tbuckley/cabot-search huggingface dataset:
Oral Pharmacologic Treatment of Type 2 Diabetes Mellitus: A Clinical Practice Guideline From the American College of Physicians
Authors: Amir Qaseem, Linda L. Humphrey, Donna E. Sweet, Melissa Starkey, Paul Shekelle
Journal: Annals of Internal Medicine (2012)

The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the comparative effectiveness and safety of type 2 diabetes medications.This guideline is based on a systematic evidence review evaluating literature published on this topic from 1966 through April 2010 that was identified by using MEDLINE (updated through December 2010), EMBASE, and the Cochrane Central Register of Controlled Trials. Searches were limited to English-language publications. The clinical outcomes evaluated for this guideline included all-cause mortality, cardiovascular morbidity and mortality, cerebrovascular morbidity, neuropathy, nephropathy, and retinopathy. This guideline grades the evidence and recommendations by using the American College of Physicians clinical practice guidelines grading system. RECOMMENDATION 1: ACP recommends that clinicians add oral pharmacologic therapy in patients diagnosed with type 2 diabetes when lifestyle modifications, including diet, exercise, and weight loss, have failed to adequately improve hyperglycemia (Grade: strong recommendation; high-quality evidence). RECOMMENDATION 2: ACP recommends that clinicians prescribe monotherapy with metformin for initial pharmacologic therapy to treat most patients with type 2 diabetes (Grade: strong recommendation; high-quality evidence). RECOMMENDATION 3: ACP recommends that clinicians add a second agent to metformin to treat patients with persistent hyperglycemia when lifestyle modifications and monotherapy with metformin fail to control hyperglycemia (Grade: strong recommendation; high-quality evidence).
Evaluation of the effectiveness of four different inhalers in patients with chronic obstructive pulmonary disease.
Authors: J van der Palen, J J Klein, A H Kerkhoff, C L van Herwaarden
Journal: Thorax (1995)

BACKGROUND--The percentage of patients inhaling their medication effectively varies widely, according to methods of assessment and inhalers used. This study was carried out to assess differences among four types of inhalers using inhaler-specific checklists. METHODS--Inhalation technique was evaluated in adult patients with chronic obstructive pulmonary disease (COPD). Inhalers investigated were either metered dose inhalers (MDIs) or the dry powder inhalers Turbohaler (Turbuhaler), Diskhaler, and Rotahaler. Errors were recorded against inhaler-specific checklists. From these, scores were derived by dividing the number of items correctly completed by the total number of items on the checklist and the result was expressed as a percentage. For every inhaler "essential actions" were identified and scores on these key manoeuvres were calculated. The percentage of patients performing all these essential actions correctly was also calculated. Scores were also compared with adjustment for differences in relevant patient characteristics. RESULTS--Important differences among inhalers were found. Of 152 patients with COPD (mean (SD) age 55.1 (8.7) years), those with MDIs performed worst, especially when only essential items were considered. Patients with a Diskhaler did best, although after correction for patient characteristics the differences tended to diminish. Only 60% of patients were able to perform all essential inhaler actions satisfactorily. Of those using the Diskhaler, 96% did so correctly, while the corresponding figure for those using the MDI was only 24%. CONCLUSIONS--Many patients with COPD use their inhaler ineffectively. After adjusting for patient characteristics, differences among inhalers, although less pronounced, persist. Patients using a Diskhaler made fewest errors, while most patients using MDIs made crucial mistakes.
Predicting treatment outcome in classical Hodgkin lymphoma: genomic advances
Authors: Enrico Derenzini, Anas Younes
Journal: Genome Medicine (2011)

