tbuckley/cabot-search huggingface dataset:
Prevalence of <i>TMPRSS2-ERG</i> Fusion Prostate Cancer among Men Undergoing Prostate Biopsy in the United States
Authors: Juan-Miguel Mosquera, Rohit Mehra, Meredith M. Regan, Sven Perner, Elizabeth M. Genega, Gerri Bueti, Rajal B. Shah, Sandra Gaston, Scott A. Tomlins, John T. Wei, Michael C. Kearney, Laura A. Johnson, Jeffrey M. Tang, Arul M. Chinnaiyan, Mark A. Rubin, Martin G. Sanda
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Fusion of the TMPRSS2 prostate-specific gene with the ERG transcription factor is a putatively oncogenic gene rearrangement that is commonly found in prostate cancer tissue from men undergoing prostatectomy. However, the prevalence of the fusion was less common in samples of transurethral resection of the prostate from a Swedish cohort of patients with incidental prostate cancer followed by watchful waiting, raising the question as to whether the high prevalence in prostatectomy specimens reflects selection bias. We sought to determine the prevalence of TMPRSS2-ERG gene fusion among prostate-specific antigen–screened men undergoing prostate biopsy in the United States. Experimental Design: We studied 140 prostate biopsies from the same number of patients for TMPRSS2-ERG fusion status with a fluorescent in situ hybridization assay. One hundred and thirty-four samples (100 cancer and 34 benign) were assessable. Results: ERG gene rearrangement was detected in 46% of prostate biopsies that were found to have prostate cancer and in 0% of benign prostate biopsies (P &amp;lt; 0.0001). Evaluation of morphologic features showed that cribriform growth, blue-tinged mucin, macronucleoli, and collagenous micronodules were significantly more frequent in TMPRSS2-ERG fusion–positive prostate cancer biopsies than gene fusion–negative prostate cancer biopsies (P ≤ 0.04). No significant association with Gleason score was detected. In addition, non-Caucasian patients were less likely to have positive fusion status (P = 0.02). Conclusions: This is the first prospective North American multicenter study to characterize TMPRSS2-ERG prostate cancer prevalence in a cohort of patients undergoing needle biopsy irrespective of whether or not they subsequently undergo prostatectomy. Our results show that this gene rearrangement is common among North American men who have prostate cancer on biopsy, is absent in benign prostate biopsy, and is associated with specific morphologic features. These findings indicate a need for prospective studies to evaluate the relationship of TMPRSS2-ERG rearrangement with clinical course of screening-detected prostate cancer in North American men, and a need for the development of noninvasive screening tests to detect TMPRSS2-ERG rearrangement.
Kevorkian and assisted death in the United States
Authors: H. Brody
Journal: BMJ (1999)

Retired pathologist Jack Kevorkian's assistance in the suicide of Janet Adkins, in June of 1990, did more than any other single action to make assisted suicide a hot button issue in the United States. Ironically, Dr Kevorkian's conviction last month on charges of second degree murder in Pontiac, Michigan, will probably have little if any impact on the further progress of the American assisted suicide “movement.”

Already acquitted by juries three times on charges of assisting suicides, Kevorkian's actions this time led armchair psychiatrists to conclude that the self proclaimed “Dr Death” must have had his own death wish. He escalated his practice from assisting suicide to direct mercy killing in the case of Thomas Youk, who suffered from amyotrophic lateral sclerosis. He prepared a video showing his every action and the exact moment of Youk's death, and appeared with the video on a national television news programme, daring the authorities to prosecute him. Brought to trial on murder charges, he insisted on representing himself in court—a task for which he was woefully unprepared, as was shown by the judge's refusal to allow the testimony from Youk's family, which Kevorkian was sure would win him the …
Prognosis in obesity: Obesity in severe mental illness poses particular problems
Authors: Paul Mackin, Allan H Young
Journal: BMJ (2005)

