tbuckley/cabot-search huggingface dataset:
A prospective study of colonoscopy practice in the UK today: are we adequately prepared for national colorectal cancer screening tomorrow?
Authors: C J A Bowles
Journal: Gut (2004)

To study the availability and quality of adult and paediatric colonoscopy in three National Health Service (NHS) regions.A prospective four month study of colonoscopies in North East Thames, West Midlands, and East Anglia.Subjects undergoing colonoscopy in 68 endoscopy units.A total of 9223 colonoscopies were studied. The mean number of colonoscopies performed over the four month period was 142 in district general hospitals and 213 in teaching hospitals. Intravenous sedation was administered in 94.6% of procedures, but 2.2% and 11.4% of "at risk" patients did not have continuous venous access or did not receive supplemental oxygen, respectively. Caecal intubation was recorded in 76.9% of procedures but the adjusted caecal intubation rate was only 56.9%. Reasons for failing to reach the caecum included patient discomfort (34.7%), looping (29.7%), and poor bowel preparation (19.6%). A normal colonoscopy was reported in 42.1%. The most common diagnosis was polyps (22.5%) followed by diverticular disease (14.9%). Inflammatory bowel disease was recorded in 13.9% and carcinoma in 3.8%. Only half of the patients remembered being told of possible adverse events prior to the procedure. Rectal bleeding requiring admission following colonoscopy was reported in six patients. The overall perforation rate was 1:769 and colonoscopy was considered a possible factor in six deaths occurring within 30 days of the procedure. Only 17.0% of colonoscopists had received supervised training for their first 100 colonoscopies and only 39.3% had attended a training course.There is serious under provision of colonoscopy service in most NHS hospitals. Endoscopy sedation guidelines are not always adhered to and there is a wide variation in practice between units. Colonoscopy is often incomplete and does not achieve the target 90% caecal intubation rate. Serious complications of colonoscopy were comparable with previous studies. Training in colonoscopy is often inadequate and improved practice should result from better training.
Analysis of polychlorinated biphenyls (PCBs) in human serum.
Authors: M Luotamo, J Järvisalo, A Aitio
Journal: Environmental Health Perspectives (1985)

Polychlorinated biphenyls (PCBs) are widely dispersed in the environment. Occupational exposure to PCBs takes place, e.g., in manufacture and repair of capacitors and transformers. A special type of exposure of workers to PCBs may occur in connection with accidents where capacitors or transformers containing PCBs products are damaged, as in the case of a fire or electric arcing. The quantitation of PCBs poses several problems: There are 209 different homologs and isomers of PCBs. The isomers of PCBs have different responses in the electron capture detector, and the pattern of PCBs in biological specimens is different from that of commercial products. In this study a method was worked out for the analysis of PCBs in serum with the purpose of estimating occupation exposure to PCBs. The PCBs were extracted to an organic solvent, and the extract was purified by use of sulfuric acid and silica columns. Capillary gas chromatography with electron capture detection was used. For separation, temperature programming was used.
Ketoconazole and Other Imidazole Derivatives as Inhibitors of Steroidogenesis
Authors: DAVID FELDMAN
Journal: Endocrine Reviews (1986)

IMIDAZOLE antifungal drugs are effective therapeutic agents in the treatment of mycotic infections (1). Because ketoconazole can be administered orally and has a broad spectrum of activity against both superficial and deep mycoses, this imidazole derivative has become widely used throughout the world as an antifungal agent (1, 2). In recent years it as become apparent that ketoconazole has additional potent actions to inhibit steroidogenesis. Much of the discussion to follow will be directed at the specific drug ketoconazole and its ability to suppress the synthesis of steroid hormones. However, other structurally related imidazole antifungal agents share in these antihormonal actions. In addition, other categories of drugs contain imidazole or azole structures, and some element of the hormonal effects to be discussed for ketoconazole may also apply to these drugs as well. Prominent examples are cimetidine, thiobendazole, and metronidazole. The ability to inhibit steroidogenesis is especially relevant for the drug etomidate, an imidazole, intravenous sedative-hypnotic agent used for the induction and/or maintenance of anesthesia. Etomidate closely resembles ketoconazole in its effects on steroidogenesis.
Formoterol and beclomethasone versus higher dose beclomethasone as maintenance therapy in adult asthma
Authors: D. Bouros, N. Bachlitzanakis, J Kottakis, P Pfister, V Polychronopoulos, E Papadakis, S Constantopoulos, M. Froudarakis, L Sichletidis, N. Siafakas
Journal: European Respiratory Journal (1999)

