tbuckley/cabot-search huggingface dataset:
Incidence of melanoma in four English counties, 1989-92
Authors: J. N Newton, J. Redburn
Journal: BMJ (1995)

Factors other than ethnic group-for example, sex- could account for some of the differences that we observed.A higher proportion of applicants to medical schools than in the population overall are from ethnic minority groups.2Medical schools may therefore inadvertently be trying to restrict the overall numbers of students from ethnic minority groups to reflect population distributions in the United Kingdom.This may explain why white students with lower A level scores (25 or less) seem to have a greater chance of being accepted than their colleagues from ethnic minority groups with similar scores.There did not seem to be any selection bias in favour of white candidates among applicants with scores of 30-26.The process of selecting students for undergraduate medical courses has long been a problem for those having to select.Admission policies are not standard or defined so the policies of individual medical schools vary greatly.3Our data suggest that some medical schools could be accused of practising discriminatory admissions policies.
Monitoring the VEGF level in aqueous humor of patients with ophthalmologically relevant diseases via ultrahigh sensitive paper-based ELISA
Authors: Min-Yen Hsu, Chung-Yao Yang, Wen-Hsin Hsu, Keng-Hung Lin, Chun-Yuan Wang, Ying-Cheng Shen, Yu-Chen Chen, Siu-Fung Chau, Hin-Yeung Tsai, Chao-Min Cheng
Journal: Biomaterials (2014)
Fatal pulmonary emboli still being missed
Authors: Elizabeth Rasche González
Journal: JAMA (1981)

Patients with pneumonia are still dying of an additional, undiagnosed condition: pulmonary embolism. So are some patients with congestive heart failure. Elderly patients are particularly likely to die with unrecognized emboli in their lungs. These are some of the findings from a study of 1,455 autopsies performed at Boston's Peter Bent Brigham Hospital (now part of Brigham and Women's Hospital). The autopsies were performed on 61% of all patients who died at the hospital between January 1973 and December 1977. Samuel Z. Goldhaber, MD, a cardiology fellow in the Department of Medicine, was chief investigator for the study and reported the findings at the recent meeting of the American Heart Association at Miami Beach, Fla. Goldhaber and co-workers Charles H. Hennekens, MD, DrPH, Denis A. Evans, MD, Elizabeth C. Newton, and John J. Godleski, MD, also reviewed all hospital admission forms for the patients who came to autopsy. They found
Medial Genicular Fat Pad Thrombosis as a Cause of Knee Pain
Authors: Irwin M. Siegel
Journal: JAMA (1961)

A COMMON orthopedic complaint is that of pain about the medial aspect of the knee. An uncommon cause is traumatic venous thrombosis of the medial genicular fat pad.  Diagnostic Considerations  Anatomy.—  A fat pad overlying the anteromedial aspect of the knee joint is among those areas of body fat which undergo hypertrophy in the obese patient. Draining this adipose deposit are branches of the greater saphenous vein (see the figure). 1 In this vulnerable position these venous tributaries are subject to trauma with subsequent thrombosis.  History.—  Patients with this syndrome are usually middle-aged obese females, presenting with pain, swelling, and occasional ecchymosis of one or both medial genicular fat pads. The history is one of gradual onset without unusual trauma. The symptoms may be somewhat relieved by rest.  Examination.—  Physical examination reveals hypertrophy of the fat pads lying along the anteromedial aspect of the knee joints. Some
Problems in Interpretation of Intestinal Mucosal Biopsies
Authors: Margot Shiner
Journal: JAMA (1964)

INTESTINAL MUCOSAL BIOPSIES by the peroral route are comparatively recent. The methods of earlier studies consisted mainly of postmortem examinations, but the findings have been discredited because of the rapid autolytic changes occurring within intestinal tissue. Opinions on the morphological appearances of sprue in postmortem investigations were divided: Manson-Bahr<sup>1</sup>and Adlersberg and Schein<sup>2</sup>reported villous clubbing in tropical sprue and idiopathic steatorrhea (nontropical sprue) while Thaysen<sup>3</sup>maintained that the small bowel was normal, at least in nontropical sprue. The latter work was challenged in 1954 by Paulley<sup>4</sup>who showed, with the aid of laparotomy biopsies of the small intestine, that villous shortening and clubbing does occur in nontropical sprue. Confirmation of this finding on a large scale has been forthcoming since 1956 when the peroral method made the study of the intestinal mucosa without the disadvantages of autolytic changes possible. Although the mucosa has been extensively
Palmitic acid induces production of proinflammatory cytokine interleukin-8 from hepatocytes
Authors: Swati Joshi-Barve, Shirish S. Barve, Kiranmayi Amancherla, Leila Gobejishvili, Daniell Hill, Matthew Cave, Prachi Hote, Craig J. McClain
Journal: Hepatology (2007)