Classical Hodgkin lymphoma is considered a highly curable disease; however, 20% of patients cannot be cured with standard first-line chemotherapy and have a dismal outcome. Current clinical parameters do not allow accurate risk stratification, and personalized therapies are lacking. In fact, Hodgkin lymphoma (HL) is often over- or undertreated because of this lack of accurate risk stratification. In recent years, the early detection of chemoresistance by fluorodeoxyglucose positron emission tomography has become the most important prognostic tool in the management of HL. However, to date, no prognostic scores or molecular markers are available for the early identification of patients at very high risk of failure of induction therapy. In the last decade, many important advances have been made in understanding the biology of HL. In particular, the development of new molecular profiling technologies, such as SNP arrays, comparative genomic hybridization, and gene-expression profiling, have allowed the identification of new prognostic factors that may be useful for risk stratification and predicting response to chemotherapy. In this review, we focus on the prognostic tools and biomarkers that are available for newly diagnosed HL, and we highlight recent advances in the genomic characterization of classical HL and potential targets for therapy.
Does a Higher Surgical Resection Rate in Lung Cancer Lead to a Higher Rate of Post-Operative Multi-Station N2 Disease?
Authors: M. Evison, S. Britton, H. Al-Najjar, P. Crosbie, P. Bishop, M. Jones, P. Krysiak, K. Rammohan, R. Shah, R. Booton
Journal: Annals of Oncology (2015)
Colin Bouwer: Professor of Psychiatry and murderer
Authors: Vincent Marks, Caroline Richmond
Journal: Journal of the Royal Society of Medicine (2008)

I first heard of Colin Bouwer on 4 March 2001 when I received an email from Detective Sergeant Brett Roberts of Dunedin, New Zealand. The story he told was a fascinating one. Nine months earlier he had arrested Colin Bouwer, who was Head of the Department of Psychiatry in Otago Medical School in Dunedin, on a charge of murdering his wife. During the three months preceding his wife's death Colin had written false prescriptions for a long list of drugs, including insulin, which would not ordinarily be prescribed by a psychiatrist except possibly for his own use. The police obtained a search warrant and found on Colin's computer a number of emails that suggested he had injected his wife with insulin some 7–12 hours before her death. He had also emailed a number of international hypoglycaemia experts claiming to be a forensic psychiatrist dealing with a 47-year-old woman who had died in her sleep. The questions he posed related to the injection of insulin or the ingestion of sulphonylurea drugs (medicines used to treat diabetes) and the likely problems of establishing them as a cause of hypoglycaemia.

I was not on Colin Bouwer's email list, nor did I know anyone who was. The police had, however, come across my name as the author of a paper entitled ‘Murder by insulin’ that I had recently published in the Medico-Legal Journal.1 They wondered whether Colin had phoned or written to me. Just in case I might dismiss his email as a hoax, Sergeant Roberts gave me his telephone number, although his email address – @police.govt.nz – was a bit of a giveaway. Nevertheless, to be on the safe side, I did phone him as well as replying to his email to say that I had never heard of Dr. Bouwer and that he had never been in touch.

I thought that was the end of it until I received a telephone call from Anne Stevens, a barrister, on 1 May 2001. She and leading counsel David More were defending Colin Bouwer on a charge of killing his wife by injecting her with insulin after weeks of trying to do so with sulphonylureas. They wanted me to review the evidence and express an opinion.

I agreed to do so and promptly received a mass of clinical notes relating to Annette Bouwer's last illness during November and December 1999 and her death on 5 January 2000. Anne Stevens also sent me witness statements by a number of local experts who had been consulted by the police. By the end of May I had received a letter from David More telling me that the current defence position was that Annette had suffered from hypoglycaemia due to an insulinoma (an insulin-secreting tumour) and that it had been missed both at operation and at postmortem. An alternative explanation was that she had committed suicide with drugs her husband had stockpiled for his own suicide when it became evident to her that her doctors could do no more than they already had done to alleviate her ongoing suffering.
Hepatosplenic T cell lymphoma in inflammatory bowel disease
Authors: M. Shale, E. Kanfer, R. Panaccione, S. Ghosh
Journal: Gut (2008)

The development of lymphoma in chronic inflammatory conditions has been a topic of great interest.  Studies in inflammatory bowel disease (IBD) have demonstrated conflicting results and it is often difficult to disassociate disease severity, disease duration and the risk attributable to drug exposure.  Recently presented results from the very large French population based CESAME study suggest a doubling of the risk of lymphoma in patients with IBD, with the majority of cases occurring in association with immunosuppressive therapy. Similarly, a meta-analysis of previous cohort studies concluded that the risk of lymphoma is increased four-fold in patients with IBD on thiopurine treatment (azathioprine and 6-mercaptopurine) compared to those not receiving such therapy.  Such analyses cannot demonstrate causation, and it is possible that an increased lymphoma risk relates to more active underlying disease rather than thiopurine therapy, an interpretation supported by results from studies in IBD patients unexposed to such treatment.
Chronic colitis after Aeromonas infection.
Authors: J M Willoughby, A F Rahman, M M Gregory
Journal: Gut (1989)

