tbuckley/cabot-search huggingface dataset:
Abstract P5-08-13: Alteration of sensitivity to chemotherapeutic agents in tamoxifen resistant estrogen receptor positive breast cancer
Authors: T Watanabe, T Okada, T Oba, A Iesato, T Hanamura, T Kanai, K Maeno, K-I Ito
Journal: Cancer Research (2013)

Abstract Background: In the treatment of estrogen receptor (ER) positive recurrent breast cancer, sequential treatment with endocrine or chemotherapy is generally used. However, there is no indicator by which we can select the appropriate chemotherapeutic agent to the endocrine resistant breast cancer in the subsequent treatment. The purpose of this study is to examine whether a preceding endocrine therapy affects the sensitivity to subsequent chemotherapy in ER positive breast cancer cells. Materials and methods: Three ER positive breast cancer cell lines (T47D, MCF7, BT474) and their tamoxifen (TAM) resistant derivatives (T47D/T, MCF7/T, BT474/T) were established and analyzed for sensitivity to doxorubicin (DOX), 5FU and paclitaxel (PTX). The mRNA levels of factors related to drug sensitivity were analyzed by RT-PCR. Results: MCF7/T became more sensitive to DOX and 5FU compared with the parental MCF7. In addition, the apoptosis induced by 5FU was significantly increased in MCF7/T compared with the parental MCF7. On the other hand, no difference of sensitivity to chemotherapeutic agents was observed in T47D/T and BT474/T compared with their parental cell lines. In MCF7/T and T47D/T, the expressions of dihydropyrimidine dehydrogenase (DPD) were significantly decreased compared with those in the parental cell lines, while no difference was observed in the expression of thymidine synthase (TS). The expression of thymidine phosphorylase (TP) was decreased in MCF7/T. Conclusion: Our data demonstrate that the sensitivity to 5FU might be altered in a subset of ER positive breast cancer cells, and suggest a possibility that the sensitivity to the chemotherapeutic agents might be modified by the preceding endocrine therapy in ER positive breast cancer cells. We are analyzing drug sensitivity in tumor-bearing mouse model and the data are going to be presented in the meeting. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-08-13.
Should we use bath emollients for atopic eczema?
Authors: A. Tarr, I. Iheanacho
Journal: BMJ (2009)

Regular topical application of an emollient cream or ointment is key in the management of patients with atopic eczema and is thought to help the skin maintain a defensive barrier effect, which is defective in atopic eczema.1 Support for such treatment comes from one (non-blinded) randomised controlled trial, which found that regular application of emollients direct to the skin reduced the amount of topical corticosteroid cream needed for atopic eczema in infants.2 Long clinical experience also suggests that directly applied emollients are safe and effective in atopic eczema.

People with atopic eczema are commonly also advised to use an emollient substitute for soap (such as aqueous cream or emulsifying ointment), as soap can irritate the skin (as can bubble bath preparations); patients are also often prescribed a bath emollient to add to their bath water.3 Bath emollients typically consist of liquid paraffin plus another emollient (usually wool fat or isopropyl myristate); a few also contain an antimicrobial drug.

Some prescribers recommend bath emollients to avoid use of bubble bath preparations. …
Secondary neoplastic infiltration of the myocardium diagnosed by two-dimensional echocardiography in seven cases with anatomic confirmation
Authors: Chiara Lestuzzi, Salvatore Biasi, Gian Luigi Nicolosi, Daniela Lodeville, Daniela Pavan, Raffaele Collazzo, Antonio Guindani, Domenico Zanuttini
Journal: Journal of the American College of Cardiology (1987)
Hepatic phosphotyrosine phosphatase activity and its alterations in diabetic rats.
Authors: J Meyerovitch, J M Backer, C R Kahn
Journal: Journal of Clinical Investigation (1989)

