tbuckley/cabot-search huggingface dataset:
Molecular characteristics of serrated adenomas of the colorectum
Authors: E J Sawyer, A Cerar, A M Hanby, P Gorman, M Arends, I C Talbot, I P M Tomlinson
Journal: Gut (2002)

<b>Background:</b> Serrated adenomas (SAs) of the colorectum combine architectural features of hyperplastic polyps and cytological features of classical adenomas. Molecular studies comparing SAs and classical adenomas suggest that each may be a distinct entity; in particular, it has been proposed that microsatellite instability (MSI) distinguishes SAs from classical adenomas and that SAs and the colorectal cancers arising from them develop along a pathway driven by low level microsatellite instability (MSI-L). <b>Aims:</b> To define the molecular characteristics of SAs of the colorectum. <b>Materials and methods:</b> We analysed 39 SAs from 27 patients, including eight SAs from patients with familial adenomatous polyposis (FAP). We screened these polyps for selected molecular changes, including loss of heterozygosity (LOH) close to <i>APC</i> (5q21) and <i>CRAC1</i> (15q13-q22), MSI, and mutations of K-ras, <i>APC</i>, p53, and β-catenin. Expression patterns of β-catenin, p53, MLH1, MSH2, E-cadherin, and O<sup>6</sup>-methylguanine DNA methyltransferase (MGMT) were assessed by immunohistochemistry. Comparative genomic hybridisation was performed on several polyps. <b>Results:</b> MSI was rare (&lt;5% cases) and there was no loss of expression of mismatch repair proteins. Wnt pathway abnormalities (<i>APC</i> mutation/LOH, β-catenin mutation/nuclear expression) occurred in 11 SAs, including 6/31 (19%) non-FAP tumours. <i>CRAC1</i> LOH occurred in 23% of tumours. K-ras mutations and p53 mutations/overexpression were found in 15% and 8% of SAs, respectively. Loss of MGMT expression occurred in 18% of polyps and showed a borderline association with K-ras mutations. Aberrant E-cadherin expression was found in seven polyps. Comparative genomic hybridisation detected no gains or deletions of chromosomal material. <b>Conclusions:</b> The serrated pathway of colorectal tumorigenesis appears to be heterogeneous. In common with classical adenomas, some SAs develop along pathways involving changes in <i>APC</i>/β-catenin. SAs rarely show MSI or any evidence of chromosomal-scale genetic instability. K-ras mutations may however be less common in SAs than in classical adenomas. Some SAs may harbour changes in the <i>CRAC1</i> gene. Changes in known genes do not account for the growth of the majority of SAs.
Early Stages of Thyroid Carcinoma
Authors: M. Dargent, P. Guinet
Journal: BMJ (1952)

The relation between benign and malignant growth is not academic.If a malignant process can really arise within the capsule of a benign tumour, enucleation of the tumour should be a suitable method of prevention.But if, on the contrary, cancer occurs round a benign nodule more radical treatment is indicated.Controversy is especially sharp in the case of the thyroid gland, as has been remarked by Brenizer and McKnight (1940).A clinician's opinion about degenera- tion in a goitre may be quite different from that of a pathologist.It is generally admitted in Europe by Swiss authors (de Quervain,
X ray specs
Authors: Des Spence
Journal: BMJ (2008)

The back pages of Marvel comics used to have advertisements for “Dynamic Tension” so you could achieve the body of Charles Atlas “in just two weeks,” “magic” insoles that made you taller than adults, and “amazing” x ray spectacles that allowed the wearer to see through people’s clothes (a truly horrifying thought). A friend bought a pair but found just a scantily clad lady painted on the inside of the lenses—it was just a scam. At medical school I took a certificate in radiology legislation, …
WHO urges reporting of clinical trials within 18 months
Authors: A. Gulland
Journal: BMJ (2014)

Campaigners have welcomed a World Health Organization proposal urging researchers to submit the main findings of clinical trials for publication in a peer reviewed journal within 18 months of completion, or 30 months at the most, through an open access method. 

It also called for key outcomes to be made publicly available on a primary clinical trial registry. And if a registry does not have a results database the findings should be posted on a free to access, publicly available, searchable institutional website of the regulatory sponsor, funder, or principal investigator, it added.

