tbuckley/cabot-search huggingface dataset:
Tuesday 1 December could be first day of industrial action, says BMA
Authors: A. Rimmer
Journal: BMJ (2015)

The BMA has confirmed the types and timing of any industrial action that junior doctors in England could take in response to the UK government’s plan to impose a new contract on them. The association opened its ballot of junior doctors on 5 November, after negotiations with the government on a new contract for junior doctors in England stalled.1 The ballot closes on 18 November.

The BMA said that the proposed dates and …
Predictors of patient uptake of colorectal cancer gene environment risk assessment
Authors: Michael J Hall, Sharon L Manne, Ronald E Myers, Eileen M Keenan, Andrew M Balshem, David S Weinberg
Journal: Genome Medicine (2012)

In an ongoing clinical trial, the genetic and environmental risk assessment (GERA) blood test offers subjects information about personal colorectal cancer risk through measurement of two novel low-to-moderate risk factors. We sought to examine predictors of uptake of the GERA blood test among participants randomized to the Intervention arm.Primary care patients aged 50 to 74 years eligible for colorectal cancer screening are randomized to receive a mailed stool blood test kit to complete at home (Control) or to the control condition plus an in-office blood test called GERA that includes assessment of red blood cell folate and DNA-testing for two MTHFR (methylenetetrahydrofolate reductase) single nucleotide polymorphisms (SNPs) (Intervention). For the present study, baseline survey data are examined in participants randomized to the Intervention.The first 351 intervention participants (161 African American/190 white) were identified. Overall, 249 (70.9%) completed GERA testing. Predictors of GERA uptake included race (African American race, odds ratio (OR) 0.51 (0.29 to 0.87)), and being more knowledgeable about GERA and colorectal cancer screening (OR 1.09 (1.01 to 1.18)). Being married (OR 1.81 (1.09 to 3.00)) was also significant in the multivariable model.Participant uptake of GERA testing was high. GERA uptake varied, however, according to socio-demographic background and knowledge.
Aberrant High Expression of B Lymphocyte Chemokine (Blc/Cxcl13) by C11b+Cd11c+ Dendritic Cells in Murine Lupus and Preferential Chemotaxis of B1 Cells towards Blc
Authors: Sho Ishikawa, Taku Sato, Masaaki Abe, Shigenori Nagai, Nobuyuki Onai, Hiroyuki Yoneyama, Yan-yun Zhang, Takuji Suzuki, Shin-ichi Hashimoto, Toshikazu Shirai, Martin Lipp, Kouji Matsushima
Journal: The Journal of Experimental Medicine (2001)

We observed here that the expression of B lymphocyte chemokine (BLC/CXCL13) was markedly enhanced in the thymus and kidney in aged (NZB × NZW)F1 (BWF1) mice developing lupus nephritis, but not in similarly aged NZB and NZW mice. BLC-positive cells were present in the cellular infiltrates in the target organs with a reticular pattern of staining. CD11b+CD11c+ dendritic cells were increased in the thymus and spleen in aged BWF1 mice and identified as the major cell source for BLC. CD4+ T cells as well as B cells were dramatically increased in the thymus in aged BWF1 mice, whereas no increase was observed in aged NZB and NZW mice. B1/B2 ratio in the thymus was significantly higher than those in the spleen and peripheral blood in aged BWF1 mice. Interestingly, BLC showed preferential chemotactic activity for B1 cells derived from several mouse strains, including nonautoimmune mice. Cell surface CXCR5 expression on B1 cells was significantly higher than that on B2 cells. Thus, aberrant high expression of BLC by myeloid dendritic cells in the target organs in aged BWF1 mice may play a pivotal role in breaking immune tolerance in the thymus and in recruiting autoantibody-producing B cells in the development of murine lupus.
Responsiveness of motion sensors to detect change in sedentary and physical activity behaviour
Authors: Ann M Swartz, Aubrianne E Rote, Young Ik Cho, Whitney A Welch, Scott J Strath
Journal: British Journal of Sports Medicine (2014)

