tbuckley/cabot-search huggingface dataset:
Activation of RhoB by Hypoxia Controls Hypoxia-Inducible Factor-1α Stabilization through Glycogen Synthase Kinase-3 in U87 Glioblastoma Cells
Authors: Nicolas Skuli, Sylvie Monferran, Caroline Delmas, Isabelle Lajoie-Mazenc, Gilles Favre, Christine Toulas, Elizabeth Cohen-Jonathan-Moyal
Journal: Cancer Research (2006)

Abstract Hypoxia is a crucial factor in tumor aggressiveness and resistance to treatment, particularly in glioma. Our previous results have shown that inhibiting the small GTPase RhoB increased oxygenation of U87 human glioblastoma xenografts, in part, by regulating angiogenesis. We investigated here whether RhoB might also control a signaling pathway that would permit glioma cells to adapt to hypoxia. We first showed that silencing RhoB with siRNA induced degradation and inhibition of the transcriptional activity of the hypoxia-inducible factor by the proteasome in U87 hypoxic cells. This RhoB-dependent degradation of hypoxia-inducible factor-1α in hypoxic conditions was mediated by the Akt/glycogen synthase kinase-3β pathway. While investigating how hypoxia could activate this signaling pathway, using the GST-Rhotekin RBD pulldown assay, we showed the early activation of RhoB by reactive oxygen species under hypoxic conditions and, subsequently, its participation in the ensuing cellular adaptation to hypoxia. Overall, therefore, our results have not only highlighted a new signaling pathway for hypoxia controlled by the small GTPase RhoB, but they also strongly implicate RhoB as a potentially important therapeutic target for decreasing tumor hypoxia. (Cancer Res 2006; 66(1): 482-9)
Rare Case of Epispadias without Extroversion of Bladder; and Account of Operation
Authors: G. Lichtenberg
Journal: BMJ (1873)

eases there are vesicles which are crowded together, but the character of the fluid uplifting the cuticle, and its subsequent behaviour, the source of this fluid, the anatomical seat of the disease, are wholly and entirely different.The disease is not the hydroa of Bazin, under which term a host of different things have been classed-urticaria bullosa, erythema papulatum, miliaria, and the like.Of course, in many diseases, excessive sweating occurs, as in the case of idrosis, miliaria, and sudamina; but then the sweating is only an accidental feature, and accounted for by the general disturbance; but in this disease, the sweat-disorder is the main and sole disease present.But I have noticed that it always occurs in those who too freely perspire, in those who are depressed, weak, and get quickly exhausted, and in connection with, oftentimes, anomalous nerve-symptoms.The cause of the sudden outpouring of sweat is doubiful.It is, probably, some disturbance of the nerve-influence.Now as to treatment.It is of no use trying to cure the disease by local measures, though you can moderate the irritation, and inflammation, and prevent the sweat from becoming sour and irritating.The internal remedies are diuretics, with a view to relieve the skin, with large doses of quinine and nux vomica.Locally, I cover up the parts in the acute and early stage, with some simple cerate, with liquor plumbi, rubbed into it, and perhaps carbolic acid, in small quantity.Then, later on, I coat the parts with starch and calamine powder, and later on prescribe the balsam of Peru, twenty grains to an ounce of lard, with a little white precipitate.Most cases do well.In the simpler instances of the dis- ease you give the quinine internally, with arsenic if you like, and diuretics if need be, and locally protect the parts with calamine lotion.I have termed the disease dysidrosis, because nature seems to have a difficulty in getting rid of the secreted sweat, which remains to distend the follicles, and to macerate the tissues.The disease is nothing more than retention of sweat and its results.Dysidrosis bears the same relation to the sweat-glands that acne does to the sebaceous glands.
Trial of early nifedipine in acute myocardial infarction: the Trent study.
Authors: R G Wilcox, J R Hampton, D C Banks, J S Birkhead, I A Brooksby, C J Burns-Cox, M J Hayes, M D Joy, A D Malcolm, H G Mather
Journal: BMJ (1986)

