tbuckley/cabot-search huggingface dataset:
Clinics in neurology and neurosurgery of sport: mass lesions. Benign brain tumours
Authors: G Davis, D W Marion, B George, P Le Roux, E R Laws, P McCrory
Journal: British Journal of Sports Medicine (2009)

When athletes are investigated for acute neurological symptoms a brain scan may reveal a tumour or mass lesion. Occasionally, these are incidental findings. The location of the tumour in the brain will critically affect its clinical presentation. A tumour compressing the optic nerve will result in visual loss, a tumour obstructing the cerebral aqueduct will cause hydrocephalus, and a tumour in the hippocampus may cause epilepsy.

The biology of the tumour determines its growth propensity and aggressiveness. Although tectal plate glioma and glioblastoma multiforme are both classified as astrocytomas, the behaviour of each is completely different. A tectal platei glioma is a very slow-growing, indolent lesion, often remaining stable for many years without the requirement for any treatment, whereas a glioblastoma multiforme is aggressive and invasive, and can grow rapidly within a few weeks. Similarly, the classification of meningiomas includes tumours with a broad spectrum of clinical behaviour. A benign convexity meningioma grows very slowly and is cured with complete resection, whereas a skull base meningioma can invade bone, brain, vascular and neural structures. Tumour biology also affects the brain’s reaction to the tumour, such as the development of cerebral oedema surrounding the lesion.

Treatment of tumours takes these and other factors into account, including patient age and functional level, comorbidity, neurological deficits and seizures. Depending on the tumour type, location and clinical presentation, treatment options include any combination of surgical resection, radiosurgery, radiotherapy, chemotherapy, and treatment of associated phenomena such as hydrocephalus and seizures.

The athlete with a high-grade aggressive tumour with pronounced neurological deficit is unlikely to return to elite sport, but a sportsman with an incidental benign brain tumour will probably want to return and may be able to do so. This forum is inappropriate for a detailed discussion of the management of all brain tumours, …
Recombinant canine B-domain–deleted FVIII exhibits high specific activity and is safe in the canine hemophilia A model
Authors: Denise E. Sabatino, Christian Furlan Freguia, Raffaella Toso, Andrey Santos, Elizabeth P. Merricks, Haig H. Kazazian, Timothy C. Nichols, Rodney M. Camire, Valder R. Arruda
Journal: Blood (2009)
Pan-cancer patterns of DNA methylation
Authors: Tania Witte, Christoph Plass, Clarissa Gerhauser
Journal: Genome Medicine (2014)

Abstract The comparison of DNA methylation patterns across cancer types (pan-cancer methylome analyses) has revealed distinct subgroups of tumors that share similar methylation patterns. Integration of these data with the wealth of information derived from cancer genome profiling studies performed by large international consortia has provided novel insights into the cellular aberrations that contribute to cancer development. There is evidence that genetic mutations in epigenetic regulators (such as DNMT3, IDH1/2 or H3.3) mediate or contribute to these patterns, although a unifying molecular mechanism underlying the global alterations of DNA methylation has largely been elusive. Knowledge gained from pan-cancer methylome analyses will aid the development of diagnostic and prognostic biomarkers, improve patient stratification and the discovery of novel druggable targets for therapy, and will generate hypotheses for innovative clinical trial designs based on methylation subgroups rather than on cancer subtypes. In this review, we discuss recent advances in the global profiling of tumor genomes for aberrant DNA methylation and the integration of these data with cancer genome profiling data, highlight potential mechanisms leading to different methylation subgroups, and show how this information can be used in basic research and for translational applications. A remaining challenge is to experimentally prove the functional link between observed pan-cancer methylation patterns, the associated genetic aberrations, and their relevance for the development of cancer.
Multiplex immunohistochemistry for immune profiling of HPV-associated head and neck cancer
Authors: Takahiro Tsujikawa, Rohan N Borkar, Vahid Azimi, El Edward Rassi, Daniel R Clayburgh, Sushil Kumar, Andrew J Gunderson, Molly F Kresz-Martin, Paul W Flint, Lisa M Coussens
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Human Papilloma Virus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) is clinically distinct from HPV-negative HNSCC, and as such requires differential therapeutic approaches. Accumulating evidence indicates a significant linkage between the immune response within the
Spirometer - Pass ATS/ERS test, but fail in real life
Authors: Juergen Reinstaedtler
Journal: European Respiratory Journal (2012)

