tbuckley/cabot-search huggingface dataset:
SURGERY OF THE THYROID OBSERVATIONS ON FIVE THOUSAND OPERATIONS
Authors: CHARLES H. MAYO
Journal: JAMA (1913)

During the twenty-five years ending May 14, 1913, 5,000 operations were performed on the thyroid in the clinic at St. Mary's Hospital. These operations were done on various types of goiters and may be classified as follows: Simple goiters....2,396 Including Transplantations in cretins.... 11 Operations for malignancy: carcinoma, 52; sarcoma, 7.. 59 Operations on syphilitic thyroids.... 1 Exophthalmic goiters, including double and single ligation, extirpation, partial thyroidectomy....2,295 Early operations not clasified, majority simple goiter.... 309 [unk] Total...5,000 An increase in the size of the thyroid may be physiologic or pathologic. In the higher invertebrates the gland has a marked sexual relationship, and through this association we have a suggestion that the thyroid may be a factor in the manifest disturbances which occur at certain periods, especially in the female, as the well-known goiter of adolescence, the congestion of the thyroid during menstruation and its not infrequent enlargement during pregnancy. While
A chimeric IgG4 monoclonal antibody directed against CD18 reduces infarct size in a primate model of myocardial ischemia and reperfusion
Authors: Thomas Aversano, Wei Zhou, Mark Nedelman, Marian Nakada, Harlan Weisman
Journal: Journal of the American College of Cardiology (1995)

This study attempted to determine whether neutrophil sequestration in reperfused myocardium can be inhibited and infarct size reduced by treatment with a chimeric, monoclonal IgG4 antibody (CLB54) directed against CD18 in a primate model of acute myocardial ischemia and reperfusion. Reperfusion injury, in part mediated by neutrophils, may limit the potential benefit of reestablishing infarctrelated artery patency in patients with acute myocardial infarction. Nineteen closed-chest baboons (10 control, 9 treated with CLB54) had the left anterior descending coronary artery occluded for 90 min, followed by 4 h of reflow. CLB54 (mean [±SD] 11 ± 2 mg/kg body weight) or saline solution was administered intravenously 20 min before reflow. Coronary flow was determined using radiolabeled microspheres, infarct size by triphenyltetrazolium chloride staining, global and regional ventricular function by contrast ventriculography and neutrophil accumulation by a myeloperoxidase assay. Risk region size was the same in both groups. CLB54 treatment reduced infarct size expressed as a percent of the risk region from 41 ± 20% in the saline-treated group to 19 ± 17% in the CLB54-treated group (p < 0.02). This was associated with diminished myeloperoxidase activity and greater postreperfusion coronary flow in the risk region in CLB54-treated than in control baboons. Ejection fraction declined to the same extent in both groups, whereas anterior wall regional cord shortening was better preserved in CLB54-treated baboons. Inhibition of neutrophil sequestration with CLB54 administered before reperfusion reduces infarct size, preserves ischemic zone microvascular perfusion and minimizes the decline of regional wall motion.
Diagnosis and Management of Adults with Pharyngitis
Authors: Norman D. Corwin
Journal: Annals of Internal Medicine (2004)

Letters4 May 2004Diagnosis and Management of Adults with PharyngitisNorman D. Corwin, MDNorman D. Corwin, MDFrom Westwood, NJ 07675.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-140-9-200405040-00021 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I take exception with the conclusions of Neuner and colleagues in their article on the diagnosis and management of adults with pharyngitis (1). I am not an academic, but the late Dr. Louis Weinstein was. He related the following tale on more than one occasion while I was a student at Haynes Memorial Hospital in Boston, Massachusetts, some years ago. Dr. Weinstein became concerned about the validity of throat cultures when he was able to obtain only a 70% positive return on known group A β-hemolytic streptococcal infections, using as his gold standard a personally documented increase ...Reference1. Neuner JM, Hamel MB, Phillips RS, Bona K, Aronson MD. Diagnosis and management of adults with pharyngitis. A cost-effectiveness analysis. Ann Intern Med. 2003;139:113-22. [PMID: 12859161] LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Westwood, NJ 07675. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoDiagnosis and Management of Adults with Pharyngitis: A Cost-Effectiveness Analysis Joan M. Neuner , Mary Beth Hamel , Russell S. Phillips , Kira Bona , and Mark D. Aronson Diagnosis and Management of Adults with Pharyngitis Stuart Cohen and Robert Centor Diagnosis and Management of Adults with Pharyngitis Joan Neuner and Mark D. Aronson Metrics 4 May 2004Volume 140, Issue 9Page: 762KeywordsBloodErythromycinImmunoassaysPenicillinPharyngitisPharynxStreptococcal infections ePublished: 4 May 2004 Issue Published: 4 May 2004 CopyrightCopyright © 2004 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
RELATIONSHIP OF EPILEPSY TO CHRONIC GASTRO-INTESTINAL DISEASE.
Authors: G. W. McCASKEY
Journal: JAMA (1904)

