tbuckley/cabot-search huggingface dataset:
Abstract A32: A urinary mRNA profile to increase the specificity of PSA and reduce the number of unnecessary biopsies
Authors: Marina Rigau, Tatiana Altadill, Andreas Doll, Tamara Sequeiros, Mireia Olivan, Marta Garcia, Alex Sanchez, Melania Montes, Israel Ortega, Juan Morote, Jaume Reventos
Journal: Cancer Research (2012)

Abstract Background: Several studies have demonstrated the usefulness of monitoring an RNA transcript, such as PCA3, in post-prostate massage (PM) urine for increasing the specificity of prostate-specific antigen (PSA) in the detection of prostate cancer (PCa). However, a single marker may not necessarily reflect the multifactorial nature of PCa. Methods: We analyzed post-PM urine samples from 154 consecutive patients, who presented for prostate biopsies because of elevated serum PSA (&amp;gt;4 ng/ml) and/or abnormal digital rectal exam. We tested whether the putative PCa biomarkers PSMA, PSGR, and PCA3 could be detected by quantitative real-time PCR in post-PM urine sediment. We combined these findings with PSAD to test if a combination of these biomarkers could improve the specificity of actual diagnosis. Afterwards, we specifically tested our model for clinical usefulness in the PSA diagnostic “gray zone” (4–10 ng/ml) on a target subset of 82 men with no prior biopsy. Results: By univariate analysis, we found that the PSMA, PSGR, PCA3 and PSAD scores were significant predictors of PCa. Using a multiplex model, the area under the multireceiver operating characteristic curve was 0.80 versus 0.89 in the diagnostic gray zone. Fixing the sensitivity at 96%, we obtained a specificity of 40% and 62% in the gray zone. By this approach it would be possible to save approximately 35% of unnecessary biopsies with a sensitivity of 95%. Conclusions: Taken together, these results provide a strategy for the development of a more accurate model for PCa diagnosis. In the future, a multiplexed, urine-based diagnostic test for PCa with a higher specificity, but the same sensitivity as the serum-PSA test, could be used to determine better which patients should undergo biopsy. Citation Format: Marina Rigau, Tatiana Altadill, Andreas Doll, Tamara Sequeiros, Mireia Olivan, Marta Garcia, Alex Sanchez, Melania Montes, Israel Ortega, Juan Morote, Jaume Reventos. A urinary mRNA profile to increase the specificity of PSA and reduce the number of unnecessary biopsies [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr A32.
Managing acute appendicitis
Authors: I. S Benjamin
Journal: BMJ (2002)

Early appendicectomy was first recommended and performed for non-perforated acute appendicitis in the 1880s. The operation remains the most common in the Western world, accounting for a million hospital days per year in the United States.1 Despite more than 100 years' experience, accurate diagnosis still evades the surgeon, and avoiding perforation and subsequent complications must be weighed against removal of a normal appendix in patients with other causes of abdominal pain—a “negative” appendicectomy—which has a rate as high as 20%.2 This is not a trivial problem. Flum and Koepsell assessed its impact in the United States—length of stay, rate of complications, and mortality (1.5% v 0.2%) were all significantly higher in the negative appendicectomy group, and the annual cost of a negative appendicectomy was calculated at $742m.3

The use of an objective scoring system such as the Alvarado system can reduce the negative appendicectomy rate to 0-5%.4The simple expedient of close observation and repeated re-evaluation has in itself been shown in several studies to reduce …
Flavonoids and heart disease
Authors: M. F Muldoon, S. B Kritchevsky
Journal: BMJ (1996)

linkage.Until recently, for example, the cause of Young's syndrome remained obscure.Young's syndrome occurs in men with bronchiectasis and is characterised by azoospermia due to epididymal obstruction.16No link has been found with mutations of the cystic fibrosis gene.18The syndrome was particularly prevalent in Britain and Australia between 1960 and 198016 but is now rarely seen.17In 1993 Hendry et alnoted that many men with Young's syndrome had a history of Pink's disease in infancy.18Pink's disease disappeared around 1960 with the removal of mercury from teething powders, and the disappearance ofYoung's syndrome some 30 years later raises the strong possibility that exposure to mercury in infancy may have caused both Pink's disease and Young's syndrome through mechanisms yet to be elucidated.Such examples, and our growing understanding of the vulnerability of the male reproductive system to environmental factors, highlight the need for vigilance.Regulatory and research agencies need to determine the most appropriate methods of assessing the actions of agents on the reproductive system, and should undertake whatever studies are necessary to confirm or refute the emerging hypotheses.Delay may compromise the fertility offuture generations.
Effects of normal and sickle erythrocytes on prostacyclin release by perfused human umbilical cord veins
Authors: Samuel O. Sowemimo‐Coker, L. Julian Haywood, Herbert J. Meiselman, Robert B. Francis
Journal: American Journal of Hematology (1992)

