tbuckley/cabot-search huggingface dataset:
Hypertension in the tropics.
Authors: K. L. Stuart
Journal: BMJ (1968)

Persistent and Occult Bleeding-Callender fBRSH 103 radiologically before removal, as is the relationship of the teeth to the length of string.The position of any blood-staining on the string is taken as an indication of the site of bleeding.Laparotomy.-This is occasionally indicated when patients go on bleeding for no obvious cause, but the operation is seldom rewarding, particularly if carried out during an interval when the bleeding has stopped.If a definitive diagnosis has not been reached it is probably better to keep the patient under observa- tion and be prepared to re-x-ray at intervals if it is suspected that a neoplasm may in fact be present.In relation to such a policy it is reassuring that of 68 patients diagnosed originally as having iron deficiency anaemia with unexplained occult bleeding 51 remained unexplained.'The majority were in good health 2 to 21 years later apart from relapse of the anaemia in some cases.Of the other 17, 12 were thought to have been bleeding because of aspirin ingestion, two had bleeding piles, one had been found to have a gastric ulcer, one a possible carcinoma of the rectum, and one a definite carcinoma of the colon.This last case is probably the only one in which laparotomy might have been helpful at the time of the original admis- sion, but even then with completely negative x-ray findings a small tumour might have been missed, since the surgeon had no guidance on where to look for it. ConclusionsPersistent and occult blood loss from the gastrointestinal tract is not necessarily a sinister symptom.It is now recognized that in a high proportion of cases the cause is ingestion of drugs of the salicylate group.A careful history and clinical examination will go far towards detecting many of the causes of persistent blood loss.Special investigations such as barium studies, gastroscopy, and sigmoidoscopy are mainly needed to look for peptic ulcers, hiatus hernia, and neoplasms.Laparotomy should not be undertaken lightly as a diagnostic procedure;
Ernest Saunders: diagnostic dilemma
Authors: P L G Gallwey
Journal: BMJ (1992)

consent, as they move within the NHS, house officers may be unaware that they are not protected against prescribed diseases such as tuberculosis and hepatitis B. It may well be that Lewisham Hospital's handbook mentions the occupational health department.Luisa Dillner's review of Stress and the Medical Profession seems to confirm my views.2The pen- ultimate paragraph suggests that doctors need an accessible counselling service and an occupational health service that is geared to recognising stress.The standard and quality of occupational health services vary considerably within the NHS, but it is essential that all staff, including doctors, become more aware of the services they offer.
Tim Bowling and colleagues reply to Des Spence
Authors: T. Bowling, M. Stroud, R. Leach, A. Holdoway
Journal: BMJ (2012)

Des Spence’s article “Bad medicine: medical nutrition” contains factual inaccuracies that could result in harm to patients if doctors believed and acted on them.1

He says that total calorie intake is the main issue in malnutrition, but protein and micronutrients are probably more important in improving clinical outcomes in sick, malnourished patients. Protein rich oral nutritional supplements (ONS) reduce the incidence of complications such as infection, poor wound healing, and ulcers in patients with hip fracture, leg ulcer, and acute illness in hospitals and community settings (10 trials, n=1830; odds ratio 0.68, 95% confidence interval 0.55 to 0.83).2 They also significantly reduce (by a quarter) the risk of developing pressure ulcers in high risk patients (four trials, n=1224; odds ratio 0.75, 0.62 to 0.89).3

ONS increase protein intake in older people in hospitals and community settings.4 5 They work in patients recently discharged home and in malnourished older patients in hospital, even compared with controls who did not receive ONS but received careful attention by nursing staff to try to ensure that they finished meals (65% v 32% protein intake, P <0.0001).6 7 That ONS improve function and clinical …
Abstract 2235: High frequency of fusion transcripts involving TCF7L2 in colorectal cancer: Novel fusion partner and splice variants
Authors: Andreas M. Hoff, Torfinn Nome, Anne Cathrine Bakken, Torleiv O. Rognum, Arild Nesbakken, Rolf I. Skotheim
Journal: Cancer Research (2014)

