tbuckley/cabot-search huggingface dataset:
Seasonality and trends in the incidence and prevalence of gout in England and Wales 1994-2007
Authors: A J Elliot, K W Cross, D M Fleming
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objectives:</h3> To examine seasonality and long-term trends in the incidence and prevalence of gout. <h3>Methods:</h3> A retrospective study (1994–2007) using routinely collected surveillance data from the Royal College of General Practitioners Weekly Returns Service sentinel general practice network in England and Wales. New cases and acute attacks of gout per 10 000 population were calculated for age groups 0–44, 45–64, 65–74 and ⩾75 years. Long-term trends of annual incidence were assessed by regression analysis. Seasonality indices were calculated using 4-weekly data, and the relative risk of gout incidence during the summer was estimated. Annual prevalence was estimated from the consulting patient population (2001–7) and from prescribing data on defined daily doses (DDD) of allopurinol (2003–7). <h3>Results:</h3> The annual incidence rate of new gout cases was stable over the period 1998–2007; acute attacks decreased on average 4% per annum. New gout cases and acute attacks combined into 4-weekly incidence rates peaked during the "summer" period of each year. There was an increased risk of gout diagnosis during summer months (late April to mid-September; odds ratio 1.22, 95% CI 1.18 to 1.26). The annual prevalence of gout in 2001–7 was 0.46%, with highest rates in men ⩾75 years (2.57%). Estimated prevalence based on a DDD of 400 mg allopurinol was 0.37%. <h3>Conclusion:</h3> The incidence of gout is seasonal. This has implications for the management of patients who currently have gout, and for those who are at risk of future attacks. The decreasing trend in the incidence of acute attacks suggests that patient management is improving.
Potential Masking Effects of Salmeterol on Airway Inflammation in Asthma
Authors: R. ANDREW McIVOR, EMILIO PIZZICHINI, MARK O. TURNER, PATRICIA HUSSACK, FREDERICK E. HARGREAVE, MALCOLM R. SEARS
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

We hypothesized that regular use of long-acting beta-agonists could delay recognition of ("mask") increasing airway inflammation. We studied steroid-sparing and "masking" effects of salmeterol versus placebo in 13 asthmatic individuals requiring >= 1,500 microgram inhaled corticosteroid daily. Corticosteroid doses were reduced weekly until criteria were met for an exacerbation or the corticosteroid was fully withdrawn. Subjects were restabilized on their original dose of inhaled corticosteroid for 4 wk before crossover to the alternative treatment. Subjects maintained symptom and peak expiratory flow (PEF) diaries, and underwent weekly spirometric, methacholine challenge, sputum eosinophil, and serum eosinophil cationic protein (ECP) measurements. Mean corticosteroid dose was reduced by 87% during salmeterol treatment, versus 69% with placebo (p = 0.04). Sputum eosinophils increased before exacerbation despite stable symptoms, FEV1, and PEF. In the week before clinical exacerbation, sputum eosinophil counts were higher in the salmeterol-treatment arm (19.9 +/- 29.8% [mean +/- SD], versus placebo 9.3 +/- 17.6%; p = 0.006). Five subjects showed > 10% sputum eosinophilia before exacerbation during salmeterol treatment, as compared with two receiving placebo. In this model, salmeterol controlled symptoms and lung function until inflammation became significantly more advanced. We conclude that the bronchodilating and symptom-relieving effects of salmeterol can mask increasing inflammation and delay awareness of worsening asthma.
Discriminatory Accuracy From Single-Nucleotide Polymorphisms in Models to Predict Breast Cancer Risk
Authors: M. H. Gail
Journal: JNCI Journal of the National Cancer Institute (2008)

