tbuckley/cabot-search huggingface dataset:
My cancer and the magic bullet
Authors: C. Richmond
Journal: BMJ (1998)

In June the first treatment for cancer that uses monoclonal antibodies was licensed. By a miracle of chance, it was designed for my particular subtype of cancer, and it has brought me complete remission. The odds against this happening are enormous. I'm as pleased as Punch, and so is my oncologist.

Rituximab costs £6000 for a course, is for low grade B cell follicular relapsed or chemoresistant stage III or IV non-Hodgkin's lymphoma, halves the size of tumours in only 48% of patients given it, of whom only one in eight gets a complete remission. I was one of these patients. So, statistically, the chances of it being for my type of (incurable) cancer, and of me being given it (considering the cost to the NHS) and getting a full remission, are slender. Having just read Innumeracy by the mathematician John Allen Paulos (he uses his middle name to avoid being taken for the Pope) I feel I should quantify the odds. If, say, 7% of all cancer patients have a lymphoma, or to put it another way are lymphomaniacs, and 80% of those are non-Hodgkin's, and 85% of those are B cell, and 60% are low grade, and 40% of those are follicular, and 30% of those are chemoresistant or relapsed … the odds of getting a full remission are around 1 in 10 000.

When you're a medical journalist, one of the first things you learn about cancer is that although there are regular “breakthroughs,” there is very little real progress. After my lymphoma was diagnosed, my interest in cancer “breakthroughs” increased, but only to the extent of collecting journal articles and press cuttings about lymphoma. I put them in a file to gather dust, and once in a while I leaf through and shake my head at the way …
Use of Liquid Crystal Thermography in the Evaluation of the Diabetic Foot
Authors: Richard M Stess, Pamela C Sisney, Kathryn M Moss, Peter M Graf, Karen S Louie, Gretchen A W Gooding, Carl Grunfeld
Journal: Diabetes Care (1986)

Liquid crystal thermography (LCT) was used to determine temperature variations on theplantar surface of feet. The purpose was to identify thermal emission patterns associated with diabetic foot ulcers. Three population groups were screened: group I, 16 nondiabetic controls; group II, 21 diabetic patients with no history of pedal ulcers; and group III, 28 diabetic patients with active pedal ulceration or history of foot ulcerations. The results demonstrate a generalized increase in plantar foot temperature in group III compared with groups I and II. Temperature readings under metatarsal heads 1–5, great toe, heel, and lateral band were significantly increased (P &amp;lt; .01) in group III. Additionally, the warm lateral surface displayed by group III patients was not significantly different in temperature from the medial arch of the foot. In groups I and II, the lateral band was significantly cooler (P &amp;lt; .01) than the medial arch. In group III patients with active ulceration on only one foot, no significant difference in temperature was found between the foot with active ulceration compared with the contralateral nonulcerated foot. When patients with active pedal ulceration were compared with patients with a history of foot ulcers, no significant difference in temperature was seen at five of seven sites tested. A warm concentric color band surrounding active plantar ulcers was identified in group III. This pattern extended from the center of the ulcer to a distance of 8 mm. A significant change in temperature (P &amp;lt; .01) was noted at 6- and 8-mm distances from the center of the ulcer. In addition, a mottled thermographic pattern was observed more frequently in group III patients than in groups I and II. In summary, group III demonstrated significantly increased skin temperatures and identifiable thermographic emission patterns, which distinguish them from normal. These findings suggest the need for prospective studies to evaluate LCT as a diagnostic modality in the prediction of foot ulceration in the diabetic population.
Causes of failure to harvest cadaver kidneys for transplantation.
Authors: A M Jenkins
Journal: BMJ (1976)

