tbuckley/cabot-search huggingface dataset:
The discovery of cortisone: a personal memory
Authors: J. H Glyn
Journal: BMJ (1998)

Fifty years ago this week, Philip Hench showed that “compound E” (cortisone) was capable of reversing the inflammation of rheumatoid arthritis. This discovery resulted from 19 years of imaginative and deductive observation together, perhaps, with that element of serendipity which seems to characterise many fundamental discoveries.

It all started in 1929 when Hench noted a clinical remission in one of his patients who suffered an intercurrent episode of jaundice. Convinced that this was no coincidence he decided to devote himself to the discovery of the nature of “antirheumatic substance X” in remissions associated with jaundice, and later, with pregnancy. His clinical researches involved giving many metabolites related to liver disease and subsequently, female hormones related to pregnancy. They were uniformly unsuccessful.

Because remissions associated with jaundice occurred as frequently in women as in men, Hench concluded that factor X, if a hormone, must be present in both sexes. This led him to consider the adrenal cortex. He also noted that the gross fatigue seen in patients with rheumatoid arthritis bore some resemblance to the anergy which characterises Addison's disease.

By happy chance, his colleague and friend at the Mayo Clinic, Edward Kendall, had, in 1929, switched his research studies to the separation and characterisation of the many unidentified hormones of the adrenal cortex. This work was laborious and …
Brain Tumor Chemotherapy
Authors: Wolff M. Kirsch
Journal: JAMA (1977)

This book emanates from a neurosurgical center with considerable experience in the chemotherapeutic management of malignant brain tumors. The dust jacket advertises the book as not only presenting the concepts underscoring the strategy of chemotherapy for primary malignant tumors of brain, but also as reviewing the extensive clinical experience at the University of California School of Medicine, San Francisco. The book delivers on the first item but unfortunately not on the second. There is no question that the management of malignant brain tumors is an exceptionally urgent clinical problem and one that merits a comprehensive review. Anyone nurturing an interest in the clinical application of a chemotherapeutic program for malignant gliomas will benefit from the superb reviews of cell kinetics, pharmacodynamics, and experimental brain tumor models. These chapters are current outlines of the state of the art and have many valuable references. The very trenchant foreword submitted by Dr Boldrey
Abstract 2388: Deciphering the role of APE1 protein variants in disease etiology
Authors: Jennifer Illuzzi, Nicole A. Harris, Brittney A. Manvilla, Daemyung Kim, Mengxia Li, Alexander C. Drohat, David M. Wilson
Journal: Cancer Research (2014)

Abstract Base excision repair (BER) is necessary for removal of DNA damage that has occurred from spontaneous decomposition, alkylation and oxidation. Defects in BER have been associated with cancer predisposition, neurodegeneration and premature aging. BER is initiated by a damage-specific DNA glycosylase that excises the damaged base, creating an apurinic/apyrimidinic (AP) site. The AP site is recognized by the multifunctional AP endonuclease 1 (APE1), which cleaves the phosphodiester backbone, producing a DNA strand break. DNA polymerase beta incorporates the correct nucleotide, and BER is completed via ligation by a protein complex of Ligase III and XRCC1. Like many BER proteins, APE1 is essential for survival, as deletion of both alleles in mice leads to embryonic lethality. We are pursuing the hypothesis that more mild reductions in APE1 activity will contribute to disease risk and development. To address this issue, we have engaged two strategies: (1) identification and characterization of APE1 missense mutations and (2) design and characterization of genetically-altered mutant human cell lines. In our first study, we have characterized eight APE1 variants found within the population or identified in endometrial cancer. Our studies reveal that while most of these proteins are normal for protein stability, biochemical activities, and intracellular localization, the endometrial cancer-associated variant Arg237Cys has decreased 3′-functions and AP-DNA binding. In our second study, we have created a heterozygous knockout HCT116 cell line, in which we have deleted one allele of APE1. The heterozygous knockout cells show a loss in AP endonuclease activity and are hypersensitive to DNA damaging drugs. Current cellular strategies are determining the essential nature of APE1 activity in HCT116 and other cell lines Citation Format: Jennifer Illuzzi, Nicole A. Harris, Brittney A. Manvilla, Daemyung Kim, Mengxia Li, Alexander C. Drohat, David M. Wilson. Deciphering the role of APE1 protein variants in disease etiology. [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 2388. doi:10.1158/1538-7445.AM2014-2388
Pathogenesis of non-insulin-dependent (type II) diabetes mellitus (NIDDM) – genetic predisposition and metabolic abnormalities
Authors: Hee-Sook Jun, Hak Yeon Bae, Byoung Rai Lee, Kwang Sam Koh, Young Soo Kim, Kwan Woo Lee, Hyun-man Kim, Ji-Won Yoon
Journal: Advanced Drug Delivery Reviews (1999)
A recombinant allergen chimer as novel mucosal vaccine candidate for prevention of multi‐sensitivities
Authors: C. Wild, M. Wallner, K. Hufnagl, H. Fuchs, K. Hoffmann‐Sommergruber, H. Breiteneder, O. Scheiner, F. Ferreira, U. Wiedermann
Journal: Allergy (2006)