Background The purpose of this study was to determine the responsiveness of two motion sensors to detect change in sedentary behaviour (SB) and physical activity (PA) during an occupational intervention to reduce sitting time. Methods SB and PA were assessed using a hip-worn Actigraph GTX3 (AG) and a thigh-worn activPAL (AP) during three consecutive workdays throughout baseline and intervention periods. Mean scores at baseline and intervention were estimated by hierarchical linear models (HLM) with robust SEs, adjusting for random variance of average scores between participants. Change scores (mean baseline minus mean intervention) were calculated for each device. Response to change was assessed for each device using the standardised response mean. Results 67 adults (45±11 years; 29.3±7.7 kg/m 2 ) wore the acceleration-based motion sensors for 8.3 (SD=1.2) and 8.3 (SD=1.1) h during the baseline and intervention periods, respectively. HLM showed that AP sitting/lying time (−16.5 min, −5%), AP stepping (+7.5 min, 19%), AP steps/day (+838 steps/day, +22%), AP sit-to-stand transitions (+3, +10%), AG SB (−14.6 min, −4%), AG lifestyle moderate-intensity PA (LMPA, +4 min, +15%) and AG MPA (+3 min, 23%) changed significantly between the baseline and the intervention period. Standardised response means for AP sitting/lying time, stepping, steps/day, sit-to-stand transitions and AG SB, LMPA and MPA were above 0.3, indicating a small but similar responsiveness to change. Conclusions Responsiveness to change in SB and PA was similar and comparable for the AP and AG, indicating agreement across both measurement devices.
Real-time, Near-Infrared Fluorescence Imaging with an Optimized Dye/Light Source/Camera Combination for Surgical Guidance of Prostate Cancer
Authors: Brian P. Neuman, John B. Eifler, Mark Castanares, Wasim H. Chowdhury, Ying Chen, Ronnie C. Mease, Rong Ma, Amarnath Mukherjee, Shawn E. Lupold, Martin G. Pomper, Ronald Rodriguez
Journal: Clinical Cancer Research (2014)

Abstract Purpose: The prostate-specific membrane antigen (PSMA) is a surface glycoprotein overexpressed on malignant prostate cells, as well as in the neovasculature of many tumors. Recent efforts to target PSMA for imaging prostate cancer rely on suitably functionalized low-molecular-weight agents. YC-27 is a low-molecular-weight, urea-based agent that enables near-infrared (NIR) imaging of PSMA in vivo. Experimental Design: We have developed and validated a laparoscopic imaging system (including an optimized light source, LumiNIR) that is capable of imaging small tumor burdens with minimal background fluorescence in real-time laparoscopic extirpative surgery of small prostate tumor xenografts in murine and porcine models. Results: In a mouse model, we demonstrate the feasibility of using real-time NIR laparoscopic imaging to detect and surgically remove PSMA-positive xenografts. We then validate the use of our laparoscopic real-time NIR imaging system in a large animal model. Our novel light source, which is optimized for YC-27, is capable of detecting as little as 12.4 pg/mL of the compound (2.48-pg YC-27 in 200-μL agarose). Finally, in a mouse xenograft model, we demonstrate that the use of real-time NIR imaging can reduce positive surgical margins (PSM). Conclusions: These data indicate that a NIR-emitting fluorophore targeted to PSMA may allow improved surgical treatment of human prostate cancer, reduce the rate of PSMs, and alleviate the need for adjuvant radiotherapy postoperatively. Clin Cancer Res; 21(4); 771–80. ©2014 AACR.
The Treat-to-Target Trial
Authors: Matthew C. Riddle, Julio Rosenstock, John Gerich
Journal: Diabetes Care (2003)

To compare the abilities and associated hypoglycemia risks of insulin glargine and human NPH insulin added to oral therapy of type 2 diabetes to achieve 7% HbA(1c).In a randomized, open-label, parallel, 24-week multicenter trial, 756 overweight men and women with inadequate glycemic control (HbA(1c) >7.5%) on one or two oral agents continued prestudy oral agents and received bedtime glargine or NPH once daily, titrated using a simple algorithm seeking a target fasting plasma glucose (FPG) <or=100 mg/dl (5.5 mmol/l). Outcome measures were FPG, HbA(1c), hypoglycemia, and percentage of patients reaching HbA(1c) <or=7% without documented nocturnal hypoglycemia.Mean FPG at end point was similar with glargine and NPH (117 vs. 120 mg/dl [6.5 vs. 6.7 mmol/l]), as was HbA(1c) (6.96 vs. 6.97%). A majority of patients ( approximately 60%) attained HbA(1c) <or=7% with each insulin type. However, nearly 25% more patients attained this without documented nocturnal hypoglycemia (<or=72 mg/dl [4.0 mmol/l]) with glargine (33.2 vs. 26.7%, P < 0.05). Moreover, rates of other categories of symptomatic hypoglycemia were 21-48% lower with glargine.Systematically titrating bedtime basal insulin added to oral therapy can safely achieve 7% HbA(1c) in a majority of overweight patients with type 2 diabetes with HbA(1c) between 7.5 and 10.0% on oral agents alone. In doing this, glargine causes significantly less nocturnal hypoglycemia than NPH, thus reducing a leading barrier to initiating insulin. This simple regimen may facilitate earlier and effective insulin use in routine medical practice, improving achievement of recommended standards of diabetes care.
Combination of ablative fractional laser and daylight-mediated photodynamic therapy for actinic keratosis in organ transplant recipients - a randomized controlled trial
Authors: K. Togsverd-Bo, U. Lei, A.M. Erlendsson, E.H. Taudorf, P.A. Philipsen, H.C. Wulf, L. Skov, M. Haedersdal
Journal: British Journal of Dermatology (2014)

