tbuckley/cabot-search huggingface dataset:
Use of vitamin B-12 in Leicestershire practices: a single topic audit led by a medical audit advisory group
Authors: R. C Fraser, A. Farooqi, R. Sorrie
Journal: BMJ (1995)

<h3>Abstract</h3> <b>Objectives</b>: To encourage active participation of Leicestershire general practitioners and their staff in audit; to examine the use of vitamin B-12 injections and to achieve a more appropriate use. <b>Design</b>: Implementation of an agreed audit protocol, with central analysis and feedback of anonymous and aggregated data by a medical audit advisory group. <b>Setting</b>: All 147 Leicestershire practices. <b>Main outcome measures</b>: Participation in the complete audit cycle, comparison of actual use of vitamin B-12 injections with agreed criteria of use, and assessment of improvement in use. <b>Results</b>: 264 general practitioners (55% of all doctors from 49% of all Leicestershire practices) completed both phases of the audit cycle, and 321 (67%) completed phase 1 only. Twenty four (16%) practices failed to participate from the outset, and a further 58 (35%) dropped out at various stages. Only 10 of the 37 singlehanded practices completed the audit, although 34 initially agreed to participate. If singlehanded practices were excluded, 56% (61) of practices completed both phases of the audit cycle. In total 1714 patients received B-12 injections. Appropriate use increased from 62% in phase 1 to 72% in phase 2 of the audit; there was a 32% reduction in the number of patients inappropriately receiving B-12 (521 to 352), and the proportion of patients receiving B-12 at the correct frequency rose from 58% to 72%. The proportion of patients in whom all the diagnostic criteria for pernicious anaemia were established before treatment with B-12 was 27% in phase 1 and 28% in phase 2. <b>Conclusion</b>: Our study suggests that single topic audits organised by a medical audit advisory group can encourage large numbers of general practitioners to participate and can bring about changes in behaviour resulting in improvements in standards of care. Nevertheless, advisory groups will need to devise strategies to encourage even higher levels of involvement, most particularly from singlehanded practices.
A climate-based model predicts the spatial distribution of the Lyme disease vector Ixodes scapularis in the United States.
Authors: John S Brownstein, Theodore R Holford, Durland Fish
Journal: Environmental Health Perspectives (2003)

An understanding of the spatial distribution of the black-legged tick, Ixodes scapularis, is a fundamental component in assessing human risk for Lyme disease in much of the United States. Although a county-level vector distribution map exists for the United States, its accuracy is limited by arbitrary categories of its reported presence. It is unknown whether reported positive areas can support established populations and whether negative areas are suitable for established populations. The steadily increasing range of I. scapularis in the United States suggests that all suitable habitats are not currently occupied. Therefore, we developed a spatially predictive logistic model for I. scapularis in the 48 conterminous states to improve the previous vector distribution map. We used ground-observed environmental data to predict the probability of established I. scapularis populations. The autologistic analysis showed that maximum, minimum, and mean temperatures as well as vapor pressure significantly contribute to population maintenance with an accuracy of 95% (p < 0.0001). A cutoff probability for habitat suitability was assessed by sensitivity analysis and was used to reclassify the previous distribution map. The spatially modeled relationship between I. scapularis presence and large-scale environmental data provides a robust suitability model that reveals essential environmental determinants of habitat suitability, predicts emerging areas of Lyme disease risk, and generates the future pattern of I. scapularis across the United States.
A pilot study of continuous imatinib vs pulsed imatinib with or without G-CSF in CML patients who have achieved a complete cytogenetic response
Authors: M W Drummond, N Heaney, J Kaeda, F E Nicolini, R E Clark, G Wilson, P Shepherd, J Tighe, L McLintock, T Hughes, T L Holyoake
Journal: Leukemia (2009)
Agricultural exposures and cancer.
Authors: A Blair, S H Zahm
Journal: Environmental Health Perspectives (1995)