Background: As conventional immunotherapy is less efficacious in patients with allergic multi‐sensitivities compared with mono‐sensitized subjects, new intervention strategies are needed. Therefore, an allergen chimer was genetically engineered for treatment of multi‐sensitization with birch and grass pollen on the basis of mucosal tolerance induction. Methods: The major birch pollen allergen Bet v 1 served as a scaffold for N‐ and C‐terminal linkage of the immunodominant peptides of the grass pollen allergens Phl p 1 and Phl p 5 and this new construct was cloned and expressed in Escherichia coli . After purification, physicochemical and immunological characterization the chimer was used for intranasal tolerance induction prior to poly‐sensitization with Bet v 1, Phl p 1 and Phl p 5. Results: The immunological characterization revealed that the conformation of Bet v 1 within the chimer was comparable to that of natural as well as recombinant Bet v 1. The chimer was immunogenic in mice for T and B cell responses to the three allergens. Intranasal application of the chimer prior to poly‐sensitization significantly suppressed humoral and cellular allergen‐specific Th2 responses and prevented development of airway inflammation upon allergen challenge. Moreover, local allergen‐specific IgA antibodies were induced by the chimer. The mechanisms of poly‐tolerance induction seemed to be mediated by regulatory cytokines, since TGF‐ β and IL‐10 mRNA in splenocytes were upregulated and tolerance was transferable with these cells. Conclusion: The data indicate that such allergen chimers harboring several unrelated allergens or allergen peptides could serve as mucosal polyvalent vaccines for prevention of multi‐sensitivities.
Approaching Difficult Communication Tasks in Oncology
Authors: A. L. Back, R. M. Arnold, W. F. Baile, J. A. Tulsky, K. Fryer-Edwards
Journal: CA A Cancer Journal for Clinicians (2005)

Effective communication skills enable physicians to improve patients' understanding of their illnesses, improve patient adherence to treatment regimens, use time efficiently, avoid burnout, and increase professional fulfillment. Common communication pitfalls include blocking, lecturing, depending on a routine, collusion, and premature reassurance. Fundamental communication skills include “ask-tell-ask,” “tell me more,” and responding empathetically. Key communication tasks that are linked to the illness trajectory include: the first visit, giving bad news, making anticancer treatment decisions, offering clinical trials, completing anticancer therapy, and discontinuing palliative chemotherapy. While enhancing or acquiring new skills ultimately requires practice and feedback over time, this article provides a cognitive map for important communication skills that physicians need over the course of caring for a person with cancer.
THE WORK OF THE CAMBRIDGE RESEARCH HOSPITAL
Authors: T. S. P. Strangeways
Journal: BMJ (1913)