A total of 132 adult asthmatics who were symptomatic on 500 microg x day(-1) inhaled beclomethasone dipropionate (BDP) were studied in an open-label randomized, parallel group, 12 week, clinical trial. The addition of 12 microg formoterol fumarate solution aerosol (pressurized metered dose inhaler) b.i.d. to BDP at a dose of 500 microg x day(-1) was compared with a higher dose of 1,000 microg x day(-1) BDP. Mean morning premedication peak expiratory flow rate (PEF) during the final week of treatment (primary end-point) increased in both groups compared to baseline. The estimated treatment difference of 20.4 L x min(-1) (95% confidence interval 3.2-37.6) after 12 weeks of treatment was statistically significant (p&lt;0.05) in favour of the formoterol/BDP group. The overall mean morning premedication PEF for the entire treatment period was higher in the formotero/BDP group (p=0.002). The overall number of puffs of rescue medication and asthma symptom scores were less in the formotero/BDP group (p&lt;0.01). Safety and tolerability evaluations were satisfactory in both groups. In conclusion, the results suggest that the addition of formoterol fumarate to the existing dose of an inhaled corticosteroid should be considered as an alternative to increasing the dose of inhaled corticosteroid in the inadequately controlled asthmatic.
ERBB Receptor Activation Is Required for Profibrotic Responses to Transforming Growth Factor β
Authors: Mahefatiana Andrianifahanana, Mark C. Wilkes, Claire E. Repellin, Maryanne Edens, Theodore J. Kottom, Rod A. Rahimi, Edward B. Leof
Journal: Cancer Research (2010)

Abstract Engagement of the transforming growth factor-β (TGF-β) receptor complex activates multiple signaling pathways that play crucial roles in both health and disease. TGF-β is a key regulator of fibrogenesis and cancer-associated desmoplasia; however, its exact mode of action in these pathologic processes has remained poorly defined. Here, we report a novel mechanism whereby signaling via members of the ERBB or epidermal growth factor family of receptors serves as a central requirement for the biological responses of fibroblasts to TGF-β. We show that TGF-β triggers upregulation of ERBB ligands and activation of cognate receptors via the canonical SMAD pathway in fibroblasts. Interestingly, activation of ERBB is commonly observed in a subset of fibroblast but not epithelial cells from different species, indicating cell type specificity. Moreover, using genetic and pharmacologic approaches, we show that ERBB activation by TGF-β is essential for the induction of fibroblast cell morphologic transformation and anchorage-independent growth. Together, these results uncover important aspects of TGF-β signaling that highlight the role of ERBB ligands/receptors as critical mediators in fibroblast responses to this pleiotropic cytokine. Cancer Res; 70(19); 7421–30. ©2010 AACR.
P245 Assessment of acute illness severity and radiological extent identify patients at heightened risk of developing major pneumonic progression in influenza A H1N1/2009 infection
Authors: J. Choy, A. Draper, E. Ribbons, I. Vlahos, S. Grubnic, T. Bicanic, P. Riley, M. Wansbrough-Jones, F. Chua
Journal: Thorax (2010)