Three patients with an acute colitis in which the only pathogen detected was either Aeromonas hydrophila or A sobria progressed to a chronic phase after the infection had been eliminated by antibiotic treatment in two and had resolved spontaneously in the third. The final diagnosis in each case was ulcerative colitis. Two of the patients have responded to anti-inflammatory medication but one has required panproctocolectomy. The sequence of symptoms and observations in these cases, as well as in others from the literature involving more familiar pathogens, suggests that bacterial infection may contribute to the development of chronic colitis. This supposition could be tested by extending the follow up of patients with acute infective colitis in a prospective multicentre trial.
Distribution of dust‐mite allergens (Lep d 2, Der p 1, Der f 1, Der 2) in pig‐farming environments and sensitization of the respective farmers
Authors: K. Radon, A. Schottky, S. Garz, F. Koops, D. Szadkowski, D. Nowak, K. Radon, D. Nowak, C. Luczynska
Journal: Allergy (2000)

Background: The aim of the present study was to determine the distribution of mite allergens in pig‐farming environments in comparison to urban homes and the relationship between exposure to mite allergens and sensitization to the respective allergens in 100 pig farmers with work‐related respiratory symptoms. Methods: The concentration of storage mite (Lep d 2) and house‐dust‐mite (Der p 1, and Der f 1, Der 2) allergens in dust collected from five different sampling sites (floor, wall, grain mill, transit floor, and farmers' mattresses) was studied in relationship to the respective sensitization rates. Allergen concentrations in the mattresses were compared to those determined in mattresses from 22 urban dwellers. Results: Median concentrations of Der p 1 and Der 2 in the mattresses of the farmers were significantly higher than in the urban dwellers' samples (53.4 μg/g dust vs 1.05 μg/g dust, P =0.001; 19.6 μg/g dust vs 2.2 μg/g dust, P &lt;0.0001, respectively). Allergen concentrations in the transit areas were strongly related to bedroom exposure. In a multiple logistic regression model, a weak but significant relationship between Der p 1 exposure and sensitization to Der p 1 was found. Despite these findings, the prevalence of sensitization to mite allergens in the farmers (18%) was comparable to the prevalence in the general population. Conclusions: Allergen exposure at the work place is strongly related to the concentration of allergens in farmers' beds. Exposure to domestic mite allergens should be taken into account when assessing occupational exposure to allergens and the respiratory health of farmers.
Upregulation of SOX9 in Lung Adenocarcinoma and Its Involvement in the Regulation of Cell Growth and Tumorigenicity
Authors: Shih Sheng Jiang, Wen-Tsen Fang, Ya-Hsiue Hou, Shiu-Feng Huang, B. Linju Yen, Junn-Liang Chang, Shih-Miao Li, Hui-Ping Liu, Ying-Lan Liu, Chih-Ting Huang, Yu-Wei Li, Te-Hsuan Jang, Shih-Hsuan Chan, Su Jing Yang, Chao A. Hsiung, Cheng-Wen Wu, Lu-Hai Wang, I-Shou Chang
Journal: Clinical Cancer Research (2010)