Prognosis in obesity Older people should not be misinformed about being overweightEditor-With reference to the editorial by Lean on prognosis in obesity, 1 advising apparently overweight older people to lose weight may do more harm than good.Evidence suggests that the risks of being "overweight" decrease with increasing age.On the basis of mortality, the ideal body mass index (BMI) is higher in older than young adults, with an optimum BMI for people older than 65 in the young adult "overweight" range of 27-30 kg/m 2 . 2 In a systematic review, Heiat et al concluded that the relation between BMI and mortality in people older than 65 is a flat bottomed, Ushaped curve, with mortality rising only at BMI > 31 kg/m 2 and perhaps not at any BMI in people older than 75. 2 Weight loss is more common than weight gain in older people, and associated with poor outcomes, even when the weight loss is intentional and the person was "overweight" at baseline. [3]4][5] In the prospective cardiovascular health study of some 4700 community dwelling people older than 65, weight loss of more than 5% over three years was substantially more common than weight gain of more than 5%. 3 Weight loss, but not weight gain, was associated with a significantly increased risk of mortality (relative risk 1.67, 95% confidence interval 1.29 to 2.15). 3 The association of increased mortality with weight loss persisted even at the highest third of baseline weight. 3 In a study of older men with BMI ≥ 30 kg/m 2 , intentional weight loss was associated (P < 0.001) with a greater rate of hip bone loss ( -1.7%/year) than in men with no weight loss ( -0.1%/year) or weight gain (0.5%/year). 5 The indiscriminate application of evidence from studies in younger adults to the management of older people is hazardous.We believe that many older people are trying to lose weight inappropriately.There is a need to ensure that most of our elders are given appropriate advice: "Keep physically active, eat sensibly, and maintain weight."
Heterogeneous distribution of a diffusional tracer in the aortic wall of normal and atherosclerotic rabbits.
Authors: H Tsutsui, H Tomoike, M Nakamura
Journal: Circulation Research (1990)

Tracer distribution as an index of nutritional support across the thoracic and abdominal aortas in rabbits in the presence or absence of atherosclerotic lesions was evaluated using [14C]antipyrine, a metabolically inert, diffusible indicator. Intimal plaques were produced by endothelial balloon denudation of the thoracic aorta and a 1% cholesterol diet. After a steady intravenous infusion of 200 microCi of [14C]antipyrine for 60 seconds, thoracic and abdominal aortas and the heart were excised, and autoradiograms of 20-microns-thick sections were quantified, using microcomputer-aided densitometry. Regional radioactivity and regional diffusional support, as an index of nutritional flow estimated from the timed collections of arterial blood, was 367 and 421 nCi.g-1 (82 and 106 ml.min-1.100 g-1) in thoracic aortic media of the normal and atherosclerotic rabbits, respectively. Radioactivity at the thickened intima was 179 nCi.g-1 (p less than 0.01 versus media). The gruel was noted at a deeper site within the thickened intima, and diffusional support here was 110 nCi.g-1 (p less than 0.01 versus an average radioactivity at the thickened intima). After ligating the intercostal arteries, regional tracer distribution in the media beneath the fibrofatty lesion, but not the plaque-free intima, was reduced to 46%. Thus, in the presence of advanced intimal thickening, the heterogeneous distribution of diffusional flow is prominent across the vessel wall, and abluminal routes are crucial to meet the increased demands of nutritional requirements.
CHALICOSIS PULMONUM OR CHRONIC INTERSTITIAL PNEUMONIA INDUCED BY STONE DUST.
Authors: WM. WINTHROP BETTS
Journal: JAMA (1900)

The advent of the cyanid process of milling makes it possible to treat large bodies of low grade ore that previously could not be handled at a profit. This involved new methods of milling and taxed the ingenuity and inventive genius of the promoters. The transition has forced the expenditure of large sums of money and involved certain loss of human life by exaggerating old causes of danger. Many of these milling plants are springing up in the mining districts of the west, all involving more or less the same difficulties, but in order to make my investigations of a scientific value I must necessarily study the history of a single plant. I, therefore, desire to report the observations and experience of myself and friends among the workers of such a plant, also to call your attention to the greatly increased rate of mortality among the employees, induced by the
Global and regional left ventricular function and tomographic radionuclide perfusion: the Western Washington Intracoronary Streptokinase In Myocardial Infarction Trial.
Authors: J L Ritchie, K B Davis, D L Williams, J Caldwell, J W Kennedy
Journal: Circulation (1984)

