tbuckley/cabot-search huggingface dataset:
Nodules behind the ears: IgG4-related skin disease
Authors: M. Kondo, S. Yamamoto, H. Goto, Y. Nara
Journal: British Journal of Dermatology (2016)

A 53‐year‐old healthy factory worker consulted our hospital complaining of small nodules of similar size, shape and location on both ears. The nodules revealed focal and massive infiltration of lymphocytes, plasma cells and eosinophils with fibrosis. They had no specific structure on pathological staining with haematoxylin and eosin. Immunostaining for IgG4 revealed that a large majority of the IgG+ cells were positive for IgG4. The ratio of IgG4+ to IgG+ plasma cells was approximately 40%. IgG4+ plasma cells were present at approximately 250 per high‐power field. The patient was diagnosed with IgG4‐related skin disease without multiple organ involvement in the systemic syndrome of IgG4‐related diseases. Because the patient was a factory worker and exposed to an environment of metallic dust, a skin patch test that included a metal series was performed. Zinc and manganese produced positive reactions. Because only skin lesions were observed in this case, not multiple organ involvement, tissue infiltration by IgG4+ plasma cells might have resulted from continuous sensitization to zinc and/or manganese.
Government's fund is improving access to drugs for patients with cancer
Authors: Z. Kmietowicz
Journal: BMJ (2011)

Since October 2010 more than 7500 patients in England, including many with rare cancers, have been treated with drugs not previously available on the NHS to treat those cancers, thanks to the cancer drugs fund set up by the coalition government, says a report from the charity Macmillan Cancer Support.

In a review of how the fund is working, the charity praises it for enabling a better understanding of the clinical effectiveness of drugs for rarer cancers by increasing the number of off-label drugs being approved by funding panels. However, it warns that regional variability exists in the number of applications being made and in the proportion approved.

It is also concerned about access to these drugs when the fund ends …
Long-Term Follow-Up of Myocardial Perfusion and Metabolic Images in a Patient With Hypertrophic Cardiomyopathy
Authors: H Sugihara, Y Adachi, T Nakamura, K Ohtsuki, C Okuyama, Y Ushijima
Journal: Clinical Nuclear Medicine (2000)

A 54-year-old woman was hospitalized in 1989 because of palpitations. She had a family history of hypertrophic cardiomyopathy. Hypertrophic cardiomyopathy was diagnosed by two-dimensional echocardiography, cardiac catheterization, and myocardial biopsy. A coronary arteriogram disclosed normal coronary arteries. She had received diltiazem and meliletine for 9 years. Her functional class, by the New York Heart Association classification, had worsened from II to III since 1995. Two-dimensional echocardiography showed a thrombus in the left ventricle in 1996, and warfarin and captopril were prescribed. Follow-up images showed that I-123 β-methyl-p-iodophenyl-pentadecanoic acid uptake preceded that of Tl-201.
AB0795 Hospital anxiety and depression scale (hads) is a ‘non-discriminatory’ patient related outcome measure (prom) in a rheumatology long term condition (ltc) clinic
Authors: Z. Fattah, S. Chita, P. Charalambous, C. B. Colaço
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Patient related outcome measures (PROMs) in research settings require vital but often complex activity scores, within which high levels of anxiety and depression scores (HADS) affecting physical and emotional quality of life in SLE and RA are noted <sup>(1</sup>,<sup>2)</sup>. Hanly and colleagues <sup>(3)</sup> show significant neuropsychiatric manifestations are common in SLE and RA at a similar frequency (SLE 53%; RA 48%; p = 0.75). We examined the discriminatory value of quick self-completed HADS questionnaires in a single-handed Rheumatology Long Term Condition outpatient setting in London. <h3>Objectives</h3> This service audit was to assess the levels of anxiety and depression in Rheumatology Long Term Condition Clinics and to clarify if HADS score can differentiate patients with Neuropsychiatric SLE (NPSLE). <h3>Methods</h3> 224 patients of 16-90 years age range with any Long Term Condition attending rheumatology clinics at Central Middlesex Hospital self-completed HADS questionnaire. HADS scores: normal (0-7), mild (8-10), moderate (11-15) and severe (16-21). Data was then matched to SLE patients, RA patients and a group of miscellaneous patients with LTC. Additionally the SLE group was split into two subgroups, SLE and NPSLE. <h3>Results</h3> There was no significant difference in self reported anxiety levels between (SLE), (RA) or (Misc), irrespective of age. Counter to expectation there was no difference in the level of anxiety or depression between SLE (n=56) and NPSLE (n=33) subgroups as illustrated by tables 1 and 2. <h3>Conclusions</h3> These relatively good outcomes in SLE/NPSLE may support the intense medical intervention model for autoimmune disease. However, individuals detected by the screen may also benefit from targeted therapy. These simply administered PROMs may allow resource management of Rheumatology LTC with follow up assessment to determine value for money. <h3>References</h3> <i>Wekking EM. Psychiatric symptoms in systemic lupus erythematosus; an update. Psychosom Med1993; 55: 219–28.</i> <i>Gandey A. Mental Health problems frequently overlooked in lupus. Medscape Medical News; 2005</i> <i>Hanly JG, Fisk JD, McCurdy G, Fougere L, Neuropsychiatric syndromes in patients with systemic lupus erythematosus and rheumatoid arthritis. J Rheumatology. 2005 Aug; 32(8): 1459-6.</i> <h3>Acknowledgements</h3> Mr Paul Bassett (Statistician), Dr Swati Shukla and Dr Bushra Kohaji (All helped in data gathering and processing). <h3>Disclosure of Interest</h3> None Declared
Modeling Pancreatic Cancer with Organoids
Authors: Lindsey A. Baker, Hervé Tiriac, Hans Clevers, David A. Tuveson
Journal: Trends in cancer (2016)