Topical photodynamic therapy (PDT) for actinic keratoses (AK) is hampered by pain during illumination and inferior efficacy in organ-transplant recipients (OTR).We assessed ablative fractional laser (AFL)-assisted daylight photodynamic therapy (PDT) (AFL-dPDT) compared with daylight PDT (dPDT), conventional PDT (cPDT) and AFL alone (AFL) in field treatment of AK in OTR.In each patient, four areas in the same region were randomized to one treatment with AFL-dPDT, dPDT, cPDT and AFL. AFL was delivered with a 2940-nm AFL at 2·3 mJ per pulse, 1·15 W, two stacks, 50-μs pulse-duration, 2·4% density. In dPDT and AFL-dPDT, methyl aminolaevulinate (MAL) was applied for 2·5 h without occlusion during daylight exposure. For cPDT, MAL was occluded for 3 h followed by red-light (630 nm) irradiation at 37 J cm(-2). The primary end-point was complete response (CR) 3 months post-treatment.Sixteen patients with 542 AK (grades I-III) in field-cancerized skin of the scalp, chest and extremities were treated during August and September 2012. After 3 months, CR (AK I-III) rates were 74% after AFL-dPDT, 46% after dPDT, 50% after cPDT and 5% after AFL (P < 0·001). CR rates in AFL-dPDT, dPDT and cPDT were also significantly different (P = 0·004). Median maximal pain scores differed significantly during AFL-dPDT (0), dPDT (0), AFL (0) and cPDT (5) (P < 0·001). Erythema and crusting were more intense following AFL-dPDT than dPDT and cPDT, but only transient hypopigmentation was observed.AFL-dPDT is a novel PDT modality that enhances CR with excellent tolerability compared with dPDT and cPDT in difficult-to-treat AK in OTR.
Retroperitoneal silicosis mimicking pancreatic carcinoma in an Alpine miner with chronic lung silicosis.
Authors: J M Tschopp, M J Rossini, C A Richon, N Letovanec, F Joris, J G Frey, R M Kaelin
Journal: Thorax (1992)

A miner, known to have had lung silicosis for 30 years, was investigated for abdominal pain. A retroperitoneal mass was found, in which histological examination showed an inflammatory reaction to silica.
A Switch in the Mechanism of Hypertension in the Syndrome of Apparent Mineralocorticoid Excess
Authors: Matthew A. Bailey, Janice M. Paterson, Patrick W.F. Hadoke, Nicola Wrobel, Christopher O.C. Bellamy, David G. Brownstein, Jonathan R. Seckl, John J. Mullins
Journal: Journal of the American Society of Nephrology (2007)

The syndrome of apparent mineralocorticoid excess arises from nonfunctional mutations in 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2), an enzyme that inactivates cortisol and confers aldosterone specificity on the mineralocorticoid receptor. Loss of 11betaHSD2 permits glucocorticoids to activate the mineralocorticoid receptor, and the hypertension in the syndrome is presumed to arise from volume expansion secondary to renal sodium retention. An 11betaHSD2 null mouse was generated on an inbred C57BL/6J genetic background, allowing survival to adulthood. 11betaHSD2(-/-) mice had BP approximately 20 mmHg higher on average compared with wild-type mice but were volume contracted, not volume expanded as expected. Initially, impaired sodium excretion associated with increased activity of the epithelial sodium channel was observed. By 80 days of age, however, channel activity was abolished and 11betaHSD2(-/-) mice lost salt. Despite the natriuresis, hypertension remained but was not attributable to intrinsic vascular dysfunction. Instead, urinary catecholamine levels in 11betaHSD2(-/-) mice were double those in wild-type mice, and alpha1-adrenergic receptor blockade rescued the hypertensive phenotype, suggesting that vasoconstriction contributes to the sustained hypertension in this model. In summary, it is proposed that renal sodium retention remains a key event in apparent mineralocorticoid excess but that the accompanying hypertension changes from a renal to a vascular etiology over time.
mTOR Inhibition Induces Upstream Receptor Tyrosine Kinase Signaling and Activates Akt
Authors: Kathryn E. O'Reilly, Fredi Rojo, Qing-Bai She, David Solit, Gordon B. Mills, Debra Smith, Heidi Lane, Francesco Hofmann, Daniel J. Hicklin, Dale L. Ludwig, Jose Baselga, Neal Rosen
Journal: Cancer Research (2006)

