign and 18 malignant.With the increasing . . .
mel-18 Negatively Regulates Cell Cycle Progression upon B Cell Antigen Receptor Stimulation through a Cascade Leading to c-myc/cdc25
Authors: Osamu Tetsu, Hiroto Ishihara, Rieko Kanno, Masaya Kamiyasu, Hiroko Inoue, Takeshi Tokuhisa, Masaru Taniguchi, Masamoto Kanno
Journal: Immunity (1998)
Glutathione peroxidase protein. Absence in selenium deficiency states and correlation with enzymatic activity.
Authors: K Takahashi, P E Newburger, H J Cohen
Journal: Journal of Clinical Investigation (1986)

Glutathione peroxidase (GSHPx) activity is an indicator of selenium status in selenium-deficient individuals. Utilizing polyclonal monospecific antibodies to purified erythrocyte GSHPx, we were able to determine the relationship between enzymatic activity and protein content. In erythrocytes from a selenium-deficient individual who was treated with selenium, and in HL-60 cells grown in the absence of selenium and then returned to selenium-containing medium, there was a direct relationship between enzymatic activity and protein content. Thus, selenium deficiency results not only in a decrease of GSHPx activity, but also in a decrease of GSHPx protein.
Abstract 2336: M402, a heparan sulfate mimetic, inhibits tumor revascularization and invasiveness after high-dose taxane treatment in a mouse breast cancer model
Authors: Birgit C. Schultes, Chia L. Chu, Alison Long, Josephine D'Alessandro, Christopher M. Honan, Takashi K. Kishimoto, Ganesh Venkataraman
Journal: Cancer Research (2012)

Abstract Treatment with certain anti-cancer agents, particularly taxanes and sunitinib, can lead to mobilization of pro-angiogenic factors and an acute mobilization of endothelial progenitor cells (EPCs) and other stromal cells, which migrate to the viable tumor rim where they can enhance tumor vascularization, invasion and metastasis. This phenomenon has been linked to rapid tumor regrowth following chemotherapy or treatment with specific angiogenesis inhibitors and may thus diminish the long-term efficacy of the treatment. Stromal cells like EPCs are mobilized in response to circulating growth factors and chemokines (VEGFR, FGF, G-CSF, IL-6, SDF1α, etc.) that are induced by the drug or the progressing tumor. Many of these factors contain heparin binding domains for their anchorage to proteoglycans on cell surfaces or the extracellular matrix. We tested a novel heparan sulfate mimetic, M402, for its ability to inhibit EPC mobilization as well as tumor vascularization and invasion. Mice bearing orthotopic 4T1 breast carcinoma and treated with a single high dose of docetaxel (40 mg/kg) showed highly vascularized tumor rims by histology and Microfil perfusion followed by microCT (vessel volume of 5.8 ± 4.6 mm3 vs. 0.6 ± 0.3 mm3; vessel surface area of 153.9 ± 65.5 mm2 vs. 21.1 ± 6.7 mm2, respectively) as compared to the saline control group. The tumors also showed a higher rate of invasion through the peritoneal wall as compared to vehicle treated mice (5 of 16 mice vs. 2 of 16 mice, respectively). The effect correlated with mobilization of EPCs and other bone marrow derived stromal cells. Treatment with M402 did not show such a response but rather inhibited the effects of docetaxel when dosed concomitantly for 3-5 days, starting with the docetaxel administration. Analysis of the blood, tumor and bone marrow indicated that M402 prevented the mobilization of progenitor cells from the bone marrow and their recruitment into the tumor microenvironment, likely through disruption of the SDF-1α/CXCR4 axis. Furthermore, we observed synergistic anti-tumor and anti-metastatic activity of M402 with docetaxel in this 4T1 model. In conclusion, the experiments provide a rationale for the clinical investigation of M402 in combination with docetaxel or other agents that induce similar effects. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2336. doi:1538-7445.AM2012-2336
Multimodality Imaging of a Retrosternal Parathyroid Adenoma With Multiple Brown Tumors
Authors: James Kirk, Iain Au-Yong, Rakesh Ganatra
Journal: Clinical Nuclear Medicine (2009)

Brown tumors of hyperparathyroidism are rare but can mimic metastatic disease on many imaging modalities. We report the case of a patient presenting with symptomatic brown tumors of hyperparathyroidism due to a large retrosternal parathyroid adenoma, with histopathological correlation of both. The initial imaging findings on plain radiography, computed tomography, and bone scintigraphy were nonspecific and difficult to differentiate from the more common diagnosis of metastatic disease. Whole body sestamibi imaging however demonstrated increased uptake within both the mediastinal mass and multiple bone lesions leading to the correct diagnosis. We demonstrate modern multimodality imaging of this rare but treatable condition, and discuss the relevant literature.
Evaluation of the Surgical Correction of Mitral Regurgitation
Authors: EARLE B. KAY, DAVID MENDELSOHN, HENRY A. ZIMMERMAN
Journal: Circulation (1961)