PDA is an extremely aggressive and lethal malignancy. There is an urgent need for research advances that could lead to improved outcomes and earlier diagnoses for PDA. While the mainstays of PDA research have traditionally been genetically engineered mouse models, as well as PDA cell lines cultured as monolayers and patient-derived xenografts, each of these model systems suffers from limitations. Organotypic culture methods, in which cells are cultured in 3D under conditions intended to mimic those in the body, have emerged as powerful new systems to circumvent some of the limitations of other models. Recently, four different methods for modeling PDA as organotypic, organoid cultures have been reported. These methods allow researchers to rapidly make new discoveries about pancreatic tumorigenesis that are highly relevant to human patients. Pancreatic ductal adenocarcinoma (PDA) is a highly lethal malignancy for which new treatment and diagnostic approaches are urgently needed. For such breakthroughs to be discovered, researchers require systems that accurately model the development and biology of PDA. While cell lines, genetically engineered murine models, and xenografts have all led to valuable clinical insights, organotypic culture models have emerged as tractable systems to recapitulate the complex 3D organization of PDA. Recently, multiple methods for modeling PDA using organoids have been reported. This review aims to summarize these organoid methods in the context of other PDA models. While each model system has unique benefits and drawbacks, ultimately, organoids hold special promise for the development of personalized medicine approaches. Pancreatic ductal adenocarcinoma (PDA) is a highly lethal malignancy for which new treatment and diagnostic approaches are urgently needed. For such breakthroughs to be discovered, researchers require systems that accurately model the development and biology of PDA. While cell lines, genetically engineered murine models, and xenografts have all led to valuable clinical insights, organotypic culture models have emerged as tractable systems to recapitulate the complex 3D organization of PDA. Recently, multiple methods for modeling PDA using organoids have been reported. This review aims to summarize these organoid methods in the context of other PDA models. While each model system has unique benefits and drawbacks, ultimately, organoids hold special promise for the development of personalized medicine approaches.
Abstract 5111: Metformin suppresses azoxymethane-induced colorectal carcinogenesis via activating AMP-activated protein kinase
Authors: Kunihiro Hosono, Hiroki Endo, Hirokazu Takahashi, Atsushi Nakajima
Journal: Cancer Research (2010)