The purpose of this report is to review the literature on cancer among persons employed in agriculture, to characterize the value of this line of research, and to recommend future directions. Farmers, despite a generally favorable mortality, appear to experience elevated rates for several cancers, including leukemia, non-Hodgkin's lymphoma, multiple myeloma, soft-tissue sarcoma, and cancers of the skin, lip, stomach, brain, and prostate. The rates for several of these tumors (i.e., non-Hodgkin's lymphoma, multiple myeloma, skin, brain, and prostate) appear to be increasing in the general population. No set of established etiologic factors explains all the cancer excesses observed among farmers, although several are associated with naturally occurring or medically induced immunodeficiencies. This suggests that there may be factors in the agricultural environment that introduce immune system deficiencies. Farmers are exposed to a variety of substances that could operate through this mechanism, including pesticides, engine exhausts, solvents, dusts, and zoonotic microbes. Studies to further characterize the cancer risk among farmers, their dependents, and farm laborers, and to identify the exposures that may be involved would not only be useful in providing a safe work environment in agriculture but may furnish considerable insight into the causes for a number of tumors that are rising in incidence in the general population.
P13 The Overlapping Prevalence Of Chronic Mucus Hypersecretion (cmh) And Chronic Cough (cc)
Authors: J. Allinson, R. Hardy, G. Donaldson, S. Shaheen, D. Kuh, J. Wedzicha
Journal: Thorax (2014)

<h3>Introduction</h3> There is considerable interest surrounding the role of chronic mucus hypersecretion (CMH) in the development of COPD but varying definitions of CMH have created uncertainty regarding its prevalence. Some studies characterise CMH as chronic phlegm production whilst others as chronic cough (CC) productive of phlegm. By understanding how these symptom groups relate to each other, we may be better equipped to interpret existing data and search for therapeutic targets. We report the prevalence and overlap of CMH and CC over 43 years of adult life from age 20 years within the nationally representative MRC National Survey of Health and Development (NSHD) birth cohort. <h3>Methods</h3> The MRC NSHD is a birth cohort study of men and women born during one week in March 1946 within England, Scotland and Wales. CMH and CC presence was determined by completion of the MRC questionnaire on respiratory symptoms in the following years (study member age in years): 1966(20), 1971(25), 1982(36), 1989(43), 1999(53) and 2009(63). The MRC questionnaire defines CMH as the production of phlegm from the chest on most days for three months of each year and defines CC as cough on most days for three months of each year. <h3>Results</h3> 1394 subjects (47% male) completed questionnaires on all six occasions between 1966 and 2009. 398 study members (26.8%) reported either symptom at least once with a majority of CMH reporters concurrently reporting CC (See Table 1). The percentage of CMH reporters concurrently reporting CC increased with age (0.5%/year increase, CI 0.18–0.82, p = 0.001). <h3>Conclusion</h3> Most chronic phlegm producers report concurrent CC, and this percentage increases with age. Restricting CMH definition to those with CC, however, misses the substantial proportion of the population who report chronic phlegm production without CC. The requirement for a chronic cough to define CMH may underestimate the total prevalence of chronic sputum producers and hence those potentially at risk of COPD development or progression.
APPENDICITIS WITH AN ILEO-APPENDICAL FISTULA
Authors: R. C. Andries
Journal: JAMA (1925)

We report this case because of the clinical and surgical interest attending it. The rarity of the condition is attested by the fact that only one other case is described, and that only in 1923, by Willour.<sup>1</sup>He reported a similar case and was unable to find a report of another in the literature, except three cases, which were found at necropsy. In our own search of the literature, we were unable to find any other case reported. <h3>REPORT OF CASE</h3> J. H., a man, aged 25, entered the hospital, Oct. 19, 1924, complaining of pain in the right lower quadrant and right loin. In November, 1923, he had an attack of pain in the right lower quadrant and was nauseated but did not vomit. At that time, he was confined to bed for two weeks and was unable to work for two weeks following. After recovery there was
P40 Increased advanced glycation end products in patients with chronic obstructive pulmonary disease (COPD)
Authors: M. John, S. Hussain, S. Selvarajah, I. Sayers, I. P. Hall, L. Fairclough, C. E. Bolton
Journal: Thorax (2011)