Abstract VTI1A-TCF7L2 was reported as a recurrent fusion gene in colorectal cancer (CRC), found to be expressed in three out of 97 primary cancers, and one cell line, NCI-H508, where a genomic deletion joins the two genes (Bass et al. Nature Genetics, 2011). To investigate this fusion further, we analyzed high-throughput DNA and RNA sequencing data from seven CRC cell lines in addition to publicly available data from the NCI-H508 cell line. From both genome and transcriptome data, the gene RP11-57H14.3 (ENSG00000225292) was identified as a novel fusion partner for TCF7L2 in the HCT 116 cell line. The originally reported fusion VTI1A-TCF7L2 was identified as expected from the analysis of NCI-H508 data. By triplicate nested RT-PCR, we tested both the novel fusion transcript and VTI1A-TCF7L2 for expression in a series of 106 CRC tissues, 21 colon cancer cell lines, 14 normal colonic mucosa, and 20 normal tissues from miscellaneous anatomical sites. Altogether, 42% and 45% of the CRC samples expressed VTI1A-TCF7L2 and TCF7L2-RP11-57H14.3 fusion transcripts, respectively. The two fusion transcripts were both seen in 29% of the normal colonic mucosa samples, and in 25% and 75% of the tested normal tissues from other organs. Seven different splice variants were detected for the VTI1A-TCF7L2 fusion, of which three are novel. Four different splice variants were detected for the TCF7L2-RP11-57H14.3 fusion. In conclusion, we have identified novel variants of VTI1A-TCF7L2 fusion transcripts, including a novel fusion partner gene, RP11-57H14.3. We demonstrated detectable levels of TCF7L2 involving fusion transcripts in a large fraction of CRC samples, as well as in normal colonic mucosa and other normal tissue types, revealing that these fusions, at transcript level, are neither specific to cancer nor to the colon and rectum. Citation Format: Andreas M. Hoff, Torfinn Nome, Anne Cathrine Bakken, Torleiv O. Rognum, Arild Nesbakken, Rolf I. Skotheim. High frequency of fusion transcripts involving TCF7L2 in colorectal cancer: Novel fusion partner and splice variants. [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 2235. doi:10.1158/1538-7445.AM2014-2235
Basic Surgical Physiology
Authors: William W. Coon
Journal: JAMA (1969)

Drs. Preston and Beal have compiled, with the help of many of their associates at Northwestern University, a text of applied physiology particularly directed to the interests of surgeons. The material presented includes the circulatory, respiratory, digestive, genitourinary and endocrine systems, the integument, and brief discussions of wound healing, burns, shock, fluid and electrolytes, blood coagulation and transfusion, the metabolic response to injury, and biologic principles of transplantation. The authors have not included any data concerning physiology of the nervous or musculoskeletal systems or of reproduction or the special senses. Each of 38 separate subject headings is concisely presented, averaging 10 to 15 pages in length. Almost all chapters are followed by 6 to 100 pertinent and recent references. A suitable number of very good tables, figures, and other illustrations are dispersed throughout the volume and, in general, make a significant contribution to each presentation. Very few typographical or editorial
Inflammatory Pathway Genes Belong to Major Targets of Persistent Organic Pollutants in Adipose Cells
Authors: Min Ji Kim, Véronique Pelloux, Erwan Guyot, Joan Tordjman, Linh-Chi Bui, Aline Chevallier, Claude Forest, Chantal Benelli, Karine Clément, Robert Barouki
Journal: Environmental Health Perspectives (2012)

