tbuckley/cabot-search huggingface dataset:
Alan Douglas Wickes
Authors: Jay Whimster
Journal: BMJ (2006)

Founder epidemiologist of the Framingham heart studyIn 1945 the Western world emerged from the second world war, only to be confronted by an epidemic of heart disease.The US government responded by setting up a study to identify the causes and to diagnose and treat early disease, though the latter aim was dropped as there was no treatment available.The town of Framingham in Massachusetts was chosen as the site for this study because it had a stable population of 28 000 and was close to Harvard University.The Framingham study, as it was known, became world famous."Along with Ancel Keys's seven country study, this was the work on which all other epidemiology of heart disease stands.There isn't a study that doesn't owe its origin to Framingham,"
New variant of type II von willebrand's disease with structural abnormality of plasma von willebrand factor in a patient with very mild bleeding history
Authors: Peter Baillod, Christine Gaucher, Beat Affolter, Claudine Mazurier, Rolf Pflugshaupt
Journal: American Journal of Hematology (1995)

Abstract A new variant of von Willebrand's disease has been discovered in 2 members of a Macedonian family of 6. The proband, an 8‐year‐old boy, showed a prolonged bleeding episode on 1 occasion. Ristocetin‐induced platelet aggregation and bleeding time were normal. In plasma, ristocetin cofactor activity (RCo) and von Willebrand factor (vWf) antigen were reduced to the same clearly low level. The determination of vWf antigen of platelets resulted in borderline values, while RCo was clearly reduced. Low‐ and intermediate‐resolution agarose gel electrophoresis showed absence of the largest multimers in plasma vWf, and slight reduction in platelet vWf. High‐resolution gels revealed abnormal multimeric structure only in plasma vWf. The smaller multimers could be resolved in a broad central band flanked by 4 fainter satellite bands; however, satellite bands close to the central band were more intense, and more distant ones were fainter, compared to normal plasma. The central band of the fastest‐moving multimer was markedly intensified, and the mobility of the whole quintuplet was slightly reduced. Heredity seems to be autosomal‐dominant. No mutation was found in exon 28 of the vWf gene. Because there was only 1 mild bleeding episode in the family, this structural variation seems to have only little clinical consequence. We conclude that this vWf abnormality is different from those observed in other type II variants previously described. Based on the revised classification by the International Society on Thrombosis and Haemostasis, we proposed designation type 2A‐Bern for this new subtype. © 1995 Wiley‐Liss, Inc.
UK mental health charities call for more psychological treatments
Authors: Claire Frauenfelder
Journal: BMJ (2006)

A group of leading UK charities has accused the NHS of failing to provide adequate psychological treatments as outlined in guidelines from the National Institute for Health and Clinical Excellence (NICE) (http://www.nice.org.uk/page.aspx?o=cg22). The treatments should have been implemented three months after publication, the report says, but there has been what the group calls two years of inaction by the government.

The report, We Need to Talk , was released on 31 October and has been produced by the five leading UK mental health charities: the Mental …
The prevalence of water-induced itching
Authors: R.A. Logan, M.D. Fehrer, H.K. Steinman
Journal: British Journal of Dermatology (1984)

Journal Article The prevalence of water‐induced itching Get access R.A. Logan, R.A. Logan St John's Hospital for Diseases of the Skin, 5 Lisle Street, Leicester Square, London WC2H 7BJ Search for other works by this author on: Oxford Academic Google Scholar M.D. Fehrer, M.D. Fehrer St John's Hospital for Diseases of the Skin, 5 Lisle Street, Leicester Square, London WC2H 7BJ Search for other works by this author on: Oxford Academic Google Scholar H.K. Steinman H.K. Steinman St John's Hospital for Diseases of the Skin, 5 Lisle Street, Leicester Square, London WC2H 7BJ Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 111, Issue 6, 1 December 1984, Pages 734–736, https://doi.org/10.1111/j.1365-2133.1984.tb14156.x Published: 01 December 1984
Genotype-based treatment of type 2 diabetes with an α <sub>2A</sub> -adrenergic receptor antagonist
Authors: Yunzhao Tang, Annika S. Axelsson, Peter Spégel, Lotta E. Andersson, Hindrik Mulder, Leif C. Groop, Erik Renström, Anders H. Rosengren
Journal: Science Translational Medicine (2014)