Over 30 months 9292 consecutive patients admitted to nine coronary care units with suspected myocardial infarction were considered for admission to a randomised double blind study comparing the effect on mortality of nifedipine 10 mg four times a day with that of placebo. Among the 4801 patients excluded from the study the overall one month fatality rate was 18.2% and the one month fatality rate in those with definite myocardial infarction 26.8%. A total of 4491 patients fulfilled the entry criteria and were randomly allocated to nifedipine or placebo immediately after assessment in the coronary care unit. Roughly 64% of patients in both treatment groups sustained an acute myocardial infarction. The overall one month fatality rates were 6.3% in the placebo treated group and 6.7% in the nifedipine treated group. Most of the deaths occurred in patients with an in hospital diagnosis of myocardial infarction, and their one month fatality rates were 9.3% for the placebo group and 10.2% for the nifedipine group. These differences were not statistically significant. Subgroup analysis also did not suggest any particular group of patients with suspected acute myocardial infarction who might benefit from early nifedipine treatment in the dose studied.
Questions and Answers in Ophthalmology
Authors: Herbert E. Kaufman
Journal: JAMA (1964)

This 354-page book of practical questions and answers  every phase of ophthalmology demonstrates an extraordinary grasp of the field and great practical experience on the part of the author. Many important clinical observations are contained therein, and yet the question-and-answer format makes the book difficult to read. Furthermore, the brevity of the answers makes it in many instances grossly inadequate for detailed reference. Many of the answers are simply lists, and others express the author's opinion and point of view without adequate documentation. Many of these opinions would be vigorously contested by other authorities in the field, and it is not clear which answers are based on established fact and which are personal opinion.
John Stuart Horner
Authors: A W Macara
Journal: BMJ (2002)

Public health physician and medical ethicist (b Leicester 1932; q Birmingham 1956; MD, FRCP, FFPHM), d 1 June 2002.


Stuart Horner proceeded from Leicester through Dewsbury, Croydon (twice), and Hillingdon to his last directorate of public health in Preston: in retirement he was visiting professor at the University of Central Lancashire. He assumed the chair of what is now the BMA's Committee of Public Health Medicine and Community Health in 1974, and for the next decade his annual reports 



BMA NEWS

drew upon tempestuous Old Testament events to illustrate contemporary travails. In 1989 he commenced another decade of leadership—of the medical ethics committee—which was winning a reputation for promoting patients' rights as well as doctors' responsibilities. His doctorate was won by a characteristically scholarly and critical review of the history of ethics in the association. He became a vice president in 1998. Stuart saw the hand of Providence in his collapse at a medical postgraduate meeting at Kingston Hospital in 1990, followed by emergency surgery at St George's Hospital. His last contribution was to organise and report upon a salutary conference on cremation, in spite of his last illness. He leaves a wife, Jacque; two children; and six grandchildren.
Asbestosis and Carcinoma of the Larynx
Authors: Herman I. Libshitz
Journal: JAMA (1974)

Three patients had carcinoma of the larynx, history of asbestos exposure, and evidence of intrathoracic changes characteristic of asbestosis. The data suggest an association between asbestosis and carcinoma of the larynx. (<i>JAMA</i>228:1571-1572, 1974)
Streptococcal Infections in Adolescents and Adults after Prolonged Freedom from Rheumatic Fever
Authors: Eloise E. Johnson, Gene H. Stollerman, Burton J. Grossman, Hugh McCulloch
Journal: New England Journal of Medicine (1960)

IT is now generally accepted practice to administer antibiotics continuously to patients with recent rheumatic fever to prevent streptococcal infections and subsequent reactivation of rheumatic fever. The duration for which such regimens should be maintained, however, is problematic. Current recommendations call for maintenance of continuous prophylaxis indefinitely, or until further data are available.1 , 2 The rate of recurrences is believed to decline during late adolescence and to be low in adult life, particularly after many years of freedom from rheumatic fever.3 4 5 The risk of discontinuing prophylaxis is difficult to assess, however, because very little information is available concerning the frequency and . . .
Fluorescence Endoscopy Using a Fluorescein-Labeled Monoclonal Antibody Against Carcinoembryonic Antigen in Patients with Colorectal Carcinoma and Adenoma
Authors: R. Keller, G. Winde, H. J. Terpe, E. C. Foerster, W. Domschke
Journal: Endoscopy (2002)