toleration of conditions which,as some autlhor has put it, catise almost as much venereal disease within the bonds of imatrirmtony as exists outside tlhem-a statement whiclh is probably true if the relote effects of the diseases are taken i[ltO account.Tlhinkl of tlle inconsistence of our laws wlicll enable tlle working man or womian to get compelnsatio-n for a trivial anid temiporary injury fromi an employer, wlho is as often as inot only techlnically respoinsible for it; or whlich do not allpow one witlh imn-ipunity to resent tlle inmiputdence of a sclhoolboy by whipping hlimin, and yet permr.its a person to imarry wlho miay by so doing damiiage another so seriously as to bring about lifelong stuffering or miiutilation, or even death, and.perhaps produce a degenerative or dlefective progeny.Thlink of the criminality of thiis, with no law to prevent it, or to punish it!rIhecrime, if tlhe perpetrator lhas a knowledge of the danger, is almiost coiiparable witlh that of the poisoner wlho, in cold- blooded secrecy, uinder thle guise of friendslip and affection, by hlis.action leads to the disease or death of hiis victim.Tlle thing is monstrous, and we as a profession shoild 'surely take tlle initiative in the way of miaking recommendations for educating every class concerning these dliseases aind tlheir results, an(l by insisting iupon tllh principle that freedom from transmissible disease slhotuld be a legal condition for marrizage.Tliere.inw'ill lie tlhe basis of trLue eugenics, and if tllis kndowledge is ground into tlle people, and u'nderstood by tlhemn, thle day mllay come, and coime slhortly, whien pulblic opinion will, for the protection of tlhe innocelnt, and for thc carrying out of eugenic principles, not only tolerate, but welcomne, the requirement by law of certificates of healthl, indicating that "no just impediment " exists before iatri-iilony is entered inte.Thlen it will lhappen thlat if a person ii airries, knowingly having any of tlhese iinpedimiieuts, and brings about any of the disastrois results whiicl 1 hiaIve referred to, there will be ino excuse for the remiiorse wvhiielh lhe or slhe mnst suffer in consequence of lhaving disrc-.arded or evade'd measures the purports of wlhichl were b jtli plainl and just.
Absorbable Gelatin Sponge in the Treatment of Decubitus Ulcers
Authors: Leslie W. Freeman
Journal: JAMA (1963)

DECUBITUS ULCERS and infected wounds have long been difficult problems in healing. In the course of handling a large number of these lesions, many different substances have been used without any change of a dramatic nature. On the basis of a report of a single observation, 1 absorbable gelatin sponge (Gelfoam) was placed in a large ulcer of a paraplegic dog. In 1 week the wound was healed. The dramatic result led to clinical trial.  To date, 24 patients have been treated. All wounds were free of necrotic tissue at the start of the treatment; this was accomplished by debridement when necessary. The wounds had culture and sensitivity studies and resistant Staphylococcus aureus was present in most, along with the usual fecal organisms. Secretions ranged from excessive to moderate; all were purulent. Within several days, the secretions became clear and diminished sharply in volume. Laboratory studies of the secretions have
Early growth delay in diabetic pregnancy: relation to psychomotor development at age 4
Authors: M. B. Petersen, S. A. Pedersen, G. Greisen, J. F. Pedersen, L. Molsted-Pedersen
Journal: BMJ (1988)

Ninety nine consecutive insulin dependent and 101 non-diabetic pregnant women were examined by ultrasonograph to assess early fetal growth. In 42 of the diabetic mothers and three of the non-diabetic mothers the scan showed early intrauterine growth delay. At 4-5 years of age all children available for study were evaluated by the Denver developmental screening test. Only 23 of the 34 children of diabetic mothers with early intrauterine growth delay had normal test scores compared with 46 of the 50 children of diabetic mothers with normal intrauterine growth. The children failed in personal-social development, gross motor development, and particularly in language and speech development. Children of diabetic mothers with normal early fetal growth had scores very similar to those of the children of non-diabetic mothers, of whom 76 of the 86 tested had normal scores. This study suggests that children with a history of growth delay in early diabetic pregnancy should be screened for possible developmental impairment.
Very early spondyloarthritis: where the inflammation in the sacroiliac joints starts
Authors: M. Bollow, K.-G. A. Hermann, T. Biedermann, J. Sieper, M. Schöntube, J. Braun
Journal: Annals of the Rheumatic Diseases (2005)

Involvement of the sacroiliac joints (SIJ) is a major and characteristic feature of the spondyloarthritides (SpA). In early ankylosing spondylitis and undifferentiated SpA (uSpA) sacroiliitis is the most common early clinical finding and the presumed first manifestation of the disease. Magnetic resonance imaging has proved useful for visualising inflammation in the SIJ in adults and children. Recently, initial localisation of the inflammation in the SIJ has been described in some detail, but it has not been completely defined to date—either in imaging or in histopathological studies. This is mainly owing to the lack of data in very early disease and the lack of follow up studies. Here we present a patient with early disease, which may augment our understanding of this stage of SpA.
Tamoxifen and Hypercalcemia
Authors: J. S. PATTERSON
Journal: Annals of Internal Medicine (1978)