The WHO proposal, which is open to consultation until 15 November, said that the proposed 18-30 month deadline …
ON THE MECHANISM OF OVERPRODUCTION OF URIC ACID IN PATIENTS WITH PRIMARY GOUT1
Authors: James B. Wyngaarden, Alberta E. Blair, Linnelle Hilley
Journal: Journal of Clinical Investigation (1958)

In order to study the rate of generation of uric acid in man, Benedict, Roche, Yu, Bien, Gutman, and Stetten (5-7) administered relatively large doses of glycine-N15 orally to control and gouty subjects and measured the appearance of isotope in urinary uric acid. With this technique, they demonstrated overincorporation of isotope into uric acid only in gouty subjects excreting large quantities of uric acid in urine. Subsequently, however, excessive incorporation of tracer quantities of glycine-1-C14 into uric acid was demonstrated in all of seven subjects studied, regardless of the stage of severity of the disease or of the magnitude of urinary uric acid excretion (8). These results indicated that overproduction of uric acid from glycine and other small molecules was the fundamental defect responsible for hyperuricemia in primary gout. The characteristics of the curves of uric acid enrichment indicated that excessive biosynthesis of uric acid occurred in these gouty subjects without the intermediary intervention of nucleic acids (5, 7, 8). Since the mechanism of overproduction of uric acid in primary gout has not been defined in detail, it was decided to investigate the incorporation of glycine-1-C'4 into various urinary purine bases and to compare enrichment patterns with those of uric acid determined simultaneously. From such comparisons, information was sought regarding purine intermediates involved in normal and abnormal uric acid production. These studies have suggested two types of mechanism resulting in uric acid synthesis in man and have strengthened the present concepts (5, 7, 8-12) that over-
Pathogen-specific antibodies: codependent no longer
Authors: Edward N. Janoff, Daniel N. Frank
Journal: Journal of Clinical Investigation (2010)

Antibody-mediated defense against pathogens typically requires complex interactions between antibodies and other constituents of the humoral and cellular immune systems. However, recent evidence indicates that some antibodies alone can inhibit pathogen function in the absence of complement, phagocytes, or NK cells. In this issue of the JCI, McClelland et al. have begun to elucidate the molecular bases by which antibodies alone can impact pathogen growth and metabolism. They show that mAbs specific for the polysaccharide capsule of the human pathogenic fungus Cryptococcus neoformans elicit diverse effects on fungal gene expression, lipid biosynthesis, susceptibility to amphotericin B, cellular metabolism, and protein phosphorylation. These data suggest that pathogens have the capacity to generate broad metabolic responses as a result of surface binding by pathogen-specific antibodies, effects that may hold therapeutic promise.
Health Disparities in Care for Depression Possibly Obscured by the Clinical Significance Criterion
Authors: James C. Coyne, Steven C. Marcus
Journal: American Journal of Psychiatry (2006)

BACKGROUND: In addition to symptoms, DSM-IV criteria for major depression require clinical significance, operationalized via reports of receipt of care or interference in functioning. The authors examined whether this confounding of symptoms with receipt of care and/or impairment affected racial differences in rates of major depression in the community. Method: Analysis of data from the 1999 National Health Interview Survey for a nationally representative community sample of 30,801 adults administered the depression module of the Composite International Diagnostic Interview–Short Form. Results: There were no differences between African American subjects and white/other subjects when diagnosis was based solely on symptoms. Symptomatic African American individuals were less likely to endorse either receipt of care or interference in functioning, so that the clinical significance criterion served to reduce their rates of DSM-IV diagnosis. Conclusions: The clinical significance criterion underestimates of the rate of depression for African American individuals relative to white/other subjects, which may in turn underestimate their need for services.
Automotive sulfate emission data.
Authors: J H Somers
Journal: Environmental Health Perspectives (1975)