One purpose for seeking common alleles that are associated with disease is to use them to improve models for projecting individualized disease risk. Two genome-wide association studies and a study of candidate genes recently identified seven common single-nucleotide polymorphisms (SNPs) that were associated with breast cancer risk in independent samples. These seven SNPs were located in FGFR2 , TNRC9 (now known as TOX3 ), MAP3K1 , LSP1 , CASP8 , chromosomal region 8q, and chromosomal region 2q35. I used estimates of relative risks and allele frequencies from these studies to estimate how much these SNPs could improve discriminatory accuracy measured as the area under the receiver operating characteristic curve (AUC). A model with these seven SNPs (AUC = 0.574) and a hypothetical model with 14 such SNPs (AUC = 0.604) have less discriminatory accuracy than a model, the National Cancer Institute's Breast Cancer Risk Assessment Tool (BCRAT), that is based on ages at menarche and at first live birth, family history of breast cancer, and history of breast biopsy examinations (AUC = 0.607). Adding the seven SNPs to BCRAT improved discriminatory accuracy to an AUC of 0.632, which was, however, less than the improvement from adding mammographic density. Thus, these seven common alleles provide less discriminatory accuracy than BCRAT but have the potential to improve the discriminatory accuracy of BCRAT modestly. Experience to date and quantitative arguments indicate that a huge increase in the numbers of case patients with breast cancer and control subjects would be required in genome-wide association studies to find enough SNPs to achieve high discriminatory accuracy.
Inhalational drug delivery from seven different spacer devices.
Authors: P. W. Barry, C. O'Callaghan
Journal: Thorax (1996)

BACKGROUND: A study was performed to determine in vitro the difference in drug output of seven currently available spacer devices when used with different inhaled medications. METHODS: A glass multistage liquid impinger (MSLI) was used to determine the amount of disodium cromoglycate (DSCG, 5 mg), salbutamol (100 micrograms), or budesonide (200 micrograms) obtained in various particle size ranges from metered dose inhalers (MDIs) actuated directly into the MSLI or via one of seven different spacer devices; the Fisonair, Nebuhaler, Volumatic, Inspirease, Aerochamber, Aerosol Cloud Enhancer, and Dynahaler. RESULTS: In particles smaller than 5 microns in diameter the dose of DSCG recovered from the Fisonair and Nebuhaler was 118% and 124%, respectively, of that recovered using the MDI alone. The dose recovered from the smaller volume spacers was 90% (Inspirease), 36% (Aerochamber), 33% (Aerosol Cloud Enhancer), and 21% (Dynahaler) of that from the MDI alone. The Volumatic increased the amount of salbutamol in particles smaller than 5 microns to 117% of that from the MDI, and the Inspirease and Aerochamber spacers decreased it by nearly 50%. The amount of budesonide in small particles recovered after use of the Nebuhaler, Inspirease, and the Aerochamber was 92%, 101%, and 78%, respectively, of that from the MDI alone. CONCLUSIONS: Under the test conditions used, large volume spacers such as the Fisonair, Nebuhaler, and Volumatic delivered significantly more DSCG and salbutamol than the smaller spacers tested. The differences between spacers were less for budesonide than the other medications studied. This study shows that there are significant differences in the amount of drug available for inhalation when different spacers are used as inhalational aids with different drugs. Spacer devices need to be fully evaluated for each drug prescribed for them.
Merkel cell carcinoma in Scotland 2000-10
Authors: R.J. Samuel, A.G. Matthews, S.A. Holme
Journal: British Journal of Dermatology (2015)

Journal Article Merkel cell carcinoma in Scotland 2000–10 Get access R.J. Samuel, R.J. Samuel University of Edinburgh Medical School 47 Little France Crescent Edinburgh EH16 4TJ U.K Search for other works by this author on: Oxford Academic Google Scholar A.G. Matthews, A.G. Matthews Alan Lyell Centre for Dermatology Western Infirmary Dumbarton Road Glasgow G11 6NT U.K Correspondence: Allan G. Matthews. E‐mail: allan.matthews@nhs.net Search for other works by this author on: Oxford Academic Google Scholar S.A. Holme S.A. Holme Department of Dermatology Royal Infirmary Lauriston Building Lauriston Place Edinburgh EH3 9HA U.K Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 173, Issue 4, 1 October 2015, Pages 1073–1075, https://doi.org/10.1111/bjd.13869 Published: 01 October 2015
The Aryl Hydrocarbon Receptor Functions as a Tumor Suppressor of Liver Carcinogenesis
Authors: Yunxia Fan, Gregory P. Boivin, Erik S. Knudsen, Daniel W. Nebert, Ying Xia, Alvaro Puga
Journal: Cancer Research (2009)