Various methods of fluorescence excitation and detection have been developed in gastrointestinal endoscopy. This study reports an endoscopic technique using locally applied fluorescein-labeled antibodies for in-vivo detection of colorectal dysplasia and carcinoma.Fluorescence endoscopy with a fluorescein-labeled monoclonal antibody against carcinoembryonic antigen (CEA) was carried out in 27 patients with colonic polypoid lesions. During conventional colonoscopy, the monoclonal antibody was applied directly onto the mucosal surface. After an incubation time of 10 min, specific fluorescence was visualized with a conventional endoscope whose optical range was increased via two narrow-band filters.Fluorescence in vivo was present in 19 out of 25 carcinomas and in three of eight adenomas. The technique failed in the presence of mucosal ulceration or bleeding. One fluorescence-positive villous adenoma showed high-grade dysplasia, and another fluorescence-positive polypoid lesion was diagnosed as carcinoma in adenoma. Normal-appearing mucosa was fluorescence-negative in all cases. Endoscopic fluorescence significantly correlated with the CEA expression of luminal epithelial cells as determined immunohistochemically (Wilcoxon-Mann-Whitney U-test, P < 0.01). In all cases without ulceration or bleeding, the specificity of fluorescence endoscopy was 100%, the sensitivity was 78.6%, and the accuracy was 89.3%.Fluorescence endoscopy using fluorescein-labeled monoclonal antibody against CEA was shown to be positive in most cancers and some adenomas. Further and larger studies will be needed to demonstrate the value of this technique for differential diagnosis.
Endobronchial valves for advanced emphysema
Authors: L.-J. E. Smith
Journal: Thorax (2011)

In this multicentre randomised trial from USA, the safety and efficacy of unilobar endobronchial valve therapy in patients with heterogeneous emphysema was compared with usual care.

In terms of effectiveness, the co-primary outcomes were percentage change in FEV1 and distance on the 6 min walk test. In terms of safety, the primary outcome was the difference in complication rate, using a composite of six …
Long-term outcomes of two rescue therapies in lamivudine-refractory patients with chronic hepatitis B: combined lamivudine and adefovir, and 1-mg entecavir
Authors: EunYoung Ze, Eun Kyung Baek, Jong Jin Lee, Han Wook Chung, Dae Geon Ahn, Hwan Jun Cho, Jae Cheol Kwon, Hyung Joon Kim, HyunWoong Lee
Journal: Clinical and Molecular Hepatology (2014)

Background/Aims Adefovir (ADV) and lamivudine (LAM) combination therapy (ADV+LAM) has been a useful option for patients with LAM-resistant (LAM-r) chronic hepatitis B (CHB). However, the long-term outcomes of LAM+ADV and 1-mg entecavir (ETV) rescue therapies have still been limited. The aim of this study was to determine the long-term outcomes of these two rescue therapies. Methods Sixty patients with LAM-r CHB underwent rescue therapy with LAM+ADV (n=36) or 1-mg ETV (n=24). We determined the duration of rescue therapy, timing and type of mutation, undetectable serum hepatitis B virus (HBV) DNA by PCR (lower limitation of detection, < 140 copies/mL), biochemical response (alanine aminotransferase < 40 IU/mL), and the incidence of hepatitis B virus e antigen (HBeAg) seroconversion and virologic breakthrough. Results Baseline characteristics did not differ between the two therapy groups. The duration of rescue therapy was 56 months (range, 14-100 months) in the ADV+LAM group and 42 months (range, 12-73 months) in the ETV group (P=0.036). The cumulative rates of HBV DNA undetectability and HBeAg seroconversion up to 6 years were 88.6% and 43.0%, respectively, in the ADV+LAM group, and 45.8% and 31.8% in the ETV group. The rate of virologic breakthrough and resistance was 14.4% in the ADV+LAM group and 71.9% in the ETV group (P=0.001). Conclusions Combination of LAM and ADV therapy for up to 6 years achieved modest rates of virological suppression and resistance. ETV is not an optimal therapy because the risk of viral breakthrough to ETV increases over time. Keywords: Chronic hepatitis B; Lamivudine; Adefovir; Entecavir; Resistance
Iron uptake from rat plasma transferrin by rat reticulocytes.
Authors: H Huebers, E Huebers, E Csiba, C A Finch
Journal: Journal of Clinical Investigation (1978)

Fast and slow rat transferrins were isolated by isoelectric focusing and prepared in their di- and monoferric forms. A comparison of the rates of iron release between fast and slow monoferric transferrins when incubated with reticulocytes or injected in vivo showed no significant difference in the behavior of the two isotransferrin species. Reticulocyte uptake of diferric transferrin resulted in the removal of both iron atoms from the transferrin molecule. A twofold greater iron uptake was observed from diferric as compared with monoferric iron, provided reticulocyte receptors were saturated. It is concluded that the two species of transferrin and their individual sites function similarly in their release of iron to tissue receptors.
"THE PHYSICIAN'S OFFICE"
Authors: E. Podolsky
Journal: JAMA (1920)

