tbuckley/cabot-search huggingface dataset:
Epilepsy and Psychiatry
Authors: Terrence L. Riley
Journal: JAMA (1982)

This thorough and interesting book is a tribute to the 100th anniversary of Gowers' classic work,<i>Epilepsy and Other Chronic Convulsive Diseases</i>. The contributors, some of whom may not be well known to Americans, are an impressive cast of Britain's preeminent neurologists and psychiatrists, among them John Gunn, George Fenton, Denis Williams, and Denis Hill, in addition to the editors. In his chapter "The Emotions and Epilepsy," Denis Williams laments the current "artificial distinction between what are called the science and the art of medicine." It is perhaps for this reason that the importance of psychiatric and psychological features in epilepsy have for so long been viewed as unrelated or at best alternative approaches to epilepsy. In the historical review that begins the book, Hill traces the evolution of this schism, noting that psychiatrists and neurologists approached problems of epilepsy from such widely different positions that their two traditions virtually
LYSOSOMAL ACID HYDROLASES AND HYPERREACTIVITY TO ENDOTOXIN IN MICE INFECTED WITH BCG
Authors: Kazuhisa Saito, Emanuel Suter
Journal: The Journal of Experimental Medicine (1965)

Experiments are reported dealing with the correlation between activities of lysosomal acid hydrolases and hyperreactivity to endotoxin induced by BCG infection. Acid hydrolases were determined quantitatively in peritoneal MP, liver homogenate, and plasma of normal and hyperreactive mice. Mice infected with BCG not only exhibited a hyperreactive state to lethal effect of endotoxin, but also responded to endotoxin by rapid increase of acid hydrolases, especially of ß-glucuronidase, in the plasma; whereas control mice responded to endotoxin by almost no change in plasma acid hydrolases. The extent of increase of ß-glucuronidase in plasma of hyperreactive mice was shown to correlate fairly well with the degree of hyperreactivity to the lethal effect of endotoxin. Desensitization of such animals with endotoxin was found to cause a decreased response of plasma ß-glucuronidase parallel with decreased mortality. A large amount of PPD exerted the similar effect to that of endotoxin in hyperreactive mice. Furthermore, the effect of PPD was decreased by desensitization of such animals with endotoxin, a fact which suggests contamination of PPD with endotoxin.
Abstract 1094: Dynamics of Gemcitabine induced interleukin-8 (IL-8) expression in pancreatic tumor microenvironment
Authors: Sobeyda Gomez, Takahiko Fujii, Haojie Huang, Rosa Hwang, Viji Ramachandran, Craig Logsdon, Thiru Arumugam
Journal: Cancer Research (2014)

Abstract Background: The clinical standard of care for patients with pancreatic ductal adenocarcinoma (PDAC) is treatment with Gemcitabine (Gem) despite Gem's limited benefits. To date, no surrogate marker has been identified to indicate whether Gem treatment directly affects PDAC tumor cells. In order to identify such a marker, we analyzed Gem treated cell lines and clinical samples. Methods: 12 PDAC cell lines were treated with 5μM Gem for three hours and then allowed to grow in the absence of Gem for 24hrs before mRNA expression analysis (Illumina Gene Expression Array). IHC and WB were used to quantify IL-8 expression. ShRNA mediated silencing was utilized to study the therapeutic value of IL-8. Results: mRNA expression and WB confirmed the induction of IL-8 after Gem treatment. Gem induced IL-8 expression was transcriptionally controlled by NFκB and C/EBP. PDAC cells (MPanc96 and BxPc-3-CXCR1), HPSC (Human Pancreatic Stellate Cells-CXCR1) and HUVEC (Human Umbilical Vein Endothelial cells-CXCR1 &amp; 2) expressed the receptor of IL-8. Conditioned media from Gem treated cells and rIL-8 treated cells, stimulated cell growth (PDAC, HPSC and HUVEC), polygon formation in HUVEC and α-SMA expression in HPSC. Stable silencing of IL-8 in Capan2 cells, which develop an abundant stroma, led to a significant reduction in tumor volume. Histologically, IL-8 silenced tumors showed reduced micro-vessel density (CD37), as well as highly reduced desmoplasia (Trichrome stain &amp; α-SMA) associated with necrosis. Further, IHC revealed strong IL-8 expression in neo-adjuvant Gem-treated human PDAC tissues (strong expression 42.1%, weak expression 57.9%, negative 0%) in comparison to tissue from patients that underwent surgery alone (strong expression 0%, weak expression 77.8%, negative 22.2%).Conclusion: Gem induced IL-8 functions as a growth factor for cancer cells and its microenvironment. Thus, IL-8 can serve as a surrogate marker to indicate Gem effects in PDAC. Citation Format: Sobeyda Gomez, Takahiko Fujii, Haojie Huang, Rosa Hwang, Viji Ramachandran, Craig Logsdon, Thiru Arumugam. Dynamics of Gemcitabine induced interleukin-8 (IL-8) expression in pancreatic tumor microenvironment. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1094. doi:10.1158/1538-7445.AM2014-1094
Long-Term Seropositivity for Human T-Lymphotropic Virus Type III in Homosexual Men Without the Acquired Immunodeficiency Syndrome: Development of Immunologic and Clinical Abnormalities
Authors: MADS MELBYE
Journal: Annals of Internal Medicine (1986)