While the pathology of epilepsy is, as yet, an unwritten chapter, there are several inferences which appear to me fairly well grounded. One of these is the existence of an organic defect in the finer and as yet inscrutable ultimate structure of the corticospinal neurons. Concerning the nature of this defect we are quite as much in the dark, but not any more so than we are with reference to the cognate defect which underlies hysteria. The assumption in both cases of such a fundamental deviation from the average normal type of construction of the nervous system, of the existence of inherent tendencies which are exceptional rather than typical, and which are possibly always inherited, or at least acquired during the early developmental period, appears to me absolutely necessary to explain why apparently identical causes will produce the clinical manifestations of these neuroses in one case and fail to do
Impact of the “July Effect” on Patient Outcomes
Authors: John Q. Young, Andrew D. Auerbach, Sumant R. Ranji
Journal: Annals of Internal Medicine (2012)

Letters17 January 2012Impact of the “July Effect” on Patient OutcomesJohn Q. Young, MD, MPP, Andrew D. Auerbach, MD, and Sumant R. Ranji, MDJohn Q. Young, MD, MPPFrom University of California, San Francisco, School of Medicine, San Francisco, CA 94143.Search for more papers by this author, Andrew D. Auerbach, MDFrom University of California, San Francisco, School of Medicine, San Francisco, CA 94143.Search for more papers by this author, and Sumant R. Ranji, MDFrom University of California, San Francisco, School of Medicine, San Francisco, CA 94143.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-156-2-201201170-00023 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We fortunately note that graduate medical education programs in the United States heeded Dr. Glick's prescient recommendation in 1966; interns typically report 9 days before July 1. However, we agree with Drs. Vaughan, Bell, and McAlister that implementing staggered start schedules over months (rather than weeks) is a promising strategy to mitigate the impact of cohort turnover. We also agree with Dr. Jarrett that more rigorous orientations that incorporate simulation and focus on essential clinical skills (procedural and cognitive), patient safety concepts, and systems knowledge need to be developed. These orientations, or “boot camps,” should use competency-based assessments ... Author, Article, and Disclosure InformationAffiliations: From University of California, San Francisco, School of Medicine, San Francisco, CA 94143.Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M11-1015. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee Also“July Effect”: Impact of the Academic Year-End Changeover on Patient Outcomes John Q. Young , Sumant R. Ranji , Robert M. Wachter , Connie M. Lee , Brian Niehaus , and Andrew D. Auerbach Impact of the “July Effect” on Patient Outcomes Shimon (Seymour) M. Glick Impact of the “July Effect” on Patient Outcomes Louella Vaughan , Derek Bell , and Graeme McAlister Impact of the “July Effect” on Patient Outcomes Mark P. Jarrett Metrics 17 January 2012Volume 156, Issue 2Page: 168KeywordsConflicts of interestDisclosureGraduate medical educationPatientsSafety ePublished: 17 January 2012 Issue Published: 17 January 2012 Copyright & PermissionsCopyright © 2012 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning
Authors: George C. Rodgers
Journal: JAMA (1997)

Since the publication of the first edition of this tome in 1988, it has been my major reference text of clinical toxicology, far surpassing in utility, in my opinion, any other single volume. Like many others in my field, I have anxiously awaited the second edition. Unfortunately, the new edition has now become a memorial to its primary editor and driving force, Matthew J. Ellenhorn, MD, who died before its publication. In the preface, Dr Ellenhorn relates the difficulties of writing a comprehensive toxicology text and his philosophy of doing so. Much of the clinical toxicology literature embodies anecdotal reports or uncontrolled case series, therefore much of our understanding of toxicology is derived from animal experimentation. In this edition, as with the first, Dr Ellenhorn has tried to limit his references to animal studies and is very selective in his use of anecdotal reports. As with the first edition, the
Black Africans have highest prevalence of tuberculosis in UK
Authors: Robert Short
Journal: BMJ (2006)

The number of cases of tuberculosis in England, Wales, and Northern Ireland rose by 10.8% from 2004 to 2005, the biggest increase in any one year since 1999. The number of cases rose from 7321 to 8113. 