<h3>To the Editor:</h3> —Your editorial comment (The Journal, Aug. 21, 1920, p. 545) on the necessity of maintaining a respectable appearing office brings to mind a certain piece of writing from a physician of several centuries ago. Here are the requisites necessary for success in medicine, as quoted by Crabtre ("Funny Side of Physic: or, the Mysteries of Medicine," Hartford, Conn., J. B. Burr and Hyde, 1872): <i>First</i>. A decent black suit, and (if your credit will stretch so far), a plush jacket, not a pin the worse if threadbare as a tailor's cloak—it shows the more reverend antiquity. <i>Second</i>. You must carry a caduceus, or cane, like Mercury, capped with a civet-box (or snuff-box like Sir Richard's), and must walk with becoming gravity, as if in deep contemplation upon an arbitrament between life and death. <i>Third</i>. You must hire convenient lodgings in a respectable neighborhood, with a hood (small
Pathological and non-pathological factors in delusional misbelief
Authors: Robyn Langdon
Journal: Behavioral and Brain Sciences (2009)

Abstract In their pursuit of adaptively biased misbelief-making systems, McKay &amp; Dennett (M&amp;D) describe a putative doxastic shear-pin system which enables misbeliefs to form in situations of extreme psychological stress. Rather than discussing their argument, I consider how this shear-pin system might combine with both pathological belief-making (“culpable” breakdowns caused by neuropathy) and normal belief-making to explain a spectrum of delusions.
Protective effect of inhaled salbutamol powder in children assessed by histamine challenge.
Authors: C R Pullan, A J Martin
Journal: BMJ (1980)

A double-blind placebo-controlled trial of 100, 400, and 800 micrograms inhaled salbutamol powder was conducted on 12 children. The protective effect at 10 minutes, two hours, and four hours was assessed by histamine challenge. At 10 minutes there was good protection with all doses, but by four hours there was significant protection only with 800 micrograms (p less than 0.01). Salbutamol powder may need to be taken at least every four hours for complete protection. There was a dose-related effect with a single dose of up to 800 micrograms; increasing the dose increased the effect and duration of action. Currently advertised dose regimens of salbutamol powder for children (200 micrograms three or four times a day) are apparently submaximal. Histamine challenge is a satisfactory method of assessing the proective effect of a drug in asthmatic children.
F-18 Fluorodeoxyglucose PET in Fournier Gangrene
Authors: Erdem Sürücü, Aras E. Canda, Gamze C. Kaya, Burçin Tuna, Tark Sengoz, Kutsal Yorukoglu, Cem Terzi
Journal: Clinical Nuclear Medicine (2010)

A 64-year-old man with a locally advanced rectum adenocarcinoma was referred for 18-fluoro-2-deoxyglucose (F-18 FDG) imaging for the purpose of restaging and tumor response. Circumferentially increased perirectal F-18 FDG uptake was seen. Three days after the first F-18 FDG positron emission tomography clinically Fournier gangrene was diagnosed and surgical debridement was performed. Increased perirectal uptake was attributed to Fournier gangrene.
Anticytoplasmic Autoantibodies: Their Immunodiagnostic Value in Wegener Granulomatosis
Authors: Bernhard Nolle, Ulrich Specks, Jens Lüdemann, Michael S. Rohrbach, Richard A. DeRemee, Wolfgang L. Gross
Journal: Annals of Internal Medicine (1989)