<h3>Introduction</h3> Advanced glycation endproducts (AGE) are markers of glycaemic and oxidative stress, pro-inflammatory and alter structure through collagen cross-linking, formed through the Maillard reaction. There has been recent interest in AGE and its receptor: RAGE in airways1 and circulating2 in subjects with COPD as well as in a GWAS of lung function.3 Skin autofluoresence permits non-invasive measurement of skin AGE, validated against biopsies. Skin levels reflect accumulation, unlike circulating levels which are more variable. We hypothesised that skin AGE was increased in subjects with COPD and related to lung function. Methods Subjects &gt;40 years, with and without COPD, all with &gt;10 smoking pack years, were recruited. All subjects were assessed at clinical stability. Control never smokers were also recruited. Detailed history, post-bronchodilator spirometry and skin AGE were determined. Circulating AGE and soluble RAGE were measured by ELISA. <h3>Results</h3> There were 49 COPD subjects; 18 current/ex-smokers without COPD; 16 never smokers, Abstract P40 table 1. The mean skin AGE was greatest in subjects with COPD compared to both control groups, p&lt;0.05, ANOVA, Abstract P40 table 1. There was an indirect relationship between FEV<sub>1</sub> % predicted and skin AGE, r=−0.46, p&lt;0.01. A stepwise multiple regression was performed, with skin AGE as the dependent, and FEV<sub>1</sub> % predicted, smoking pack years, age, BMI and gender entered into the model. FEV<sub>1</sub> % predicted and smoking pack years were independent variables, p&lt;0.01. There was no significant difference in serum AGE between groups. Mean soluble RAGE was lowest in the COPD subjects and significantly lower than control never smokers, p&lt;0.05, ANOVA, Abstract P40 table 1. <h3>Conclusions</h3> People with COPD have increased skin AGE compared to subjects with a smoking history and control never smokers. Subjects with COPD also have decreased serum soluble RAGE levels compared to never smokers. The FEV<sub>1</sub> % was an independent variable of skin AGE. Further research should explore the potential role of AGE in the co-morbidities of COPD.
Pancytopenia Associated with Sulfamethoxypyridazine Administration
Authors: F. Deborah Johnson
Journal: JAMA (1961)

A 63-year-old man was treated with sulfamethoxypyridazine (SMP) for urinary infection following a transurethral prostatic resection. The dosage taken was 1.0 Gm. of SMP per day for a week, then 0.5 Gm. every other day for about 3 weeks. At that time it was found that his blood picture, in sharp contrast to the preoperative findings, had become strikingly abnormal, with complete disappearance of granulocytes from the blood and corresponding abnormalities in the sternal marrow. Leucocyte-agglutinin studies corroborated the assumption that the SMP was related to the blood dyscrasia. After discontinuing this medication the patient recovered.
Allelic Imbalance of 12q22–23 Associated with <b> <i>APAF-1</i> </b> Locus Correlates with Poor Disease Outcome in Cutaneous Melanoma
Authors: Akihide Fujimoto, Hiroya Takeuchi, Bret Taback, Eddy C. Hsueh, David Elashoff, Donald L. Morton, Dave S. B. Hoon
Journal: Cancer Research (2004)

Abstract Cutaneous melanoma is a highly aggressive tumor that is relatively resistant to chemotherapy and radiotherapy. This resistance may be in part due to inhibition of apoptosis. Apoptotic protease activating factor-1(APAF-1), a candidate tumor suppressor gene, mediates p53-induced apoptosis, and its loss promotes oncogenic transformation. To determine whether loss of the APAF-1 locus influences tumor progression, we assessed loss of heterozygosity microsatellites on the APAF-1 locus (12q22–23) in 62 primary and 112 metastatic melanomas. We discovered that frequency of allelic imbalance was significantly higher in metastatic tumors (n = 36 of 98; 37%) than in primary melanomas (n = 10 of 54; 19%; P = 0.02). In metastatic melanomas, APAF-1 loss significantly correlated with a worse prognosis (P &amp;lt; 0.05) in the patients, and its loss during melanoma tumor progression suggests that APAF-1 is a tumor suppressor gene. Furthermore, loss of heterozygosity was frequent in the 12q22–23 chromosome region centromeric to the APAF-1 locus suggesting that other tumor-related genes may be present in the 12q22–23 region. In summary, the study demonstrates that allelic imbalance in the 12q22–23 region is a genomic surrogate of poor disease outcome for cutaneous melanoma patients.
929-66 Validation of a New Method for Calculating Continuous Transmural Distributions of Strain in the Ventricles Using Magnetic Resonance Tagging
Authors: Michael J. Moulton, Lawrence L. Creswell, Stephen W. Downing, Barna A. Szabó, Michael W. Vannier, Michael K. Pasque
Journal: Journal of the American College of Cardiology (1995)
Levels of transforming growth factor β and transforming growth factor β receptors in rat liver during growth, regression by apoptosis and neoplasia
Authors: Bettina Grasl-Kraupp, Walter Rossmanith, Branislav Ruttkay-Nedecky, Leonhard Müllauer, Bettina Kammerer, Wilfried Bursch, Rolf Schulte-Hermann
Journal: Hepatology (1998)

