tbuckley/cabot-search huggingface dataset:
First Steps toward Harmonized Human Biomonitoring in Europe: Demonstration Project to Perform Human Biomonitoring on a European Scale
Authors: Elly Den Hond, Eva Govarts, Hanny Willems, Roel Smolders, Ludwine Casteleyn, Marike Kolossa-Gehring, Gerda Schwedler, Margarete Seiwert, Ulrike Fiddicke, Argelia Castaño, Marta Esteban, Jürgen Angerer, Holger M. Koch, Birgit K. Schindler, Ovnair Sepai, Karen Exley, Louis Bloemen, Milena Horvat, Lisbeth E. Knudsen, Anke Joas, Reinhard Joas, Pierre Biot, Dominique Aerts, Gudrun Koppen, Andromachi Katsonouri, Adamos Hadjipanayis, Andrea Krskova, Marek Maly, Thit A. Mørck, Peter Rudnai, Szilvia Kozepesy, Maurice Mulcahy, Rory Mannion, Arno C. Gutleb, Marc E. Fischer, Danuta Ligocka, Marek Jakubowski, M. Fátima Reis, Sónia Namorado, Anca Elena Gurzau, Ioana-Rodica Lupsa, Katarina Halzlova, Michal Jajcaj, Darja Mazej, Janja Snoj Tratnik, Ana López, Estrella Lopez, Marika Berglund, Kristin Larsson, Andrea Lehmann, Pierre Crettaz, Greet Schoeters
Journal: Environmental Health Perspectives (2014)

For Europe as a whole, data on internal exposure to environmental chemicals do not yet exist. Characterization of the internal individual chemical environment is expected to enhance understanding of the environmental threats to health.We developed and applied a harmonized protocol to collect comparable human biomonitoring data all over Europe.In 17 European countries, we measured mercury in hair and cotinine, phthalate metabolites, and cadmium in urine of 1,844 children (5-11 years of age) and their mothers. Specimens were collected over a 5-month period in 2011-2012. We obtained information on personal characteristics, environment, and lifestyle. We used the resulting database to compare concentrations of exposure biomarkers within Europe, to identify determinants of exposure, and to compare exposure biomarkers with health-based guidelines.Biomarker concentrations showed a wide variability in the European population. However, levels in children and mothers were highly correlated. Most biomarker concentrations were below the health-based guidance values.We have taken the first steps to assess personal chemical exposures in Europe as a whole. Key success factors were the harmonized protocol development, intensive training and capacity building for field work, chemical analysis and communication, as well as stringent quality control programs for chemical and data analysis. Our project demonstrates the feasibility of a Europe-wide human biomonitoring framework to support the decision-making process of environmental measures to protect public health.
Outbreak of Influenza A2 Among Immunized Children
Authors: Hugh L. Moffet, Henry G. Cramblett, Jacqueleene Dobbins, Winston Salem
Journal: JAMA (1964)

An outbreak of influenza A2 occurred in 1963 in a children's home five months after half the population had been given two injections of commercial polyvalent vaccine. About 90% of the children who had received the influenza vaccine before the outbreak had an antibody titer of 1:80 or higher against the 1962 strain of influenza A2. The frequency of clinical illnesses for immunized children was slightly but significantly less than for the nonimmunized children. The 1963 outbreak of influenza A2 had a lower infectivity rate, occurred over a longer period of time, and was associated with fewer severe illnesses than the outbreak of influenza B which occurred in the same home in 1962, when no child had received influenza vaccine.
Urinary Sympathin Excretion of Normal Infants and of Infants with Pink Disease
Authors: J. W. Farquhar, T. B. B. Crawford, W. Law
Journal: BMJ (1956)

NITROFURANTOIN IN URINARY INFECTIONBMETISN and the presence of such resistant organisms might prove to be of importance if it was desired to give prolonged treatment.Toxic symptoms were often encountered, but could usually be controlled by slightly reducing the dosage.
What is the optimal age for starting lipid lowering treatment? A mathematical model
Authors: S. Ulrich
Journal: BMJ (2000)

Coronary heart disease is the major cause of morbidity and mortality in industrialised countries. The Framingham cohort study has identified the quantitative impact of different risk factors and their interactions,1–3 and large intervention studies have confirmed that drug treatment to reduce risk factors decreases progression to heart attack and stroke.4 5 However, with this increased understanding have come additional problems. The treatments to reduce cholesterol concentrations or blood pressure are often expensive, and the population that might benefit is vast. Indeed if every individual who might benefit was treated with a statin or fibrate, a large portion of the total drugs budget would be consumed.6 Thus some form of rationing is inevitable, and various recommendations have emerged in an attempt to contain cost while targeting treatment at those who stand to gain the most. Current UK policy recommends treatment should be offered to anyone with an absolute annual risk of 3% or more.7 Others, however, favour a 1.5%-2% absolute threshold before beginning treatment, 8 9 and some have argued that estimates of relative risk should form the basis for treatment guidelines.10 Since age is the major determinant of absolute risk, treatment thresholds based on absolute risk will tend to postpone treatment to older age, whereas guidelines based on relative risk will tend to lead to treatment of younger people.

