tbuckley/cabot-search huggingface dataset:
Biomarker Associations with Efficacy of Abiraterone Acetate and Exemestane in Postmenopausal Patients with Estrogen Receptor–Positive Metastatic Breast Cancer
Authors: Weimin Li, Joyce O'Shaughnessy, Daniel Hayes, Mario Campone, Igor Bondarenko, Irina Zbarskaya, Etienne Brain, Marina Stenina, Olga Ivanova, Marie-Pascale Graas, Patrick Neven, Deborah Ricci, Thomas Griffin, Thian Kheoh, Margaret Yu, Michael Gormley, Jason Martin, Michael Schaffer, Kathy Zelinsky, Peter De Porre, Stephen R.D. Johnston
Journal: Clinical Cancer Research (2016)

Abiraterone may suppress androgens that stimulate breast cancer growth. We conducted a biomarker analysis of circulating tumor cells (CTCs), formalin-fixed paraffin-embedded tissues (FFPETs), and serum samples from postmenopausal estrogen receptor (ER)+ breast cancer patients to identify subgroups with differential abiraterone sensitivity.Patients (randomized 1:1:1) were treated with 1,000 mg/d abiraterone acetate + 5 mg/d prednisone (AA), AA + 25 mg/d exemestane (AAE), or exemestane. The biomarker population included treated patients (n = 293). The CTC population included patients with ≥3 baseline CTCs (n = 104). Biomarker [e.g., androgen receptor (AR), ER, Ki-67, CYP17] expression was evaluated. Cox regression stratified by prior therapies in the metastatic setting (0/1 vs. 2) and setting of letrozole/anastrozole (adjuvant vs. metastatic) was used to assess biomarker associations with progression-free survival (PFS).Serum testosterone and estrogen levels were lowered and progesterone increased with AA. Baseline AR or ER expression was not associated with PFS in CTCs or FFPETs for AAE versus exemestane, but dual positivity of AR and ER expression was associated with improved PFS [HR, 0.41; 95% confidence interval (CI), 0.16-1.07; P = 0.070]. For AR expression in FFPETs obtained <1 year prior to first dose (n = 67), a trend for improved PFS was noted for AAE versus exemestane (HR, 0.56; 95% CI, 0.24-1.33; P = 0.19).An AA pharmacodynamic effect was shown by decreased serum androgen and estrogen levels and increased progesterone. AR and ER dual expression in CTCs and newly obtained FFPETs may predict AA sensitivity. Clin Cancer Res; 22(24); 6002-9. ©2016 AACR.
Book: Tony Copperfield's Primary Care Scream
Authors: Kevin Barraclough
Journal: BMJ (2003)

I mostly gave up reading the general practitioner trade magazines some years ago. Reading them was like having an endlessly pessimistic friend following you around, whispering in your ear all the time. I would alternate between impotent rage and mute depression. Now that they go into the bin, I no longer feel the entire world is against me, and I've stopped having the injections. The exception, which I always read, is Tony Copperfield's splenic rant in Doctor magazine against all that is wrong with being a doctor in general, and a GP in particular.​particular.




Figure 1



Butterworth-Heinemann, £17.99, pp 248 plus CD Rom ISBN 0 7506 8793 2 www.elsevierhealth.com

Rating: ★ ★ ★ ★




For a while I did wonder if Tony might be my doppelganger. He seemed to have attended the same farcical management meetings as me, in which banal “mission statements,” entirely devoid of use or content, were endlessly (“inclusively”) debated. He was obviously there on that out of hours home visit to one of the “lumpen proletariat at the shallow end of the gene pool.” He was at my shoulder when I “knelt in the pool of vomit, by the fag burnt sofa, illuminated only by the light from the satellite decoder and a rerun of Peak Practice.”

Not only did he seem to follow me around, but he also seemed to read my thoughts. Otherwise how did he know what I was thinking when I got that nice private consultant's letter about the “delightful” patient telling me that, surprisingly, her whole body, multisytem pan-investogram was normal.

Tony's targets are not just the “clinical governance gestapo” (with their “patronising bullshit”), academics pontificating on one clinic a month (“until you've felt your feet stick to a hallway carpet you can't call yourself a frontline medic”), nurses (“they must learn to suppress their desire to cover their own arses”), and patients. GPs also earn his ire. As he stingingly points out: “Nobody with their eyes open could deny that there are plenty of pretty iffy GPs out there.”