The new figures were presented by John Watson, head of the respiratory disease department at the Health Protection Agency. 

London alone had 3479 cases in 2005, 43% of the total. The regions with the biggest rises in new cases were the North West, East Midlands, and the East of England. The …
Save yourself, cancer cell
Authors: Mitch Leslie
Journal: The Journal of Experimental Medicine (2009)

Some neuroblastoma tumors are addicts, Delloye-Bourgeois et al. report on [page 833][1]. The tumor cells need a steady supply of a molecule called netrin-1, and they get their fix by making the compound themselves. Forcing the cells to go cold turkey could provide a new treatment for neuroblastoma,
P4-02-11: Insulin-Like Growth Factor I Promotes Estrogen Receptor Positive Breast Cancer Cell Proliferation, in Part, through CYP1A1 Signaling.
Authors: M Rodriguez, M Becker, D Yee, D Potter
Journal: Cancer Research (2011)

Abstract Activation of the transmembrane tyrosine kinase insulin-like growth factor 1 receptor (IGF-1R) contributes to breast cancer progression. Nonetheless, the mechanisms by which the IGF-1R contributes to breast cancer progression need to be better characterized to further develop therapeutic strategies that target this pathway. It is known that cytochrome P450 monooxygenases synthesize metabolites from endogenous and exogenous sources that promote breast cancer proliferation. Here we propose that activity of the IGF-1R modulates the activity of CYP1A1 to promote breast cancer cell proliferation. We have found that IGF-IR activation by treatment with IGF1 (5nM ) for 4hrs induces cytochrome P450 1A1 (CYP1A1) mRNA levels in estrogen receptor (ER) positive line T47D-CO, but not ER negative line MDA-MB-231. Treatment with IGF1 promotes the proliferation of ER positive lines T47D-CO and MCF7. Interestingly, we found that treatment with IGF1 only partially compensates the growth-inhibition induced by CYP1A1 knock down by siRNA, suggesting that IGF1 requires CYP1A1 for full promotion of cell growth. These preliminary data suggest that IGF-1 signaling functions, in part, through CYP1A1 to promote ER positive breast cancer cell proliferation. The mechanism of IGF-1 signaling through CYP1A1 is novel and may represent an effector mechanism for IGF-1. Further understanding the role of CYP1A1 downstream of the IGF-1R may allow novel approaches for inhibition of breast cancer cell proliferation downstream of the IGF-1R. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-02-11.
The Watering-Places of the Auvergne: the Mont Dore
Authors: A. Rabagliati
Journal: BMJ (1880)

The effects of the Davos climate appear to be due to-I.The rare- faction of the atmosphere; 2. Its dryness; 3. The absence of wind, partly owing to the shelter of the mountains, and partly to the uniform layer of snow spread around; 4. The large amount of sun's rays transmitted through the rarefied atmosphere, as reflected on to the village from the extensive snow-plain lying to the east of it.
Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25– T cells
Authors: Mindi R.Walker, Deborah J. Kasprowicz, Vivian H. Gersuk, Angéle Bènard, Megan Van Landeghen, Jane H. Buckner, Steven F. Ziegler
Journal: Journal of Clinical Investigation (2003)

CD4+CD25+ regulatory T (TR) cells have been described in both humans and mice. In mice, TR are thymically derived, and lack of TR leads to organ-specific autoimmunity. Recently, the forkhead/winged helix transcription factor, FoxP3, has been shown to be important for the function of TR cells in mice. In this study, human TR cells were examined and, in results similar to those of studies done in mice, expression of FoxP3 was found exclusively in CD4+CD25+ T cells and correlated with the suppressive activity of these cells. In contrast to the mouse studies, activation of human CD4+CD25– T cells led to expression of FoxP3. Expression of FoxP3 in activated human CD4+CD25+ cells also correlated with suppression of proliferation by these cells in freshly isolated CD4+CD25– T cells from the same donor. This suppression was cell-contact dependent and cytokine independent. Thus, in humans, during activation of CD4+CD25– T cells in an immune response, two populations of cells may arise, effector CD4+CD25+ and regulatory CD4+CD25+ T cells, with expression of FoxP3 correlated with regulatory activity. These data also raise the possibility that a failure to generate peripheral TR cells properly may contribute to autoimmune disease and suggest a possible therapeutic role for FoxP3 in the treatment of such diseases.
The effect of targeted delivery of anti-TNF-α oligonucleotide into CD169+ macrophages on disease progression in lupus-prone MRL/lpr mice
Authors: Zhen Huang, Zhengping Zhang, Yinhe Zha, Jialin Liu, Yucui Jiang, Yang Yang, Juan Shao, Xulun Sun, Xin Cai, Yuan Yin, Jiangning Chen, Lei Dong, Junfeng Zhang
Journal: Biomaterials (2012)
Combinations of susceptible genotypes and individual responses to toxicants.
Authors: A Hirvonen
Journal: Environmental Health Perspectives (1997)