The 2005 ATS/ERS guidelines on spirometry recommend validating the quality of a spirometer by simulating forced expirations with computerized syringes. It was recently shown, that these test-curves have non-physiological flow spikes of approximately 150 mL/s instead of a slow drop towards the end of the expiration(1). Spirometers vary in their minimal detectable flow, especially turbine type spirometers. Due to the spiky flow, such difference might not be detected by the current ATS/ERS waveform tests.

We used the interpolated form of the ATS curves(1) to calculate the effect on the measured FVC of the curves with varying lowest detectable flows. We evaluated flow cut-offs of 10 – 150 mL/s in 10 mL/s increments. Only flows that were above this cut-off were integrated for volume.

![Figure][1] 



Figure 1: Underestimation of FVC at different cut off flows (the ATS/ERS repeatability limit is shown for comparison)

The effect on FVC was high for those ATS curves that have a low tapering end (e.g. curves 3, 17, 19), while those curves that end suddenly had small effects (e.g. curves 7, 16).

The deviations in FVC become larger than the ATS/ERS repeatability criterion even with lowest detectable flows of 50 – 100 mL/sec. But those failures would be missed by the currently used ATS/ERS waveforms. We recommend to urgently adapting the test curves to the interpolated version to avoid missing poor performing spirometers in the future.

(1): Reinstaedtler J. ATS congress 2012, Abstract 31123.

 [1]: pending:yes
Diffuse Mesothelioma and Exposure to Asbestos Dust in the Merseyside Area
Authors: W. G. Owen
Journal: BMJ (1964)

Patients suffering from pulmonary asbestosis show a high incidence of malignant-tumour formation. Particular attention has been given in the past to the occurrence of carcinoma of the lung. Doll (1955) assessed the average risk among men employed for 20 or more years at one asbestos factory as 10 times that among the general population. More recently a close association has been found to exist between exposure to asbestos and the development of diffuse mesothelioma. Wagner et al. (1960) described 33 examples of diffuse pleural meso thelioma from the North Western Cape Province of South Africa. All but one of the patients had been exposed to asbestos and many had worked in the local asbestos mines. Later, Wagner (1962) described 75 cases of diffuse pleural meso thelioma together with three examples of diffuse peritoneal mesothelioma. Occupational or environmental exposure to asbestos had occurred in all but two of the patients. In the present investigation a study has been made of 17 examples of diffuse mesothelioma occurring in the Merseyside area. In each case evidence has been sought of exposure to asbestos dust.
THE SIGNIFICANCE OF A DICHOTOMY IN CLINICAL PSYCHIATRIC CLASSIFICATION
Authors: G. LANGFELDT
Journal: American Journal of Psychiatry (1959)

I wish to stress the fact that it has always been the differentiation of aetiologically different psychiatric syndromes, that has made useful psychiatric classification possible by providing clear description of inherent characteristics. However, as there are several psychiatric disorders the causes of which are still unknown, clinical experience calls urgently for a classification of psychiatric groups that have several common traits in respect to symptomatology, course and treatment. Such a systematization might be of great significance to research into prognostication and treatment of the individual case. As team work from our clinic(6) has shown, it is possible even in the initial stage of a case of schizophrenia to predict the course with a certainty of more than 90%. In addition it is also possible in the initial stage to indicate which of the modern treatments has the best chance of success. Consequently if the significance of the dichotomy in psychiatry were generally accepted it would probably mean a great advantage in international comparative psychiatry.
Diagnosis and definition of severe refractory asthma: an international consensus statement from the Innovative Medicine Initiative (IMI)
Authors: E. H. Bel, A. Sousa, L. Fleming, A. Bush, K. F. Chung, J. Versnel, A. H. Wagener, S. S. Wagers, P. J. Sterk, C. H. Compton
Journal: Thorax (2010)