The long-term effects of seropositivity for human T-lymphotropic virus type III (HTLV-III) on T-lymphocyte subsets and health status were evaluated in longitudinal studies of 250 initially healthy homosexual men. The relative risk of having an inverted T-lymphocyte helper-to-suppressor ratio rose from 14.3-fold among short-term seropositive subjects (less than 19 months) to 46.9-fold among long-term seropositive subjects (greater than 29 months) in comparison with the risk among seronegative subjects. Overall, 91.7% of long-term seropositive men had inverted ratios, compared with 12.9% of seronegative men. None of the seropositive men who developed an inverted ratio later reestablished a normal ratio. Both decreased T-helper cell number and percentage (p = 0.003) and increased T-suppressor cell number and percentage (p = 0.03) were significantly correlated with duration of seropositivity. Among seropositive persons, lymphadenopathy was a highly significant short-term as well as long-term consequence, whereas diarrhea, oral thrush, and herpes zoster were correlated with long-term seropositivity. Overall, 50% of long-term seropositive men compared with 16% of seronegative men developed at least one of five clinical symptoms (p less than 0.003). We conclude that a high proportion of persons infected with HTLV-III will develop measurable immunologic and clinical abnormalities.
Fluoridation: Slow Diffusion of a Proved Preventive Measure
Authors: Diana Chapman Walsh
Journal: New England Journal of Medicine (1977)

Drawing on two decades of experience in the United States with controlled fluoridation, Dunning1 reported in 1965 that few public-health measures are so unequivocally effective against widespread disease. Fluoridation of community water supplies is safe, practical, economical and beneficial: costing about 10 to 40 cents a year per capita, fluoridation can reduce by up to 65 per cent the amount of tooth decay in school-aged children, decrease by approximately 75 per cent the loss of first permanent molars among children 12 to 14 years old and increase six-fold the number of children at this age still caries-free, and prevent all . . .
Treating major depression in children and adolescents
Authors: Andrew Herxheimer
Journal: BMJ (2004)

Screening without evidence of efficacy Thyroid ultrasonography is another exampleEditor-I agree with Law's view of screening, that screening of unproved value should not be advocated. 1 As a clinical endocrinologist I often have to deal with patients' anxieties about non-palpable incidental findings on thyroid ultrasonography, often performed for wrong or unjustified reasons.Sometimes patients arrive with already established surgical complications after unnecessary thyroid operations.Although a substantial number of incidental thyroid nodules may be histologically malignant, 2 their clinical importance has never been proved.A recent preliminary study indicates that the progression rate of non-palpable proved thyroid malignant nodules to clinically significant lesions may be very low. 3 Thyroid ultrasonography is an additional example of an often used, often non-efficacious screening modality that may lead to "cascade iatrogenesis." 4
Antibody-dependent cellular cytotoxicity (ADCC) is mediated by genetically modified antigen-specific human T lymphocytes
Authors: Béatrice Clémenceau, Nicolas Congy-Jolivet, Géraldine Gallot, Régine Vivien, Joëlle Gaschet, Gilles Thibault, Henri Vié
Journal: Blood (2006)