The α 2A -adrenergic receptor antagonist yohimbine improves insulin secretion in type 2 diabetics carrying the ADRA2A risk variant.
Hunk is required for HER2/neu-induced mammary tumorigenesis
Authors: Elizabeth S. Yeh, Thomas W. Yang, Jason J. Jung, Heather P. Gardner, Robert D. Cardiff, Lewis A. Chodosh
Journal: Journal of Clinical Investigation (2011)

Understanding the molecular pathways that contribute to the aggressive behavior of human cancers is a critical research priority. The SNF1/AMPK-related protein kinase Hunk is overexpressed in aggressive subsets of human breast, ovarian, and colon cancers. Analysis of Hunk(–/–) mice revealed that this kinase is required for metastasis of c-myc–induced mammary tumors but not c-myc–induced primary tumor formation. Similar to c-myc, amplification of the proto-oncogene HER2/neu occurs in 10%–30% of breast cancers and is associated with aggressive tumor behavior. By crossing Hunk(–/–) mice with transgenic mouse models for HER2/neu-induced mammary tumorigenesis, we report that Hunk is required for primary tumor formation induced by HER2/neu. Knockdown and reconstitution experiments in mouse and human breast cancer cell lines demonstrated that Hunk is required for maintenance of the tumorigenic phenotype in HER2/neu-transformed cells. This requirement is kinase dependent and resulted from the ability of Hunk to suppress apoptosis in association with downregulation of the tumor suppressor p27(kip1). Additionally, we find that Hunk is rapidly upregulated following HER2/neu activation in vivo and in vitro. These findings provide what we believe is the first evidence for a role for Hunk in primary tumorigenesis and cell survival and identify this kinase as an essential effector of the HER2/neu oncogenic pathway.
Relapsing or reinfectious lyme hepatitis
Authors: Robert T. Schoen
Journal: Hepatology (1989)

Lyme disease, a multi-system disorder caused by the tick-borne spirochete, Borrelia burgdorferi, is characterized by malaise, fever, headache, arthralgia, myalgia, stiff neck, lymphadenopathy, paresthesias, and a distinctive rash, erythema chronicum migrans (ECM) in its early phase. Neurologic, cardiac, and joint abnormalities may follow within weeks to months. A patient is described in whom acute recurrent Lyme disease occurred and in which spirochetes were identified in the skin and liver histologically.
Toll-like receptor–induced arginase 1 in macrophages thwarts effective immunity against intracellular pathogens
Authors: Karim C El Kasmi, Joseph E Qualls, John T Pesce, Amber M Smith, Robert W Thompson, Marcela Henao-Tamayo, Randall J Basaraba, Till König, Ulrike Schleicher, Mi-Sun Koo, Gilla Kaplan, Katherine A Fitzgerald, Elaine I Tuomanen, Ian M Orme, Thirumala-Devi Kanneganti, Christian Bogdan, Thomas A Wynn, Peter J Murray
Journal: Nature Immunology (2008)
Community care for severely disabled people on low incomes
Authors: V L Phillips
Journal: BMJ (1995)

<h3>Abstract</h3> <b>Objective</b>: To examine the volume and distribution of formal and informal care received by severely disabled adults living at home in the community on low incomes according to type of disease. <b>Design</b>: Analysis of computerised reports from social workers which include information on disabling conditions and on the weekly hours of care at home from formal and informal sources. <b>Subjects</b>: 1298 severely disabled people aged 16 to 98 who received financial assistance from the Independent Living Fund in 1991-2. <b>Results</b>: Over half (733; 56.6% (53.8 to 59.2)) of the sample were completely unable to perform five or more of the basic activities of daily living. On average the whole sample received 6.8 (6.1 to 7.6) hours of care at home a week from formal sources and 64.2 (62.4 to 65.9) hours from informal sources. In seven out of 14 disease groups, less than half in each group received any formal help at home. There were large differences in the volume of formal care within groups. In most cases no significant differences were found within diagnostic groups between those receiving care at home from district health authorities or local authorities, or both, and those who received no help at home with regard to age, dependency score, and duration of disability. Weekly hours of informal care were an important determinant of who received formal help in nine out of 14 groups. <b>Conclusions</b>: The amount of care received at home by low income, severely disabled people from formal sources differs across and within diagnostic groups. The fact that the variation was not systematically related to age, dependency, or duration suggests that the existing distribution of community care resources needs to be examined. Weekly hours of informal care and diagnosis seem to affect the volume and type of care received. The methods by which people in need of assistance receive help merit further investigation.
Subarachnoid haemorrhage in first and second degree relatives of patients with subarachnoid haemorrhage
Authors: J. E C Bromberg, G. J E Rinkel, A. Algra, P. Greebe, C. M van Duyn, D. Hasan, M. Limburg, H. W M t. Berg, E. F M Wijdicks, J. van Gijn
Journal: BMJ (1995)