Abstract Purpose: SOX9 is an important transcription factor required for development and has been implicated in several types of cancer. However, SOX9 has never been linked to lung cancer to date. Here, we show that SOX9 expression is upregulated in lung adenocarcinoma and show how it is associated with cancer cell growth. Experimental Design: Data mining with five microarray data sets containing 490 clinical samples, quantitative reverse transcription-PCR validation assay in 57 independent samples, and immunohistochemistry assay with tissue microarrays containing 170 lung tissue cores were used to profile SOX9 mRNA and protein expression. Short interference RNA suppression of SOX9 in cell lines was used to scrutinize functional role(s) of SOX9 and associated molecular mechanisms. Results: SOX9 mRNA and protein were consistently overexpressed in the majority of lung adenocarcinoma. Knockdown of SOX9 in lung adenocarcinoma cell lines resulted in marked decrease of adhesive and anchorage-independent growth in concordance with the upregulation of p21 (CDKN1A) and downregulation of CDK4. In agreement with higher SOX9 expression level in lung adenocarcinoma, the p21 mRNA level was significantly lower in tumors than that in normal tissues, whereas the opposite was true for CDK4, supporting the notion that SOX9 negatively and positively regulated p21 and CDK4, respectively. Finally, whereas SOX9-knockdown cells showed significantly attenuated tumorigenicity in mice, SOX9 transfectants consistently showed markedly stronger tumorigenicity. Conclusions: Our data suggest that SOX9 is a new hallmark of lung adenocarcinoma, in which SOX9 might contribute to gain of tumor growth potential, possibly acting through affecting the expression of cell cycle regulators p21 and CDK4. Clin Cancer Res; 16(17); 4363–73. ©2010 AACR.
Chaperone-Mediated Autophagy Is Required for Tumor Growth
Authors: Maria Kon, Roberta Kiffin, Hiroshi Koga, Javier Chapochnick, Fernando Macian, Lyuba Varticovski, Ana Maria Cuervo
Journal: Science Translational Medicine (2011)

The cellular process of autophagy (literally "self-eating") is important for maintaining the homeostasis and bioenergetics of mammalian cells. Two of the best-studied mechanisms of autophagy are macroautophagy and chaperone-mediated autophagy (CMA). Changes in macroautophagy activity have been described in cancer cells and in solid tumors, and inhibition of macroautophagy promotes tumorigenesis. Because normal cells respond to inhibition of macroautophagy by up-regulation of the CMA pathway, we aimed to characterize the CMA status in different cancer cells and to determine the contribution of changes in CMA to tumorigenesis. Here, we show consistent up-regulation of CMA in different types of cancer cells regardless of the status of macroautophagy. We also demonstrate an increase in CMA components in human cancers of different types and origins. CMA is required for cancer cell proliferation in vitro because it contributes to the maintenance of the metabolic alterations characteristic of malignant cells. Using human lung cancer xenografts in mice, we confirmed the CMA dependence of cancer cells in vivo. Inhibition of CMA delays xenograft tumor growth, reduces the number of cancer metastases, and induces regression of existing human lung cancer xenografts in mice. The fact that similar manipulations of CMA also reduce tumor growth of two different melanoma cell lines suggests that targeting this autophagic pathway may have broad antitumorigenic potential.
Computer Simulation of Plasma Insulin and Glucose Dynamics After Subcutaneous Insulin Injection
Authors: Markus Berger, David Rodbard
Journal: Diabetes Care (1989)

We developed a computer program for the simulation of plasma insulin and glucose dynamics after subcutaneous injection of insulin. The program incorporates a pharmacokinetic model to calculate the time courses of plasma insulin for various combinations of popular preparations (regular, NPH, lente, and ultralente). With the use of a pharmacodynamic model describing the dependence of glucose dynamics on plasma insulin and glucose levels, the program can predict the expected time course of plasma glucose in response to a change in carbohydrate intake, insulin dose, timing, or regimen. A set of typical parameters has been obtained by analysis of data from the literature. The results of several computer simulations are presented showing the effect on a 24-h insulin and glucose profile of systematically changing insulin regimen, dose, timing of meals, or timing of preprandial insulin administration. The program can be used to explore on a theoretical basis the impact of various factors associated with glycemic control in insulin-dependent diabetes mellitus. As an educational tool, the program provides a realistic environment for demonstration of the combined or isolated effects of insulin and diet on glycemia
STUDIES ON NATURAL ANTIBODIES TO GRAM-NEGATIVE BACTERIA
Authors: J. Gabriel Michael, James L. Whitby, Maurice Landy
Journal: The Journal of Experimental Medicine (1962)