Abstract We compared the effects of normal (AA) and sickle (SS) erythrocytes (RBC) on endothelial cell release of prostacyclin by perfused human umbilical cord veins. Two equal‐length segments of fresh umbilical cords were perfused first with serum‐free Dulbecco's modified Eagle's medium (DMEM) to establish the basal prostacyclin production rate for each segment; then one segment was perfused with SS RBC and/or plasma, while the other segment was simultaneously perfused with AA RBC and/or plasma. Aliquots of perfusate were removed at intervals for measurement of the stable prostacyclin metabolite 6‐ketoprostaglandin F 1α (6‐keto‐PGF). Basal prostacyclin production by segments from the same cord was very similar, but it varied considerably among segments from different cords. Therefore, the ratio of prostacyclin release with RBC and/or plasma to basal prostacyclin release for each segment was used to compare prostacyclin release among segments from different cords. Mean prostacyclin release was significantly higher from segments perfused with SS RBC in autologous plasma than from segments perfused with AA RBC in autologous plasma at 15, 30, and 60 min. However, no significant differences in mean prostacyclin production were observed between segments perfused with SS vs. AA RBC in DMEM or between segments perfused with SS vs. AA plasma alone. No significant correlations were observed between prostacyclin production and either the viscosity of SS and AA RBC in autologous plasma or DMEM or the adhesiveness of SS and AA RBC to cultured human umbilical vein endothelial cells. We conclude that SS RBC in autologous plasma cause increased prostacyclin release from perfused human umbilical cord veins. The perfused human umbilical cord vein system may be a useful model for comparing the response of vascular endothelium to SS and AA RBC and plasma under controlled‐flow conditions. © 1992 Wiley‐Liss, Inc.
48 hours of cisatracurium reduced 90-day mortality in patients with early, severe ARDS
Authors: Jonathan Sevransky
Journal: Annals of Internal Medicine (2011)

ACP Journal Club18 January 201148 hours of cisatracurium reduced 90-day mortality in patients with early, severe ARDSJonathan Sevransky, MDJonathan Sevransky, MDJohns Hopkins University, Baltimore, Maryland, USA (J.S.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-154-2-201101180-02003 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationPapazian L, Forel JM, Gacouin A, et al. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med. 2010;363:1107-16. https://pubmed.ncbi.nlm.nih.gov/20843245Clinical Impact RatingsCritical Care: Pulmonology: References1 Schweickert WD, Pohlman MC, Pohlman AS, et al. Early physical and occupational therapy in mechanically ventilated, critically ill patients: a randomised controlled trial. Lancet. 2009;373:1874-82. [PMID: 19446324] Google Scholar2 De Jonghe B, Sharshar T, Lefaucheur JP, et al. Paresis acquired in the intensive care unit: a prospective multicenter study. JAMA. 2002;288:2859-67. [PMID: 12472328] Google Scholar Author, Article, and Disclosure InformationAuthors: Jonathan Sevransky, MDAffiliations: Johns Hopkins University, Baltimore, Maryland, USA (J.S.)This article was published at Annals.org on 4 January 2011. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 18 January 2011Volume 154, Issue 2Page: JC1-3KeywordsAcute respiratory distress syndromeCritical careIntensive care unitsMortalityRespiratory system proceduresSedationSedativesSimplified acute physiology scoreTidal volumeVentilators ePublished: 18 January 2011 Issue Published: 18 January 2011 Copyright & PermissionsCopyright © 2011 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Unanswered questions on ectopic pregnancy.
Authors: E G Jonas
Journal: BMJ (1980)