Abstract Stimulation of the insulin and insulin-like growth factor I (IGF-I) receptor activates the phosphoinositide-3-kinase/Akt/mTOR pathway causing pleiotropic cellular effects including an mTOR-dependent loss in insulin receptor substrate-1 expression leading to feedback down-regulation of signaling through the pathway. In model systems, tumors exhibiting mutational activation of phosphoinositide-3-kinase/Akt kinase, a common event in cancers, are hypersensitive to mTOR inhibitors, including rapamycin. Despite the activity in model systems, in patients, mTOR inhibitors exhibit more modest antitumor activity. We now show that mTOR inhibition induces insulin receptor substrate-1 expression and abrogates feedback inhibition of the pathway, resulting in Akt activation both in cancer cell lines and in patient tumors treated with the rapamycin derivative, RAD001. IGF-I receptor inhibition prevents rapamycin-induced Akt activation and sensitizes tumor cells to inhibition of mTOR. In contrast, IGF-I reverses the antiproliferative effects of rapamycin in serum-free medium. The data suggest that feedback down-regulation of receptor tyrosine kinase signaling is a frequent event in tumor cells with constitutive mTOR activation. Reversal of this feedback loop by rapamycin may attenuate its therapeutic effects, whereas combination therapy that ablates mTOR function and prevents Akt activation may have improved antitumor activity. (Cancer Res 2006; 66(3): 1500-8)
Polymorphisms and functional activity in superoxide dismutase and catalase genes in smokers with COPD
Authors: J. C. W. Mak, S. P. Ho, W. C. Yu, K. L. Choo, C. M. Chu, W. W. Yew, W. K. Lam, M. Chan-Yeung
Journal: European Respiratory Journal (2007)

Increased oxidative stress has been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). This study investigated the risk of COPD and the substitution of alanine 16 with valine (Ala16Val) polymorphism of manganese-superoxide dismutase (Mn-SOD) and the cytosine to thymidine transition of nucleotide -262 (-262C&gt;T) polymorphism of the catalase gene, and the activity of erythrocyte SOD and catalase. The subjects were stable COPD patient ever smokers (n = 165) and healthy controls, matched for age and cigarette consumption. Genotyping of Mn-SOD at Ala16Val and the catalase gene at -262C&gt;T was performed, and the functional activity of SOD and catalase in erythrocytes determined. There were no significant differences in the distribution of the different genotypes or allele frequencies between patients and controls for both the Mn-SOD and catalase genes. Among healthy controls or COPD patients, no differences were observed in erythrocyte SOD and catalase activity, irrespective of genotype. Significantly higher erythrocyte catalase activity was found in COPD patients than in healthy controls. The T/T catalase genotype and Ala/Ala Mn-SOD genotype were uncommon in the present Chinese population. The increase in erythrocyte catalase activity in Chinese patients with chronic obstructive pulmonary disease probably indicates dysfunction of the oxidant/antioxidant defence system, but it is unclear whether this increase is compensatory or a pathogenic factor.
S61 RAPID score: the development of a validated clinical score in pleural infection, to identify at presentation those at risk of poor outcome
Authors: N. M. Rahman, B. C. Kahan, R. Miller, N. A. Maskell
Journal: Thorax (2011)