Letters and Corrections1 December 1978Tamoxifen and HypercalcemiaJ. S. PATTERSON, M.B., CH.B., M.R.C.P., B. J. A. FURR, PH.D., L. A. BATTERSBY, M.A.J. S. PATTERSON, M.B., CH.B., M.R.C.P.Search for more papers by this author, B. J. A. FURR, PH.D.Search for more papers by this author, L. A. BATTERSBY, M.A.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-89-6-1013_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The recent letter from Dr. Veldhuis (Ann Intern Med 88:574-575, 1978) raises the question of tamoxifen-related hypercalcaemia. We wish to add to this report and place it in perspective.An analysis of all the written information available to us by 31 March 1978 yielded 36 patients who had developed hypercalcaemia while receiving tamoxifen therapy for advanced breast cancer. This worldwide survey included all published and directly reported data. Although we cannot assume that these 36 reports represent the total cases of hypercalcaemia in patients receiving tamoxifen treatment, this number would give an occurrence rate of less than...References1. GALASKOBURN CJ: Hypercalcaemia in patients with advanced mammary carcinoma. Br Med J 3:573-577, 1971 CrossrefMedlineGoogle Scholar2. KLEINFELD G: Acute fatal hypercalcemia. A complication in estrogen therapy of metastatic breast cancer. JAMA 181:1137-1138, 1962 CrossrefMedlineGoogle Scholar3. JESSIMANEMERSONSHAHMOORE AKRF: Hypercalcemia in carcinoma of the breast. Ann Surg 157:377-392, 1963 CrossrefMedlineGoogle Scholar4. COUNCIL ON PHARMACY AND CHEMISTRY: Current status of hormone therapy of advanced mammary cancer. JAMA 146:471-477, 1951 MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Imperial Chemical Industries Ltd. Alderley Park Macclesfield, Cheshire, England PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByFlare hypercalcemia after letrozole in a patient with liver metastasis from breast cancer: a case reportTamoxifen flare hypercalcemia: an additional support for gallium nitrate usageThe pharmacology and clinical uses of tamoxifenTreatment of early localized breast cancer in elderly patients by TamoxifenTamoxifen-induced hypercalcemia in breast cancerTamoxifen and HypercalcemiaSALLY D. LANE, M.D., EMMANUEL C. BESA, M.D., ROSALINE R. JOSEPH, M.D.Glucocorticoids and æstrogens in the management of hypercalcaemiaTamoxifen Hormonal EffectsJ. D. VELDHUIS, M.D. 1 December 1978Volume 89, Issue 6Page: 1013-1013KeywordsBreast cancerHypercalcemiaResearch design Issue Published: 1 December 1978 PDF DownloadLoading ...
Pressure-Induced Vascular Activation of Nuclear Factor-κB
Authors: Catherine A. Lemarié, Bruno Esposito, Alain Tedgui, Stéphanie Lehoux
Journal: Circulation Research (2003)

The effects of mechanical factors on nuclear factor (NF)-kappaB activation and its potential functional roles have been very little explored in the intact vessel. Thus, we chose to study the regulation of NF-kappaB by intraluminal pressure using an organ culture model of mouse carotid arteries maintained at 80 or 150 mm Hg during 24 hours. Gel shift analysis revealed an increase in the DNA-binding capacity of NF-kappaB in vessels at high pressure compared with vessels at normal pressure (304+/-49%; P<0.001). This coincided with reduced levels of the endogenous NF-kappaB inhibitor IkappaBalpha in arteries at 150 mm Hg (52+/-7%; P<0.001), as detected by Western blot. To study the functional role of the pressure-induced activation of NF-kappaB, we evaluated the rate of apoptosis (TUNEL method) in carotid arteries cultured with or without an inhibitor peptide blocking nuclear translocation of NF-kappaB. No apoptosis was detected in control arteries either at 80 or 150 mm Hg. However, in the presence of the NF-kappaB inhibitor peptide, we observed apoptosis in vessels at 80 mm Hg (5+/-1%; P<0.001 versus untreated controls), which was markedly increased in vessels at 150 mm Hg (14+/-2%; P<0.001). These results were corroborated by immunohistochemical analysis showing positive staining for cleaved caspase 3 in vessels at 80 mm Hg treated with the NF-kappaB inhibitor peptide, which was additionally enhanced in treated vessels at 150 mm Hg. Our findings demonstrate that high intraluminal pressure activates NF-kappaB in arteries. Moreover, the activation of NF-kappaB seems to play a key role in preventing apoptosis in vascular cells, especially when vessels are exposed to high intraluminal pressure.
Dynamic variability of binding of antiarrhythmic drugs during the evolution of acute myocardial infarction.
Authors: K M Kessler, B Kissane, J Cassidy, K C Pefkaros, P Kozlovskis, C Hamburg, R J Myerburg
Journal: Circulation (1984)