Obesity and the metabolic syndrome are closely correlated with hepatic steatosis. Simple hepatic steatosis in nonalcoholic fatty liver disease can progress to nonalcoholic steatohepatitis (NASH), which can be a precursor to more serious liver diseases, such as cirrhosis and hepatocellular carcinoma. The pathogenic mechanisms underlying progression of steatosis to NASH remain unclear; however, inflammation, proinflammatory cytokines, and oxidative stress have been postulated to play key roles. We previously reported that patients with NASH have elevated serum levels of proinflammatory cytokines, such as interleukin-8 (IL-8), which are likely to contribute to hepatic injury. This study specifically examines the effect of hepatic steatosis on IL-8 production. We induced lipid accumulation in hepatocytes (HepG2, rat primary hepatocytes, and human primary hepatocytes) by exposing them to pathophysiologically relevant concentrations of palmitic acid to simulate the excessive influx of fatty acids into hepatocytes. Significant fat accumulation was documented morphologically by Oil Red O staining in cells exposed to palmitic acid, and it was accompanied by an increase in intracellular triglyceride levels. Importantly, palmitic acid was found to induce significantly elevated levels of biologically active neutrophil chemoattractant, IL-8, from steatotic hepatocytes. Incubation of the cells with palmitate led to increased IL-8 gene expression and secretion (both mRNA and protein) through mechanisms involving activation of nuclear factor kappaB (NF-κB) and c-Jun N-terminal kinase/activator protein-1. Conclusion: These data demonstrate for the first time that lipid accumulation in hepatocytes can stimulate IL-8 production, thereby potentially contributing to hepatic inflammation and consequent liver injury. (Hepatology 2007.)
Why the Nursing Shortage Persists
Authors: Thomas Hale
Journal: New England Journal of Medicine (1964)

THE shortage of registered nurses persists, and affects every hospital, every doctor on the attending staff of a hospital and every hospital patient in this country. This continuing shortage seems incredible in view of the fact that since 1948, the number of girl high-school graduates (potential candidates for nursing) has increased from 627,046 to 990,000 a year, an increase of over 50 per cent (Table 1).In the September, 1960, issue of The Modern Hospital 1 I described at some length a number of major factors tending to produce and perpetuate the nationwide shortage of nurses. In that article I made . . .
Thrombophilia, Clinical Factors, and Recurrent Venous Thrombotic Events
Authors: Sverre C. Christiansen
Journal: JAMA (2005)