In a previous article (3 May, p. 1127), the British Medical Journal attempted to assess the demography of ectopic pregnancy and noted that a rise in incidence might lead to a better diagnosis of the condition. Cited as possible causes of ectopic pregnancy are pelvic sepsis and IUD usage. There is clinical confirmation of the relationship between pelvic sepsis and IUD usage. A review of the records of 325 consecutive patients diagnosed as having ectopic pregnancy in 4 large London Hospitals during the period 1967-79 revealed that PID (Pelvic Inflammatory Disease) was uncommon (11%). 12% of the remaining patients had IUDs and a further 2% were progestogen-only contraceptive failures. As regards the role of IUDs in ectopic pregnancy, failed intrauterine contraception is hypothesized to result in pregnancy, but with an incidence of ectopic, mainly tubal, implantation by reasons of disturbed ovum migration along the oviduct. The physiology of the human oviduct is not well known. Further research should be done on the many common aberations of human reproduction, iatrogenic and spontaneous.
Influence of Dietary Protein Intake on Whole-Body Protein Turnover in Humans
Authors: Peter J Garlick, Margaret A McNurlan, Peter E Ballmer
Journal: Diabetes Care (1991)

Methods for measuring rates of protein synthesis and degradation in the whole body of humans with isotopes of carbon and nitrogen are described and attention is drawn to their relative merits and drawbacks for studying the nutritional control of protein metabolism. A review of published work on dietary protein and protein metabolism leads to the conclusion that protein is the major dietary determinant of whole-body protein turnover rates, and that energy intake is comparatively unimportant. Dietary protein affects protein turnover at two levels: an immediate response to the intake of protein in meals and a longer-term adaptation after a change in protein intake. An increase in the level of dietary protein enhances the response to meals, which mainly consists of a decrease in the rate of protein degradation. The adaptation to higher protein intakes involves an increase in the basal (postabsorptive) rates of both synthesis and degradation. Suggestions for future investigation include more detailed studies of the acute and adaptive responses, to facilitate understanding of dietary protein requirements, and the effects of very-high-protein intakes with continued development of techniques for studying protein turnover in individual tissues in humans.
Abstract 462: Chromatin signatures of DLBCL subtypes
Authors: Ron McCord, Megan Field, Philip Jordan, Ewan Hunter, Alexandre Akoulitchev, Kirsten E. Mundt
Journal: Cancer Research (2014)