Tony inhabits a world that lies in that hinterland between the real and the surreal. That it is so startlingly familiar to us is testament to the ludicrous nature of our work. We see his characters every day. Ms Stargazer, the vegetarian urban road warrior who brings her unvaccinated children Moon Calf and Poppy Seed for homoeopathic treatment, may be a fictional character—but only just.

Tony Copperfield is quite simply fantastic. He is unbelievably funny and, strangely, he is also extraordinarily and improbably wise. He cuts, searingly, through the sanctimonious dishonesty that so often pollutes healthcare politics (“I once sank so low that I used the word `autonomy' without irony”). Most importantly, everything he writes is truer than fact.

My only fear is that, if the wind changes while I'm reading this book, I may end up looking like Kingsley Amis and sounding like Auberon Waugh. But hey, as Tony says, sometimes shit happens.
Inappropriate secretion of antidiuretic hormone
Authors: J Aloia
Journal: JAMA (1968)

A 16-month-old white boy was admitted to hospital following one day of fever and obtundation.He was well until four days before admission when a nasal discharge and cough developed.On the day of admission a temperature of 104°F had been noted.He had become obtunded, crying only when touched.Consequently, he was seen at the United States Naval Hospital, San Diego, where a lumbar puncture was done.The spinal fluid contained 2,700 leukocytes per cu mm with 94 percent polymorphonuclear leukocytes and many Gram-negative coccobacilli.The patient was transferred to University Hos- pital.On admission a temperature of 101°F was recorded, with a pulse rate of 140 and a respiratory rate of 44 per minute.Blood pressure was normal.The pertinent positive physical findings were pronounced nuchal rigidity; a dull, thickened right tympanic membrane; and a slight amount of clear rhinorrhea.The blood and cerebrospinal fluid cultures grew Hemophilus influenza.Ampidillin was given parenterally at a dosage of 300 mg per kg of body weight every 24 hours.Fluids were given at a rate half that of his cal- culated maintenance requirements.The fever cleared on the second hospital day.On day one, oliguria developed.Tests of urine showed a spe-
Role of Polyoxyethylene Sorbitan Monostearate in Skin Carcinogenesis in Mice&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;3&lt;/xref&gt;
Authors: Giuseppe della Porta, Philippe Shubik, Kai Dammert, Benedetto Terracini
Journal: JNCI Journal of the National Cancer Institute (1960)

A detailed record of tumors induced in mouse skin by repeated applications of polyoxyethylene sorbitan monostearate (Tween 60) with and without a prior single application of a carcinogenic hydrocarbon is reported. Most tumors induced subsequently regressed. Only a small proportion, approximately 3 percent, progressed to carcinomas. Tween 60, at a dose of 60 mg. administered twice weekly or daily, was effective as a promoting agent. When given alone at the same dosage, Tween 60 gave rise to an appreciable number of tumors, with a far longer latent period. The effects of dosage, different initiating agents, the interval between initiation and the Tween applications, and the individual caging of animals are described. The nature of the activity of Tween 60 is compared with croton oil and discussed.
59PD Comparison of incidental radiation dose to axilla and internal mammary nodal area by conventional, 3DCRT, and IMRT technique in carcinoma of breast
Authors: H.B. Govardhan, N.T.K. Ibrahim, S. Pallad, P. Sridhar, B.L. Nabiza, D.S. Nihanthy, K. Pramod, U. Krishna, S. Sunder
Journal: Annals of Oncology (2015)
Does Preventive Care Save Money?
Authors: Jonathan E Fielding, Corinne G Husten, Jordan H Richland
Journal: New England Journal of Medicine (2008)

n engl j med 358;26 www.nejm.org june 26, 2008 2847 As mentioned by Myrianthefs et al. and Lima et al., acinetobacter can manifest as wound infections. As we noted, in one series of patients affected by a natural disaster, 20% of wounds were infected with acinetobacter; acinetobacter was also a common cause of infected wounds in the battlefield and burn injuries. Our experience in the greater Chicago area is that acinetobacter detected in wounds more frequently tends to be a contaminant than an actual pathogen. Nevertheless, in the majority of settings, the most common presentations are respiratory, urinary, and blood infections. L. Silvia Munoz-Price, M.D.
Thiazide-lithium synergy in refractory mood swings
Authors: J M Himmelhoch, J Forrest, J F Neil, T P Detre
Journal: American Journal of Psychiatry (1977)