Aggregation of subarachnoid haemorrhage has been described in numerous families,1 but whether relativxes of patients are at increased risk is unknown. If they are, they might benefit from screening for unruptured intracranial aneurysms since the outcome of subarachnoid haemorrhage is poor and asymptomatic aneurysms can now be repaired with low morbidity and mortality. We therefore studied the cumulative incidence of subarachnoid haemorrhage among first and second degree relatives of patients with recent haemorrhage.

We prospectively collected a series of 163 patients with subarachnoid haemorrhage verified by computed tomography from the University Hospitals of Rotterdam, Utrecht, and Amsterdam, and for every patient we constructed a pedigree including all first and second degree relatives. All these relatives were interviewed by telephone in a standardised manner; they were asked about episodes of subarachnoid haemorrhage, sudden severe headache, stroke, and sudden death. For deceased relatives a next of kin was interviewed about the cause of …
Engineering Multiple U7snRNA Constructs to Induce Single and Multiexon-skipping for Duchenne Muscular Dystrophy
Authors: Aurélie Goyenvalle, Jordan Wright, Arran Babbs, Vivienne Wilkins, Luis Garcia, Kay E Davies
Journal: Molecular Therapy (2012)

Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disorder caused by mutations in the dystrophin gene. Antisense-mediated exon skipping is one of the most promising approaches for the treatment of DMD but still faces personalized medicine challenges as different mutations found in DMD patients require skipping of different exons. However, 70% of DMD patients harbor dystrophin gene deletions in a mutation-rich area or "hot-spot" in the central genomic region. In this study, we have developed 11 different U7 small-nuclear RNA, to shuttle antisense sequences designed to mask key elements involved in the splicing of exons 45 to 55. We demonstrate that these constructs induce efficient exon skipping both in vitro in DMD patients' myoblasts and in vivo in human DMD (hDMD) mice and that they can be combined into a single vector to achieve a multi skipping of at least 3 exons. These very encouraging results provide proof of principle that efficient multiexon-skipping can be achieved using adeno-associated viral (AAV) vectors encoding multiple U7 small-nuclear RNAs (U7snRNAs), offering therefore very promising tools for clinical treatment of DMD.
“A Hospital the Enemy Calls Bach Mai”
Authors: F.J. Ingelfinger
Journal: New England Journal of Medicine (1973)

On January 2, a Pentagon spokesman confirmed, "that some limited accidental damage has occurred — at a hospital the enemy calls Bach Mai."* An associate dean at Yale University Divinity School who had just returned from Hanoi is reported as saying, "By all standards I know, the hospital was destroyed."* Hanoi accounts of the damage may well be propaganda, but the Pentagon's version is in all likelihood hardly less so — a suspicion heightened by the initial denial by that agency that the hospital had been hit at all.The chances are that the hospital, although not totally demolished, was at . . .
Salmonella enteritidis endocarditis.
Authors: D C Shanson, W Brigden, E J Weaver
Journal: BMJ (1977)

Infectious mononucleosis and fibrosing alveolitisI report a case of infectious mononucleosis with acute diffuse fibrosing alveolitis.Pulmonary lesions in this disease have been reported but without detailed pulmonary physiological studies.' 2 The aetiology of acute fibrosing alveolitis is obscure,3 but in this case the Epstein-Barr virus was implicated. Case reportA previously fit 21-year-old woman was admitted to hospital with a short history of a "head cold" and sore throat which had responded to oral penicillin.An irritating unproductive cough persisted.She became progressively more dyspnoeic, initially only on exertion but eventually also when at rest.She complained of headache, profuse sweating, and general malaise.She was cyanosed and feverish (38-8 C).There was no finger clubbing.Cervical and supraclavicular lymphadenopathy was noted but no splenomegaly.Chest expansion was reduced and a few fine crepitations were audible at both bases.On admission the haemoglobin was 13-1 g/dl, and the white cell count
Preferential Conduction Across the Ventricular Outflow Septum in Ventricular Arrhythmias Originating From the Aortic Sinus Cusp
Authors: Takumi Yamada, Yoshimasa Murakami, Naoki Yoshida, Taro Okada, Takeshi Shimizu, Junji Toyama, Yukihiko Yoshida, Naoya Tsuboi, Masahiro Muto, Yasuya Inden, Makoto Hirai, Toyoaki Murohara, Hugh T. McElderry, Andrew E. Epstein, Vance J. Plumb, G. Neal Kay
Journal: Journal of the American College of Cardiology (2007)
Tolerability of Rofecoxib versus Naproxen
Authors: John M. Rusche
Journal: Annals of Internal Medicine (2004)