Epidemiological studies emphasize the possible role of persistent organic pollutants (POPs) in obesity and the metabolic syndrome. These pollutants are stored in adipose tissue (AT).Our aim was to study the effects of POPs on human adipose cells and rodent AT.Using human multipotent adipose-derived stem cells, we carried out large-scale gene expression analysis to identify the major pathways modified by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), polychlorinated biphenyl (PCB) congener 126 (PCB-126), and PCB-153 and to evaluate their toxic effects. The effects of TCDD on gene expression and AT histology were also assessed in mice.The most significantly regulated genes in both precursor cells and adipocytes were those involved in the inflammatory/immune response, cancer, and metabolism pathways. Interestingly, the fold induction and the number of modulated genes were higher in precursors than in adipocytes, suggesting that the former could be more sensitive to the effect of pollutants. When cells were treated with combinations of pollutants, the effects of the AhR ligands TCDD and PCB-126 were dominant compared with those of the non-dioxin-like PCB-153. The effects of AhR ligands were reduced by the AhR antagonist α-naphthoflavone. The regulation of inflammatory pathway was observed in wild-type AT but not in AhR-knockout mice.Both in vitro and in vivo studies showed that adipose cells were targets of AhR ligands and suggest that inflammation is one of the main regulated pathways. These observations suggest a possible contribution of pollutants to low-grade AT inflammation that accompanies the pathogenesis of metabolic diseases.
Bioreducible Carboxymethyl Dextran Nanoparticles for Tumor‐Targeted Drug Delivery
Authors: Thavasyappan Thambi, Dong Gil You, Hwa Seung Han, V. G. Deepagan, Sang Min Jeon, Yung Doug Suh, Ki Young Choi, Kwangmeyung Kim, Ick Chan Kwon, Gi‐Ra Yi, Jun Young Lee, Doo Sung Lee, Jae Hyung Park
Journal: Advanced Healthcare Materials (2014)

Bioreducible carboxymethyl dextran (CMD) derivatives are synthesized by the chemical modification of CMD with lithocholic acid (LCA) through a disulfide linkage. The hydrophobic nature of LCA allows the conjugates (CMD‐SS‐LCAs) to form self‐assembled nanoparticles in aqueous conditions. Depending on the degree of LCA substitution, the particle diameters range from 163 to 242 nm. Doxorubicin (DOX), chosen as a model anticancer drug, is effectively encapsulated into the nanoparticles with high loading efficiency (&gt;70%). In vitro optical imaging tests reveal that the fluorescence signal of DOX quenched in the bioreducible nanoparticles is highly recovered in the presence of glutathione (GSH), a tripeptide capable of reducing disulfide bonds in the intracellular compartments. Bioreducible nanoparticles rapidly release DOX when they are incubated with 10 m m GSH, whereas the drug release is greatly retarded in physiological buffer (pH 7.4). DOX‐loaded bioreducible nanoparticles exhibit higher toxicity to SCC7 cancer cells than DOX‐loaded nanoparticles without the disulfide bond. Confocal laser scanning microscopy observation demonstrate that bioreducible nanoparticles can effectively deliver DOX into the nuclei of SCC7 cells. In vivo biodistribution study indicates that Cy5.5‐labeled CMD‐SS‐LCAs selectively accumulate at tumor sites after systemic administration into tumor‐bearing mice. Notably, DOX‐loaded bioreducible nanoparticles exhibit higher antitumor efficacy than reduction‐insensitive control nanoparticles. Overall, it is evident that bioreducible CMD‐SS‐LCA nanoparticles are useful as a drug carrier for cancer therapy.
Pseudolipoma and Pseudolobulation
Authors: T. G. E. Loosemore
Journal: BMJ (1966)

MDICLOUINAend of a long and relatively narrow building.Dry developed films are returned to the clinic in an average time of nine minutes.I believe that this may be the first tube system to be so used, and it has been found to be very effective in practice.The -exposed film is removed from its cassette in a dark cubicle some 3 ft.square (0.8 sq.metre), marked with the patient's name, date, etc., rolled in its original packing paper in order to avoid unnecessary handling and static marks, and placed in the cylindrical aluminium carrier, which is then put into the sending tube.Two or even three films, if necessary, can be put into a carrier at any one time.The carriers are long enough to take the largest x-ray films, and are, of course, light-tight.The receiving end of the return tube has been separated from the sending tube, and is situated outside the dark cubicle so that the developed films can be delivered to the clinic without interrupting the radiographer.The cost of installation of this system was not greater than the cost of constructing and equipping a small but conventional dark- room, for which, in any case, there was insufficient space available in the area, and the need for additional dark-room technical assistance was avoided.Although this simple point-to-point system was installed for one particular purpose, trials using special inserts in the carriers have shown that laboratory specimens and blood samples can be safely transmitted without damage or lysis.These experiments suggest that larger installations, either fully or semi- automatic, and relying on the operation of recently developed and much more reliable proximity switches, should play a major role in future hospital design and equipment.-Iam, etc.,
HERMANN VON HELMHOLTZ—THE INVENTOR OF THE OPHTHALMOSCOPE.
Authors: CASEY A. WOOD
Journal: JAMA (1902)