Abstract Metformin is widely used in the treatment of diabetes mellitus. Previous epidemiological reports suggest metformin reduce cancer incidence. Adenosine monophosphate-activated protein kinase (AMPK) is known to be activated by metformin, and inhibit the mammalian target of rapamycin (mTOR) pathway. The mTOR pathway plays an important role for protein translational machinery and cell proliferation. We examined the effect of metformin on the suppression of colorectal carcinogenesis in chemical carcinogen-induced models. Seven-week-old BALB/c mice i.p. injected with azoxymethane (AOM, 10 mg/kg) were treated with metformin (250 mg/kg/day) or without, for 6 weeks (for aberrant crypt foci (ACF) formation) or for 32 weeks (for polyp formation). We investigated colonic epithelial proliferation using the bromodeoxyuridine (BrdU) and proliferating cell nuclear antigen (PCNA) labeling indices. Western blot analysis was performed to elucidate the mechanism which affected colorectal carcinogenesis. Furthermore, to examine the indirect effect of metformin, the status of insulin resistance and serum lipid levels were assessed. Treatment with metformin significantly reduced the colon polyp and ACF formation, but there was no significant difference in body weight or glucose concentration. BrdU and PCNA indices decreased in mice treated with metformin. Western blot analysis revealed that phosphorylated mTOR, S6 kinase and S6 protein levels significantly decreased in mice treated with metformin. In conclusion, Metformin suppressed colonic epithelial proliferation via inhibition of the mTOR pathway by activation of AMPK. Metformin is already used daily as an antidiabetic drug, so it may be a safer and promising candidate for the chemoprevention of colorectal cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5111.
"Arming" the chimeric oncolytic adenovirus enadenotucirev to deliver checkpoint inhibitors and other therapeutics directly to tumours
Authors: Brian R Champion, Prithvi Kodialbail, Sam Illingworth, Nalini Rasiah, Dan Cochrane, John Beadle, Kerry Fisher, Alice CN Brown
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Enadenotucirev (EnAd; formerly called ColoAd1) is a potent, chimeric Ad11p/Ad3 adenovirus active against a range of epithelial cancer cells, with a shorter time-to-lysis than either wild type Ad11p, Ad3 or Ad5. In normal cells, EnAd is attenuated and shows little or no activity by
Assembling a Coherent Story
Authors: Ran Oren, Yaacov Matzner
Journal: New England Journal of Medicine (1994)

A 44-year-old Israeli-born farmer who lived in the Jordan Valley was admitted to the hospital for evaluation with a two-week history of fever, jaundice, and malaise. His family history was unremarkable, and he had no history of liver disease. He had not drunk unpasteurized milk or consumed alcohol. He did not smoke or abuse drugs, and he was heterosexual. He had taken no medications recently.Although fever and malaise are nonspecific symptoms that could be attributed to almost any inflammatory disease process, the patient clearly has involvement of the hepatobiliary system. I would first have to rule out . . .
AB1153 Functional status assessed by the moroccan version of chaq in children with hemophilic arthropathy:
Authors: M. Rkain, D. El Badri, I. Bouaddi, H. Rkain, F. Allali
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> We aimed to assess functional status in children with hemophilic arthropathy and to search eventual factors related to this functional status. <h3>Methods</h3> In this cross sectional study, we included 25 children affected by haemophilia with chronic involvement of at least one joint (all boys, age of 11.6±3.7 years, mean disease duration of 10.8±3.4years, severe haemophilia (28%) and moderate (72%)). Characteristics of haemophilic arthropathy were collected. Children were asked to complete The Moroccan version of child health assessment questionnaire (CHAQ). <h3>Results</h3> The median CHAQ was 0.5 (0.06, 1.37) and the median global assessment was 30 (5,60). The CHAQ does not correlate to number of affected joints. A fair correlation was found between CHAQ and VAS pain (r=0.521; p=0.01). CHAQ correlated strongly with age onset of haemophilic arthropathy in 2 sites: shoulders (r=-1; p&lt;0.0001) and hips (r=-1; p&lt;0.0001). <h3>Conclusions</h3> This study suggests that functional status seems to be strongly associated to involvement of hip and shoulder and that it's also related to pain. Those results should be verified by larger studies. <h3>Disclosure of Interest</h3> None Declared
Abstract 4507: Discovery of a novel single chain ribosome inactivating protein that selectively kills human melanoma cells
Authors: Melissa Cheung, Leigh Revers, Subodini Perampalam, Xin Wei, Reza Kiarash, David Green, Erin Green, Jean Gariepy
Journal: Cancer Research (2010)