Patients with severe refractory asthma pose a major healthcare problem. Over the last decade it has become increasingly clear that, for the development of new targeted therapies, there is an urgent need for further characterisation and classification of these patients. The Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) consortium is a pan-European public-private collaboration funded by the European Commission Innovative Medicines Initiative of the European Union. U-BIOPRED aims to subphenotype patients with severe refractory asthma by using an innovative systems biology approach. This paper presents the U-BIOPRED international consensus on the definition and diagnosis of severe asthma, aligning the latest concepts in adults as well as in children. The consensus is based on existing recommendations up to 2010 and will be used for the selection of patients for the upcoming U-BIOPRED study. It includes the differentiation between ‘problematic’, ‘difficult’ and ‘severe refractory’ asthma, and provides a systematic algorithmic approach to the evaluation of patients presenting with chronic severe asthma symptoms for use in clinical research and specialised care.
Hypertension and ethnic group
Authors: Morris J Brown
Journal: BMJ (2006)

Are there ethnic differences in the pathogenesis of hypertension and are these sufficient to influence choice of treatment? I will also consider prevalence and complications. Because hypertension is the biggest and an almost entirely treatable cause of cardiovascular disease, even small ethnic differences in its optimum management have large implications for health resources. Ethnic differences in the type of hypertension give us the strongest evidence that we have for the concept that hypertension exists in two broad types. As for diabetes, hypertension can usefully be considered as of type 1 or type 2, each with its own preferred treatment. Results of recent trials support this view and emphasise the importance of choosing the right strategy for the type of hypertension to be treated.

Numerous published studies, including many reviews, compare one or more of the four parameters to be discussed in different ethnic groups. A few have prospectively identified similar numbers in the ethnic groups being compared or a minimum proportion of the ethnic minority. But most are retrospective analyses of studies in which a multi-ethnic population was recruited. I found relevant studies with Medline and Google-Scholar, searching for “hypertension” with either “ethnic” or the names of individual ethnic groups. White and black people are the key ethnic groups to have been compared. Some prevalence studies included Asians, but these studies give insufficient information on which to make reliable statements about pathogenesis or treatment.

Progress in understanding the pathogenesis of hypertension has been slow because essential hypertension is extremely complex at a molecular level.1 Conversely, hypertension exists in only two broad physiological types. This has been long predictable in theory from Poiseuille's law (that blood pressure is the product of vasoconstriction and volume) and supported in practice from the observation that a few of the syndromes where hypertension is …
Trends in the use of intracytoplasmatic sperm injection marked variability between countries
Authors: A. Nyboe Andersen, E. Carlsen, A. Loft
Journal: Human Reproduction Update (2008)

ICSI is used increasingly often compared with standard IVF. The aim of the present study was to analyse the changes in the use of ICSI, and discuss possible causes and consequences.Data from National and Regional registers were analysed for trends in the use of ICSI and indications for assisted reproductive technology (ART).The use of ICSI increased from 39.6% of ART cycles in 1997 to 58.9% in 2004 (USA 57.5%, Australia/New Zealand 58.6%, Europe 59.3%). The Nordic countries, the Netherlands and the UK used ICSI to a low extent (40.0-44.3%), whereas Austria, Belgium and Germany (68.5-72.9%) and the southern European countries like Greece, Italy and Spain used ICSI frequently (66.0-81.2%). The marked increase in the proportion of ICSI cycles seems primarily due to an increased use in couples classified as having mixed causes of infertility, unexplained infertility and advanced age together with a relative decline in tubal factor infertility. An absolute increase in the prevalence of couples with impairment in semen quality remains a possibility.ICSI is used increasingly, but huge differences exist between countries within Europe. It is not possible to determine specific factors that explain the differences. As ICSI does not give higher pregnancy rates than IVF in couples without male factors, and as it adds additional costs, infertile couples and society may benefit from a less frequent use of ICSI in some countries.
Assessment of rituximab's immunomodulatory synovial effects (ARISE trial). 1: clinical and synovial biomarker results
Authors: A Kavanaugh, S Rosengren, S J Lee, D Hammaker, G S Firestein, K Kalunian, N Wei, D L Boyle
Journal: Annals of the Rheumatic Diseases (2007)