Fifty-two possible donors of cadaver kidneys were referred to the Nuffield Transplantation Surgery Unit, Edinburgh, in 12 months. Only 12 (23%) yielded kidneys, while a further 12 were medically unsuitable as donors. Refusal by relatives to allow cadaver nephrectomy was the largest avoidable loss of potentially transplantable kidneys. A similar but unavoidable loss occurred through sudden death of the possible donor.
Interleukin-17 Is Required for T Helper 1 Cell Immunity and Host Resistance to the Intracellular Pathogen Francisella tularensis
Authors: Yinyao Lin, Shane Ritchea, Alison Logar, Samantha Slight, Michelle Messmer, Javier Rangel-Moreno, Lokesh Guglani, John F. Alcorn, Heather Strawbridge, Sang Mi Park, Reiko Onishi, Nikki Nyugen, Michael J. Walter, Derek Pociask, Troy D. Randall, Sarah L. Gaffen, Yoichiro Iwakura, Jay K. Kolls, Shabaana A. Khader
Journal: Immunity (2009)
Erratum: Corrigendum: Genome-wide profiling of PRC1 and PRC2 Polycomb chromatin binding in Drosophila melanogaster
Authors: Bas Tolhuis, Inhua Muijrers, Elzo de Wit, Hans Teunissen, Wendy Talhout, Bas van Steensel, Maarten van Lohuizen
Journal: Nature Genetics (2006)
Marine ω-3 Fatty Acid Intake
Authors: L. Maria Belalcazar, David M. Reboussin, Steven M. Haffner, Rebecca S. Reeves, Dawn C. Schwenke, Ron C. Hoogeveen, F. Xavier Pi-Sunyer, Christie M. Ballantyne
Journal: Diabetes Care (2009)

OBJECTIVE To examine usual marine ω-3 fatty acid (mO-3FA) intake in individuals with diabetes; its association with adiposity, lipid, and glucose control; and its changes with behavioral lifestyle intervention for weight loss. RESEARCH DESIGN AND METHODS Cross-sectional and 1-year longitudinal analyses were performed on 2,397 Look AHEAD (Action for Health in Diabetes) participants. Look AHEAD is a cardiovascular outcome trial evaluating the effects of intensive lifestyle intervention for weight loss in overweight/obese subjects with type 2 diabetes. RESULTS Baseline mO-3FA intake was 162 ± 138 mg/day. It was inversely associated with triglycerides (β = −0.41, P &amp;lt; 0.001) and weakly with HDL (β = 4.14, P = 0.050), after multiple covariate adjustment. One-year mO-3FA and fried/sandwich fish intake decreased with intensive lifestyle intervention (P &amp;lt; 0.001). CONCLUSIONS mO-3FA intake in Look AHEAD participants was low but associated favorably with lipids. These results encourage investigation on the potential benefits of increasing mO-3FA intake in lifestyle interventions for weight loss in individuals with diabetes.
Use of bumetanide in the treatment of ascites due to liver disease
Authors: P. J. A. Moult, M. R. Lunzer, D. B. Trash, S. Sherlock
Journal: Gut (1974)

Bumetanide is an effective diuretic for the treatment of ascites. Fifteen out of 17 patients with chronic liver disease responded satisfactorily and the incidence of hepatic encephalopathy and electrolyte disturbances was similar to that previously observed with frusemide. Colicky abdominal pain was reported in three patients but no other adverse effects were noted. An unexpected response was obtained in two patients who had diuresis without natriuresis.
Certain Aspects of Allergy in Children
Authors: Lewis Webb Hill
Journal: New England Journal of Medicine (1961)

AsthmaBuffum,14 who has done so much to clarify asthma in infancy, discusses the diagnosis. He reports on 79 patients seen with suspected asthma before the age of two years. It was possible to demonstrate the allergic state in 52. Twenty-seven of these at some time had eczema, 34 had positive scratch tests to some allergen or allergens, 7 had obvious clinical response to some allergen, and 2 had many eosinophils in the nasal smears. About half these infants began with what was apparently a respiratory infection, and they wheezed continuously for one to several months. The severe attacks of . . .
Abnormal Captopril Scintigraphy in Bartter Syndrome
Authors: Flavio Zelmanovitz, Jairo Antonio Fregapani, Themis Zelmanovitz, Bernardo Le??o Spiro
Journal: Clinical Nuclear Medicine (2005)