In the context of transplantation, donor and virus-specific T-lymphocyte infusions have demonstrated the dramatic potential of T cells as immune effectors. Unfortunately, most attempts to exploit the T-cell immune system against nonviral malignancies in the syngeneic setting have been disappointing. In contrast, treatments based on monoclonal antibodies (Abs) have been clinically successful and have demonstrated the clinical relevance of several antigens as therapeutic targets and the importance of the antibody-dependent cellular cytotoxicity (ADCC) pathway. In the present study, we considered the possibility of arming specific T cells with a receptor that would enable them to mediate ADCC. After transduction with a CD16/gamma receptor gene, CD4(+) and CD8(+) cytotoxic T lymphocytes displayed stable expression of the CD16 receptor at their surface. In the absence of Ab, CD16/gamma expression did not affect the capacity of specific T lymphocytes to kill their target following "natural" T-cell receptor recognition. When tested against the autologous B-lymphoblastoid cell line (BLCL) coated with anti-CD20 mAb, the newly expressed Fc receptor enabled the T cells to kill the BLCL through ADCC. Adoptive transfer of such newly designed immune effector may be considered to increase antibody efficiency by harnessing the immune potential of T cells.
Prenatal versus postnatal sensitization to environmental allergens in a high-risk birth cohort
Authors: Julie Rowe, Merci Kusel, Barbara J. Holt, Devinda Suriyaarachchi, Michael Serralha, Elysia Hollams, Stephanie T. Yerkovich, Lily S. Subrata, Claire Ladyman, Agata Sadowska, Jamie Gillett, Elizabeth Fisher, Richard Loh, Lars Soderstrom, Staffan Ahlstedt, Peter D. Sly, Patrick G. Holt
Journal: Journal of Allergy and Clinical Immunology (2007)
Modulation of Aspirin-Insensitive Eicosanoid Biosynthesis by 6-Methylprednisolone in Unstable Angina
Authors: Francesco Cipollone, Antonina Ganci, Anita Greco, Maria Rosaria Panara, Massimo Pasquale, Domenico Di Gregorio, Ettore Porreca, Andrea Mezzetti, Franco Cuccurullo, Paola Patrignani
Journal: Circulation (2003)

The evidence that inflammation plays a pivotal role in the pathophysiology of acute coronary syndromes prompted us to investigate the effects of glucocorticoid treatment on leukotriene (LT) C4 and thromboxane (TX) A2 biosynthesis in unstable angina.Urinary LTE4 and 11-dehydro-TXB2 were significantly higher in 12 patients with unstable angina than in 12 patients with stable angina and 12 patients with nonischemic chest pain. Furthermore, we randomized the unstable angina patients to receive intravenous 6-methylprednisolone (6-MP; 1 mg/kg BID for 2 days) or matching placebo and collected 12 consecutive 6-hour urine samples before and during the infusions. LTE4 excretion showed a time-dependent decrease in the 6-MP group but did not decrease during placebo. Furthermore, during myocardial ischemia, LTE4 was significantly higher before 6-MP infusion than during steroid therapy. In contrast, 11-dehydro-TXB2 did not differ significantly during 6-MP versus placebo. Myocardial ischemia elicited by stress test in the stable angina patients was not accompanied by any change in LTE4 and 11-dehydro-TXB2, thus ruling out a role of ischemia per se in the induction of increased eicosanoid production.Increased production of vasoactive LT and TX may occur in unstable angina despite conventional antithrombotic and antianginal treatment. Glucocorticoids can suppress LTC4 biosynthesis in the short term and may provide an interesting tool to explore the pathophysiological significance of inflammatory cell activation in this setting.
Characteristics of Highly Ranked Applicants to General Surgery Residency Programs
Authors: Steven C. Stain, Jonathan R. Hiatt, Ashar Ata, Stanley W. Ashley, Kevin K. Roggin, John R. Potts, Richard A. Moore, Joseph M. Galante, L. D. Britt, Karen E. Deveney, E. Christopher Ellison
Journal: JAMA Surgery (2013)

Importance: With duty hour debates, specialization, and sex distribution changes in the applicant pool, the relative competitiveness for general surgery
STUDIES ON THE CHEMISTRY OF THE TRANSFORMING ACTIVITY
Authors: Stephen Zamenhof, Hattie E. Alexander, Grace Leidy
Journal: The Journal of Experimental Medicine (1953)