Letters15 June 2004Tolerability of Rofecoxib versus NaproxenJohn M. Rusche, MDJohn M. Rusche, MDFrom Regence BlueShield of Idaho, Lewiston, ID 83501.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-140-12-200406150-00021 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:In the article by Lisse and colleagues (1), the real message of a head-to-head comparison of rofecoxib and naproxen was obscured. Regarding discontinuation of treatment due to clinical adverse events, Figure 1 shows that 374 of 2785 patients receiving rofecoxib stopped treatment. In the naproxen group, 386 of 2788 patients had clinical adverse events and cessation of therapy. On my calculator, these data show that the rate of discontinuation due to adverse events was 13.4% in the rofecoxib group and 13.9% in the naproxen group.While the rate of GI intolerance may be lower with rofecoxib, to ...References1. Lisse JR, Perlman M, Johansson G, Shoemaker JR, Schechtman J, Skalky CS, et al . Gastrointestinal tolerability and effectiveness of rofecoxib versus naproxen in the treatment of osteoarthritis: a randomized, controlled trial. Ann Intern Med. 2003;139:539-46. [PMID: 14530224] LinkGoogle Scholar Author, Article, and Disclosure InformationAuthors: John M. Rusche, MDAffiliations: From Regence BlueShield of Idaho, Lewiston, ID 83501. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoGastrointestinal Tolerability and Effectiveness of Rofecoxib versus Naproxen in the Treatment of Osteoarthritis Jeffrey R. Lisse , Monica Perlman , Gunnar Johansson , James R. Shoemaker , Joy Schechtman , Carol S. Skalky , Mary E. Dixon , Adam B. Polis , Arthur J. Mollen , and Gregory P. Geba , for the ADVANTAGE Study Group*Tolerability of Rofecoxib versus Naproxen M. L. Jenkinson Tolerability of Rofecoxib versus Naproxen Jeffrey R. Lisse , Monica Perlman , Adam B. Polis , and Gregory P. Geba Tolerability of Rofecoxib versus Naproxen Lonnie B. Hanauer Metrics Cited byAnti-inflammatory effects of IL-4 and dynamic compression in IL-1β stimulated chondrocytes 15 June 2004Volume 140, Issue 12Page: 1059KeywordsAdverse eventsDrugs ePublished: 15 June 2004 Issue Published: 15 June 2004 Copyright & PermissionsCopyright © 2004 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Absence of Fer protein tyrosine kinase exacerbates endotoxin induced intestinal epithelial barrier dysfunction in vivo
Authors: W Qi
Journal: Gut (2005)

<b>Background and aims:</b> Fer kinase is activated by a number of growth factors and cytokines, and phosphorylates cortactin during cell shape change induced cortical actin reorganisation. In addition, Fer participates in cytoskeletal interactions mediated by cadherins, platelet endothelial cell adhesion molecule 1 (PECAM-1), and integrins, and has recently been implicated in limiting the innate immune response. Here we examined the role of Fer in modulating leucocyte recruitment and epithelial barrier function in the gut in response to lipopolysaccharide (LPS). <b>Methods:</b> Mice targeted with a kinase inactivating mutation (FerDR) or strain matched wild-type (129Sv/J) mice were studied after intraperitoneal injection of LPS. Intravital microscopy was used to examine intestinal leucocyte kinetics, and leucocyte infiltration was assessed by fluorescence activated cell sorting. Systemic inflammation was assessed by measuring lung myeloperoxidase activity. Epithelial barrier function was assessed in vivo using blood to lumen <sup>51</sup>Cr-EDTA clearance, with or without antibody based depletion of circulating neutrophils. <b>Results:</b> LPS induced a significant increase in leucocyte adhesion and neutrophil infiltration into the intestinal tissue, and increased blood to lumen <sup>51</sup>Cr-EDTA clearance. Pretreatment with neutrophil depleting antibody completely abrogated this response in wild-type mice. In FerDR mice, LPS induced leucocyte adhesion within the intestinal venules was exacerbated and associated with a trend towards increased neutrophil transmigration relative to wild-type mice. Surprisingly, LPS induced epithelial barrier permeability was increased 2.5-fold in FerDR mice relative to wild-type mice, and this barrier defect was only partly attenuated by depleting circulating neutrophils by &gt;93 %. <b>Conclusions:</b> Fer plays a role in regulating LPS induced epithelial barrier dysfunction in vivo through both neutrophil dependent and neutrophil independent mechanisms.
Improving Access to Primary Care
Authors: Donald Wexler
Journal: JAMA (1993)