Transforming growth factor β 1 (TGF-β 1 ) has been implicated as inhibitor of cell proliferation and a potent inducer of apoptosis in vitro and in vivo after the administration of high doses. To assess the role of endogenous TGF-β 1 , we quantitated the cytokine and its receptors in rat liver during regenerative and hyperplastic growth, regression by apoptosis, and in hepatocellular carcinoma (HCC). This was accomplished by Northern blot analysis and by RNase protection assay of the messenger RNA (mRNA) of TGF-β 1 and TGF-β receptors (TβR) types I to III and by an activity bioassay of the TGF-β proteins. Untreated rat livers were found to contain 15.6 ± 4.8 ng TGF-β 1 protein/g tissue; TGF-β 2 protein was not detected. To induce toxic cell death and subsequent regenerative DNA synthesis in the liver, rats were treated with a necrogenic dose of carbon tetrachloride (CCl 4 ). After 24 and 48 hours, there was an upregulation of TGF-β 1 (mRNA, up to tenfold; protein, about twofold) and of TβRs (mRNA: two- to fourfold); that indicates an overall enhanced production of and sensitivity to TGF-β 1 , which may serve to confine the regenerative response. Hyperplastic liver growth and regression of the hyperplasia were induced by treatment with cyproterone acetate (CPA) or nafenopin (NAF) followed by withdrawal; neither mRNAs of TGF-β 1 and TβR types I to III nor TGF-β 1 protein exhibited significant changes during the growth phase or during regression by apoptosis. We also studied neoplastic growth. HCC, obtained after long-term treatment with NAF, exhibited high rates of cell replication and apoptosis. The majority of lesions contained mRNA and protein of TGF-β 1 and mRNA of TβR types I to III at concentrations similar to those of the surrounding tissue. In conclusion, during liver regeneration there is a pronounced upregulation of expression of both TGF-β 1 and TβRs I to III, but not during mitogen-induced liver growth or regression. It appears that apoptosis is induced via altered local concentration of TGF-β 1 in a paracrine and/or autocrine way. By this mechanism the lethal effects of TGF-β 1 may be locally confined, and overshoots of apoptosis in the liver may be prevented.
THE BEDSIDE STUDY OF AIR HUNGER
Authors: C. F. HOOVER
Journal: JAMA (1926)

A great scientist said, "The last thing a deep sea fish would discover is water," an apothem which pointedly expresses the idea that we must transcend our most intimate contacts before we can comprehend them. This is literally true in the history of science, for scientific study of the heavens and the earth long preceded scientific study of the air, and only the most recent studies in medicine have been concerned about the medium in which we live and our adjustments to it. Respiration is such a nicely directed function and our respiratory need is so exquisitely balanced with our breathing mechanism that, until recent years, physicians were contented with the observation that there was a disturbed relation between these two factors, but analysis of the disturbance seemed superfluous, because the phenomenon was too obvious. Now that chemical research has revealed so much concerning respiration, clinicians should aspire from objective
Determination of Glomerular Filtration Rate Using a Dual-Detector Gamma Camera and the Geometric Mean of Renal Activity
Authors: EBRAHIM S. DELPASSAND, KAVEH HOMAYOON, TIMOTHY MADDEN, MATHEW MATHAI, DONALD A. PODOLOFF
Journal: Clinical Nuclear Medicine (2000)

In this study, the authors studied the use of a dual-detector gamma camera to measure the glomerular filtration rate (GFR).Thirty-three patients with a wide range of renal function participated in this study. The GFR was measured using a dual-detector gamma camera by calculating the geometric mean of activity from each kidney and using an outline background. These results were compared with the GFR estimates obtained from Tc-99m DTPA plasma clearance using a multiple blood sample method.Correlation was excellent between GFR estimated using the dual-detector gamma camera and GFR measured using the plasma clearance of Tc-99m DTPA with multiple blood samples (r = 0.89). The correlation was especially strong in children younger than 13 years (r = 0.94).Measuring the GFR using a dual-detector gamma camera and calculating the geometric mean of renal activity yields relatively accurate results.
Patterns of monoclonal immunoglobulins and serum free light chains are significantly different in black compared to white monoclonal gammopathy of undetermined significance (MGUS) patients
Authors: Brendan M. Weiss, Alex Minter, Jude Abadie, Robin Howard, Joao Ascencao, Geraldine P. Schechter, Michael Kuehl, Ola Landgren
Journal: American Journal of Hematology (2011)