<h3>Introduction</h3> In 2009, high transmissibility of a novel influenza A H1N1 virus produced a global outbreak of febrile pneumonic illness. Clinical criteria for its’ diagnosis suffered from low sensitivity and specificity. We evaluated clinical, laboratory and radiological abnormalities in virologically proven H1N1/2009 infection to identify risk factors associated with severe pulmonary involvement. <h3>Methods</h3> Data were collected at one London acute care Trust during two phases (June–August and September–November 2009) of the pandemic. Initial 24-h Acute Physiology and Chronic Health Evaluation (APACHE)-II scores and radiological findings were evaluated. All data were analysed by logistic regression (STATA). <h3>Results</h3> 64 patients (31 female, 33 male; median age 32) hospitalised with H1N1/2009 were studied, comprising 22 white British, 19 African-Caribbean, 21 Asian and 2 of other ethnicity. Only three patients were aged &gt;60 and only two deaths were encountered. Six pregnant patients were treated, including five in phase 2. Higher mean APACHE-II scores (7.9 vs 6.6) were recorded during this phase but were unrelated to demographic factors. ICU admission rate was high (12/64 patients, 19%; including three who were pregnant). Asthma was the commonest co-morbidity (17/64 patients, 27%) but only featured in two ICU cases. By contrast, pregnancy was a predictor of ICU admission (Pearson χ<sup>2</sup> 4.2, P 0.03). Asian males more than any other demographic were also more frequently identified than expected for this population (χ<sup>2</sup> 4.94, p=0.026). Radiographic abnormalities were noted in ≥2 quadrants of 28 (44%) initial chest films, most frequently basal peribronchial thickening and perihilar opacities. Progressive infiltrates or multifocal consolidation were noted in 15/58 (26%) patients, two-thirds (9/15) of whom ultimately requiring intubation. Nosocomial infections or co-pathogens were found in six cases, all with underlying malignancy, transplanted organ or pregnancy. <h3>Conclusions</h3> Most patients hospitalised with H1N1/2009 were young, with mild clinical and radiological disease. Asian males were more likely to be hospitalised with the illness, while pregnancy was correlated with an increased likelihood of ICU admission. Neither subgroup had evidence of worse acute illness severity. Basal non-lobar changes were the commonest radiographic finding. Overall, diffuse early abnormalities frequently preceded the development of severe and progressive pneumonia.
B cell resistance to Fas-mediated apoptosis contributes to their ineffective control by regulatory T cells in rheumatoid arthritis
Authors: Laetitia Rapetti, Konstantia-Maria Chavele, Catherine M Evans, Michael R Ehrenstein
Journal: Annals of the Rheumatic Diseases (2013)

Objective To investigate whether regulatory T cells (Treg) can control B cell function in rheumatoid arthritis (RA) and if not to explore the basis for this defect. Methods Suppression of B cell responses by Treg was analysed in vitro by flow cytometry and ELISA using peripheral blood mononuclear cells from 65 patients with RA and 41 sex-matched and aged-matched healthy volunteers. Blocking and agonistic antibodies were used to define the role of Fas-mediated apoptosis in B cell regulation. Results Treg failed to restrain B cell activation, proinflammatory cytokine and antibody production in the presence of responder T cells in RA patients. This lack of suppression was not only caused by impaired Treg function but was also due to B cell resistance to regulation. In healthy donors, control by Treg was associated with increased B cell death and relied upon Fas-mediated apoptosis. In contrast, RA B cells had reduced Fas expression compared with their healthy counterparts and were resistant to Fas-mediated apoptosis. Conclusions These studies demonstrate that Treg are unable to limit B cell responses in RA. This appears to be primarily due to B cell resistance to suppression, but Treg defects also contribute to this failure of regulation. Our data identify the Fas pathway as a novel target for Treg-mediated suppression of B cells and highlight a potential therapeutic approach to restore control of B cells by Treg in RA patients.
Effects of angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists on mortality and renal outcomes in diabetic nephropathy: systematic review
Authors: Giovanni F M Strippoli, Maria Craig, Jonathan J Deeks, Francesco Paolo Schena, Jonathan C Craig
Journal: BMJ (2004)

To evaluate the effects of angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists (AIIRAs) on renal outcomes and all cause mortality in patients with diabetic nephropathy.Medline, Embase, the Cochrane controlled trials register, conference proceedings, and contact with investigators.Trials comparing ACE inhibitors or AIIRAs with placebo or with each other in patients with diabetic nephropathy.Mortality, renal outcomes (end stage renal disease, doubling of serum creatinine concentration, prevention of progression of microalbuminuria to macroalbuminuria, remission of microalbuminuria), and quality of trials.36 of 43 identified trials compared ACE inhibitors with placebo (4008 patients), four compared AIIRAs with placebo (3331 patients), and three compared ACE inhibitors with AIIRAs (206 patients). We obtained unpublished data for 11 trials. ACE inhibitors significantly reduced all cause mortality (relative risk 0.79, 95% confidence interval 0.63 to 0.99) compared with placebo but AIIRAs did not (0.99, 0.85 to 1.17), although baseline mortality was similar in the trials. Both agents had similar effects on renal outcomes. Reliable estimates of the unconfounded relative effects of ACE inhibitors compared with AIIRAs could not be obtained owing to small sample sizes.Although the survival benefits of ACE inhibitors for patients with diabetic nephropathy are known, the relative effects of ACE inhibitors and AIIRAs on survival are unknown owing to the lack of adequate head to head trials.
It is Settled: The ‘Is’ Can (and Should) Inform the ‘Ought’!
Authors: Alexander A. Kon
Journal: The American Journal of Bioethics (2009)