The Western Washington Intracoronary Streptokinase In Myocardial Infarction Trial enrolled 250 patients with acute myocardial infarction. After the coronary angiographic diagnosis of thrombosis, patients were randomly assigned to receive either conventional therapy with heparin or intracoronary streptokinase followed by heparin. Of the 232 patients who survived at least 60 days, 207 (89%) underwent radionuclide ventriculographic determination of global and regional ejection fraction at a single institution at 62 +/- 35 days after infarction. In the first 100 patients, infarct size was also determined by quantitative single-photon emission tomographic imaging with thallium-201 (201Tl) and expressed as a percentage of the left ventricle with a perfusion defect. Overall, global ejection fraction did not differ between patients treated with streptokinase (45.9 +/- 13.9%; n = 115) and control patients (46.1 +/- 14.4%; n = 92, p = NS). Similarly, the regional posterolateral, inferior, and anteroseptal ejection fraction did not differ between the two groups. Infarct size as measured by 201Tl tomography was 19.4 +/- 12.8% (n = 52) of the left ventricle for the streptokinase group and 19.6 +/- 11.8% (n = 48; p = NS) for the control group. When patients were compared within groups by electrocardiographic location of infarction, time to treatment, or the presence or absence of vessel opening, there were no significant differences between streptokinase and control patients. Statistical inclusion of the 18 patients who died early and were unavailable for study also failed to modify the results, except for a possible reduction in inferior infarct size as measured by 201Tl tomography.(ABSTRACT TRUNCATED AT 250 WORDS)
Heartbroken, not heartsink
Authors: Ruth Booker
Journal: BMJ (2006)

From the start our relationship was an uneasy one. As a young GP, I struggled to cope with this prickly, querulous woman who treated me with an air of irritated disapproval and deep dissatisfaction. Nothing pleased her, and whatever I did was wrong. Despite my best efforts, little changed as time passed, and the sight of her name on my appointment list became a heartsink moment. However, we battled on together—I wary and cautious, she imperious and demanding, both equally unsatisfied.

It was perhaps 10 years later that my partners and I were trying to improve the quality …
Transitional Cell Carcinoma in Dialysis Patients
Authors: Jiann-Hui Ou, Cheng-Chin Pan, Johnny Shinn-Nan Lin, Tzong-Shin Tzai, Wen-Horng Yang, Chien-Chen Chang, Hong-Lin Cheng, Yung-Ming Lin, Yat-Ching Tong
Journal: European Urology (2000)
Points from Letters: Toxaemia and Intravascular Coagulation
Authors: J. Sophian
Journal: BMJ (1970)

further "dram" before entering the ambulance.On admission he was confused and in pain with noticeably cold extremities.Oral temperature was 97' F. (36' C.).Blood pressure 140/80, pulse 72 and small volume.The abdomen was distended and diffusely tender.There was some guarding, and bowel sounds were faint and infrequent.The pupils were unequal, moderately dilated, and did not react to light.Tendon jerks were brisk and the plantar responses flexor.Urine: some albumin and trace of acetone, but no sugar.Blood pH 7-08, Pco2
Effect of long-term therapy with fasidotril, a mixed inhibitor of neprilysin and angiotensin-converting enzyme (ACE), on survival of rats after myocardial infarction
Authors: C Marie
Journal: Cardiovascular Research (1999)

Objective: Two hormonal systems with opposite effects are activated in congestive heart failure: the renin–angiotensin system that promotes vasoconstriction, cardiac hypertrophy and salt retention, and the atrial natriuretic factor (ANF), which has vasorelaxant and natriuretic effects. It could be of therapeutic interest to associate prevention of angiotensin II formation, by inhibition of angiotensin I-converting enzyme (ACE), with potentiation of the ANF effects, by inhibition of neprilysin (NEP). Methods: The effects of long-term therapy with fasidotril, a mixed NEP/ACE inhibitor, were assessed in rats submitted to coronary artery ligation. Twenty-four hours after ligation, 172 rats were assigned to either placebo or fasidotril therapy (180 mg/kg/day, orally) for 40 weeks. The date of spontaneous death was recorded, myocardial infarct size was determined and rats were classified as having small, moderate or large infarcts. Results: In rats with moderate infarcts, fasidotril prolonged survival, 50% of the control rats dying during the 40-week observation period compared with 30% of treated rats (P=0.04, log-rank test)). In rats with large infarcts, mortality was significantly reduced during the initial 25 weeks of therapy, during which 23.5% of animals died compared to 53.8% in untreated rats (P=0.015). Cardiac hypertrophy was significantly attenuated by fasidotril for the three infarct sizes. Plasma renin activity was not increased by therapy, which presumably reflected the inhibition of renal renin secretion by endogenous ANF. Fasidotril therapy had no significant effects on arterial blood pressure and heart rate. Conclusion: In addition to its beneficial effects on survival and cardiac hypertrophy, the lack of hypotensive effect of fasidotril is of interest by reducing the risk of renal hypoperfusion and differentiates the mixed inhibitor from selective ACE inhibitors.
Association of Insurance with Cancer Care Utilization and Outcomes
Authors: E. Ward, M. Halpern, N. Schrag, V. Cokkinides, C. DeSantis, P. Bandi, R. Siegel, A. Stewart, A. Jemal
Journal: CA A Cancer Journal for Clinicians (2008)