Abstract Monoclonal gammopathy of undetermined significance (MGUS), the precursor to multiple myeloma, is more common in blacks than whites. The serum free light chain (sFLC) assay is an important prognostic test in MGUS, but no study has evaluated sFLC levels and ratios in black MGUS patients. One‐hundred and twenty‐five black MGUS patients at two urban centers were compared to the white population of the Mayo Clinic. The median age for blacks was 73 years [41–94] and 75% were male. The M‐protein isotype in blacks was 81% IgG, 13% IgA, 2% IgM, and 4% biclonal compared to 70%, 12%, 16%, and 2%, respectively, in whites, ( P &lt; 0.0005). The median M‐protein concentration for blacks was 0.44 gm/dL (trace‐2.33) compared to 1.2 gm/dl in whites. An abnormal sFLC ratio was present in 45% of black compared to 33% of white ( P = 0.01) patients. Using the Mayo Clinic risk model, black patients had a significantly lower proportion of higher risk MGUS compared to whites: low 43%, low‐intermediate 45%, high‐intermediate 10%, and high 2% ( P = 0.014). Black patients with MGUS have significantly different laboratory findings compared to whites. The biologic basis for these disparities and their effect on prognostic assessment is unknown. Prognostic models based on these biomarkers should be used cautiously in nonwhite populations. Am. J. Hematol. 2011. © 2011 Wiley‐Liss, Inc.
Platelet inhibitors influence cardioprotection: importance in preclinical study design: reply
Authors: S. Lecour, R. Schulz, P. Ferdinandy, D. J. Hausenloy
Journal: Cardiovascular Research (2015)

We would like to thank Professors Cohen and Downey for highlighting platelet inhibitors, in particular platelet P2Y12 receptor antagonists, as an important confounder to take into consideration in pre-clinical studies designed to study novel cardioprotective strategies …
RASA3 is a critical inhibitor of RAP1-dependent platelet activation
Authors: Lucia Stefanini, David S. Paul, Raymond F. Robledo, E. Ricky Chan, Todd M. Getz, Robert A. Campbell, Daniel O. Kechele, Caterina Casari, Raymond Piatt, Kathleen M. Caron, Nigel Mackman, Andrew S. Weyrich, Matthew C. Parrott, Yacine Boulaftali, Mark D. Adams, Luanne L. Peters, Wolfgang Bergmeier
Journal: Journal of Clinical Investigation (2015)

The small GTPase RAP1 is critical for platelet activation and thrombus formation. RAP1 activity in platelets is controlled by the GEF CalDAG-GEFI and an unknown regulator that operates downstream of the adenosine diphosphate (ADP) receptor, P2Y12, a target of antithrombotic therapy. Here, we provide evidence that the GAP, RASA3, inhibits platelet activation and provides a link between P2Y12 and activation of the RAP1 signaling pathway. In mice, reduced expression of RASA3 led to premature platelet activation and markedly reduced the life span of circulating platelets. The increased platelet turnover and the resulting thrombocytopenia were reversed by concomitant deletion of the gene encoding CalDAG-GEFI. Rasa3 mutant platelets were hyperresponsive to agonist stimulation, both in vitro and in vivo. Moreover, activation of Rasa3 mutant platelets occurred independently of ADP feedback signaling and was insensitive to inhibitors of P2Y12 or PI3 kinase. Together, our results indicate that RASA3 ensures that circulating platelets remain quiescent by restraining CalDAG-GEFI/RAP1 signaling and suggest that P2Y12 signaling is required to inhibit RASA3 and enable sustained RAP1-dependent platelet activation and thrombus formation at sites of vascular injury. These findings provide insight into the antithrombotic effect of P2Y12 inhibitors and may lead to improved diagnosis and treatment of platelet-related disorders.