The unfortunate experience with lithium chloride as a salt substitute in the 1940s still directs the clinical usuage of lithium carbonate to a certain extent. We are still warned that lithium salts should never be used in low-sodium situations (e.g., with thiazide diuretics or salt-restricted diets); however, it has recently been shown that thiazide diuretics may be safely used in the treatment of lithium-induced nephrogenic diabetes insipidus (NDI). The authors recapitulate the dangers inherent in the use of this drug combination and present detailed clinical-pharmacologic data on 13 patients which suggest that thiazides are useful in the treatment of lithium-induced NDI and may actually synergize with lithium to produce improved mood control in some lithium-refractory manic-depressive patients.
PWE-202 Outcomes in patients with acute idiopathic pancreatitis
Authors: S Dharmayan, A Ahmad, N Bostan, Y Khatun, M Barua, AA Ayantunde
Journal: Gut (2015)

<h3>Introduction</h3> The management of acute idiopathic pancreatitis (AIP) remains a challenge. There are no strong recommendations available to help with its management. Its impact on patient outcome is still not clear. Our aim was to compare the outcomes between patients presenting with AIP to those with acute non-idiopathic pancreatitis (NIP). <h3>Method</h3> A retrospective data collection was performed for all patients presenting with acute pancreatitis in a district general hospital during a 4-year period between January 2011 and December 2014. Data was collected using electronic patient records. Patient demographics, aetiology of pancreatitis and outcomes for all patients were analysed. Outcomes were defined as mortality due to acute pancreatitis, ITU admission, pancreatic necrosis and multi organ failure. <h3>Results</h3> During the 4-year study period 569 patients were diagnosed with acute pancreatitis. Out of all the patients 142/569 (25%) were diagnosed as having AIP. There was no significant difference in mean age in the two groups (AIP 59yrs; NIP 60yrs). There was a significantly higher incidence of female patients diagnosed with AIP (63%) compared to the NIP group (51%; P = 0.012). Twenty-one out of 142 patients with AIP (15%) had overall poor outcomes compared to 30/427 (7%) patients in the NIP group (OR 2.29; 95% CI 1.27 – 4.16; P = 0.006). AIP has significantly poor outcome compared with NIP for pancreatitis specific mortality (OR 3.79; CI 1.70 – 8.38; P = 0.0001), ITU admission (OR 2.73; CI 1.36 – 5.46; P = 0.003) and multi organ failure (OR 2.97; CI 1.36 – 6.49; P = 0.004). <h3>Conclusion</h3> Patients with IP have a significantly higher morbidity and pancreatitis specific mortality compared with NIP. This reflects our lack of understanding about the mechanisms that trigger pancreatitis in this group of patients. In addition, a more vigorous management pathway needs to be established to optimise the investigations and further management of this high-risk group of patients. <h3>Disclosure of interest</h3> None Declared.
Дисфункція біліарного тракту в дітей: традиційні підходи й нові постулати
Authors: O.Yu. Lukianenko, T.I. Panteleeva
Journal: GASTROENTEROLOGY (2017)

Захворюваність органів травлення в дітей посідає одне з провідних місць у структурі соматичної патології дитячого віку. Функціональні розлади біліарного тракту являють собою комплекс клінічних симптомів, що розвинулись у результаті моторно-тонічних дисфункцій жовчного міхура, жовчних проток та сфінктерного апарату жовчних шляхів. Для написання огляду здійснювався пошук даних із використанням даних Scopus, Web of Science, MedLine, PubMed, Google Scholar, CyberLeninka, РІНЦ за такими ключовими словами: біліарна дисфункція, функціональний розлад жовчного міхура, функціональний розлад сфінктера Одді, біліарна дискінезія, діти. У статті розглядаються етіопатогенетичні аспекти біліарної патології в дитячому віці. Розглянуті сучасні діагностичні та терапевтичні підходи щодо розладів жовчного міхура та сфінктера Одді в педіатричних пацієнтів у розрізі Римських критеріїв функціональних гастроінтестинальних розладів IV перегляду.
PTU-032 Explant organ model testing of the ‘robotic’ colonoscope: first experience in the UK
Authors: N Grasso, N Safinia, A Haq, A Haji, B Hayee
Journal: Gut (2015)