To the Editor.  —Unfortunately, Ginzberg1completely omits the present role of midlevel health care providers, nurse practitioners and physician assistants, in his suggestions for solving the shortage of primary health care providers.  An analysis of the impact these two midlevel professions already have on primary care today could be of great value in developing plans for increasing the numbers of primary care providers in the near future and significantly reducing the cost of health care as well.  The only mention made by Ginzberg of either nurse practitioners  physician assistants is in the statement on page 3116: It is not irrelevant to note, however, that the earnings of one physician are equivalent to those of three  four nurse practitioners. To which one could add, or physician assistants.  So, while there may be reasons to figure out how to persuade  subsidize more medical students to practice primary care,
Abstract 1798: Effective lymphoma and leukemia therapy with epratuzumab (anti-CD22 IgG) conjugated to SN-38 (Emab-SN-38), with enhanced activity in combination with veltuzumab (anti-CD20 IgG)
Authors: Robert M. Sharkey, Thomas M. Cardillo, Serengulam V. Govindan, David M. Goldenberg
Journal: Cancer Research (2011)

Abstract A number of B-cell malignancies, including lymphomas (NHL) and leukemia (ALL), can be treated effectively with antibodies, but these usually are combined with chemotherapy to enhance efficacy. We conjugated SN-38, a topoisomerase I inhibitor with nanomolar potency, to an anti-CD22 IgG (6:1 SN-38:IgG) by coupling to the tert-hydroxy group on the lactone ring of SN-38. This inhibits formation of the inactive carboxylate, a common problem with irinotecan, its prodrug, but the linker allows the active SN-38 to be released slowly from the IgG (∼50% decouples every 1 to 1.5 days) in serum or in the acidic environment of the lysosome. In vitro, Emab-SN-38 had nanomolar potency against a number of human NHL and ALL cell lines. Specific (as compared to an irrelevant anti-CEACAM5-SN-38 conjugate) and enhanced anti-tumor activity were demonstrated in mice bearing Ramos (Burkitt NHL), WSU-FSCCL (follicular NHL), or 697 (ALL) when compared to the unconjugated antibody (anti-CD22 or anti-CD20) alone or when combined with irinotecan. For example, animals bearing 0.3 to 0.8 cm3 Ramos xenografts treated with 3.75 mg/kg of an irrelevant immunoconjugate (54.5 µg/kg SN-38 equivalents) progressed to 3.0 cm3 in 1.0 week (median), while Emab-SN-38-treated animals had a median time to progression (TTP) of 4.05 weeks (P = 0.003) and 3/10 cures. Increasing the Emab-SN-38 dose to 12.5 mg/kg improved TTP to &amp;gt;12 weeks with 7/10 cures, while the irrelevant conjugate's TTP was just 3.5 wk (P = 0.023). Improvements in TTP and cures were also found for the Emab-SN-38 in FSCCL and 697. Additionally, in Ramos and FSCCL, the anti-tumor response was enhanced by co-treating animals with veltuzumab. For example, median survival in animals treated 5 days after IV implantation of FSCCL was &amp;gt;161 days for Emab-SN-38 + veltuzumab vs. 63 days and 91 days for Emab-SN-38 alone and veltuzumab alone, respectively (untreated, 42 days). Importantly, these treatments were tolerated without toxicity, with other studies showing tolerability in mice at doses of 1500 mg/kg. These data suggest the Emab-SN-38 is a potent, minimally toxic therapeutic in both NHL and ALL, with the added value when combined with anti-CD20 antibody therapy for enhanced responses. 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 1798. doi:10.1158/1538-7445.AM2011-1798