This paper discusses automotive sulfate emission results obtained by the Office of Mobile Source Air Pollution Control of EPA, General Motors, Ford, Chrysler, and Esso. This work has been directed towards obtaining sulfate emission factors for cars with and without catalyst. While the EPA and Chrysler investigations have found significant sulfate formation in noncatalyst cars, GM, Ford, and Esso have found only trace levels from noncatalyst cars. All of these investigators agree that much higher quantities of sulfate are emitted from catalyst cars. The work done to date shows pelleted catalysts to have much lower sulfate emissions over the low speed-EPA Federal Test Procedures than monolith catalysts. This is probably due to temporary storage of sulfates on the catalyst due to chemical interaction with the alumina pellets. The sulfate compounds are, to a large degree, emitted later under higher speed conditions which result in higher catalyst temperatures which decompose the alumina salt. Future work will be directed towards further elucidation of this storage mechanism as well as determining in detail how factors such as air injection rate and catalyst location affect sulfate emissions.
Primary Sjogren's syndrome presenting as a case of sarcoidosis and a suspected pancreatic tumour.
Authors: P P Koopmans, C Bodeutsch, P C de Wilde, A M Boerbooms
Journal: Annals of the Rheumatic Diseases (1990)

A 45 year old man, previously diagnosed as having sarcoid, presented with signs and symptoms of a pancreatic malignancy. An explorative laparotomy, however, showed only chronic pancreatitis. He was found to have a raised erythrocyte sedimentation rate, normocytic normochromic anaemia, renal insufficiency, hypergammaglobulinaemia, and a strongly positive rheumatoid factor and antinuclear antibody titre. Bilateral hilar lymph node enlargement was noted on chest x ray. Subsequently, the patient complained of xerostomia and keratoconjunctivitis sicca. Large lymphocytic infiltrates and a shift in the relative number of IgA bearing plasma cells in favour of IgG and IgM bearing plasma cells were seen in tissue obtained by sublabial salivary gland biopsy. A transbronchial lung biopsy and review of the biopsies of the pancreas, the lung, liver, and a lymph node all failed to show granulomatous disease. These findings strongly suggested a diagnosis of Sjögren9s syndrome instead of sarcoidosis. This case shows the difficulty sometimes encountered in differentiating between sarcoid and systemic Sjögren9s syndrome, and the value of a sublabial salivary gland biopsy.
Dulcet tones of a surgeon's voice may have a hidden meaning
Authors: R. Dobson
Journal: BMJ (2002)

Surgeons who speak with a dominating tone and who sound less concerned in conversation with their patients than other surgeons are more likely to have been sued for malpractice.

In what is described as the first study to show clear links between communication and malpractice among surgeons, researchers found that sampling just a few seconds of conversations between doctors and patients was sufficient to …
Low Plasma Adiponectin Levels Are Associated With Increased Hepatic Lipase Activity In Vivo
Authors: Jochen G. Schneider, Maximilian von Eynatten, Stephan Schiekofer, Peter P. Nawroth, Klaus A. Dugi
Journal: Diabetes Care (2005)

OBJECTIVE—Hepatic lipase plays a key role in hydrolyzing triglycerides and phospholipids present in circulating plasma lipoproteins. Plasma hepatic lipase activity is known to be regulated by several hormonal and metabolic factors, but hepatic lipase responsiveness to insulin is still controversial. Hypoadiponectinemia is known to be associated with insulin resistance, diabetes, and obesity. These conditions are often characterized by high plasma triglyceride and low HDL cholesterol levels, and they have been shown to be associated with high plasma hepatic lipase activity. We therefore raised the question whether adiponectin may be associated with plasma hepatic lipase activity in vivo. RESEARCH DESIGN AND METHODS—We measured plasma adiponectin and postheparin hepatic lipase activity in 206 nondiabetic men and in a second group of 110 patients with type 2 diabetes. The correlation of these parameters with markers of insulin resistance and systemic inflammation was investigated. RESULTS—In nondiabetic patients, adiponectin levels were significantly inversely correlated with plasma hepatic lipase activity (r = −0.4, P &amp;lt; 0.01). These results were confirmed in the group of patients with type 2 diabetes (r = −0.32, P = 0.004). Multivariate analysis revealed that adiponectin was the strongest factor influencing hepatic lipase activity. The association was independent of age, sex, BMI, plasma triglycerides, insulin, HDL cholesterol, and high-sensitivity C-reactive protein and accounted for ∼10 and 12% of the variation in hepatic lipase activity in the two different patient cohorts, respectively. CONCLUSIONS—These results demonstrate for the first time a significant inverse association between adiponectin and postheparin plasma hepatic lipase activity that is independent of other factors such as markers of insulin resistance or inflammation. Therefore, adiponectin, rather than insulin, may represent an important factor contributing to the regulation of hepatic lipase activity in both nondiabetic individuals and patients with type 2 diabetes. The effect of adiponectin on hepatic lipase activity may also help to explain the HDL cholesterol–elevating action of adiponectin.
Response to measles, mumps, and rubella revaccination among HIV-positive and HIV-negative children and adolescents with hemophilia
Authors: Margaret W. Hilgartner, Margaret A. Maeder, Elizabeth M. Mahoney, Sharyne M. Donfield, Bruce L. Evatt, W. Keith Hoots
Journal: American Journal of Hematology (2001)