<h3>Introduction</h3> Colonoscopy practice in the UK has improved over the past decade.<sup>1,2</sup>There remains, however, a small but significant failure rate and the use of sedation and analgesia remains the norm. There is a clear clinical need for alternatives to traditional colonoscopy. An automatic self-propelled, user-guided colonoscope has been developed that abolishes the need for sedation or analgesia in the vast majority of cases, even where traditional colonoscopy has failed or may incur excess risks.<sup>3</sup>The new model colonoscope also has a 3.1 mm working channel for diagnostic and some therapeutic options. Given that the apparatus is operated by a controller resembling those used in gaming consoles, we hypothesised that it would take little time to become familiar with controls and achieve efficient colonic intubation. <h3>Method</h3> Using an animal explant model (Erlangen-type; porcine colon) we asked a variety of operators to achieve a timed caecal intubation (total colon length 1.65 m). The Endotics colonoscopy system mark II (ECS-II) was used. Two CMT-grade doctors, two ‘JAG-independent’ SpRs, an Endoscopy nurse (non-Endoscopist), a consultant Colorectal surgeon and a Consultant Gastroenterologist were asked to try to match the performance of an expert operator (from the manufacturers). A short tutorial on the controls was given to each operator and they were allowed to intubate the simulated sigmoid-descending junction before withdrawing and conducting a timed intubation. <h3>Results</h3> The expert operator set a time of 6:21 min to reach the caecum. The experienced colonoscopists achieved a median time of 6:28 (range 6:21–6:56) with their first attempt. Subsequent attempts were not deemed necessary to improve on this. The Endoscopy nurse achieved 6:26 on first attempt. The two CMT doctors recorded times of 9:44 and 8:02 on their first attempt, then 6:48 and 6:22 on their second and 6:33 and 6:23 on their third. Withdrawal of the scope was qualitatively assessed but not timed. All operators were satisfied with image resolution. <h3>Conclusion</h3> The acquisition of operator skills to use the ECS-II was rapid and was not limited, nor hindered, by previous colonoscopy experience. Human studies have been conducted in the EU with success<sup>4,5</sup>and we expect the first UK studies to be completed soon, focussing on clinically-relevant performance indicators. <h3>Disclosure of interest</h3> None Declared. <h3>References</h3> Bowles CJ, <i>et al</i>. Gut 2004;53:277–83 Gavin DR, <i>et al</i>. Gut 2013;62:242–9 Pallotta S, <i>et al</i>. Poster, SIGE; 2011 Tumino E, <i>et al</i>. World J Gastroenterol. 2010;16:5452–6 Perri F, <i>et al</i>. Dig Liver Dis. 2010;42:839–43
Psychosocial aspects of a Tay-Sachs screening clinic
Authors: G Schneiderman, J A Lowden, Q Rae-Grant
Journal: American Journal of Psychiatry (1978)

The authors administered questionnaires to participants in a Tay-Sachs screening clinic. They received 322 responses. Although the majority of the respondents expressed anxiety about the possibility that they might be carriers, most indicated that this anxiety brought them to the clinic. The authors conclude that a well-publicized and well-organized screening clinic can function successfully and deal with the issue of anticipated loss without producing mass fear. An important factor in their clinic was the fact that they were able to offer an alternative to a Tay-Sachs child through amniocentesis.
On the Protein Metabolism of Tissue Cells &lt;italic&gt;in Vitro&lt;/italic&gt;&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/xref&gt;
Authors: Albert Fischer
Journal: JNCI Journal of the National Cancer Institute (1953)