ContextData on the recurrence rate of venous thrombotic events and the effect of several risk factors, including thrombophilia, remain controversial. The potential benefit of screening for thrombophilia with respect to prophylactic strategies and duration of anticoagulant treatment is not yet known.ObjectivesTo estimate the recurrence rate of thrombotic events in patients after a first thrombotic event and its determinants, including thrombophilic abnormalities.Design, Setting, and PatientsProspective follow-up study of 474 consecutive patients aged 18 to 70 years without a known malignancy treated for a first objectively confirmed thrombotic event at anticoagulation clinics in the Netherlands. The Leiden Thrombophilia Study (LETS) was conducted from 1988 through 1992 and patients were followed up through 2000.Main Outcome MeasuresRecurrent thrombotic event based on thrombophilic risk factors, sex, type of initial thrombotic event (idiopathic or provoked), oral contraceptive use, elevated levels of factors VIII, IX, XI, fibrinogen, homocysteine, and anticoagulant deficiencies.ResultsA total of 474 patients were followed up for mean (SD) of 7.3 (2.7) years and complete follow-up was achieved in 447 (94%). Recurrence of thrombotic events occurred in 90 patients during a total of 3477 patient-years. The rate of thrombotic event recurrence was 25.9 per 1000 patient-years (95% confidence interval [CI], 20.8-31.8 per 1000 patient-years). The incidence rate of recurrence was highest during the first 2 years (31.9 per 1000 patient-years; 95% CI, 20.3-43.5 per 1000 patient-years). The risk of thrombotic event recurrence was 2.7 times (95% CI, 1.8-4.2 times) higher in men than in women. Patients whose initial thrombotic event was idiopathic had a higher risk of a thrombotic event recurrence than patients whose initial event was provoked (hazard ratio [HR], 1.9; 95% CI, 1.2-2.9). Women who used oral contraceptives during follow-up had a higher thrombotic event recurrence rate (28.0 per 1000 patient-years; 95% CI, 15.9-49.4 per 1000 patient-years) than those who did not (12.9 per 1000 patient-years; 95% CI, 7.9-21.2 per 1000 patient-years). Recurrence risks of a thrombotic event by laboratory abnormality ranged from an HR of 0.6 (95% CI, 0.3-1.1) in patients with elevated levels of factor XI to an HR of 1.8 (95% CI, 0.9-3.7) for patients with anticoagulant deficiencies.ConclusionsProthrombotic abnormalities do not appear to play an important role in the risk of a recurrent thrombotic event. Testing for prothrombotic defects has little consequence with respect to prophylactic strategies. Clinical factors are probably more important than laboratory abnormalities in determining the duration of anticoagulation therapy.
Delayed Testing, Tainted Transfusions Alleged
Authors: Charles Marwick
Journal: JAMA (1991)

IN 1985, French licensing authorities delayed use of an American-made test to detect antibody to the acquired immunodeficiency syndrome (AIDS) virus while France's researchers developed and marketed their own antibody test. So says a report by Michel Lucas, France's inspector general of social affairs, who investigated this incident under pressure from several groups, including persons with hemophilia, who are demanding indemnity.  According to the report, Abbott Laboratories, Chicago, Ill, one of several companies in the United States that by late 1984 had developed tests for detecting antibodies to the AIDS virus, submitted an application for registration (licensure) of its test to the French National Laboratory of Health on February 11, 1985. On May 9, a meeting that included representatives from the ministries of health and industry discussed Abbott's application and one received by then from Pasteur (Institute) Diagnostics, Paris.  The result, the report says, was that the French licensed the
MS-29 * SORAFENIB AND REGORAFENIB INHIBIT GROWTH AND MIGRATION OF MENINGIOMA CELLS
Authors: A. Wilisch-Neumann, D. Pachow, E. Kirches, C. Mawrin
Journal: Neuro-Oncology (2014)

Sorafenib and Regorafenib (Fluoro-Sorafenib) are closely related multikinase inhibitors, which possess activity in the treatment of some human cancers. The potential role of both drugs in meningiomas have not been elucidated so far. Therefore, we have studied their anti-tumor activity in various in vitro meningioma models. A moderate antiproliferative activity of both drugs applied for 48 h (p < 0.001) to malignant IOMM-Lee meningioma cells was found in microtiter-tetrazolium (MTT) assays with an IC50 of 15 µM for Regorafenib and an IC50 between 7.5 and 15 µM for Sorafenib. MTT assays just reflect the number of viable cells and may thus indicate solely an inhibition of proliferation of the rapidly growing IOMM-Lee cells. However, some degree of cell death induction must have been occured, because a strong induction of nucleosome liberation (p < 0.05) was observed for both drugs by ELISA. Both drugs consistently had lower effects (MTT assay) in two syngenous derivatives of the benign SF4068 meningioma line exhibiting a massive NF2 loss (shRNA mediated) as compared to two syngenous SF4068 derivatives with NF2 wildtype. This suggests a modifying role of the NF2 status on the effects of Regorafenib and Sorafenib. Moreover, both drugs (15 µM) dramatically inhibited cell migration (gap assay, p < 0.05) and invasion (matrigel transwell assay, p < 0.01). Therefore, Sorafenib and Regorafenib seem to target preferentially meningioma cell motility and brain invasion.
Virtual Reality Colonoscopy Simulation: A Compulsory Practice for the Future Colonoscopist?
Authors: G. Ahlberg, R. Hultcrantz, E. Jaramillo, A. Lindblom, D. Arvidsson
Journal: Endoscopy (2005)