Treatment with the anti-CD20 monoclonal antibody (mAb) rituximab is effective in rheumatoid arthritis (RA). Marked depletion of circulating B cells, seen in almost all patients, does not correlate with efficacy. The potential synovial immunomodulatory effects of rituximab have not been fully defined.The ARISE trial is an open label, serial synovial biopsy (pre-treatment and 8 weeks) study of rituximab, given 1 g intravenously on days 0 and 14 without peri-infusional steroids, in active RA patients on concomitant methotrexate (MTX). Synovial tissue was analysed by immunohistochemistry with digital image analysis and gene expression by real-time PCR.The mean (SD) baseline DAS28 score was 6.5 (0.4), and mean MTX dose 17.3 mg/week. Of 13 patients, 11 had failed prior tumour necrosis factor (TNF) inhibitor therapy. With treatment, all patients experienced near complete depletion of circulating B cell numbers. During the 6 months after treatment, 7/13 patients achieved an American College of Rheumatology (ACR) 20% improvement (ACR20) response, 3/13 an ACR50 response and 2/13 an ACR70 response. There was a significant decrease in synovial B cells after treatment, but only a small trend towards greater reduction among clinical responders. Among the three patients with ACR50 responses there was a significant decrease in synovial immunoglobulin synthesis.These data suggest that unlike those in circulation, synovial B cells are decreased but are not eliminated by rituximab therapy. Patients with higher levels of response may have more consistent depletion of synovial B cells, and may also have an alteration in synovial B cell function, as indicated by decreases in synovial immunoglobulin synthesis. Thus, effects on synovial B cells may be necessary but not sufficient for inducing clinical efficacy. Other effects, such as on primary lymph organ B cell antigen presentation or cytokine production, may be operative.
Dissatisfaction with Medical Practice
Authors: Abigail Zuger
Journal: New England Journal of Medicine (2003)

This article reviews the subjective and objective indicators of dissatisfaction with medical practice. Discontent seems to have increased substantially during the past two decades, after a period of unprecedented satisfaction within the medical profession. Some of the sources of dissatisfaction include pressures from managed-care systems, the malpractice crisis, aggravation with bureaucratic red tape, and constant time pressures. However, most physicians still take satisfaction in their work.
A role for stem cell factor (SCF): c-kit interaction(s) in the intestinal tract response to Salmonella typhimurium infection.
Authors: G R Klimpel, K E Langley, J Wypych, J S Abrams, A K Chopra, D W Niesel
Journal: The Journal of Experimental Medicine (1996)

Cholera toxin (CT) has been shown to induce stem cell factor (SCF) production in mouse ligated intestinal loops. Further, SCF interaction(s) with its receptor (c-kit) was shown to be important for the intestinal tract secretory response after CT exposure. In this study, we have investigated whether SCF production is induced in the intestinal tract after exposure to Salmonella typhimurium and whether this production could be an important intestinal tract response to Salmonella infection. Using a mouse ligated intestinal loop model, increased levels of SCF mRNA were detected at 2-4 h post-Salmonella challenge. Intestinal fluid obtained from Salmonella-challenged loops contained high levels of SCF by ELISA. Human and murine intestinal epithelial cell lines were also shown to have increased levels of SCF mRNA after exposure to Salmonella. Inhibition of Salmonella invasion of epithelial cells was shown to be one potentially important role for SCF:c-kit interactions in host defense to Salmonella infection. Pretreatment of human or murine intestinal cell lines with SCF resulted in a cellular state that was resistant to Salmonella invasion. Finally, mice having mutations in the white spotting (W) locus, which encodes the SCF-receptor (c-kit), were significantly more susceptible to oral Salmonella challenge than their control littermates. Taken together, the above results suggest that an important intestinal tract response to Salmonella infection is an enhanced production of SCF and its subsequent interactions with c-kit.
Obesity Among US Immigrant Subgroups by Duration of Residence
Authors: Mita Sanghavi Goel
Journal: JAMA (2004)