The transforming principles of Hemophilus influenzae have been purified by a new method including fractional extraction. The active molecule behaves in these extractions like the bulk of the DNA preparation. The minimal amount of DNA necessary for transformation appeared to be of the same order of magnitude as the amount of DNA in a single cell. Quantitative study has been made of the resistance of transforming activity to various agents. When subjected to heat, the temperature at which the activity starts to decrease corresponds rather closely to the temperature at which the viscosity of the bulk of the DNA preparations starts to decrease. Similar correspondence was found when the transforming principle was subjected to pH changes. This is further evidence that the behavior of the active molecules is similar to the behavior of the average DNA molecule of the preparation. The activity is reduced by exposure to low ionic strength and by dehydration. Desoxyribonuclease in concentrations less than 10(-4) gamma/cc. is able to destroy the activity; a lag period during which the activity but not the viscosity decreases has been observed. NaNO(2) at pH 5.3, HCHO and 10(-5)M Fe(++) reduce or destroy the activity; the importance of intact amino groups in the DNA molecule for the activity is discussed. Several protein-denaturing, sterilizing, and mutagenic agents have been found to have no effect on the transforming activity.
Functional, Cellular, and Molecular Characterization of the Angiogenic Response to Chronic Myocardial Ischemia in Diabetes
Authors: Munir Boodhwani, Neel R. Sodha, Shigetoshi Mieno, Shu-Hua Xu, Jun Feng, Basel Ramlawi, Richard T. Clements, Frank W. Sellke
Journal: Circulation (2007)

Background— Ischemic heart disease is the most common cause of mortality in diabetic patients. Although therapeutic angiogenesis is an attractive option for these patients, they appear to have reduced collateral formation in response to myocardial ischemia. The aims of this study were to establish a large animal model of diabetes and chronic myocardial ischemia, evaluate the effects of diabetes on the angiogenic response, and elucidate the molecular pathways involved. Methods and Results— Diabetes was induced in male Yucatan miniswine using a pancreatic β-cell specific toxin, alloxan (150 mg/kg; n=8). Age-matched swine served as controls (n=8). Eight weeks after induction, chronic ischemia was induced by ameroid constrictor placement around the circumflex coronary artery. Myocardial perfusion and function were assessed at 3 and 7 weeks after ameroid placement using isotope-labeled microspheres. Endothelial cell density and myocardial expression of angiogenic mediators was evaluated. Diabetic animals exhibited significant endothelial dysfunction. Collateral dependent perfusion and LV function were significantly impaired in diabetic animals. Diabetic animals also demonstrated reduced endothelial cell density (173±14 versus 234±23 cells/hpf, P =0.03). Expression of VEGF, Ang-1, and Tie-2 was reduced, whereas antiangiogenic proteins, angiostatin (4.4±0.9-fold increase, P &lt;0.001), and endostatin (2.9±0.4-fold increase, P =0.03) were significantly elevated in the diabetic myocardium. Conclusions— Diabetes results in a profound impairment in the myocardial angiogenic response to chronic ischemia. Pro- and antiangiogenic mediators identified in this study offer novel targets for the modulation of the angiogenic response in diabetes.
Performance of a Colonoscopy Simulator: Experience from a Hands-On Endoscopy Course
Authors: L. Aabakken, S. Adamsen, A. Kruse
Journal: Endoscopy (2000)

The Simbionix (Tel Hashomer, Israel) GI-Mentor is an interactive computerized simulator, designed to provide medical experts with hands-on training for endoscopic procedures. The system uses a specially designed mannequin and a computer simulation program, utilizing a texture-mapped simulation of the endoluminal view, combined with a force-feedback mechanism and a real Pentax colonoscope to mimic the look and feel of an actual endoscopy procedure.
System Failure versus Personal Accountability — The Case for Clean Hands
Authors: Donald Goldmann
Journal: New England Journal of Medicine (2006)

A new mother sits by her tiny, premature baby in a neonatal intensive care unit. She watches as a physician touches the baby without first washing his hands or using the waterless, alcohol-based hand antiseptic just a couple of feet away. A few minutes later, a nurse and then another doctor also fail to perform these basic procedures. When her baby was admitted to the unit, the mother was told to remind caregivers to wash their hands, but only after witnessing repeated failures does she muster the courage to speak up about the practice she thought would be routine. By . . .
Hospitalization for Possible Myocardial Infarction-Reply
Authors: Stanley S. Schor
Journal: JAMA (1977)