The effect of human immunodeficiency virus (HIV) infection on response to measles, mumps, and rubella revaccination in children and adolescents with hemophilia was evaluated. Antibody levels of measles, mumps, and rubella were assayed at baseline and two annual examinations in 207 HIV-positive and 126 HIV-negative hemophiliacs participating in the Hemophilia Growth and Development Study (HGDS). Response to revaccination was analyzed for participants whose antibody levels were below the cut-off at the start of a year-long observation period. Among HIV-positive participants, antibody levels were below cut-off in 52 subjects for measles, in 71 for mumps, and in 96 for rubella. Among HIV-negative participants, antibody levels were low in 23 subjects for measles, in 23 for mumps, and in 31 for rubella. For measles and mumps antigens, revaccination was associated with a significant increase in redraw antibody levels for HIV-negative participants. Although there was an increase in the mean measles titers for revaccinated HIV-positive participants, it was not significant. Revaccination was associated with an increase in rubella antibodies in HIV-positive and HIV-negative participants. Revaccination with measles and mumps was associated with an increase in antibody levels in HIV-negative participants but not in HIV-positive participants. Both HIV-positive and HIV-negative participants responded to rubella revaccination with an increase in antibody levels. Am. J. Hematol. 66:92–98, 2001. © 2001 Wiley-Liss, Inc.
Leaching of Chemicals From Plastic Intravenous Fluid Bags
Authors: Win L. Chiou
Journal: JAMA (1973)

<h3>To the Editor.—</h3> We have previously reported<sup>1</sup>that Vitamin A could disappear rapidly from the solutions stored in the polyvinyl chloride plastic intravenous fluid bags that are marketed under the trade name, Viaflex, by Baxter-Travenol. In light of a recent study<sup>2</sup>showing that a rather significant amount of the plasticizer, diethylhexyl phthalate (DEH-phthalate), leached at a constant rate into the blood from the plastic blood bags also marketed by the same company, we have conducted some preliminary investigations as to the possible leaching of chemicals from the Viaflex fluid bags. In this preliminary phase of the study, the ultraviolet absorption spectra of solutions (200 ml) stored in 250-ml bags were recorded as a function of time. The samples were kept at room temperature (24 ± 2 C), and the solutions stored in volumetric flasks served as controls. The ultraviolet absorbencies of distilled water, normal saline, and 5% dextrose solution
The binding affinity of anti-Aβ1-42 MAb-decorated nanoliposomes to Aβ1-42 peptides in vitro and to amyloid deposits in post-mortem tissue
Authors: Mara Canovi, Eleni Markoutsa, Adina N. Lazar, Georgios Pampalakis, Carla Clemente, Francesca Re, Silvia Sesana, Massimo Masserini, Mario Salmona, Charles Duyckaerts, Orfeu Flores, Marco Gobbi, Sophia G. Antimisiaris
Journal: Biomaterials (2011)
Intractable rheumatoid arthritis. Treatment with combined cyclophosphamide, azathioprine, and hydroxychloroquine
Authors: D. J. McCarty
Journal: JAMA (1982)

Seventeen patients (15 women, two men) with progressive, erosive seropositive rheumatoid arthritis (RA) refractory to conventional therapy were treated with cyclophosphamide, azathioprine, and hydroxychloroquine sulfate for an average of 27 +/- 19 months (mean +/- SD throughout) (range, five to 60 months). Disease suppression began in 14 patients within three to 16 months (mean, seven months). Five patients achieved complete remission, two had activity in a single joint only, seven had partial disease suppression, and three showed no response. Prednisone dosage was decreased or administration discontinued in nine of ten patients (5.8 +/- 1.2 to 2.7 +/- 3 mg/day). Serial hand roentgenograms showed recortication of erosions in nine patients, with "filling in" of some erosions in three of these. No change was seen in the roentgenograms of five patients, while progressive disease occurred in three instances. Combined therapy with small doses of three drugs, each with proved antirheumatic activity when used separately in larger doses, may provide satisfactory long-term disease control in patients with intractable RA. This regimen is experimental. Proof of efficacy requires a controlled study. Until such data are obtained, this drug combination is not recommended for general use.
New Zealand Olympic experience—Sydney 2000
Authors: C Milne
Journal: British Journal of Sports Medicine (2001)