Phosphotyrosine phosphatase (PTPase) activity in rat liver was measured using a phosphopeptide substrate containing sequence identity to the major site of insulin receptor autophosphorylation. PTPase activity was detected in both cytosolic and particulate fractions of rat liver and produced linear dephosphorylation over a 15-min time course. In rats made insulin-deficient diabetic by streptozotocin treatment (STZ), cytosolic PTPase activity increased to 180% of the control values after 2 d of diabetes and remained elevated at 30 d (P less than 0.02). Gel filtration on Sephadex-75 revealed a single peak of activity in the cytosol in both control and diabetic animals and confirmed the increased levels. In BB diabetic rats, another model of insulin deficiency, the PTPase activity in the cytosolic fraction was increased to approximately 230% of control values. PTPase activity in the particulate fraction of liver was also increased by 30 and 80% after 2 and 8 d of STZ diabetes, respectively. However, this increase was not sustained and after 30 d of STZ diabetes, PTPase activity associated with the particulate fraction in the BB diabetic rat was reduced to approximately 70% of the control levels. Treatment of STZ diabetic rats with subcutaneous insulin or vanadate in their drinking water for 3 d reduced tyrosine PTPase activity in the particulate, but not in the cytosolic fraction. This was associated with a change in blood glucose toward normal. These data indicate insulin deficient diabetes is accompanied by significant changes in hepatic PTPase activity. Since tyrosine phosphorylation plays a central role in the cellular action of insulin receptor, an increase in PTPase activity may be an important factor in the altered insulin action associated with these diabetic states.
Rapid Latex Agglutination Assay Using Recombinant Envelope Polypeptide for the Detection of Antibody to the HIV
Authors: Thomas C. Quinn
Journal: JAMA (1988)

Unscreened blood transfusions continue to be one of the major modes of transmission of the human immunodeficiency virus (HIV) in developing countries, such as in Central Africa, where 5% to 18% of blood donors are HIV seropositive. We evaluated a rapid latex agglutination assay using a novel recombinant envelope polypeptide of HIV for the detection of HIV antibodies among 2820 blood donors and clinical patients from diverse geographic regions, including on-site testing in Central Africa of 1600 blood donors. Overall, 29.2% of the serum samples were positive by Western blot assay. On a single determination, the latex agglutination slide test was found to be highly sensitive and specific compared with Western blot results in these populations with a relatively high prevalence of infection. Use of this assay will allow the immediate implementation of serologic screening for HIV in developing areas of the world, where standard screening procedures are impractical or not available, and in many other clinical settings, such as sexually transmitted diseases clinics and hospitals, where testing and counseling could be promptly implemented.
Simple linear regression
Authors: P. Sedgwick
Journal: BMJ (2013)

<b>1319</b> <b>Objectives</b>: The rate of gastric emptying of a solid meal varies depending on many factors, including meal volume and composition, patient position, and imaging methodology. We have found published standardized methods that report normal reference values to be difficult to implement. Our objective was to establish normal reference values using a protocol that any nuclear medicine department can adopt, using an easily duplicated and palatable meal, image aquisition that is well tolerated by patients, and simple processing. <b>Methods</b>: The meal consisted of an egg white sandwich, prepared with 1 mCi of Tc99 sulfur colloid cooked into 50 cc of egg white (separated from fresh whole eggs), an English Muffin, and 150 cc of water. Twenty nine healthy volunteers were imaged using simultaneous anterior and posterior one minute static images, acquired every 15 minutes for two hours. Imaging was supine, but the subjects were allowed off the table to sit in a chair between images. Percent gastric emptying at each time point was calculated using decay corrected geometric mean counts. The upper and lower limits of normal were calculated for each time point using the mean + and - 2.048SD (t critical value = 2.048 with 28 df). <b>Results</b>: The results are in the attached table. Because nearly all our of our clinical exams are done for gastroparesis, we were most interested in the lower limits of normal gastric emptying. At 60 minutes, the lower limit of normal is 18%, with mean emptying of 54%. At 90 minutes the lower limit is 46%, with mean emptying of 75%. <b>Conclusions</b>: We have described a standardized method for scintigraphic measurement of gastric emptying of solids, which can be duplicated in nearly any nuclear medicine department, and have established normal values based on 29 normal subjects.
Regulation of Ion Channels by Pyridine Nucleotides
Authors: Peter J. Kilfoil, Srinivas M. Tipparaju, Oleg A. Barski, Aruni Bhatnagar
Journal: Circulation Research (2013)