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediates the biological and toxic effects of its xenobiotic ligands. Previous cell culture studies have shown that, in addition to controlling the xenobiotic detoxification response, AHR activation leads to G0-G1 arrest, diminished capacity for DNA replication, and inhibition of cell proliferation. In fact, recent work from our own and from other laboratories suggests that AHR may function as a tumor suppressor gene that becomes silenced during the process of tumor formation. To test this hypothesis and determine whether the mouse Ahr gene acts as a tumor suppressor gene in vivo, we have examined the role of Ahr ablation in liver tumorigenesis induced by the genotoxic chemical diethylnitrosamine (DEN), a hepatic carcinogen that is not an AHR ligand. In mice given a single i.p. injection of DEN, AHR antagonized liver tumor formation and growth by regulating cell proliferation, inflammatory cytokine expression, and DNA damage, parameters which were significantly elevated in the livers of control and, more so, of DEN-exposed Ahr-/- mice. Ahr-/- hepatocytes also showed significantly higher numbers of 4N cells, increased expression of proliferative markers, and repression of tumor suppressor genes. These data support the concept that in its basal state in the absence of a xenobiotic ligand, the Ahr gene functions as a tumor suppressor gene, and that its silencing may be associated with cancer progression.
Apolipoprotein A-IV inhibits experimental colitis
Authors: Thorsten Vowinkel, Mikiji Mori, Christian F. Krieglstein, Janice Russell, Fumito Saijo, Sulaiman Bharwani, Richard H. Turnage, W. Sean Davidson, Patrick Tso, D. Neil Granger, Theodore J. Kalogeris
Journal: Journal of Clinical Investigation (2004)

The antiatherogenic properties of apoA-IV suggest that this protein may act as an anti-inflammatory agent. We examined this possibility in a mouse model of acute colitis. Mice consumed 3% dextran sulfate sodium (DSS) in their drinking water for 7 days, with or without daily intraperitoneal injections of recombinant human apoA-IV. apoA-IV significantly and specifically delayed the onset, and reduced the severity and extent of, DSS-induced inflammation, as assessed by clinical disease activity score, macroscopic appearance and histology of the colon, and tissue myeloperoxidase activity. Intravital fluorescence microscopy of colonic microvasculature revealed that apoA-IV significantly inhibited DSS-induced leukocyte and platelet adhesive interactions. Furthermore, apoA-IV dramatically reduced the upregulation of P-selectin on colonic endothelium during DSS-colitis. apoA-IV knockout mice exhibited a significantly greater inflammatory response to DSS than did their WT littermates; this greater susceptibility to DSS-induced inflammation was reversed upon exogenous administration of apoA-IV to knockout mice. These results provide the first direct support for the hypothesis that apoA-IV is an endogenous anti-inflammatory protein. This anti-inflammatory effect likely involves the inhibition of P-selectin-mediated leukocyte and platelet adhesive interactions.
Treatment of malignant tumors of the skull base with multi-session radiosurgery
Authors: Nicholas D Coppa, Daniel MS Raper, Ying Zhang, Brian T Collins, K William Harter, Gregory J Gagnon, Sean P Collins, Walter C Jean
Journal: Journal of Hematology & Oncology (2009)

Malignant tumors that involve the skull base pose significant challenges to the clinician because of the proximity of critical neurovascular structures and limited effectiveness of surgical resection without major morbidity. The purpose of this study was to evaluate the efficacy and safety of multi-session radiosurgery in patients with malignancies of the skull base.Clinical and radiographic data for 37 patients treated with image-guided, multi-session radiosurgery between January 2002 and December 2007 were reviewed retrospectively. Lesions were classified according to involvement with the bones of the base of the skull and proximity to the cranial nerves.Our cohort consisted of 37 patients. Six patients with follow-up periods less than four weeks were eliminated from statistical consideration, thus leaving the data from 31 patients to be analyzed. The median follow-up was 37 weeks. Ten patients (32%) were alive at the end of the follow-up period. At last follow-up, or the time of death from systemic disease, tumor regression or stable local disease was observed in 23 lesions, representing an overall tumor control rate of 74%. For the remainder of lesions, the median time to progression was 24 weeks. The median progression-free survival was 230 weeks. The median overall survival was 39 weeks. In the absence of tumor progression, there were no cranial nerve, brainstem or vascular complications referable specifically to CyberKnife radiosurgery.Our experience suggests that multi-session radiosurgery for the treatment of malignant skull base tumors is comparable to other radiosurgical techniques in progression-free survival, local tumor control, and adverse effects.
Functional disorders of the anus and rectum
Authors: W E Whitehead, A Wald, N E Diamant, P Enck, J H Pemberton, S S C Rao
Journal: Gut (1999)