Background and Study Aim: As for any manual procedure, the learning curves for medical interventions can have undesirable phases, occurring mostly in the early experience of applying a technique. There have been impressive advances in endoscopic procedures during recent years, and there is an emerging trend that the number of procedures is increasing in parallel with these. In addition, the introduction of screening programs for colorectal cancer will also increase the numbers of procedures needed. Recent developments in medical simulation seem promising with regard to the possibility of "training out" undesirable parts of the learning curve outside the operating room. The aim of this study was to investigate whether the use of the AccuTouch flexible endoscopy simulator improves the early part of the learning curve in colonoscopy training. Method: 12 endoscopy trainees, 10 surgeons and two medical gastroenterologists, all with experience in gastroscopy but with no specific colonoscopy experience, were randomly assigned to either simulator training or to a control group. They all received the same theoretical study package and the training group practiced with the AccuTouch colonoscopy simulator until a predefined expert level of performance was reached. All trainees performed their first ten individual colonoscopies described in detail in a separate protocol. Results: Trainees in the simulator-trained group performed significantly better (P = 0.0011) and managed to reach the cecum in 52 % of their cases (vs. 19 % in the control group), and were 4.53 times more likely to succeed compared with the controls. Additionally, there was a significantly shorter procedure time and less patient discomfort in the hands of the simulator-trained group. Conclusion: Skills acquired using the AccuTouch simulator transfer well into the clinical colonoscopy environment. The results of this trial clearly support the plan to integrate simulator training into endoscopic education curricula.
NHS Modernisation Agency's way to improve health care
Authors: Hugh Rogers, Kate Silvester, Jill Copeland
Journal: BMJ (2004)

EDITOR—As leaders in the NHS Modernisation Agency, we were delighted to see the paper by Young et al summarising three key approaches to improving manufacturing systems.1 Improvement programmes in the agency have been adapting these approaches successfully to NHS healthcare systems for several years.2

We now refer to this body of knowledge as “clinical systems improvement.” At its …
Origin and Formation of Immunoglobulin.
Authors: Matthew Block
Journal: Annals of Internal Medicine (1965)

s1 May 1965Origin and Formation of Immunoglobulin.Matthew Block, M.D., Ph.D.Matthew Block, M.D., Ph.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-62-5-1090_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAn early and major role in development of immunologic capacity is played by the thymus, which induces development of extrathymic lymphatic tissue and of immunologically competent cells in this tissue. Except possibly for formation of beta 2M immune globulins, antibody formation is restricted to postnatal life in mammals and consists of synthesis of L and H chains and their combination into specific antibodies. After birth lymphatic tissues are self perpetuating, and their maintenance and function is independent of the thymus.One may postulate abnormalities at any stage in this basically simple scheme. The thymus may not form, or if formed... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Matthew Block, M.D., Ph.D.Affiliations: Denver, Colorado PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1965Volume 62, Issue 5Page: 1090-1090KeywordsAntibody responseBirthCellsGlobulinsLymphoid tissueThymus ePublished: 1 December 2008 Issue Published: 1 May 1965 PDF downloadLoading ...
Relationship Between Autonomic Neuropathy, 24-h Blood Pressure Profile, and Nephropathy in Normotensive IDDM Patients
Authors: Vincenza Spallone, Sergio Gambardella, Maria R Maiello, Angela Barini, Slmona Frontoni, Guido Menzinger
Journal: Diabetes Care (1994)