Click to increase image sizeClick to decrease image size Acknowledgment This work was funded in part by grant number UL1 RR024146 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. The author also thanks Professor Robert A. Burt for his review and constructive criticism of an earlier version of this manuscript.
Activation of Glomerular Basement Membrane–Specific B Cells in the Renal Draining Lymph Node after T Cell–Mediated Glomerular Injury
Authors: Julie Robertson, Jean Wu, Jon Arends, Cindy Zhou, John McMahon, Lisa Torres, Ya-Huan Lou
Journal: Journal of the American Society of Nephrology (2005)

Linear binding of IgG to the glomerular basement membrane (GBM) is the hallmark of anti-GBM glomerulonephritis (GN). However, the precise mechanism by which diverse autoantibodies to GBM are induced in GN has not been determined. It was demonstrated previously that a single T cell epitope pCol(28-40) derived from collagen IV alpha3 chain not only induced severe GN in Wistar Kyoto rats but also triggered a diversified anti-GBM antibody response through "B cell epitope spreading." In this study, an expansion of T and B cells in the renal draining lymph node (RDLN) of diseased animals after glomerular injury was observed. RDLN was demonstrated to be the location of GBM-specific B cell activation. First, B cells from RDLN of pCol(28-40)-immunized rats produced in vitro anti-GBM antibodies and antinuclear antibodies. Second, B cells specific to the peptidic B cell epitope in pCol(28-40) were absent among expanding B cells in RDLN. Those findings provided a unique opportunity to track activation of diverse GBM-specific B cells in RDLN. Expression of B lymphocyte-induced maturation protein-1, which is involved in differentiation of plasma cells, in B cells of RDLN was detected and further elevated only after T cell-mediated prominent glomerular injury (day 19). This was supported by the fact that anti-GBM antibodies became detectable only after day 20. Those results suggest that T cell-mediated glomerular injury may trigger de novo internal immunization of autoantigens released from damaged GBM, which further leads to activation of a group of GBM-specific B cells in RDLN.
A case of pulmonary typical carcinoid with an extensive oncocytic component showing intense uptake of FDG
Authors: T. Kadowaki, S. Yano, K. Araki, T. Tokushima, N. Morioka
Journal: Thorax (2010)

Pulmonary carcinoid tumours, especially typical carcinoid, usually have lower FDG uptake than lung carcinoma.1 We present an unusual case of pulmonary carcinoid showing intense uptake of 18F-fluoro-deoxy-glucose (FDG).

FDG-PET CT scan showed increased tracer concentration corresponding to the 3 cm round tumour in the left lingula (figure 1). The maximal standardised uptake value (SUV) of the tumour was 39. Bronchoscopy was performed to show an endobronchial red-coloured polypoid mass with a smooth surface in the left B5a. Cytology obtained by endobronchial brushing showed uniform round to oval …
Scrofulous Diseases of the External Lymphatic Glands: Their Nature, Variety, and Treatment
Authors: P. C. Price
Journal: BMJ (1860)

stance is answered in a very curious manner.On questioning the mother of the boy, I elicited that he had been in the habit of buyving arild eating the very coarse plum-pudding which is sold in tlhe neighbourhood of this hospital.I sent a little boy of his owvn class to purchase some of a similar kind, and bring it to me.On examination by the nmicroscope, I found it to contain hairs having identically the sanme appearance as those which formed the bulk of the concretion.I have since examined many s-pecimens of coarse farinaceous food, but none have shown similar adulteration, nor do I find any record thereof in Dr. Hassall's great work.
Development and Validation of Pedigree Classification Criteria for Frontotemporal Lobar Degeneration
Authors: Elisabeth M. Wood, Dana Falcone, EunRan Suh, David J. Irwin, Alice S. Chen-Plotkin, Edward B. Lee, Sharon X. Xie, Vivianna M. Van Deerlin, Murray Grossman
Journal: JAMA Neurology (2013)