A study was made of the origin, occurrence, and properties of natural antibodies to Gram-negative bacteria in the normal serum of several species. Antibody was measured by a procedure based on the bactericidal reaction carried out under conditions in which activity was a function of the amount of antibody contributed by the test serum. Antibody to seven genera of the family Enterobacteriaceae were demonstrated in normal human serum. The specificity of these antibodies was affirmed by absorption with homologous bacteria and by inhibition of bactericidal activity with purified homologous somatic antigen. Absorption with graded amounts of bacterial suspensions showed that a large excess of bacteria led to non-specific removal of antibodies. Analogous findings were also made with immune antibody. As determined by quantitative absorption tests no difference could be found in the avidity of natural and immune antibody. Natural antibody in the serum of various species differed considerably as regards their lability to heat, but in parallel tests immune antibody of each species was significantly more heat-stable. The time and appearance of the antibodies varied in young animals, of different species. Mice developed these antibodies at the earliest age, with guinea pigs, rats, and rabbits following in that order. Serum from germ-free rats and chickens had no demonstrable antibodies to E. coli or S. typhosa whereas these antibodies were present in the serum of litter mates reared under conventional conditions. On the other hand germ-free and conventional mice did not differ appreciably as regards the levels of these same antibodies.
Prognostic Factors and Therapeutic Decisions in Axillary Node-Negative Breast Cancer
Authors: Richard M. Elledge, William L. McGuire
Journal: Annual Review of Medicine (1993)

The incidence of node-negative breast cancer is increasing, and it is becoming a more commonly encountered clinical problem. Prognostic factors such as tumor size, histopathological characteristics, receptor status, proliferative markers, biochemical alterations, and gene abnormalities can be useful in assessing the risk of cancer recurrence after primary local therapy. By accurately assessing the risk of recurrence, informed decisions can be made about whether or not to treat with adjuvant systemic therapy.
Behcet's disease: infectious aetiology, new autoantigens, and HLA-B51
Authors: H Direskeneli
Journal: Annals of the Rheumatic Diseases (2001)

Behçet's disease: infectious aetiology, new autoantigens, and HLA-B51 H DireskeneliBehçet's disease (BD) is a multisystemic disorder with mucocutaneous, ocular, arthritic, vascular, and central nervous system involvements. 1Recent developments in the immunopathogenesis of BD are discussed in this review.Box 1 summarises the major aspects covered. Neutrophil activationNeutrophils are mature immune cells with a very short life in vitro and have a pivotal role in innate immune responses.As typical BD lesions such as pustular folliculitis, pathergy reactions, and hypopyon have significant neutrophil infiltrations, neutrophil functions and activation status have been extensively investigated. 1 2][5][6][7][8][9] In a recent study, which showed decreased fMLP stimulated superoxide production in BD and patients with sepsis, consecutive restimulations of prestimulated BD neutrophils produced a smaller increase in superoxide production than in healthy controls, implying a state of in vivo neutrophil preactivation. 9An in vivo "primed" state of neutrophils with a dual signalling system for activating neutrophil oxidase has been suggested previously. 10Agents such as fMLP or the cytokines, tumour necrosis factor (TNF ) and granulocyte monocyte colony stimulating factor, have been shown to increase tyrosine phosphorylation of various intracellular proteins and to prime neutrophils in vivo without full activation, which might also be the case in BD with its proinflammatory cytokines.In HLA-B51 transgenic mice, a presumed model for BD, the only abnormality seen is increased superoxide release in response to fMLP. 6High superoxide responses were also present in HLA-B51+ patients and healthy controls in the same study, 6 but this has not been confirmed. 9Cellular and humoral immunity T cell activation, both in the peripheral blood and tissue specimens, is present in BD.A possibly antigen driven change in the peripheral blood CD4+ and CD8+ T cell repertoire, with oligoclonal T cell receptor V subset increases,
A study of pulmonary artery pressure, electrocardiography, and mechanocardiography in thoracic scoliosis.
Authors: J M Shneerson, A Venco, F J Prime
Journal: Thorax (1977)

Cardiac catheterisation was carried out in 40 patients with thoracic scoliosis in order to measure the pulmonary artery pressure. Statistical correlations were calculated between these results and the electrocardiographic and mechanocardiographic findings determined on a separate occasion. The pulmonary artery pressure was normal in 72% of subjects. It was inversely correlated with arterial oxygen tension but not with the aetiology, severity, or age at onset of the scoliosis. The accuracy of electrocardiography and mechanocardiography in predicting the pulmonary artery pressure was assessed. The closet correlates were found to be a tall P wave in lead II or III and a prolonged interval between pulmonary valve closure and tricuspid valve opening.