In this report the functional anorectal disorders, the etiology of which is currently unknown or related to the abnormal functioning of normally innervated and structurally intact muscles, are discussed. These disorders include functional fecal incontinence, functional anorectal pain, including levator ani syndrome and proctalgia fugax, and pelvic floor dyssynergia. The epidemiology of each disorder is defined and discussed, their pathophysiology is summarized and diagnostic approaches and treatment are suggested. Some suggestions for the direction of future research on these disorders are also given.
Improvement of drug delivery with a breath actuated pressurised aerosol for patients with poor inhaler technique.
Authors: S P Newman, A W Weisz, N Talaee, S W Clarke
Journal: Thorax (1991)

BACKGROUND The metered dose inhaler is difficult to use correctly, synchronising actuation with inhalation being the most important problem. A breath actuated pressurised inhaler, designed to help patients with poor inhaler technique, was compared with a conventional metered dose inhaler in terms of aerosol deposition and bronchodilator response. METHODS Radioaerosol deposition and bronchodilator response to 100 micrograms salbutamol were measured in 18 asthmatic patients, who inhaled from a conventional metered dose inhaler by their own chosen metered dose inhaler technique, from a conventional metered dose inhaler by a taught metered dose inhaler technique, and from a breath actuated pressured inhaler (Autohaler). RESULTS In the 10 patients who could coordinate actuation and inhalation of the inhaler on their own deposition of aerosol in the lungs and bronchodilator response were equivalent on the three study days. By contrast, in the eight patients who could not coordinate the mean (SEM) percentage of the dose deposited in the lungs with their own inhaler technique (7.2% (3.4%] was substantial lower than those attained by the taught metered dose inhaler technique (22.8% (2.5%] and by Autohaler (20.8% (1.7%]. CONCLUSION Although of little additional benefit to asthmatic patients with good coordination, the Autohaler is potentially a valuable aid to those with poor coordination, and should be considered in preference to a conventional metered dose inhaler in any patient whose inhaler technique is not known to be satisfactory.
p53 regulates epithelial–mesenchymal transition through microRNAs targeting ZEB1 and ZEB2
Authors: Taewan Kim, Angelo Veronese, Flavia Pichiorri, Tae Jin Lee, Young-Jun Jeon, Stefano Volinia, Pascal Pineau, Agnès Marchio, Jeff Palatini, Sung-Suk Suh, Hansjuerg Alder, Chang–Gong Liu, Anne Dejean, Carlo M. Croce
Journal: The Journal of Experimental Medicine (2011)

p53 suppresses tumor progression and metastasis. Epithelial–mesenchymal transition (EMT) is a key process in tumor progression and metastasis. The transcription factors ZEB1 and ZEB2 promote EMT. Here, we show that p53 suppresses EMT by repressing expression of ZEB1 and ZEB2. By profiling 92 primary hepatocellular carcinomas (HCCs) and 9 HCC cell lines, we found that p53 up-regulates microRNAs (miRNAs), including miR-200 and miR-192 family members. The miR-200 family members transactivated by p53 then repress ZEB1/2 expression. p53-regulated miR-192 family members also repress ZEB2 expression. Inhibition or overexpression of the miRNAs affects p53-regulated EMT by altering ZEB1 and ZEB2 expression. Our findings indicate that p53 can regulate EMT, and that p53-regulated miRNAs are critical mediators of p53-regulated EMT.
Fifty-Year Study of Lung and Bladder Cancer Mortality in Chile Related to Arsenic in Drinking Water
Authors: G. Marshall, C. Ferreccio, Y. Yuan, M. N. Bates, C. Steinmaus, S. Selvin, J. Liaw, A. H. Smith
Journal: JNCI Journal of the National Cancer Institute (2007)