Recent research suggests that in addition to their role as soluble electron carriers, pyridine nucleotides [NAD(P)(H)] also regulate ion transport mechanisms. This mode of regulation seems to have been conserved through evolution. Several bacterial ion–transporting proteins or their auxiliary subunits possess nucleotide-binding domains. In eukaryotes, the Kv1 and Kv4 channels interact with pyridine nucleotide–binding β-subunits that belong to the aldo-keto reductase superfamily. Binding of NADP + to Kvβ removes N-type inactivation of Kv currents, whereas NADPH stabilizes channel inactivation. Pyridine nucleotides also regulate Slo channels by interacting with their cytosolic regulator of potassium conductance domains that show high sequence homology to the bacterial TrkA family of K + transporters. These nucleotides also have been shown to modify the activity of the plasma membrane K ATP channels, the cystic fibrosis transmembrane conductance regulator, the transient receptor potential M2 channel, and the intracellular ryanodine receptor calcium release channels. In addition, pyridine nucleotides also modulate the voltage-gated sodium channel by supporting the activity of its ancillary subunit—the glycerol-3-phosphate dehydrogenase-like protein. Moreover, the NADP + metabolite, NAADP + , regulates intracellular calcium homeostasis via the 2-pore channel, ryanodine receptor, or transient receptor potential M2 channels. Regulation of ion channels by pyridine nucleotides may be required for integrating cell ion transport to energetics and for sensing oxygen levels or metabolite availability. This mechanism also may be an important component of hypoxic pulmonary vasoconstriction, memory, and circadian rhythms, and disruption of this regulatory axis may be linked to dysregulation of calcium homeostasis and cardiac arrhythmias.
Anemia of inflammation: the cytokine-hepcidin link
Authors: Nancy C. Andrews
Journal: Journal of Clinical Investigation (2004)

The anemia of inflammation, commonly observed in patients with chronic infections, malignancy, trauma, and inflammatory disorders, is a well-known clinical entity. Until recently, we understood little about its pathogenesis. It now appears that the inflammatory cytokine IL-6 induces production of hepcidin, an iron-regulatory hormone that may be responsible for most or all of the features of this disorder.
Endocan Is Upregulated on Tumor Vessels in Invasive Bladder Cancer Where It Mediates VEGF-A–Induced Angiogenesis
Authors: Filip Roudnicky, Cedric Poyet, Peter Wild, Sarah Krampitz, Fabrizia Negrini, Reto Huggenberger, Anja Rogler, Robert Stöhr, Arndt Hartmann, Maurizio Provenzano, Vivianne I. Otto, Michael Detmar
Journal: Cancer Research (2012)

Tumor-associated blood vessels differ from normal vessels and proteins present only on tumor vessels may serve as biomarkers or targets for antiangiogenic therapy in cancer. Comparing the transcriptional profiles of blood vascular endothelium from human invasive bladder cancer with normal bladder tissue, we found that the endothelial cell-specific molecule endocan (ESM1) was highly elevated on tumor vessels. Endocan was associated with filopodia of angiogenic endothelial tip cells in invasive bladder cancer. Notably, endocan expression on tumor vessels correlated strongly with staging and invasiveness, predicting a shorter recurrence-free survival time in noninvasive bladder cancers. Both endocan and VEGF-A levels were higher in plasma of patients with invasive bladder cancer than healthy individuals. Mechanistic investigations in cultured blood vascular endothelial cells or transgenic mice revealed that endocan expression was stimulated by VEGF-A through the phosphorylation and activation of VEGFR-2, which was required to promote cell migration and tube formation by VEGF-A. Taken together, our findings suggest that disrupting endocan interaction with VEGFR-2 or VEGF-A could offer a novel rational strategy to inhibit tumor angiogenesis. Furthermore, they suggest that endocan might serve as a useful biomarker to monitor disease progression and the efficacy of VEGF-A-targeting therapies in patients with bladder cancer.
Postpsychiatry: Mental Health in a Postmodern World
Authors: Jack Piachaud
Journal: BMJ (2006)

You would imagine thinking about thinking to be the province of psychiatry. This, surprisingly, is not the case. There are many differing views and approaches to the mental world, but these largely reside in the discipline of philosophy. Psychiatry has been taken over by a biomedical model, leaving little space for other considerations; this book attempts to open up that space. 