Study Objective: To determine disease specificity and sensitivity of anticytoplasmic autoantibodies (ACPA) for Wegener granulomatosis, as well as their value as a marker of disease activity. Design: Blind analysis of serum samples, retrospective analysis of clinical data on patients, and prospective follow-up of a subgroup of patients with Wegener granulomatosis. Patients: The study included 277 patients with Wegener granulomatosis (222 with biopsy-proven disease) and 1657 control patients. Setting: University hospital and academic medical center. Laboratory Investigations: Analysis of 2653 serum samples from 1934 patients for ACPA. Antibody detection was by indirect immunofluorescence and a new type of enzyme-linked immunoadsorbent assay (ELISA). Prospective follow-up was on 172 patients with Wegener granulomatosis. Measurements and Main Results: Specificity of ACPA for Wegener granulomatosis measured by indirect immunofluorescence was 99% (CI, 98.9% to 99.7%) and 98% (CI, 97.4% to 99.2%) by ELISA. Sensitivity of ACPA depended on disease activity and extent: It was 67% (CI, 38% to 89%) by immunofluorescence and 60% (CI, 32% to 84%) by ELISA for patients with active locoregional symptomatology (n = 15); and 32% (CI, 14% to 54%) by immunofluorescence and 40% (CI, 21% to 61%) by ELISA for patients in full remission after initial locoregional symptoms (n = 25). The sensitivity was 96% (CI, 89% to 99%) by immunofluorescence and 93% (CI, 86% to 98%) by ELISA for patients with active generalized disease (n = 92). Serial testing was done; every patient with active generalized disease eventually had at least one positive serum sample. Sensitivity decreased to 41% (CI, 22% to 62%) by both immunofluorescence and ELISA for patients in full remission after active generalized disease (n = 27). Levels of ACPA expressed both as immunofluorescence titers and ELISA values (U/mL) correlated well with disease activity. Conclusions: Testing for ACPA in serum of patients with Wegener granulomatosis is valuable for differential diagnosis; furthermore, APCA can be used as a marker to follow disease activity. A new type of ELISA yielded the same results as indirect immunofluorescence for the specificity, sensitivity, and correlation with disease activity of ACPA.
PWE-066 Impact of Right Colon Retroflexion on Adenoma Detection Rate
Authors: M Widlak, H Muhammad, M Smith, S Shetty, S C Cooper, S De Silva, N Fisher, S Ishaq
Journal: Gut (2013)

<h3>Introduction</h3> Colonoscopy is less effective in visualising the right colon compared with the rest of the colon and small adenomas are frequently missed during routine procedures. The aim of this study was to determine whether retroflexion in the right colon would improve adenoma detection rate. <h3>Methods</h3> We carried out a prospective pilot study on a total of 37 adults who underwent elective diagnostic colonoscopy with a EC3490 TFi (Pentax retro-view) colonoscope between October 2012 and January 2013. A careful colonic examination to the caecum in the forward view was performed. The colonoscope was then retroflexed in the right colon to identify any additional adenomas. Success rate of retroflexion, adenoma detection rate in forward-viewing as well as in retroflexion were assessed along with comfort scoring and incidence of adverse events. <h3>Results</h3> Study population of 37 patients, mean age 62 yrs, F: M ratio 1:0.8.Retroflexion in the right colon was successful in 34 patients (92%), with looping on insertion the cause of the failures. On forward viewing 28 polyps were identified, of which 11 adenomas were in the proximal colon. Retroflexion identified an additional 3 adenomas (all &lt; 1cm), improving the overall adenoma detection rate by 9%. 81% of patients did not experience any discomfort (comfort score 0) during the procedure. Apart from one minor post-polypectomy haemorrhage no adverse events were recorded. <h3>Conclusion</h3> This preliminary data suggests that right colon retroflexion may improve the adenoma detection rate of colonoscopy. Although the procedure is feasible, safe and easy to carry out, further high power studies are needed to establish whether retroflexion should be incorporated into standard colonoscopy technique. <h3>Disclosure of Interest</h3> None Declared.
Endoscopic Injection for the Treatment of Bleeding Ulcers: Local Tamponade or Drug Effect?
Authors: K. H. Lai, S. N. Peng, W. S. Guo, F. Y. Lee, F. Y. Chang, U. Malik, J. Y. Wang, G. H. Lo, J. S. Cheng, S. D. Lee, Y. T. Tsai
Journal: Endoscopy (1994)

Fifty-two patients with Forrest Ia or Ib bleeding ulcers were randomized to receive endoscopic injection therapy with either 1:10,000 epinephrine in water (Group I) or distilled water (Group II). Twenty-five out of 27 patients in group I, versus 22 out of 25 patients in group II, achieved initial hemostasis after endoscopic injection therapy (p > 0.05). Five patients who did not respond to local injection had bleeding controlled by heater probe thermocoagulation or surgical intervention. Three patients in each group developed rebleeding after initial hemostasis. Four of these patients had bleeding controlled by surgical intervention, while the other two died of underlying diseases. No change in systemic blood pressure, but a significant drop in the pulse rate were noted in both groups after injection therapy. Patients with shock at admission or ulcer size greater than 2 cm had a significantly higher rebleeding rate after initial hemostasis than patients with normal blood pressure and ulcers under 2 cm (p < 0.05). No serious complications were observed after injection therapy, and no significant difference in the amounts of solution required for successful hemostasis was noted between the two groups. We conclude that a local tamponade with distilled water is as effective and safe as diluted epinephrine solution for endoscopic injection therapy.