OBJECTIVE To evaluate the relationship between autonomic neuropathy, nephropathy, and 24-h blood pressure (BP) pattern in insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS We studied 30 normotensive IDDM patients without overt nephropathy, divided into two groups and matched for age, duration of diabetes, and HbA1 according to the presence of cardiovascular autonomic neuropathy. We simultaneously measured 24-h BP and urinary albumin excretion rate (UAE) on urine collections timed overnight and at 2-h intervals during the day. RESULTS Mean day and night systolic and diastolic BP values did not significantly differ between the groups. Mean night albuminuria was significantly higher in patients with autonomic neuropathy than in those without (61.4 ± 104.6 [mean ± SD] vs. 16 ± 25.2 μg/min, P &amp;lt; 0.04). The percentages day-night changes in systolic BP, diastolic BP, and UAE were significantly lower in neuropathic patients (systolic BP: 2.4 ± 7.7 vs. 9.6 ± 4.2%, P &amp;lt; 0.001; diastolic BP: 8.4 ± 6.9 vs. 15.5 ± 5.4%, P &amp;lt; 0.002; UAE: – 8 ± 99.4 vs. 49.3 ± 29.4%, P &amp;lt; 0.02) and were inversely related to autonomic score, index of autonomic neuropathy degree (r = –0.54, P &amp;lt; 0.002; r = –0.58, P &amp;lt; 0.001; and r = –0.53, P &amp;lt; 0.005, respectively). In patients with autonomic neuropathy, 2-h day periods and day and night UAE were more strongly related, respectively, to mean 2-h day periods (r = 0.58, P &amp;lt; 0.0001), day systolic BP (r = 0.67, P &amp;lt; 0.04), and night systolic BP (r = 0.69, P &amp;lt; 0.04) than in patients without autonomic neuropathy (2-h day periods: r = 0.32, P &amp;lt; 0.001; day: r = 0.37, NS; night: r = 0.35, NS). CONCLUSIONS Autonomic neuropathy in IDDM patients is associated with reduced nocturnal falls in BP and UAE and with a stronger relationship of UAE to systolic BP. We suggest a pathogenetic role of autonomic neuropathy in the development of diabetic nephropathy through changes in nocturnal glomerular function and by enhanced kidney vulnerability to hemodynamic effects of BP.
S6K1 deficiency protects against apoptosis in hepatocytes
Authors: Águeda González-Rodriguez, Javier Alba, Valeri Zimmerman, Sara C. Kozma, Ángela M. Valverde
Journal: Hepatology (2009)

The mammalian target of rapamycin (mTOR)/S6K1 signaling pathway controls cell growth and proliferation. To assess the importance of S6K1 in the balance between death and survival in the liver, we have generated immortalized hepatocyte cell lines from wild-type and S6K1-deficient (S6K1(-/-)) mice. In S6K1(-/-) hepatocytes, caspase-8 and the pro-apoptotic protein Bid were constitutively down-regulated as compared with wild-type. Moreover, S6K1(-/-) hepatocytes failed to respond to the apoptotic trigger of death receptor activation. Neither caspase-8 activation nor FLIP(L) degradation in response to tumor necrosis factor alpha (TNF-alpha) or anti-Fas antibody (Jo2) was observed in cells lacking S6K1. Downstream events such as Bid cleavage, cytochrome C release, caspase-3 activation, DNA laddering, as well as the percentage of apoptotic cells were attenuated as compared with wild-type. In addition, the anti-apoptotic protein Bclx(L) was down-regulated in TNF-alpha-treated or Jo2-treated wild-type hepatocytes, but this response was abolished in S6K1(-/-)cells. In vivo, S6K1-deficient mice were protected against concanavalin A-induced apoptosis. The withdrawal of growth factors strongly induced apoptosis in wild-type, but not in S6K1(-/-) hepatocytes. S6K1 deficiency did not decrease Bclx(L)/Bim ratio on serum withdrawal, thereby protecting cells from cytochrome C release and DNA fragmentation. At the molecular level, the lack of S6K1-mediated negative feedback decreased insulin receptor substrate-1 (IRS-1) serine phosphorylation, resulting in activation of survival pathways mediated by phosphatidylinositol 3-kinase/Akt and extracellular signal-regulated kinase (ERK). However, S6K1(-/-) hepatocytes underwent apoptosis on serum withdrawal in combination with phosphatidylinositol 3-kinase (PI3K) or ERK inhibitors.This finding might explain the mechanism of resistance to mTOR inhibitors in cancer treatments and strongly suggests that the inhibition of S6K1 could protect against acute liver failure and, in combination with inhibitors that abrogate the sustained activation of Akt and ERK, could improve the efficacy of hepatocarcinoma (HCC) treatment.
Report was overpositive about their benefits
Authors: R. S. Scheffel, B. D. Schaan
Journal: BMJ (2012)

Although Karagiannis and colleagues’ study has methodological strengths worth citing, we disagree with some of the conclusions.

In the evaluation of the prespecified primary endpoint (difference in glycated haemoglobin (HbA1c); fig 2), the performance of the dipeptidyl peptidase-4 (DPP-4) inhibitors was far below that of the drugs used as active comparators …