Journal Article On the Protein Metabolism of Tissue Cells in Vitro Get access Albert Fischer Albert Fischer Biological Institute, Carlsberg Foundation, Copenhagen, Denmark Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 13, Issue 6, June 1953, Pages 1399–1423, https://doi.org/10.1093/jnci/13.6.1399 Published: 01 June 1953 Article history Received: 05 February 1953 Published: 01 June 1953
THU0023 Soluble Uric Acid Exerts a Suppressive Effect on the Response of Macrophages to Monosodium Urate Crystals
Authors: E. Garcia-Melchor, M. Guma, J. Yagüe, M. Juan, J. Harper
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> There is extensive published literature about the interaction of monosodium urate (MSU) crystals with immune cells, however, less information exists about the impact of soluble uric acid (SUA) on these cells. As deposits of MSU crystals can be present in asymptomatic joints,<sup>[1]</sup> and changes in uric acid levels can initiate an arthritis flare in gout patients,<sup>[2]</sup> we investigated the effect of SUA on the response of macrophages to MSU crystals. <h3>Objectives</h3> To analyze the effect of SUA on macrophage polarization and function of M-CSF polarized M2-like macrophages. <h3>Methods</h3> Blood was collected from healthy donors after informed consent. Peripheral blood mononuclear cells (PBMC) were separated from whole blood by centrifugation with a density gradient. Monocytes were then isolated by negative selection with magnetic beads and cultured for 1 week with M-CSF (20 ng/ml) in the presence or absence of biologically relevant concentrations of SUA (0.3 mM and 0.6 mM representing normouricemia and hyperuricemia respectively). Macrophages were then stimulated with MSU (200 μg/mL), LPS (100 ng/mL) or both for 18 hours. Alternatively, M-CSF polarized M2-like macrophages were generated and subsequently exposed to SUA for 24 hours prior to stimulation with MSU and LPS. MSU phagocytosis and cell viability were analyzed by flow cytometry. IL-1β and IL-10 concentrations in culture supernatants were quantified by ELISA. Flow cytometry and statistical analyses were performed with FACSDiva and GraphPad Prism 5 softwares respectively. <h3>Results</h3> M2 macrophages polarized in the presence of SUA produced less IL-1β upon challenging with MSU and LPS, that was most significant in conditions equivalent to hyperuricemia (0.6mM), whereas there was a modest inhibitory effect on IL-10 production only for macrophages exposed to high uric acid concentrations. On the other hand, exposure of already polarized macrophages to both low and high concentrations of SUA notably suppressed both IL-1β and IL-10 production. No differences in phagocytosis or cell viability were observed with exposure to SUA either during or after macrophage polarization. <h3>Conclusions</h3> Unexpectedly, our results show that SUA exerts a suppressive effect on MSU-induced IL-1β and IL-10 production by M-CSF polarized macrophages. To our knowledge this is the first time that the effect of SUA on macrophages has been analyzed. Uric acid lowering therapy has been associated with an increased risk of gout flares. Our results indicate that one mechanism contributing to the development of gout flares could be the diminution of the local regulatory effect of SUA on macrophage activation. <h3>References</h3> Pascal E. Br J Rheumatol 1995;34(8):724-6. [2] Latourte A. Rheumatology 2014;53(11):1920-6. <h3>Disclosure of Interest</h3> None declared
Primary Myxoedema Apparently Dating from Post-partum Shock
Authors: R. Fraser, O. Garrod
Journal: BMJ (1955)

BuDrL sHMIEDICAL JOURNAL tance of acute haemorrhagic pancreatitis with two com- mon acute abdominal conditions are noted.The serum amylase and lipase levels were measured in 25 normal subjects and in 12 patients with past or present pancreatic disease.No significant serum enzyme response was obtained after pancreatic stimulation with morphine, methacholine, secretin, or pancreozymin in any of the individuals investigated, and the suggestion that the response obtained with these substances may be of value as an indication of the presence of pancreatitis was not confirmed.The serum amylase and lipase levels were investigated in three cases of acute haemorrhagic pancreatitis and in certain other acute abdominal conditions; the highest readings were obtained in acute pancreatitis, but a two- fold or threefold increase was found to be fairly com- mon in cases of perforated duodenal and juxtapyloric ulcers, and high levels were recorded in patients with calculi in the common bile duct.The excretion of urinary diastase during the first twenty-four hours in hospital was measured in three cases of acute pancreatitis and in 41 other patients with acute abdominal disease: wide variations were recorded, and this investigation is not considered useful or reliable.