The path for psychiatry was largely determined by two major social processes of the 18th and 19th centuries: the development of institutions for the insane and the Enlightenment. As society became increasingly complex, institutions emerged for not only the …
Prevalence of multiple sclerosis in five rural Suffolk practices.
Authors: M J Lockyer
Journal: BMJ (1991)

OBJECTIVE--To determine a point prevalence of multiple sclerosis in part of Suffolk. DESIGN--Multiple source search for patients with multiple sclerosis in five general practices. Patients were reviewed and categorised by using general practice notes. SETTING--Five rural general practices in Suffolk, 12 May 1988. SUBJECTS--31,379 patients registered with five practices. MAIN OUTCOME MEASURES--Multiple sclerosis diagnosed by a specialist. RESULTS--The search produced a provisional list of 62 eligible patients with multiple sclerosis. Review of case notes showed that 48 had probable disease, 10 early disease, and four possible disease. The probable cases gave a crude prevalence of 153/100,000 population (95% confidence interval 109/100,000 to 196/100,000). CONCLUSIONS--Although the results should be interpreted cautiously because of the small sample size, they suggest that the prevalence of multiple sclerosis in Suffolk is higher than has been estimated from hospital data.
A CAUSE OF ADHESIONS IN THE RIGHT UPPER QUADRANT
Authors: ARTHUR H. CURTIS
Journal: JAMA (1930)

For several years it has been my custom to make a thorough survey of the abdominal contents in nearly all cases in which the abdomen is opened. This examination differs materially from casual notation of the condition of the gallbladder and the appendix, such as is common practice with gynecologists. Palpation is conducted with painstaking gentleness, as well as thoroughness; I aim always to be so gentle that patients under light anesthesia are not aroused or stimulated to strain because of the forcefulness or harshness of manipulation. Thorough routine examination, as indicated, has led to the discovery that there is a frequent incidence of "violin-string" adhesions between the anterior surface of the liver and the anterior abdominal wall. I wish particularly to emphasize the location and the character of these adhesions in distinction from isolated adhesion bands and commonly encountered liver-kidney or gastrohepatic adhesions or adhesions on the under surface
Spatial variations in the Soviet health service.
Authors: M Ryan, R Prentice
Journal: BMJ (1983)

According to the familiar propaganda, the Soviet Union is a  of nations and, to quote from the state anthem, a union of indissoluble republics. Arguably, it might also be identified as the last of the great empires, in which one half of the population rules over the numerous ethnic groups making up the other half. These mutually irreconcilable views are relevant to this article, since they both allow for a degree of autonomy in the development of health services in different parts of the USSR. We analysed data on the numbers of doctors, middle grade staff, and hospital beds in each of the 15 Union republics, which are the main divisions of the Union's territorial-administrative rtructure. (In constitutional theory they enjoy the status of sovereign nation states and have the right to secede from the USSR.) The period covered ran from 1950 to 1980, respectively the first and, currently, the last postwar year for which pub? lished data are available.1 During this period no discontinuity or historic break with the past occurred comparable with the inception of the National Health Service in the United Kingdom.
Furaltadone
Authors: William R. McCabe, John C. Davis, Burton R. Andersen, George Gee Jackson
Journal: New England Journal of Medicine (1960)

FURALTADONE is the generic name given to a nitrofuran chemically described as 5-morpholinol-methyl-3-(5-nitrofurfurylideneamino) -2-oxazolidone.1 As has been observed for various other nitrofurans, furaltadone is inhibitory and bactericidal in vitro for staphylococci. In contrast to nitrofurantoin, which also inhibits staphylococci in vitro,2 furaltadone is not rapidly excreted in the urine, at least not in an active form. It was hoped, therefore, that inhibitory concentrations could be produced in the plasma and that it would serve as effective treatment for serious systemic staphylococcal infections. The present studies were undertaken to test this thesis by observation of the results obtained from the administration . . .
Rapid, reversible activation of AgRP neurons drives feeding behavior in mice
Authors: Michael J. Krashes, Shuichi Koda, ChianPing Ye, Sarah C. Rogan, Andrew C. Adams, Daniel S. Cusher, Eleftheria Maratos-Flier, Bryan L. Roth, Bradford B. Lowell
Journal: Journal of Clinical Investigation (2011)