ContextThe prevalence of obesity has increased substantially since the 1980s. While immigrants are the fastest growing segment of the US population, little is known about obesity or clinician counseling about diet and exercise in this group.ObjectivesTo estimate the prevalence of obesity among immigrant subgroups and quantify the magnitude of the association with duration of US residence, and to describe reported diet and exercise counseling by birthplace, race, and ethnicity.Design, Setting, and ParticipantsCross-sectional study using data from the 2000 National Health Interview Survey.Main Outcome MeasuresBody mass index (BMI, measured as weight in kilograms divided by the square of height in meters) based on self-reported height and weight measurements, and self-reported rates of diet and exercise counseling.ResultsOf 32 374 respondents, 14% were immigrants. The prevalence of obesity was 16% among immigrants and 22% among US-born individuals. The age- and sex-adjusted prevalence of obesity was 8% among immigrants living in the United States for less than 1 year, but 19% among those living in the United States for at least 15 years. After adjusting for age, sociodemographic, and lifestyle factors, living in the United States for 10 to 15 and at least 15 years was associated with BMI increases of 0.88 and 1.39, respectively. The association for 15 years or more was significant for all immigrant subgroups except foreign-born blacks. Additionally, immigrants were less likely than US-born individuals to report discussing diet and exercise with clinicians (18% vs 24%, P&lt;.001; 19% vs 23%, P&lt;.001, respectively). These differences were not accounted for by sociodemographic characteristics, illness burden, BMI, or access to care among some subgroups of immigrants.ConclusionsAmong different immigrant subgroups, number of years of residence in the United States is associated with higher BMI beginning after 10 years. The prevalence of obesity among immigrants living in the United States for at least 15 years approached that of US-born adults. Early intervention with diet and physical activity may represent an opportunity to prevent weight gain, obesity, and obesity-related chronic illnesses.
Cancer-Testis Antigens and Immunosurveillance in Human Cutaneous Squamous Cell and Basal Cell Carcinomas
Authors: Anne Walter, Marjam J. Barysch, Silvia Behnke, Piotr Dziunycz, Bruno Schmid, Erika Ritter, Sacha Gnjatic, Glen Kristiansen, Holger Moch, Alexander Knuth, Reinhard Dummer, Maries van den Broek
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Nonmelanoma skin cancer is the most common cancer and comprises basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). The incidence of SCC increases drastically in immunosuppressed individuals, suggesting a critical role of the immune system in controlling SCC. To find an explanation for the selective immunosurveillance of SCC, we investigated the expression of cancer-testis (CT) antigens and MHC class I (MHC-I) and the infiltration by immune cells in BCC and SCC. Experimental Design: We determined the expression of 23 different CT-antigens in 63 BCC and 40 SCC biopsies of immunocompetent and in 20 biopsies of immunosuppressed SCC patients by reverse transcription-PCR and immunohistochemistry. IgG responses to 36 tumor antigens were measured by Western blotting and ELISA. MHC-I expression and CD8+ T-cell infiltration were analyzed by immunohistochemistry in BCC and SCC of immunocompetent and immunosuppressed patients and in imiquimod-treated BCC patients. Results: We found expression of at least one CT-antigen in 81% of BCC and in 40% of SCC. We did not detect CT-antigen–specific serum IgG. Most SCC, but not BCC, expressed MHC-I and were infiltrated with CD8+ cells. Imiquimod-treated BCC expressed MHC-I and were infiltrated by CD8+ T cells. Conclusions: We propose that immunosurveillance controls SCC, but not BCC, because the latter lacks MHC-I. This fits with the increased incidence of SCC in immunosuppressed individuals and may explain the relatively low prevalence of CT-antigen expression in SCC as a result of CD8+ T-cell–driven immunoediting. Clin Cancer Res; 16(14); 3562–70. ©2010 AACR.