A 37-year-old patient with severe hypokalemia (approximately 1.7 mEq/L) and muscular weakness had a very high serum renin level. No renin-producing tumor was found and she was diagnosed with Bartter Syndrome The parathyroid hormone level was high due to concomitant renal calcium loss. Tc-99m-DTPA captopril scintigraphy was performed to confirm the diagnosis.
Presentation of continuous outcomes in randomised trials: an observational study
Authors: D. L. Schriger, D. F. Savage, D. G. Altman
Journal: BMJ (2012)

<b>Objective</b> To characterise the percentage of available outcome data being presented in reports of randomised clinical trials with continuous outcome measures, thereby determining the potential for incomplete reporting bias. <b>Design</b> Descriptive cross sectional study. <b>Data sources</b> A random sample of 200 randomised trials from issues of 20 medical journals in a variety of specialties during 2007–09. <b>Main outcome measures</b> For each paper's best reported primary outcome, we calculated the fraction of data reported using explicit scoring rules. For example, a two arm trial with 100 patients per limb that reported 2 sample sizes, 2 means, and 2 standard deviations reported 6/200 data elements (1.5%), but if that paper included a scatterplot with 200 points it would score 200/200 (100%). We also assessed compliance with 2001 CONSORT items about the reporting of results. <b>Results</b> The median percentage of data reported for the best reported continuous outcome was 9% (interquartile range 3–26%) but only 3.5% (3–7%) when we adjusted studies to 100 patients per arm to control for varying study size; 17% of articles showed 100% of the data. Tables were the predominant means of presenting the most data (59% of articles), but papers that used figures reported a higher proportion of data. There was substantial heterogeneity among journals with respect to our primary outcome and CONSORT compliance. <b>Limitations</b> We studied continuous outcomes of randomised trials in higher impact journals. Results may not apply to categorical outcomes, other study designs, or other journals. <b>Conclusions</b> Trialists present only a small fraction of available data. This paucity of data may increase the potential for incomplete reporting bias, a failure to present all relevant information about a study's findings.
Why do qualitative research?
Authors: R. Jones
Journal: BMJ (1995)

mental health, and health economics, also have key con- tributions to make.Secondly, health professionals should join the social and environmental critics of macroeconomic policy to ensure that the health costs and benefits of macroeconomic policies are examined in policymaking.Thirdly, more health professionals can contribute locally to healthy cities projects and other intersectoral activities.The health sector can also promote wider understanding of the many positive implications for public health of environmentally sustainable development.7Do these suggestions take the health sector beyond reason- able limits?The battles for public health in the 19th century offer some help.Doctors themselves did not build sewers or provide clean drinking water, but they had a crucial role in seeing that the health costs of not providing these expensive services were widely understood.Though it did not sail under the flag of intersectoral policy, that was a period of hard fought and highly effective intersectoral activity with pro- found economic implications.Many of the battles were about
The neurofibromin GAP-related domain rescues endothelial but not neural crest development in Nf1-/- mice
Authors: F. A. Ismat
Journal: Journal of Clinical Investigation (2006)

Neurofibromatosis type I (NF1; also known as von Recklinghausen's disease) is a common autosomal-dominant condition primarily affecting neural crest–derived tissues. The disease gene, NF1, encodes neurofibromin, a protein of over 2,800 amino acids that contains a 216–amino acid domain with Ras–GTPase-activating protein (Ras-GAP) activity. Potential therapies for NF1 currently in development and being tested in clinical trials are designed to modify NF1 Ras-GAP activity or target downstream effectors of Ras signaling. Mice lacking the murine homolog (Nf1) have mid-gestation lethal cardiovascular defects due to a requirement for neurofibromin in embryonic endothelium. We sought to determine whether the GAP activity of neurofibromin is sufficient to rescue complete loss of function or whether other as yet unidentified functions of neurofibromin might also exist. Using cre-inducible ubiquitous and tissue-specific expression, we demonstrate that the isolated GAP-related domain (GRD) rescued cardiovascular development in Nf1–/– embryos, but overgrowth of neural crest–derived tissues persisted, leading to perinatal lethality. These results suggest that neurofibromin may possess activities outside of the GRD that modulate neural crest homeostasis and that therapeutic approaches solely aimed at targeting Ras activity may not be sufficient to treat tumors of neural crest origin in NF1.
Respiratory syncytial virus infection results in airway hyperresponsiveness and enhanced airway sensitization to allergen.
Authors: J Schwarze, E Hamelmann, K L Bradley, K Takeda, E W Gelfand
Journal: Journal of Clinical Investigation (1997)