Advances in the prevention, early detection, and treatment of cancer have resulted in an almost 14% decrease in the death rates from all cancers combined from 1991 to 2004 in the overall US population, with remarkable declines in mortality for the top 3 causes of cancer death in men (lung, colorectal, and prostate cancer) and 2 of the top 3 cancers in women (breast and colorectal cancer). However, not all segments of the population have benefited equally from this progress, and evidence suggests that some of these differences are related to lack of access to health care. Lack of adequate health insurance appears to be a critical barrier to receipt of appropriate health care services. This article provides an overview of systems of health insurance in the United States, demographic and socioeconomic characteristics associated with health insurance coverage, and economic burdens related to health care among individuals and families. This article also presents data on the association between health insurance status and screening, stage at diagnosis, and survival for breast and colorectal cancer based on analyses of the National Health Interview Survey and the National Cancer Data Base. Although this article focuses on associations between health insurance and cancer care utilization and outcomes, it is important to recognize that barriers to receipt of optimal cancer care are complex and involve patient-level, provider, and health system factors. Evidence presented in this paper suggests that addressing insurance and cost-related barriers to care is a critical component of efforts to ensure that all Americans are able to share in the progress that can be achieved by access to high-quality cancer prevention, early detection, and treatment services.
Zinc state in anorexia nervosa.
Authors: C C Ainley, J Cason, L Carlsson, R P Thompson, B M Slavin, K R Norton
Journal: BMJ (1986)

Hypothyroidism after treatment with ketoconazole I report on two patients, a father and his son, who both developed hypothyroidism after treatment with ketoconazole. Case1This patient, a 40 year old white man, had had severe chronic mucocutaneous candidiasis since the age of 5.The diagnosis had been confirmed by nail biopsy, and he had subsequently remained infected in the mouth, pharynx, larynx, oesophagus, and nails despite numerous and varied treatments, includig treatment with vitamin B complex, dilute hydrochloric acid, and sodium thiosulphate in the 1950s; with dequalinium chloride paint, nystatin, ampho- tericin lotion andlozenges, and polynoxylin in the 1960s; and with intramuscular iron, clotrimazole, flucytosine, and miconazole in the 1970s.All of these treatments had been stopped because they were either ineffective or toxic.In May 1982 he was given ketoconazole 200 mg orally twice daily, which
Serum Cholesterol and Death From Coronary Heart Disease-Reply
Authors: Jeremiah Stamler
Journal: JAMA (1987)

<h3>In Reply.—</h3> In reply to Dr Burch, to estimate ability to reduce coronary death rates in different age groups by control of established major risk factors, one needs age-specific data on the numbers of people in the population with these risk factors (ie, their<i>prevalence rates</i>) and age-specific data on<i>absolute excess risks</i>(ie,<i>differences</i>in coronary death rates between population subgroups with and without risk factors); relative risks do not suffice. Here are two estimates, one for serum cholesterol and one for systolic pressure, from the age-specific data on the 356 222 MRFIT primary participants: For the subgroups with serum cholesterol levels of 182 mg/dL (4.71 mmol/L) or more and 181 mg/dL (4.68 mmol/L) or less, six-year coronary death rates increased markedly with age, from 184.0 and 59.2 per 100000, respectively, for men aged 35 to 39 years at baseline to 1535.9 and 830.9, respectively, for men aged
Sustained 3-year efficacy of pre- and coseasonal 5-grass-pollen sublingual immunotherapy tablets in patients with grass pollen–induced rhinoconjunctivitis
Authors: Alain Didier, Margitta Worm, Friedrich Horak, Gordon Sussman, Olivier de Beaumont, Martine Le Gall, Michel Melac, Hans-Jorgen Malling
Journal: Journal of Allergy and Clinical Immunology (2011)
325 HEPATITIS B VIRUS X GENE-UPREGULATED GENE 4 INDUCES CELL PROLIFERATION AND PROMOTES TUMORIGENICITY IN HUMAN HEPATOCELLULAR CARCINOMA THROUGH DOWNREGULATION OF FOXO3A
Authors: C. Xie, J. Li, J.-H. Wu, L.-B. Song, D.-Y. Xie, B.-L. Lin, M.-F. Li, Z.-L. Gao
Journal: Journal of Hepatology (2012)
Intramural esophageal dissection resolved by endoscopic treatment
Authors: E. Kim, B. Keum, Y. Seo, Y. Jeen, H. Chun, S. Um, C. Kim, H. Ryu, J. Hyun
Journal: Endoscopy (2009)