We tested the hypothesis that the changes in free fatty acid and alpha 1-glycoprotein concentrations, which occur during acute myocardial infarction, exert asynchronous and opposing influences on the serum protein binding of selected drugs. Free drug fractions of two antiarrhythmic agents with contrasting binding characteristics, quinidine and procainamide, were related to free fatty acid and alpha 1-glycoprotein concentrations on days 1 through 5 and 10 in 20 patients with acute myocardial infarction. The mean free quinidine fraction was elevated on day 1 (9.0 +/- 4.4% vs 6.7 +/- 2.7% in patients with stable heart disease; p less than .05) and fell progressively to day 10 (4.0 +/- 2.8%; p less than .0002) as free fatty acid concentration decreased (day 1 = 464 +/- 272 meq/liter; day 10 = 264 +/- 155 meq/liter; p less than .01) and alpha 1-glycoprotein concentration increased (day 1 = 98 +/- 31 mg/dl; day 10 = 141 +/- 47 mg/dl; p less than .02). Multiple stepwise regression showed a major influence of changing alpha 1-glycoprotein concentration on the observed sequential changes in the free quinidine fraction (p less than .005). In contrast, no serial changes in procainamide binding were noted. In conclusion, metabolic changes during the course of acute myocardial infarction sequentially alter free quinidine fraction and, consequently, may influence pharmacodynamics.
Abstract IA01: Gene regulatory network approaches to interpreting breast cancer GWAS results
Authors: Bruce A. J. Ponder, Kerstin Meyer, Michael Fletcher, Florian Markowetz, Ines de Santiago, Mauro Castro
Journal: Cancer Research (2014)

Abstract Six years after the publication of the first breast cancer GWAS, skepticism is expressed about the usefulness of the results. The GWAS loci identified to date explain only a minority of the estimated genetic variance, and the risks conferred by even the strongest individual variants are small. Classical biochemical pathway approaches to elucidating mechanism have had modest success. I will argue that an attempt to examine the combined effects by common and rare variants and their interactions through analysis based on gene regulatory networks may yield new and useful information. Although still speculative, I will present initial data that provide support for this approach. Citation Format: Bruce A. J. Ponder, Kerstin Meyer, Michael Fletcher, Florian Markowetz, Ines de Santiago, Mauro Castro. Gene regulatory network approaches to interpreting breast cancer GWAS results. [abstract]. In: Proceedings of the AACR Special Conference: Cancer Susceptibility and Cancer Susceptibility Syndromes; Jan 29-Feb 1, 2014; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(23 Suppl):Abstract nr IA01. doi:10.1158/1538-7445.CANSUSC14-IA01
Report to the House of Delegates
Authors: M. O. Rouse
Journal: JAMA (1967)

I thank you once again for the confidence you have placed in me. I promise you once again that I shall do my simple best to serve in a way that will bring honor to this Association, respect to our profession, and benefit to the public we serve. I am human and therefore lacking in perfection. You will, I am certain, continue to be understanding and considerate. Most earnestly will I try to merit your continued personal esteem, respect, and cooperation. I am particularly pleased to have the opportunity of opening my year as President by addressing this House of Delegates. I would like to devote just a minute to the unique responsibilities of delegates, alternate delegates, officers, and all council and committee members of our Association. That responsibility is to interpret the actions and policies of the AMA to physicians back at home—to bring the nationwide significance of House