Abstract Diffuse Large B-cell Lymphoma (DLBCL) is a common and aggressive type of Non-Hodgkin's Lymphoma. Gene expression profiling long ago identified two distinct subtypes: Activated B-Cell (ABC) and Germinal Center B-Cell (GCB), reflecting the biology associated with the cell of origin of the lymphoma (Alizadeh et al, Nature 2000). These subtypes are histologically non distinguishable, yet are associated with distinct outcomes. Emerging clinical data also suggests that they are predictive of outcome for novel therapeutics, including a BTK inhibitor, a proteasome inhibitor and an immune modulatory agent. Reliable diagnosis of the DLBLC subtype may therefore become a requirement for choosing the best treatment for DLBCL patients. Since gene regulation is known to be associated with changes in chromatin structures, we decided to investigate the chromatin conformation around key regulators of ABC/ GCB biology using a Chromatin Conformation Capture Assay (3C). For this assay, chromatin loops are cross-linked; the DNA is digested and re-ligated, joining topologically proximal ends that may be very distant along the length of the chromosome into distinct novel fusion products. After reversing the cross-links, the presence of these novel DNA fusions can be detected by PCR, resulting in a binary read-out. Composites of these PCR products form a signature that may be characteristic of disease, disease state or subtype. The EpiSwitchTM technology has been optimized to identify these epigenetic patterns not only in tissue, but also from blood borne tumor DNA. To investigate characteristic changes in chromatin conformation in ABC- and GCB- DLBCL cell lines, we focused on key genes known to be differentially expressed in the two sub-types, including Bcl-6, IRF-4 and LMO-2 (Wright et al. PNAS 2003,). We mapped several interactions indicating that these loci are subject to epigenetic regulation. We also applied the assay to blood from DLBCL patients and from healthy volunteers to exclude background signals from normal B-cell maturation. The assay was able to detect the same signatures as seen in cell lines. These results demonstrate the potential of this technology to detect DLBCL subtype specific chromatin conformation associated biomarkers in patient blood. Citation Format: Ron McCord, Megan Field, Philip Jordan, Ewan Hunter, Alexandre Akoulitchev, Kirsten E. Mundt. Chromatin signatures of DLBCL subtypes. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 462. doi:10.1158/1538-7445.AM2014-462
Country of training and ethnic origin of UK doctors: database and survey studies
Authors: Michael J Goldacre, Jean M Davidson, Trevor W Lambert
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objectives</b> To report on the country of training and ethnicity of consultants in different specialties in the NHS, on trends in intake to UK medical schools by ethnicity, and on the specialty choices made by UK medical graduates in different ethnic groups. <b>Design</b> Analysis of official databases of consultants and of students accepted to study medicine; survey data about career choices made by newly qualified doctors. <b>Setting and subjects</b> England and Wales (consultants), United Kingdom (students and newly qualified doctors). <b>Results</b> Of consultants appointed before 1992, 15% had trained abroad; of those appointed in 1992-2001, 24% had trained abroad. The percentage of consultants who had trained abroad and were non-white was significantly high, compared with their overall percentage among consultants, in geriatric medicine, genitourinary medicine, paediatrics, old age psychiatry, and learning disability. UK trained non-white doctors had specialty destinations similar to those of UK trained white doctors. The percentage of UK medical graduates who are non-white has increased substantially from about 2% in 1974 and will approach 30% by 2005. White men now comprise little more than a quarter of all UK medical students. White and non-white UK graduates make similar choices of specialty. <b>Conclusions</b> Specialist medical practice in the NHS has been heavily dependent on doctors who have trained abroad, particularly in specialties where posts have been hard to fill. By contrast, UK trained doctors from ethnic minorities are not over-represented in the less popular specialties. Ethnic minorities are well represented in UK medical school intakes; and white men, but not white women, are now substantially under-represented.
THE IMMUNIZING POWER OF NUCLEOHISTON AND OF HISTON
Authors: F. O. Novy
Journal: The Journal of Experimental Medicine (1896)

THE RESULTS OBTAINED IN THE PRECEDING EXPERIMENTS MAY BE BRIEFLY SUMMARIZED AS FOLLOWS: 1. Nucleohiston does not protect against a separate and subcutaneous injection of tetanus toxin, diphtheria toxin, hog-cholera bacillus, or anthrax bacillus. 2. Mixtures of nucleohiston and either tetanus toxin or diphtheria toxin lose their specific toxic action-the latter much more rapidly than the former. Animals that recover after inoculation of such mixtures are not rendered immune. 3. In a mixture of nucleohiston and anthrax bacillus the latter is unaffected, even after the lapse of eleven days. 4. The destruction of specific toxins in a solution of nucleohiston, though in part due to sodium carbonate, is probably chiefly due to the nucleohiston. 5. Histon does not protect against a separate and subcutaneous injection of tetanus toxin, diphtheria toxin, hog-cholera bacillus, or anthrax bacillus. 6. In a mixture of histon and diphtheria toxin the latter is destroyed in a few minutes. This action is in part, if not wholly, due to the acidity of the histon solution. Similar mixtures of closely related bodies, serum globulin or albumoses, in Witte's pepton, give analogous results. The animals that recover from such inoculations are not rendered immune. Histon does not destroy the tetanus toxin as readily as the diphtheria toxin. 7. Histon possesses decided and marked toxic properties which are not due to the hydrochloric acid present.
FOUR CASES OF MALARIA ASSOCIATED WITH ACUTE ABDOMINAL PAIN.
Authors: JOSEPH A. CAPPS
Journal: JAMA (1900)

For the privilege of reporting the following cases from the wards of the Massachusetts General Hospital, I am indebted to Dr. E. S. Cutler, of the visiting staff. <h3>Case 1.</h3> —A married woman of 25 years, living in Arlington, Mass., entered the hospital July 14, 1896. Her father died of pulmonary tuberculosis. Catamenia was always normal. She has one healthy child. Until recently her health had been excellent, with no history of malarial fever nor any of pelvic disease. For three weeks she had not felt as well as usual, and for ten days had suffered from malaise, headache, occasional vomiting, chilly feelings and backache. During the preceding five days she had been confined to bed with daily fever. Two days before admission, upon attempting to walk, she was taken with a chill and vomiting, accompanied by severe pain in the lower abdomen. Since then all food had caused a
Carbon-monoxide Encephalopathy
Authors: E. B. Gordon
Journal: BMJ (1965)