Viral respiratory infections can predispose to the development of asthma by mechanisms that are presently undetermined. Using a murine model of respiratory syncytial virus (RSV) infection, acute infection is associated with airway hyperresponsiveness as well as enhanced responses to subsequent sensitization to allergen. We demonstrate that acute viral infection results in increased airway responsiveness to inhaled methacholine and pulmonary neutrophilic and eosinophilic inflammation. This response is associated with predominant production of Th-1-type cytokines in peribronchial lymph node cells in vitro. Mice sensitized to ovalbumin via the airways after RSV infection developed increased airway responsiveness to methacholine and pulmonary eosinophilic and neutrophilic inflammation, associated with the predominant production of Th-2-type cytokines. Treatment of the mice with anti-IL-5 antibody abolished airway hyperresponsiveness and eosinophilic but not neutrophilic inflammation in both acutely infected mice and mice sensitized after infection. We conclude that RSV infection results in airway hyperresponsiveness in the acute phase and leads to changes in immune function that can enhance the effects of airway sensitization to antigen after infection. In both situations, airway hyperresponsiveness is closely associated with pulmonary eosinophilic inflammation. This model provides a means for further analyzing the influence of viral respiratory infections on airway sensitization and the development of altered airway responsiveness.
Abstract 2041: Inhibition of autophagy in melanoma: using cell lines to model chloroquine sensitivity.
Authors: Kirsten A. White, Salina M. Torres, Natalia J. Gurule, Marianne Berwick, Chien-An A. Hu
Journal: Cancer Research (2013)

Abstract Metastatic melanoma offers an ongoing clinical challenge. According to the American Cancer Society, the 5-year survival rate in 2012 for stage IV melanoma is only about 15% even with therapies. To improve outcomes, it is important to investigate new pathways involved in the regulation of metastasis as possible targets for prevention or treatment, such as autophagy. Autophagy (self-eating pathway) destroys a cell's damaged proteins and organelles through lysosomal degradation and has been shown to play roles in a wide variety of normal physiological processes including energy metabolism, nutrient or stress responses, growth regulation, and aging. The role of dysregulated autophagy in melanoma has not been well characterized. Preliminary research found cutaneous malignant melanoma cells display high levels of autophagy suggesting that this cellular process may provide an active metabolic state for invasive and metastatic melanoma. Chloroquine (CLQ), a classic antimalarial agent, is a potent inhibitor of autophagy and has been used safely in human patients for decades. This study is designed to dissect the role of autophagy in melanoma using melanoma cell lines (e.g. SK-Mel 19, 103, and 147), and primary melanocytes as controls to determine whether these cell types respond to CLQ as measured by cell viability . Similar to pancreatic and prostate cancer cell lines, our preliminary results indicate that metastatic melanoma cells require autophagy for growth and show high sensitivity to CLQ at doses as low as 20uM which resulted in greater than 60% decreases in cell viability. These findings suggest that metastatic melanoma cell lines rely on lysosomal degradation to a greater extent than what has been reported for other cell types. In addition, both N-ras mutation and androgen deprivation mitigate the effects of CLQ on melanoma cells. Ongoing experiments will confirm the expression of autophagy related genes, as well as imaging to determine the rate of autophagy in these cell lines. Finally, we will introduce stripped hormonal factors including vitamin D and estrogen, to evaluate whether this addition will progressively restore the original chloroquine sensitive phenotype. Findings from this work have the potential to be immediately translatable to patients as CLQ is already approved for therapeutic use in other human diseases. Citation Format: Kirsten A. White, Salina M. Torres, Natalia J. Gurule, Marianne Berwick, Chien-An A. Hu. Inhibition of autophagy in melanoma: using cell lines to model chloroquine sensitivity. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2041. doi:10.1158/1538-7445.AM2013-2041
Cost-effective multiplexing before capture allows screening of 25 000 clinically relevant SNPs in childhood acute lymphoblastic leukemia
Authors: A Wesolowska, M D Dalgaard, L Borst, L Gautier, M Bak, N Weinhold, B F Nielsen, L R Helt, K Audouze, J Nersting, N Tommerup, S Brunak, T Sicheritz-Ponten, H Leffers, K Schmiegelow, R Gupta
Journal: Leukemia (2011)
Functional Roles of<i>Src</i>and<i>Fgr</i>in Ovarian Carcinoma
Authors: Hye-Sun Kim, Hee Dong Han, Guillermo N. Armaiz-Pena, Rebecca L. Stone, Eun Ji Nam, Jeong-Won Lee, Mian M. K. Shahzad, Alpa M. Nick, Sun Joo Lee, Ju-Won Roh, Masato Nishimura, Lingegowda S. Mangala, Justin Bottsford-Miller, Gary E. Gallick, Gabriel Lopez-Berestein, Anil K. Sood
Journal: Clinical Cancer Research (2011)