Several different neuronal populations are involved in regulating energy homeostasis. Among these, agouti-related protein (AgRP) neurons are thought to promote feeding and weight gain; however, the evidence supporting this view is incomplete. Using designer receptors exclusively activated by designer drugs (DREADD) technology to provide specific and reversible regulation of neuronal activity in mice, we have demonstrated that acute activation of AgRP neurons rapidly and dramatically induces feeding, reduces energy expenditure, and ultimately increases fat stores. All these effects returned to baseline after stimulation was withdrawn. In contrast, inhibiting AgRP neuronal activity in hungry mice reduced food intake. Together, these findings demonstrate that AgRP neuron activity is both necessary and sufficient for feeding. Of interest, activating AgRP neurons potently increased motivation for feeding and also drove intense food-seeking behavior, demonstrating that AgRP neurons engage brain sites controlling multiple levels of feeding behavior. Due to its ease of use and suitability for both acute and chronic regulation, DREADD technology is ideally suited for investigating the neural circuits hypothesized to regulate energy balance.
Role of Transplantation in the Treatment of Benign Solid Tumors of the Liver
Authors: Sayee Sundar Alagusundaramoorthy, Valery Vilchez, Anthony Zanni, Achuthan Sourianarayanane, Erin Maynard, Malay Shah, Michael F. Daily, Luis R. Pena, Roberto Gedaly
Journal: JAMA Surgery (2015)

The role of orthotopic liver transplantation for the treatment of benign solid liver tumors (BSLT) is not well defined.To analyze outcomes in the United Network of Organ Sharing data set of patients with a diagnosis of BSLT who underwent transplantation.A retrospective analysis of the United Network of Organ Sharing data set was performed for all (N = 87,280) patients who underwent transplantation for BSLT in the United States from October 1, 1988, through January 31, 2013.Demographics, clinicopathological characteristics, distribution of the procedures by region and state, and overall survival rates.During the study period, 147 liver transplants (0.17%) were to treat BSLT. Sixty-two patients (42.2%) had adenomas, 29 (19.7%) had focal nodular hyperplasia, 25 (17.0%) had hemangiomas, 11 (7.5%) had hepatic epithelioid hemangioendotheliomas, and 20 (13.6%) were classified as having unknown benign tumors. The overall 1-, 3-, and 5-year survival rates were 90.9%, 85.2%, and 81.8%, respectively. Using multivariable analysis, we found that age was the only independent factor associated with patient survival. The overall 5-year survival rate for patients older than 50 years was 88% compared with 91% in younger individuals (95% CI, 148-384; P = .005). Region 3 (Alabama, Arkansas, Florida, Georgia, Louisiana, Mississippi, and Puerto Rico) contributed the maximum number (33 [22.4%]) of these transplants.Although liver transplantation cannot be considered a first-line treatment, it is a valid therapeutic option in selected patients who are not amenable to resection. Only 0.17% of the transplants in the United States are performed for this indication, with satisfying long-term results. Age was an independent predictor of patient survival. Further studies are needed to better understand the role of liver transplantation in the treatment of BSLT.
Consultant struck off over research fraud
Authors: C. Dyer
Journal: BMJ (1997)

A senior consultant physician and former registrar and secretary of the Royal College of Physicians in Edinburgh was struck off the medical register last week for conducting a 15 month sham drug trial.

John Anderton, a consultant for 26 years, who retired after his deception came to light, pleaded guilty to a charge of serious professional misconduct. The General Medical Council's professional conduct committee heard that he had forged consent forms for 17 patients who were never given the drug, got his assistant falsely to attest that she had witnessed patients' signatures on consent forms, and invented echocardiographic and magnetic resonance imaging data for patients.

Dr Anderton, aged 63, was paid £42000 ($70500) for the …
Transient urinary tract dilatation associated with hypokalaemia
Authors: B I Hoffbrand
Journal: BMJ (1985)

result.6With this technique cure rates of 97-99% are to be expected even when dealing with the most recidivist of tumours.Microscopically controlled excision is now used extensively in the USA, where the surgery is carried out by properly trained dermatological surgeons.Otolaryngologists and ophthalmic and plastic surgeons commonly refer patients for Mohs's surgery.78We hope that the facilities for this procedure will soon be more widely available in the United Kingdom so that full advantage can be taken of this important technique in the management of difficult cutaneous tumours.