Neuropsychiatric sequelae of carbon-monoxide poisoning are now well documented.A recent Lancet annotation (1962) referred, however, to the less-well-recognized occurrence of postanoxic encephalopathy after a period of apparent clinical recovery ; a series of five such cases reported by Plum et al.(1962) is quoted.The present case provides a further example of delayed neurological and psychiatric effects of coal-gas poisoning; it demonstrates in addition the occurrence of temporary clinical improvement.
A Survey of Clinical Trials of Antibiotic Prophylaxis in Colon Surgery: Evidence against Further Use of No-Treatment Controls
Authors: Mark L. Baum, David S. Anish, Thomas C. Chalmers, Henry S. Sacks, Harry Smith, Richard M. Fagerstrom
Journal: New England Journal of Medicine (1981)

Abstract To evaluate the use of antibiotics given prophylactically in colon surgery, we examined 26 trials published from 1965 to 1980 in which patients given various antibiotic regimens were compared with controls given no antibiotic treatment. In 22 (85 per cent of these trials) antibiotics reduced postoperative wound infection (P<0.05 in 14). Combining the results of the trials published from 1965 to 1975 reveals a 95 per cent confidence interval for the true difference in infection rates of 14±6 per cent (36 per cent for control group vs. 22 per cent for treatment group) and the true difference in death rates of 6.7±4.4 per cent (11.2 per cent for control group vs. 4.5 per cent for treatment group). Yet trials employing control groups given no treatment continue to be reported. Since the use of such controls is justified only when no effective alternative therapy exists, we believe that any further trials of antibiotic prophylaxis in colon surgery should employ a previously proved standard. However, steadily increasing efficacy of treatment means that comparisons of new therapies with standard therapies will become prohibitively expensive because of the large number of patients required. (N Engl J Med. 1981; 305:795–9.)
Hypercatabolism of C3 and C4 in active and inactive systemic lupus erythematosus.
Authors: J A Charlesworth, P W Peake, J Golding, J D Mackie, B A Pussell, V Timmermans, D Wakefield
Journal: Annals of the Rheumatic Diseases (1989)

Rationale: The growing utilization of high-resolution computed tomography (HRCT) for clinical diagnosis and lung cancer screening results in identification of pulmonary nodules of unknown clinical significance. Non-invasive strategies for the individualized management of these lesions are required. In a pilot study we have demonstrated the consistent classification of pulmonary nodules of the adenocarcinoma spectrum using CALIPER. Methods: Two pumonary patholgists independently assessed histopathologic tissue invasion in 72 surgically resected pulmonary nodules (≤ 3cm) of adenocarcinoma spectrum from 68 patients. Based on consensus, all lesions were categorized as either NINV-"non-invasive" (≤5mm invasion), n=6 or INV-"invasive" (&gt;5mm invasion), n=66. CALIPER mapped the individual HRCT voxels (pre-operative HRCT) within all the nodules to one of the previously identified 9 unique radiological patterns. The nodules were categorized as INV or NINV based on the relative distribution of the patterns. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for CALIPER-based detection of tissue invasion were calculated. Results: Sensitivity, specificity, NPV and PPV were respectively 98.5%[90.7-99.9%], 66.7%[24.1-94%], 97%[88.7-99.4%] and 80%[30-98%]. Only one case was identified as NINV by CALIPER and as INV by the pulmonary pathologists. Conclusion: CALIPER represents a promising tool for non-invasive risk stratification of pulmonary nodules of the adenocarcinoma spectrum. Further prospective and retrospective validation of our data is currently ongoing.
US panel finds insufficient evidence to support mammography
Authors: F. Charatan
Journal: BMJ (2002)

An independent panel of US medical experts that writes information for the National Cancer Institute's online database (http://www.cancer.gov/) has concluded that there is insufficient evidence to show that mammography prevents deaths from breast cancer.

The panel, known as the PDQ screening and prevention editorial board, is going to rewrite its assessment of mammography for the institute's website in March.

It reached …