Src is an attractive target because it is overexpressed in a number of malignancies, including ovarian cancer. However, the effect of Src silencing on other Src family kinases (SFKs) is not known. We hypothesized that other SFK members could compensate for the lack of Src activity.Cell viability after either Src or Fgr silencing was examined in ovarian cancer cell lines by MTT assay. Expression of SFKs after Src silencing in ovarian cancer cells was examined by real-time reverse transcriptase (RT)-PCR. Therapeutic effect of in vivo Src and/or Fgr silencing was examined using siRNA incorporated into chitosan nanoparticles (siRNA/CH-NP). Microvessel density, cell proliferation, and apoptosis markers were determined by immunohistochemical staining in ovarian tumor tissues.Src silencing enhanced cytotoxicity of docetaxel in both SKOV3ip1 and HeyA8 cells. In addition, Src silencing using siRNA/CH-NP in combination with docetaxel resulted in significant inhibition of tumor growth compared with control siRNA/CH-NP (81.8% reduction in SKOV3ip1, P = 0.017; 84.3% reduction in HeyA8, P < 0.005). These effects were mediated by decreased tumor cell proliferation and angiogenesis, and increased tumor cell apoptosis. Next, we assessed the effects of Src silencing on other SFK members in ovarian cancer cell lines. Src silencing resulted in significantly increased Fgr levels. Dual Src and Fgr silencing in vitro resulted in increased apoptosis that was mediated by increased caspase and AKT activity. In addition, dual silencing of Src and Fgr in vivo using siRNA/CH-NP resulted in the greatest reduction in tumor growth compared with silencing of either Src or Fgr alone in the HeyA8 model (68.8%, P < 0.05).This study demonstrates that, in addition to Src, Fgr plays a biologically significant role in ovarian cancer growth and might represent an important target.
Order of Roentgenographic Examinations-Reply
Authors: Roscoe E. Miller
Journal: JAMA (1977)

In Reply.—  Ms Chancy's letter raises important questions and states some common misconceptions. My answer was based on extensive experience, not only in this country but in Sweden, Holland, England, and Japan. I have studied and performed gastrointestinal examinations in all of these places.  As for the relation of the barium enema to the upper gastrointestional examination, I quote from Margulis and Goldberg. 1 In many instances the upper gastrointestinal examination is done before the barium enema examination when the large bowel is not obstructed clinically or radiologically. Seemingly, this type of approach is easier on the patient as rigorous preparation of the colon is necessary only once. This sequence also facilitates a meticulous preparation of the colon. It allows inpatients more time for a clear liquid or low residue diet and for administration of cleansing enemas. Residual barium in the colon from the upper gastrointestinal examination is easily seen
Any questions: Why does HIV infection progress to AIDS?
Authors: B. Gazzard
Journal: BMJ (1997)

The answer to this deceptively simple question has aroused controversy,1 much of it clarified recently. From the beginning of the epidemic it was clear that progression to AIDS was marked by the development of opportunistic infections or tumours, associated with immunological failure and T4 cell lymphocyte depletion. Overwhelming epidemiological evidence showed that a retrovirus, …