Region II of Chile (the second most northerly administrative region) experienced dramatic increases in average arsenic water concentrations beginning in 1958, followed by marked declines in the 1970s when water treatment plants were installed. This history provides a unique opportunity to study time trends in the development of arsenic-related cancers, including lung and bladder cancers. We investigated lung and bladder cancer mortality from 1950 to 2000 for region II compared with region V, where drinking water was not contaminated with arsenic. Mortality data were obtained from 218174 death certificates for the two regions for 1950–1970 and from mortality data tapes that identified 307 541 deaths in the two regions for 1971–2000. Poisson regression models were used to identify time trends in rate ratios (RRs) of mortality from lung and bladder cancers comparing region II with region V. Lung and bladder cancer mortality rate ratios for region II compared with region V started to increase about 10 years after high arsenic exposures commenced and continued to rise until peaking in 1986–1997. The peak lung cancer mortality RRs were 3.61 (95% confidence interval [CI] = 3.13 to 4.16) for men and 3.26 (95% CI = 2.50 to 4.23) for women. The peak bladder cancer RRs were 6.10 (95% CI = 3.97 to 9.39) for men and 13.8 (95% CI = 7.74 to 24.5) for women. Combined lung and bladder cancer mortality rates in region II were highest in the period 1992–1994, with mortality rates of 153 and 50 per 100000 men and women, respectively, in region II compared with 54 and 19 per 100000 in region V. Such large increases in total population cancer mortality rates have, to our knowledge, not been documented for any other environmental exposure. The long latency pattern is noteworthy, with mortality from lung and bladder cancers continuing to be high until the late 1990s, even though major decreases in arsenic exposure occurred more than 25 years earlier.
Surgical treatment of myasthenia gravis in two major Middle East teaching hospitals: factors influencing outcome.
Authors: S. A. Hassantash, D. G. Ashbaugh, E. D. Verrier, R. V. Maier
Journal: Thorax (1996)

The results of thymectomy on patients with generalised myasthenia gravis have been widely reported. However, there is no information on whether the experience of western countries can be generalised to the population of the Middle East. The purpose of this study was to evaluate the safety and efficacy of thymectomy in patients with myasthenia gravis in a Middle East patient population and to identify clinical and histopathological factors associated with improved long term outcome of surgery.In a prospective study, sixty three patients (aged 1.5-51 years) were treated in two university teaching hospitals between 1984 and 1991 and followed up for a mean of four years. Close communication was established with neurologists to obtain early referral. Radical anterior mediastinal dissection through a median sternotomy was performed in all patients. The response was evaluated by modified Osserman's classification.Eighteen patients achieved complete remission and a further 39 improved, producing an overall response rate of 90.5%. Patients with milder disease (stage II) had a higher response rate (97%) than those with more advanced disease (78%). Patients operated on with less than three years of symptoms had a better outcome (94%) than those with longer duration of preoperative symptoms, especially in non-thymomatous patients. Age and sex had no effect on the outcome. There was no effect on response rate if patients had hyperplastic or non-specific thymic histological findings, but patients with thymoma fared worse.These results are comparable with reports from the western world and represent the first prospective study from the Middle East. Thymectomy is indicated for all patients suffering from generalised myasthenia gravis soon after the diagnosis is made, regardless of age, stage, thymic pathology, and preoperative clinical status.
Yearly Re-examination by Mass Radiography
Authors: W. P. Dick
Journal: BMJ (1948)

Tests of the effect on cartilage and bone of bacteria associ- ated with dental caries are described.Cartilage and bone sterilized by heat are shown to be broken down when incubated at 37' C. in the presence of bacteria taken from carious teeth.Pure cultures of a bacillus repeatedly isolated from carious teeth are shown to be capable of attacking some proteins.Following bacterial hydrolysis at 37' C., quantitative estima- tions of free amino-groups have been made by the use of Sorenson's formol titration method.Bacterial hydrolysis of bone collagen is shown to have occurred in media with pH values close to 7.Two stages of attack on bone are presented, one more advanced than the other.