The football club doctor system EDITOR,-I read with interest the paper by Waddington et al 1 highlighting the inadequacies of the football club doctor system in Britain.This paper confirms the situation that many people already knew to exist.Advertisements for club doctors are rarely published in medical journals, doctors normally being appointed on a "who you know" basis.It is also particularly disappointing that, at a time when the specialty of sports and exercise medicine is being established in this country, the majority of doctors working with professional footballers have no qualifications or little experience in the specialty.However, this is not confined to football clubs and probably also applies to rugby clubs and many other sporting associations.One aspect not mentioned in the paper is medical litigation.It is to be hoped that doctors involved with football clubs have arranged medical defence cover, because, if a situation arises in which a player's sporting career is threatened by medical mismanagement and the doctor involved has no professionally recognised sports medicine qualification, he or she could be found guilty of medical negligence.With the amount of money involved in professional football, this could lead to dire consequences for the medical career of the practitioner involved.From a report commissioned by the Football League on the Hillsborough tragedy, the concept of the "crowd doctor" was introduced, meaning that any doctor involved in the medical care of the crowd at a football stadium would be required to possess at least the Diploma in Immediate Medical Care. 2 Before that, the situation was similar to that of the present club doctor system, and few doctors held any recognisable qualifications or training in medical emergencies and resuscitation.A similar recommendation by sports medicine authorities is required to enhance the quality of service provided to football clubs and increase the stature of the specialty.However, it is not a one sided situation.Football clubs must realise the importance of a medical team in looking after their prime assets, the players.Advertising of jobs in medical journals, insisting on experience and qualifications, adequate remuneration, and the provision of job descriptions and contracts should all be implemented.By working together to improve the current situation, a service can be provided in which both professional football players and the medical profession can have confidence.
New US abstinence programme guidelines criticised
Authors: Janice Tanne
Journal: BMJ (2006)

A US Congressman and two not for profit health policy organisations have said that new guidelines for government funded programmes advocating sexual abstinence are false, misleading, and dangerous. The guidelines must be followed by organisations seeking federal grants for abstinence programs. The newly expanded rules, published at the end of January 2006, say that to get funding, such courses must teach teenagers that abstinence from all sexual activity—which, as defined by the rules, might include kissing—is the norm until marriage, that contraceptives often fail, and that abstinence until marriage will lead to a longer, healthier, more prosperous life (www.acf.hhs.gov/grants/pdf/HHS-2006-ACF-ACYF-AE-0099.pdf).

“I ask that the entire funding announcement be retracted,” said …
Responding to unexpected events: Patients have to be treated as individuals
Authors: H. M Iwanowska
Journal: BMJ (2003)

Editor—Saunders et al discussed responding to unexpected events in planning for a good death.1 I was recently in a very similar, difficult, and sad situation.

My husband for 14 years had been treated for prostate cancer for three years, in an outpatient clinic, where he received chemotherapy, radiotherapy, and intravenous isotopes, focusing on bone metastases. He had no pain and was full of plans and ideas for the future. Iliac artery thrombosis developed; he was taken to hospital and was given heparin as an antithrombosis regimen. A few days after returning home he began to have intense bleeding from the bladder. His condition deteriorated, but he was full of hope, knowing that new treatments had prolonged his life on many occasions.

A urology specialist from another hospital decided to try to detect the cause of the bleeds and, seeing his expectation, we transferred my husband by ambulance to a hospital 30 km away. The bleeding came from a ligated artery, but the mucosa of the bladder was swollen and brittle. He was very weak but still full of hope. Three days later he started to have massive bleeding from the bladder and stomach, and he died—very still, in the presence of family, almost to the end conscious.

I think that with every patient we have to look at the individual person, taking into consideration the patient's physical, mental, and psychological state. We cannot deprive a patient of hope, even knowing that his or her chances are minimal.