The variation in individual responses to exogenous agents has been shown to be exceptionally wide. It is because of this large diversity of responsiveness that risk factors to environmentally induced diseases have been difficult to pinpoint, particularly at low exposure levels. Opportunities now exist for studies of host factors in environmentally induced cancer or other diseases in which an environmental component can be presumed. Many of the studies have shown an elevated disease proneness for individuals carrying the potential at-risk alleles of metabolic genes, but a number of controversial results have also been reported. One possible explanation for the divergent findings is lack of knowledge of the other potentially relevant genotypes for a given exposure. This paper gives an overview of the published data on combinations of metabolic genotypes in relation to individual susceptibility to environmental toxicants.
Long-term Outcomes of Rituximab Therapy in Ocular Granulomatosis with Polyangiitis
Authors: Lavnish Joshi, Anisha Tanna, Stephen P. McAdoo, Nicholas Medjeral-Thomas, Simon R.J. Taylor, Gurpreet Sandhu, Ruth M. Tarzi, Charles D. Pusey, Sue Lightman
Journal: Ophthalmology (2015)
A lymphatic defect causes ocular hypertension and glaucoma in mice
Authors: Benjamin R. Thomson, Stefan Heinen, Marie Jeansson, Asish K. Ghosh, Anees Fatima, Hoon-Ki Sung, Tuncer Onay, Hui Chen, Shinji Yamaguchi, Aris N. Economides, Ann Flenniken, Nicholas W. Gale, Young-Kwon Hong, Amani Fawzi, Xiaorong Liu, Tsutomu Kume, Susan E. Quaggin
Journal: Journal of Clinical Investigation (2014)

Glaucoma is a leading cause of blindness, afflicting more than 60 million people worldwide. Increased intraocular pressure (IOP) due to impaired aqueous humor drainage is a major risk factor for the development of glaucoma. Here, we demonstrated that genetic disruption of the angiopoietin/TIE2 (ANGPT/TIE2) signaling pathway results in high IOP, buphthalmos, and classic features of glaucoma, including retinal ganglion degeneration and vision loss. Eyes from mice with induced deletion of Angpt1 and Angpt2 (A1A2Flox(WB) mice) lacked drainage pathways in the corneal limbus, including Schlemm's canal and lymphatic capillaries, which share expression of the PROX1, VEGFR3, and FOXC family of transcription factors. VEGFR3 and FOXCs have been linked to lymphatic disorders in patients, and FOXC1 has been linked to glaucoma. In contrast to blood endothelium, in which ANGPT2 is an antagonist of ANGPT1, we have shown that both ligands cooperate to regulate TIE2 in the lymphatic network of the eye. While A1A2Flox(WB) mice developed high IOP and glaucoma, expression of ANGPT1 or ANGPT2 alone was sufficient for ocular drainage. Furthermore, we demonstrated that loss of FOXC2 from lymphatics results in TIE2 downregulation, suggesting a mechanism for ocular defects in patients with FOXC mutations. These data reveal a pathogenetic and molecular basis for glaucoma and demonstrate the importance of angiopoietin ligand cooperation in the lymphatic endothelium.
Ambulance services to have access to telephone and email records
Authors: O. Dyer
Journal: BMJ (2003)

The Home Office has released for public consultation its new proposals on access to telephone and communications data, a watered down successor to the plan denounced last summer as a “snooper's charter.”

Home Secretary David Blunkett promised to scale down the plan after admitting he had blundered in drawing the line between public security and the protection of privacy.

Under the initial proposals, all local councils, seven Whitehall departments, and 11 quangos (quasi-autonomous non-governmental organisations] would have had complete access to telephone and email records under the Regulation of Investigatory Powers Act (RIPA) 2000. Such powers of access have previously been the exclusive domain of the police, Customs, Inland Revenue, and security services.