<h3>Vormals im Leben ehrten wir dich, wie einen der Goetter, Nun du todt bist, so herrscht über die Geister dein Geist.</h3> Quite apart from the interest that is naturally excited by the life-story of the great scientist who invented the instrument that revolutionized the science and art of ophthalmology, there are, at least, two reasons why this gathering should be especially interested in the life of Hermann Ludwig Ferdinand Von Helmholtz. In the first place it was as a student and practitioner of medicine that he entered upon those studies that carried his name and spread his fame throughout the world of science. Then, in the second place, there coursed in his veins the bluest of American blood. His mother was the daughter of a Hanoverian artillery officer named Penne, a direct descendant of William Penn. It is more than possible that the calm, thoughtful spirit which distinguished all the
Recurrent hypoglycaemia in a diabetic patient as a result of unexpected renal failure
Authors: Malvinder S Parmar
Journal: BMJ (2004)

Hypoglycaemia is the most frequent complication of diabetes, affecting 10% to 25% of diabetic patients at least once a year and accounting for 3% to 4% of deaths in those treated with insulin.1 Diabetic renal disease is a common complication and is the most prevalent cause of end stage renal disease in the western world.2

The kidney plays an important role in glucose homoeostasis: in addition to metabolising between30% and 40% of insulin,3 it provides up to 45% of endogenous glucose through gluconeogenesis during a prolonged fast.4 In renal failure, it cannot metabolise insulin or generate glucose, thereby increasing the risk of hypoglycaemia. Hypoglycaemia affects 67% of diabetic patients with renal failure, and in almost half (46%) of patients it is often related to the medication they are taking.5 I present a case where a decline in renal function after treatment with diclofenac resulted in …
Mortality associated with foodborne bacterial gastrointestinal infections: Statistical method is worth examining
Authors: L. A. Cox
Journal: BMJ (2003)

EDITOR—Helms et al report a significant association between common foodborne infections, including campylobacteriosis, and increased short term and long term mortality.1 As this conflicts with conventional clinical wisdom,2 it is worth scrutinising the statistical method supporting the claim.

Helms et al compare ill cases with healthier (general population) controls by using a comorbidity index to adjust for the fact that underlying conditions were more common …
The Return on INVEST
Authors: Michael H. Alderman
Journal: JAMA (2003)

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Abstract 2421: Small molecule inhibitors of DNA glycosylases as potential drugs in cancer therapy
Authors: Miral Dizdaroglu, Pawel Jaruga
Journal: Cancer Research (2014)

Abstract DNA glycosylases are required to initiate the DNA base excision repair pathway of lesions that are formed by DNA damage. Recently, several DNA glycosylases including NEIL1, OGG1 and NTH1 were identified as potential targets in combination chemotherapeutic strategies for cancer treatment. The potential therapeutic benefit for the inhibition of DNA glycosylases was validated by demonstrating synthetic lethality with drugs that are commonly used to limit DNA replication through dNTP pool depletion. Additionally, NEIL1-associated synthetic lethality has been achieved in combination with Fanconi anemia, group G. In this work, we designed experimental strategies to discover small molecule inhibitors of NEIL1, with subsequent analyses of the specificity of those molecules for other DNA glycosylases. Using NEIL1 as the proof-of-principle DNA glycosylase, we developed a fluorescence-based assay that utilizes incision of site-specifically modified oligodeoxynucleotides to detect enzymatic activity. Among the top hits of these screens were several purine analogs, whose postulated presence in the active site of NEIL1 was consistent with the paradigm of NEIL1 recognition and excision of purine-derived lesions. We also applied gas chromatography/isotope-dilution tandem mass spectrometry for the measurement of the effect of preferred small molecule inhibitors on activities of the DNA glycosylases NEIL1, OGG1 and NTH1. The release of modified bases, which are known substrates of these enzymes, was measured in the presence and absence of the inhibitors. These data revealed that several of the purine analogs were general glycosylase inhibitors with one compound being the most effective inhibitor for all three enzymes. However, there were significance differences in inhibition of enzymatic activities among these three DNA glycosylases. Overall, this work forms the foundation for the future discovery of DNA repair inhibitors as drugs in cancer therapy for the entire family of DNA glycosylases. Citation Format: Miral Dizdaroglu, Pawel Jaruga. Small molecule inhibitors of DNA glycosylases as potential drugs in cancer therapy. [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 2421. doi:10.1158/1538-7445.AM2014-2421
Diagnosis and management of prosthetic joint infection
Authors: P. C Matthews, A. R Berendt, M. A McNally, I. Byren
Journal: BMJ (2009)