<h3>Introduction</h3> Pleural infection remains common with an increasing incidence. It is associated with a high morbidity and mortality. The development of a validated clinical risk score at presentation to identify those at high risk may help formulate early management strategies. <h3>Methods</h3> The RAPID score was constructed based on a large cohort of patients entering a multicentre UK pleural infection trial—MIST1 (n=411). Out of 32 baseline clinical characteristics recorded at trial entry, model selection was undertaken to find variables predictive of poor clinical outcome. Results were obtained by using backwards selection with a p value of 0.05. Multiple imputation was used to account for patients with missing baseline variables. The primary outcome assessed was mortality at 3 months. Total time in hospital was also assessed. <h3>Results</h3> Age, urea, albumin, hospital acquired infection, and non-purulence were all found to be clinical predictors or poor outcome. A score was developed using these variables. R - urea &lt;5=0, 5–8=1, &gt;8=2 A - age &lt;50=0, 50–70=1, &gt;70=2 P - purulence=0, non purulence=1 I - iatrogenic/hospital acquired infection =1 community acquired =0 D - dietary factors. Albumin &gt;27=0 &lt;27=1 Total RAPID score range 0–7 In order to help interpret the RAPID score, we stratified patients into low-risk, medium-risk, and high-risk groups. Patients with a RAPID score of 0–2 are considered low risk, a score of 3–4 indicates a medium risk, and a score of 5–7 indicates high risk. This scoring system was then validated using another large cohort of patients with pleural infection who had been enrolled in a UK multicentre trial –MIST2 (n=210). Abstract S61 table 1 shows the main results. Time in hospital increased with increasing RAPID score. In MIST1 patients with RAPID 0–2 had median stay 10 (7–16) days, compared to RAPID &gt;5 who had a median stay of 18 (9–26) days. This trend was also seen in MIST2. <h3>Conclusion</h3> The RAPID score appears to allow for risk-stratification of patients with pleural infection at presentation and could prove useful in clinical practice in guiding initial management.
Wilson disease in septuagenarian siblings: Raising the bar for diagnosis
Authors: Aftab Ala, Jimo Borjigin, Arnold Rochwarger, Michael Schilsky
Journal: Hepatology (2005)

Wilson Disease (WD) usually presents in the first decades of life, although rare patients have a later presentation. We report the clincial features, diagnostic evaluation, and outcome with treatment of two septuagenarian siblings evaluated as part of a research trial for treatment of neurological WD. The index case was a 72-year-old woman who suffered progressive neurological disability, then developed sub-fulminant liver failure. Her sibling was a 70-year-old man with minimal neurological symptoms and a mild depressive disorder. His liver biopsy revealed only steatosis and minimal fibrosis and an elevated hepatic copper content (671 μg/g dry weight liver). Molecular studies demonstrated compound heterozygosity for disease specific ATP7B mutations E1064A and H1069Q in both patients. Both individuals were treated with trientine and Zn followed by Zn maintenance therapy. Over the last 5 years, the clincial course stabilized and improved, although the index case recently died from bronchopneumonia. In conclusion, advanced age and different clinical presentations of these two subjects with identical ATP7B mutations raises the question of the degree of penetrance for these and other ATP7B mutations. Environmental and extragenic factors are pivotal determinants of disease phenotype. We suggest that WD must be considered at all ages in patients with hepatic disease, neurological disease, or psychiatric symptoms. (HEPATOLOGY 2005;41:668–670.)
Dosage and delivery of nebulised beta agonists in hospital.
Authors: J N Stainforth, R A Lewis, A E Tattersfield
Journal: Thorax (1983)

A questionnaire was sent to physicians with an interest in chest disease to determine the dose and method of delivery of nebulised beta agonists in hospital. All of the 67 physicians replying gave beta agonists by nebuliser, and all reported either salbutamol (72%) or terbutaline (10%) as the drug they prescribed most commonly (18% gave either drug). There was a fivefold difference in the dose of salbutamol they prescribed most commonly (range 2.5-12.5 mg, mode 5 mg), a 20 fold difference in the volume of diluent solution used (range 0.5-10 ml, mode 2 ml), and a 10 fold variation in the flow rates of gas driving the nebuliser (range 1-10 1/min, mode 4 1/min). There are therefore very large variations in the dose and method of delivery of beta agonists nebulised in hospital. Studies attempting to determine the optimum dose of beta agonist for use in a nebuliser need to take the type of nebuliser, diluent volume, and gas flow rate into account.
A not-so-simple collapse
Authors: E Raw, L Hudsmith, G P Aithal, T Jaspan
Journal: Journal of the Royal Society of Medicine (2003)

measurement of CO-Hb, levels may have fallen substantially.Measurement of CO either in the exhaled breath or in the ambient air at the scene can be helpful.The cornerstone of treatment is high-flow oxygen.This reduces the half-life of CO-Hb to 4-6 hours.With hyperbaric oxygen this comes down to 15-30 minutes. 3 Whilst hyperbaric oxygen confers theoretical advantage, the absolute indications for its use remain in question.In England, Northern Ireland and Wales, the British Hyperbaric Association runs a 24-hour telephone helpline (01752 209 999) to discuss cases and advise on referral.CO poisoning is avoidable, and household detectors are widely available at modest cost.