The new …
E-selectin supports neutrophil rolling in vitro under conditions of flow.
Authors: O Abbassi, T K Kishimoto, L V McIntire, D C Anderson, C W Smith
Journal: Journal of Clinical Investigation (1993)

E-selectin was evaluated for its ability to support neutrophil adhesion under conditions of flow. At a wall shear stress of 1.85 dyn/cm2, neutrophils were found to attach to E-selectin expressed on the apical surface of L cell monolayers. The initial intercellular contact was most often evidenced by neutrophils rolling on the monolayer at a mean rate of congruent to 10 microns/s. Anti-E-selectin monoclonal antibody, CL2/6, inhibited this interaction by > 90%. Rolling neutrophils often transiently stopped, but in contrast to the behavior on stimulated endothelial cells, they remained spherical in shape and did not migrate on or beneath the monolayer. A possible contribution of neutrophil L-selectin to this interaction was indicated by the findings that anti-L-selectin monoclonal antibody, DREG-56, inhibited E-selectin-dependent adhesion under flow by > 65%, and there was a highly significant correlation between surface levels of L-selectin and E-selectin-dependent adhesion under flow. E-selectin also appeared to support neutrophil adhesion to IL-1 beta-stimulated endothelial cells under conditions of flow, but it accounted for only congruent to 30% of the level of adherence, in contrast to L-selectin which accounted for > 65%. Thus, both L-selectin and E-selectin can support neutrophil adhesion at wall shear stresses that preclude intercellular adhesion molecule-1-dependent adhesion, and they participate in neutrophil adherence to stimulated endothelial cells under conditions of flow.
Breast feeding and diabetes mellitus
Authors: M R Kiln, D Henschel, L Kiln
Journal: BMJ (1994)

EDITOR, - K G M M Alberti briefly mentions that “breast feeding has been shown to protect against the development of insulin dependent diabetes mellitus.”1 Two papers have strongly suggested that infants born into families with a family history of diabetes have a lesser chance of developing insulin dependent diabetes if they are breast …
Abstract 3438: Selective inhibitors of Mcl-1 with potent activity against multiple myeloma patient cells and animal xenografts.
Authors: Asfar S. Azmi, Zaneta Nikolovka-Coleska, Muneer Abidi, Kelley Marsack, Ashiq Masood, Hiroshi Yano, Silvana Pregja, Jeffrey Zonder, Ramzi M. Mohammad
Journal: Cancer Research (2013)

Abstract To date most of the studies targeting apoptotic machinery have focused on inhibiting Bcl2 and BclXL proteins that have shown limited clinical utility. This could be in part due to the over-expression of Myeloid Leukemia-1 (Mcl-1) that carries similar anti-apoptotic functions. Our recent evaluations of Multiple Myeloma (MM) patient derived samples have shown consistent over-expression of Mcl-1 suggesting that it is an attractive therapeutic target. We have discovered a novel druggable site in Mcl-1 protein. Using structure based drug design we have developed small molecule inhibitors (SMIs) of Mcl-1 that bind with high affinity to the BH-3 hydrophobic groove of the protein thereby displacing different pro-apoptotic partners such as Bax, Bak, Bok and Bid with activity against MM cells (IC50 5 μM) and anti-tumor activity in animal xenografts. The lead SMI (UMI-77) inhibits growth and induces apoptosis in MM cells. Molecular analysis of MM cells reveals activation of pro-apoptotic factors post UMI-77 treatment. Co-immunoprecipitation studies show that UMI-77 disrupts the Mcl-1-Bax and Mcl-1-Bak interactions. The drug synergizes with standard proteasome inhibitor Velcade (5 nM) and Carfilosimib (1 nM). In patient derived MM cells (n=45), UMI-77 inhibits growth and induces apoptosis that is concurrent with induction of Bax, Bak and enhancement in cleaved fractions of caspases 3 and 9. At similar concentrations UMI-77 does not affect normal peripheral lymphocytes. UMI-77 is well tolerated by animals at MTD (60 mg/kg i.v.). In a mice lymphoma model, oral administration of UMI-77 significantly reduced tumor growth and histological examination of tumors revealed suppression of Mcl-1 protein expression along with enhancement of pro-apoptotic markers. Our novel Mcl-1 inhibitors provide a new therapeutic option for cancers for MM that overexpress Mcl-1 that have failed standard therapies. Citation Format: Asfar S. Azmi, Zaneta Nikolovka-Coleska, Muneer Abidi, Kelley Marsack, Ashiq Masood, Hiroshi Yano, Silvana Pregja, Jeffrey Zonder, Ramzi M. Mohammad. Selective inhibitors of Mcl-1 with potent activity against multiple myeloma patient cells and animal xenografts. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3438. doi:10.1158/1538-7445.AM2013-3438