Abstract Few treatment options exist for patients with metastatic melanoma. The standard treatment, dacarbazine (DTIC), shows low response rates ranging from 15% to 25 % with an 8-month median survival time. The development of targeted therapeutics with novel mechanisms of action may improve patient outcome. Ribosome-inactivating proteins (RIPs) such as Shiga-like Toxin 1 (SLT-1) represent powerful scaffolds for developing selective anticancer agents. Here we report the discovery and properties of a single chain, ribosome-inactivating protein (scRIP), termed SLT-1AIYSNKLM that selectively targets and kills human melanoma cells. SLT-1AIYSNKLM was identified following the purification and screening of cytotoxic A chain mutants derived from a combinatorial SLT-1A library This scRIP was shown to selectively kill 7 out of 8 human melanoma cell lines while being ineffective at killing non-melanoma cell lines. Biodistribution and imaging studies of radiolabeled SLT-1AIYSNKLM in SCID mice bearing a human melanoma xenograft indicate that it readily accumulates at the tumor site. Furthermore, the co-administration of SLT-1AIYSNKLM [i.v.] with DTIC [i.p.] resulted in tumor regression and greatly increased animal survival in this mouse xenograft model in comparison to DTIC or SLT-1AIYSNKLM treatments alone. SLT-1AIYSNKLM is stable in serum and binds to human melanoma 518-A2 cells with a dissociation constant of 18 nM. The intravenous administration of SLT-1AIYSNKLM resulted in modest immune responses following repeated i.v. injections in immunocompetent CD1mice. These results suggest that scRIP templates can be evolved to target cancer cells and in the case of SLT-1AIYSNKLM can specifically kill human melanoma cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4507.
A Controlled Study of the Effect of Prednisone on Air-Flow Obstruction in Severe Pulmonary Emphysema
Authors: Frederick Beerel, Hershel Jick, John M. Tyler, Susan Gordon, Hugo Muench
Journal: New England Journal of Medicine (1963)

A LARGE body of evidence attests to the beneficial results obtained from the use of adrenal steroids in bronchial asthma.1 2 3 4 5 6 The relief produced in this condition is most probably due to the suppressive influence of steroids on the inflammatory process. When steroids have been employed in pulmonary emphysema, which is characterized by destruction of lung tissue and only partially reversible bronchial narrowing, the improvement has not been as clear cut.7 Subjective benefit has been reported to outweigh objective changes assessed by pulmonary-function studies.8 Nevertheless, steroids have been widely recommended9 10 11 12 13 14 as treatment although one study denied any benefit.15 To study further . . .
Diversification of the antigen-specific T cell receptor repertoire after varicella zoster vaccination
Authors: Qian Qi, Mary M. Cavanagh, Sabine Le Saux, Hong NamKoong, Chulwoo Kim, Emerson Turgano, Yi Liu, Chen Wang, Sally Mackey, Gary E. Swan, Cornelia L. Dekker, Richard A. Olshen, Scott D. Boyd, Cornelia M. Weyand, Lu Tian, Jörg J. Goronzy
Journal: Science Translational Medicine (2016)

Adult vaccination with an attenuated herpes zoster virus broadens the T cell receptor repertoire without reinforcing clonal dominance.
P37 Which Bronchodilator Reversibility Definition Best Avoids Bias
Authors: HM Ward, BG Cooper, MR Miller
Journal: Thorax (2012)