Joint replacement is safe, cost effective,1 and widely undertaken. Most prosthetic joint replacements are hips and knees; more than 130 000 people underwent such procedures in England and Wales in the 12 months from April 2006.w1 Subsequent prosthetic joint infection is uncommon—the incidence varies between 0.6% and 2% per joint per year.2 3 4 5 However, this complication is associated with substantial morbidity and economic cost ($30 000 (£20 500; €22 800) to $50 000 per patient).3 4 6 w2 The diagnosis of prosthetic joint infection is difficult,w2 because symptoms, signs, and investigations may all be non-specific.7 w3 Defining diagnostic criteria and optimum management is complicated by patient heterogeneity and the small numbers in many published studies.w4 However, prompt recognition and diagnosis of prosthetic joint infection facilitates timely intervention to salvage infected joints, preserve joint function, prevent morbidity, and reduce costs.

#### Summary points

#### Sources and selection criteria

We performed Medline searches between November 2008 and January 2009 using the search terms “prosthetic joint” and “arthroplasty” combined with “infection”, “guidelines”, “septic arthritis”, “infection diagnosis”, “infection epidemiology”, and “infection revision arthroplasty”. Where possible, we focused on articles published in the past five years and restricted our search to literature published in English. We also drew from the experience of, and articles and documents published by, our multidisciplinary bone infection unit in the United …
Phagocytosis of aged human neutrophils by macrophages is mediated by a novel "charge-sensitive" recognition mechanism.
Authors: J S Savill, P M Henson, C Haslett
Journal: Journal of Clinical Investigation (1989)

The removal of neutrophils and their histotoxic contents from the inflamed site is a prerequisite for resolution of tissue injury, and a point at which factors critical to the pathogenesis of chronic inflammation may act. Engulfment of intact, senescent neutrophils by macrophages represents an important neutrophil disposal process. In this study the mechanism by which human monocyte-derived macrophages (M phi) recognized and ingested human neutrophils that had been aged in culture was studied using an in vitro phagocytic assay. Inhibition of M phi receptors for Ig Fc and the opsonic complement fragments C3b and iC3b with MAbs to M phi FcR, CR1, CR3, and CR4 had no effect on recognition, and the pattern of inhibition observed when polyanions were included in the medium at 1 mg/ml was different from that reported for the M phi receptor for protein advanced glycosylation end products (AGE), indicating a recognition mechanism different from those proposed for M phi phagocytosis of senescent erythrocytes. Furthermore, although aging neutrophils undergo programmed cell death (or apoptosis), which is directly related to recognition by M phi, the pattern of inhibition observed with monosaccharides was different from that reported to inhibit the binding of apoptotic mouse thymocytes to isologous M phi. By contrast, evidence was obtained for a novel recognition mechanism inhibitable by cationic sugars and amino acids in a charge-dependent fashion, and directly modulated by pH but not affected by inhibitors of the mannose-6-phosphate, sheep erythrocyte, mannosyl-fucosyl, asialoglycoprotein, and scavenger receptors of the macrophage. These observations suggest that hydrogen ions and charged molecules may modulate M phi uptake of senescent neutrophils at inflamed sites, and that recognition itself may involve charged structures on the cells.