When making decisions in the face of uncertainty, physicians, like anyone else, assume a risk of being wrong. When a physician in an emergency room makes a decision, he bases it on all the available evidence, his previous knowledge, and an idea that one type of error—denying admission to a patient who needs it—is worse than the other type—hospitalizing a patient not in need of such hospitalization. A person may be justifiably hospitalized on the basis of the best medical knowledge available and yet by hindsight he may not have needed it.  Dr Berger may infer a pejorative connotation to the word error, but we certainly did not imply it. From the point of view of the physician, he did what every other physician would have done. Even though he is not at fault, it is still an error.
Persistence—luck—Avastin
Authors: Laurie Goodman
Journal: Journal of Clinical Investigation (2004)

ests."So, Ferrara, thinking it might be useful for anticancer therapy, continued to work on VEGF.A breakthrough came in 1993, when Ferrara and colleagues developed a mouse antibody that blocked VEGF function and inhibited tumor growth in mice (2).At that time, Ferrara said, these results "were really surprising.It was thought
Innate immunity for biodefense: A strategy whose time has come
Authors: C AMLIELEFOND, D PAZ, M CONNELLY, G HUFFNAGLE, K DUNN, N WHELAN, H WHELAN
Journal: Journal of Allergy and Clinical Immunology (2005)

Defense against biothreat agents requires a broad-spectrum approach. Modulation of the innate immune system might fulfill this requirement. Hackett's previous review of innate immune activation as a broad-spectrum biodefense strategy identified several unresolved questions. The current article is a systematic approach to answering those questions with the focused participation of research groups developing this technology. Our team of academic and industry participants reviewed the promising agents and came to the following conclusions. It is feasible to construct a biodefense platform combining synergistic agents that activate the innate immune system against a broad range of pathogens on the basis of conserved microbial components by using a nasal spray for immune activation in the respiratory and gastrointestinal tracts because these are the most likely routes of attack. It might also be possible to include agents that inhibit molecular events leading to septic shock. Innate immune-activating agents designed to activate Toll-like and other receptors will probably provide protection against the biothreat pathogen spectrum for periods ranging from 2 to 14 days for IFNs up to 26 weeks for immunomodulatory oligonucleotides. Initial treatment is proposed on the first index case or biosensor alert. Boost doses would be required. Harmful inflammation is possible, but thus far, only transient fever has been observed. Autoimmune reaction and retroviral activation have not been seen thus far in preclinical and human trials of many of these compounds. Toll-like receptor agonists caused cytokine production in all subjects tested, but genetic polymorphism reduced the response to IFN in African American subjects.
DEATH FROM RATTLESNAKE BITE.
Authors: W. A. LEWIS
Journal: JAMA (1906)

<h3>Patient.</h3> —A boy, aged 14, was bitten by a large rattlesnake, Oct. 7, 1906. A companion tied a cord around the leg above the bite, killed the snake, and brought the boy home. <h3>Examination.</h3> —I saw the boy something over two hours after he was bitten. I found that he was bitten on the calf of the right leg about the junction of the upper with the middle third, both fangs having penetrated their entire length. The cord was very tightly drawn above the knee and the circulation was nearly cut off. The points of entrance of the fangs were ecchymotic and the entire leg was greatly swollen. The patient complained of pain. His condition indicated the absorption of large quantities of poison. The pulse was about 140 and weak, the extremities were cold, and he was considerably nauseated. <h3>Treatment.</h3> —I made free crucial incisions where the fangs entered and
Evaluation of skin ageing: a systematic review of clinical scales
Authors: G. Dobos, A. Lichterfeld, U. Blume-Peytavi, J. Kottner
Journal: British Journal of Dermatology (2014)

Clinical scales are widely used in anti‐ageing research and practice. More than 100 skin ageing scales exist, which makes it difficult to choose outcome measures and to compare study results. The objectives were to assess and evaluate the quality of measurement properties of available clinical skin ageing scales. A systematic review was conducted. Electronic databases including Medline (1970 to June 2013) and EMBASE (1974 to June 2013) were searched via Ovid SP. To enhance the sensitivity forward searches were conducted in Scopus and Web of Science. We identified 111 scales in 52 included publications. Thirty studies had good methodology for at least one measurement property. Forty‐two scales were evaluated for their test–retest or interrater reliability. Nineteen showed high reliability coefficients. A further 15 instruments were partly supported by content and/or structural and/or criterion validity and/or hypotheses‐testing evidence. The majority of existing clinical skin ageing scales were developed for evaluating facial characteristics. Many scales quantify similar constructs. In contrast to the high number of available scales there is limited evidence supporting their measurement properties. Recommendations for the use of specific skin ageing scales for clinical studies must be made with caution because of the high number of studies with poor methodology. Development of new instruments should be justified, and existing ones investigated for scale behaviour using appropriate methods. Future research should aim to select and/or adapt existing scales to identify the 'best' to improve clinical research and practice.