<h3>Introduction</h3> There is little agreement between the international respiratory societies over how bronchodilator reversibility (BDR) should be expressed. Several methods are currently being used worldwide including FEV1 change as % of predicted, as % from baseline, as absolute change or a combination of these methods. We explored 8 different definitions of BDR by testing the null hypothesis that the best method for expressing BDR should show no difference between the sexes. <h3>Methods</h3> We obtained the pre and post FEV1 results for the first BDR studies using salbutamol 400 µg via a spacer for white Caucasian subjects in our laboratory database up to 11/1/12 [n=5369, 49.6% men, mean (SD) age 50.7 (10.6) years]. The results were expressed as per the definitions of the international societies and also as their individual components if there were combined criteria: ≥15% change from baseline (ACCP 1974), &gt;12% change from baseline and &gt;200ml (ATS 1991 and ATS/ERS 2005), &gt;9% change from predicted (ERS 1994), &gt;10% change from predicted (ERS 1995), &gt;400ml (BTS), &gt;12% baseline, &gt;200ml, and &gt;12% predicted. <h3>Results</h3> The distribution of change was right skewed with 416 subjects having a fall in FEV1 post BD. The table shows the median baseline FEV1 and the male to female ratio for those meeting (+ve) and not meeting (-ve) the various BDR criteria. Definitions based on % change from baseline were biased to positive results in those with smaller pre BD FEV1. BDR criteria including absolute change were biased to those with a larger FEV1 and gave a higher proportion of males with a positive BDR result. The criterion &gt;400ml FEV1 change gave the highest male to female ratio of 2.34. Criteria including both absolute and change as % predicted had both sex and FEV1 size bias whereas using only change as % predicted avoided these biases. <h3>Conclusion</h3> The most appropriate method for expressing bronchodilator response is based on change as % of the predicted FEV1 (ERS 1994 or 1995) as it avoids sex and FEV1 size bias.
Successful Post-Mortem Cesarean Section Following Death from Pulmonary Tuberculosis
Authors: Macey Kronick
Journal: New England Journal of Medicine (1950)

SUCCESSFUL post-mortem cesarean sections performed on patients who have died from various causes have not been frequently reported in the past. In all the medical literature there are fewer than 100 cases recorded. Rescuing a living baby from a patient who has died of pulmonary tuberculosis is relatively uncommon, one of the earliest successful cases having been described by Huguier1 in 1829. The following case is presented because of the scarcity of such reports and because it is believed to be the first in this country.Case ReportB. W., an 18-year-old Negress, was admitted to the Rutland State Sanatorium . . .
Long-term stability of polarity distinctions in the affective disorders
Authors: W Coryell, J Endicott, J D Maser, M B Keller, A C Leon, H S Akiskal
Journal: American Journal of Psychiatry (1995)

This analysis aimed to quantify the long-term stability of distinctions between nonbipolar, bipolar II, and bipolar I affective disorders and to determine the predictors of shifts in patients' diagnoses among these categories.Probands entered the study as they sought treatment for manic, major depressive, or schizoaffective disorder diagnosed according to the Research Diagnostic Criteria. After thorough baseline evaluations, 605 patients with nonbipolar major depressive disorder or schizoaffective disorder, depressed type; 96 with bipolar II disorder; and 231 with bipolar I disorder or schizoaffective disorder, manic type, began the follow-up study. Direct interviews took place at 6-month intervals for the first 5 years and annually thereafter.Only 20 (5.2%) of the 381 initially nonbipolar probands who completed 10 years of follow-up developed mania during that time, and only 19 (5.0%) developed hypomania. A slightly higher proportion of the 67 who began with bipolar II disorder developed mania during the 10 years. Although 101 (66.4%) of the 152 bipolar I or schizoaffective manic probands developed subsequent manic episodes, only 11 (7.2%) developed hypomanic episodes and no mania. Young age at intake and at onset and chronicity of the index episode predicted shifts from nonbipolar to bipolar II disorder. Psychosis and a family history of mania predicted shifts from nonbipolar to bipolar I disorder.The high stability of baseline distinctions between nonbipolar, bipolar II, and bipolar I disorders, in combination with previously described family study data, strongly supports the separation of these disorders for both clinical and research purposes.