Intramural esophageal dissection (IED) is a longitudinal separation between the submucosa and muscular layers of the esophagus without perforation [1]. We report a case of long-segment IED that was successfully treated with an endoscopic cap and hook-knife.
1184 CHARACTERIZATION OF HCV VARIANTS IN GENOTYPE 1 TREATMENT-NAIVE PATIENTS ADMINISTERED THE COMBINATION OF TVR AND VX-222 IN DUAL ARMS OF ZENITH STUDY
Authors: E.Z. Zhang, A. Tigges, M. Jiang, J. Dorrian, J. Spanks, A. Ardzinski, K. Alves, C. De Souza, D.J. Bartels, M.J. Koziel, A.M. Di Bisceglie, T.L. Kieffer
Journal: Journal of Hepatology (2012)
Abstract P2-09-07: Inhibition of aurora-A by MLN8237 decreases SMAD5 expression and increases effectiveness of chemotherapeutic agents in breast cancer cells
Authors: M Opyrchal, I Iankov, JN Ingle, E Galanis, AB D'Assoro
Journal: Cancer Research (2013)

Abstract BACKGROUND: Breast cancer affects thousands of women each year. Epithelial to Mesenchymal transition (EMT) has been associated with increased metastatic potential of cancer cells as well as resistance to chemotherapy. Predicatively, presence of EMT leads to worse prognosis in patients with breast cancer. We have recently showed that Aurora-A plays a key role in development of EMT and increased ability of breast cancer cells for self renewal. Therefore we hypothesized that inhibition of Aurora-A in breast cancer cells will lead to increased sensitivity to chemotherapy. RESULTS: Increased Aurora-A expression, as assessed by IHC staining, in patients with locally advanced disease was associated with worse prognosis. We show that in ER+ cell line, MCF7, activating MAPK pathway through overexpression of Raf1 leads to increase in Aurora-A activity. These cells have decreased sensitivity to treatment with paclitaxel when compared to untransfected cells in MTT assays. This effect is even more exacerbated with over-expression of Aurora-A. The sensitivity to paclitaxel was restored with inhibition of Aurora-A by specific inhibitor, Alisertib. This was further explored in triple negative (MDA-MB-231) or Her-2/neu expressing (SUM149) cell lines. These cells express higher levels of Aurora-A. Inhibition of Aurora-A activity in combination with paclitaxel was superior when compared to either therapy alone. Similar effect was seen with use of anthracyclines. Inhibition of Aurora-A resulted in decreased SMAD5 expression as well as decreased Akt phosphorylation. Current studies are looking at a role of Aurora-A in activating SMAD5 and its role in resistance to chemotherapy. In vivo experiments evaluating combination therapies in breast cancer animal model are ongoing. CONCLUSIONS: Inhibition of Aurora-A by a specific inhibitor, MLN8237, resulted in decreased SMAD5 expression and increased effectiveness of chemotherapeutic agents in breast cancer cells. These results contribute to better understanding of signaling pathways involved in resistance of breast cancer cells to chemotherapy. This knowledge could be very useful in developing more effective treatments for breast cancer patients in neo-adjuvant, adjuvant and metastatic settings. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-09-07.
The Risks of "Massage."
Authors: J. Althaus
Journal: BMJ (1883)

had been amputated, and in each instance the disease had recurred in the stump.The patient' was admitted into the hospital-under Mr. Heath, and both feet were eventually amputated.A microscopic examination of the nerves from both feet was made by Mr. Priestley (Lamncet, 1883, vol.i, page 452), and in each instance he found well- marked evidence of sclerosis. MFl;In this case, which has now been in progress for six years, and which is still under observation as an out-patient, there has never, from first to last, been any evidence of locomotor ataxy.The changes here found in the peripheral nerves resemble very closely those met with in a case recorded by vol.lxii, Case v, page 378).Almost iden- tical cases have also been described by other writers; so that it appears probable that perforating ulcer may, in some cases, be dependent simply on disease of the peripheral nerves, without any apparent implication of the nerve-centres.Of course, it is quite possible that, in cases of this kind, symptoms of central disease (e.g., of locomotor ataxy) may eventually develop themselves ; but, in Case IV, six years have now elapsed, and as yet no indications of the onset of that condition are present.