A significant portion of frontotemporal lobar degeneration (FTLD) is due to inherited gene mutations, and we are unaware of a large sequential series that includes a recently discovered inherited cause of FTLD. There is also great need to develop clinical tools and approaches that will assist clinicians in the identification and counseling of patients with FTLD and their families regarding the likelihood of an identifiable genetic cause.To ascertain the frequency of inherited FTLD and develop validated pedigree classification criteria for FTLD that provide a standardized means to evaluate pedigree information and insight into the likelihood of mutation-positive genetic test results for C9orf72, MAPT, and GRN.Information about pedigrees and DNA was collected from 306 serially assessed patients with a clinical diagnosis of FTLD. This information included gene test results for C9orf72, MAPT, and GRN. Pedigree classification criteria were developed based on a literature review of FTLD genetics and pedigree tools and then refined by reviewing mutation-positive and -negative pedigrees to determine differentiating characteristics.Academic medical center.Patients with FTLD.Familial risk.The rate of C9orf72, MAPT, or GRN mutation-positive FTLD in this series was 15.4%. Categories designating the risk level for hereditary cause were termed high, medium, low, apparent sporadic, and unknown significance. Thirty-nine pedigrees (12.7%) met criteria for high, 31 (10.1%) for medium, 46 (15.0%) for low, 91 (29.7%) for apparent sporadic, and 99 (32.4%) for unknown significance. The mutation-detection rates were as follows: high, 64.1%; medium, 29%; low, 10.9%; apparent sporadic, 1.1%; and unknown significance, 7.1%. Mutation-detection rates differed significantly between the high and other categories.Mutation rates are high in FTLD spectrum disorders, and the proposed criteria provide a validated standard for the classification of FTLD pedigrees. The combination of pedigree criteria and mutation-detection rates has important implications for genetic counseling and testing in clinical settings.
Pulmonary function in infants with neonatal chronic lung disease with or without hyaline membrane disease at birth
Authors: IT Merth, JP de Winter, HM Zonderland, GJ Borsboom, PH Quanjer
Journal: European Respiratory Journal (1997)

We studied whether neonatal chronic lung disease (NCLD), hyaline membrane disease (HMD) and differences in ventilatory support affected pulmonary function during the first year of life, in 65 infants born prematurely. The relationship between body weight and oxygen consumption (V'O2) was also analysed. The study comprised 14 infants without cardiorespiratory disease, 19 infants with HMD but without NCLD, 9 infants with NCLD without prior HMD, and 23 infants with NCLD following HMD. At 6 and 12 months corrected postnatal age, static respiratory system compliance (Crs) was measured by weighted spirometry and the functional residual capacity by closed circuit helium dilution (FRCHe) combined with assessment of ventilation distribution from the mixing index (MI). Ventilatory support during the first 5 days of therapy was quantified from peak inspiratory pressure (PIP), mean airway pressure (MAP) and fractional inspiratory concentration of oxygen (FI,O2). Infants with NCLD had a shorter duration of gestation and lower birth weight than those without NCLD (Wilcoxon, p=0.002 and p=0.001, respectively). Pulmonary function at 6 and 12 months corrected age was not different between NCLD infants with or without HMD at birth. Infants with NCLD had lower Crs and MI than those without NCLD (analysis of variance (ANOVA), p&lt;0.011), but their FRCHe was not different. V'O2 adjusted for body weight was comparable in the four groups. PIP and FI,O2 were higher (Wilcoxon, p&lt;0.01) in the NCLD infants than in those with HMD alone, but MAP was not different. Except for FI,O2, these indices were not different among the infants with NCLD. We conclude that birth weight is the major determinant of the development of neonatal chronic lung disease. At 6 and 12 months corrected age, the abnormal pulmonary function is not associated with prior hyaline membrane disease.