U SUALLY the first questions to be asked by patients, their relatives, and their physicians, are: "What are the dangers of operation, and will it be a cure?"' Obviously, any patient with rheumatic valvu- lar disease will not be cured but may be given varying degrees of benefit dependent upon the degree of pathology, the degree of myocardial reserve, and the degree of effectiveness of the operative technic.The best results are obtained in good-risk patients who have less than severe cardi- omegaly, reversible pulmonary vascular sclerosis, and a valvular mechanism amen- able to correction.The myocardial component of valvular dysfunction cannot be over- emphasized.No operative technic will be highly successful when employed in the presence of a failing heart.Similarly, the persistence of pulmonary vascular sclerosis may negate benefit gained by valvular cor- rection.Only too often in the past have physicians lost sight of the fact that cardiac disease is compensated at the expense of cardiac re- serve.Only too often a patient with rheu- matic valvular disease is followed medically until rapidly progressive deterioration be- comes obvious, before surgical intervention is sought in the hopes of stopping this otherwise hopeless course.In the past this policy has been justified in that surgical technics were not adequate to provide reasonable safety or assurance of benefit.The recent progress in surgical cor- rection has now reversed this situation, so that safety and benefit are not so dependent upon the technic employed as they are on
Heterosexual spread of human immunodeficiency virus in Edinburgh
Authors: A J France, C A Skidmore, J R Robertson, R P Brettle, J J K Roberts, S M Burns, C A Foster, J M Inglis, W B F Galloway, S J Davidson
Journal: BMJ (1988)

Heterosexual transmission of human immunodeficiency virus (HIV) was investigated in 123 subjects with no apparent risk factor for infection other than having had heterosexual intercourse with a person who was either infected with HIV or at high risk of being infected with it. Seven subjects were found to be infected with the virus. Risk factors for transmission included being the regular sexual partner of an abuser of intravenous drugs and having a sexual relationship of more than 18 months9 duration. Anal intercourse was not a risk factor in the three subjects who admitted to it. There were 41 regular partnerships with abusers of intravenous drugs in which the antibody state and history were fully known for both partners. In these partnerships male to female transmission of the virus occurred in five out of 34 (15%) and female to male in one out of seven. In 30 couples in whom one partner was known to be positive for HIV and an abuser of intravenous drugs four female partners were found to be seropositive at first testing, but there were no new positive results on subsequent serial testing. In six of these 30 couples both partners abused intravenous drugs but the partner who was negative for HIV remained so. Few of the partnerships always practised safe sexual techniques, even after a partner was known to be positive for HIV. Heterosexual transmission of HIV occurred but was incomplete and may be related to the timing of the relationship with the infection.
Science in American Society: A Social History
Authors: Lester S. King
Journal: JAMA (1972)

In large part the history of science has been deemed the story of great discoveries and the great men who made them. If this were a correct interpretation, then the history of science in America would have relatively little to report until the 20th century. But fortunately, we can have different interpretations. Science actually is a major phase of our western culture, an important part of our intellectual heritage. Hence the history of science must try to understand the growth of this discipline in our intellectual and material environment; the way that it occupied different levels of importance at different periods; the social, political, and economic influences to which science has been subjected; and correlatively, the influence which it has exerted on the rest of American life and thought. Viewed in this light, the history of science in America is an important part of history in its broad sense, particularly
Serious methodological flaws compromise study findings
Authors: A. H. Pande, S. B. Soumerai
Journal: BMJ (2011)

Dumanovsky and colleagues investigated the effect of calorie labelling in restaurants.1 However, their study uses one of the weakest research designs (uncontrolled pre-post study) that would not merit inclusion in a Cochrane Systematic Review of health systems. This un-interpretable paper has received widespread publicity and has been presented as a causal argument against labelling food …
INCREASED INCIDENCE OF RENAL SIMPLE CYSTS IN PATIENTS WITH AORTIC DISSECTION AND INTRAMURAL HEMATOMA
Authors: Eunkyung Kim, E Ryoung Choi, Mi-rae Lee, Min Ho Kang, Hyjin Han, Ji Hyun Yang, Jeong Rang Park, Bong Gun Song, Yeon Hyun Choe, Young-Soo Do, Wook Sung Kim, Kiick Sung, Pyo-Won Park, Duk-Kyung Kim, Seung-Hyuk Choi
Journal: Journal of the American College of Cardiology (2010)
Diagnostic markers of viral hepatitis B and C.
Authors: C Trepo, F Zoulim, C Alonso, M A Petit, C Pichoud, L Vitvitski
Journal: Gut (1993)

Hepatitis B virus (HBV) serology has become extremely refined. As well as the recognised hepatitis B surface (HBs), hepatitis B core (HBc), and hepatitis B e (HBe) antigen-antibody systems, new markers have been introduced including pre-S1, pre-S2 for the envelope and the functional X protein. New automates have been introduced allowing flexibility in the different tests according to precise needs. The monitoring of pre-S1 antigen provides a relevant correlate of viral replication. The quantitative determination of HBV-DNA, pre-S1 Ag, and IgM anti-HBc seem most useful for the decision to use, and the monitoring of, antiviral treatment. Second generation ELISAs detect antibodies to three sets of hepatitis C virus (HCV) protein including the c22 core, and c33, and c100, which correspond to the non-structural regions (NS3 and NS4, respectively). Second generation ELISAs require confirmation by supplement assays, but their biggest limitation is the delayed appearance of anti-HCV after primary infection. In addition 10% of chronic infections with liver disease still remain seronegative despite circulating HCV RNA in serum or liver, or both. Much progress still has to be made before HCV serology can reach the level of sophistication of HBV.