#### Summary points

Lipid lowering drugs are expensive and the population that might benefit from treatment is potentially vast

Current guidelines recommend targeting treatment to those who will gain the most; gain being cardiovascular events avoided over a fixed period of 5 or 10 years

Modeling of lifetime risk of cardiovascular disease suggests that many individuals will have accumulated most of their risk before they become eligible for treatment

It is possible to predict an age at …
Studies on fibronectin in the skin
Authors: OLE FYRAND
Journal: British Journal of Dermatology (2006)

Fibronectin is a glycoprotein mediating contact between cellular elements and collagen. As judged by indirect immunofluorescence studies fibronectin is abundantly present in normal human skin. It is located in the dermo-epidermal junction area, in the papillary and reticular dermis, about epidermal appendages (pilosebaceous units and eccrine sweat glands) and in the vascular and neural structures.
Overproduction of cholesterol and fatty acids causes massive liver enlargement in transgenic mice expressing truncated SREBP-1a.
Authors: H Shimano, J D Horton, R E Hammer, I Shimomura, M S Brown, J L Goldstein
Journal: Journal of Clinical Investigation (1996)

The NH2-terminal domain of sterol-regulatory element binding protein-1a (SREBP-1a) activates transcription of genes encoding enzymes of cholesterol and fatty acid biosynthesis in cultured cells. This domain is synthesized as part of a membrane-bound precursor that is attached to the nuclear envelope and endoplasmic reticulum. In sterol-depleted cells a two-step proteolytic process releases this NH2-terminal domain, which enters the nucleus and activates transcription. Proteolysis is suppressed by sterols, thereby suppressing transcription. In the current experiments we produce transgenic mice that overexpress a truncated version of human SREBP-1a that includes the NH2-terminal domain but lacks the membrane attachment site. This protein enters the nucleus without a requirement for proteolysis, and therefore it cannot be down-regulated. Expression was driven by the phosphoenolpyruvate carboxykinase (PEPCK) promoter, which gives high level expression in liver. When placed on a low carbohydrate/high protein diet to induce the PEPCK promoter, the transgenic mice developed progressive and massive enlargement of the liver, owing to the engorgement of hepatocytes with cholesterol and triglycerides. The mRNAs encoding 3-hydroxy-3-methylglutaryl CoA (HMG CoA) synthase, HMG CoA reductase, squalene synthase, acetyl-CoA carboxylase, fatty acid synthase, and stearoyl-CoA desaturase-1 were all elevated markedly, as was the LDL receptor mRNA. The rates of cholesterol and fatty acid synthesis in liver were elevated 5- and 25-fold, respectively. Remarkably, plasma lipid levels were not elevated. The amount of white adipose tissue decreased progressively as the liver enlarged. These studies indicate that the NH2-terminal domain of SREBP-1a can produce major effects on lipid synthesis and storage in the liver.
The Psychological Problems of Vietnam Veterans
Authors: John Ingram Walker
Journal: JAMA (1981)

ALMOST a decade after the end of the longest war in US history, there are indications that our society is becoming aware of the emotional conflicts of the Vietnam combat veteran.<sup>1</sup>Current releases by the cinema, television, and the popular press have helped us view the Vietnam serviceman in a more empathetic light. With researchers<sup>2,3</sup>estimating that as many as 1.5 million Vietnam combat veterans may be suffering from a stress disorder, the renewed interest in the Vietnam veteran will result in friends and relatives of servicemen questioning physicians about the diagnosis and treatment of posttraumatic stress disorder. <h3>Problems of the Vietnam Veteran</h3> Problems of the Vietnam veteran are immense and continue to escalate. Of the 2,769,000 men who served in Vietnam, 57,002 were killed, 303,704 were wounded (<i>Center Magazine</i>, July-August 1979, pp 27-36), and 512,000 Vietnam-era veterans have sustained some kind of medical disability rating.<sup>4</sup>It
Viral Hepatitis: Scientific Basis and Clinical Management
Authors: E H Boxall
Journal: BMJ (1994)

The editors of Viral Hepatitis have gathered a formidable international collection of authors representing many major research groups. The first part of the book is an alphabetical approach to hepatitis virology, topics including, for each virus: structure and molecular virology; natural history and epidemiology (for all except hepatitis B); diagnosis and, when appropriate, prevention; treatment; and liver cancer (heapatitis B and C). It is a good time to review progress in hepatitis C virology since the molecular cloning of the virus in 1989 - and a sobering thought that we are capable of providing diagnostic …
Needs of teenagers with chronic disability
Authors: C. Williams
Journal: BMJ (1999)

EDITOR—In Smith's editorial on the needs of teenagers with epilepsy, he states that “the consultation must focus on the needs and independence of the teenager, with the parents taking a back seat.”1 This view replicates the individualistic approach of health education by treating teenagers as autonomous individuals, with little recognition of the constraints that might impact on choices.

In line with other work,2 my qualitative research on teenagers with either diabetes or asthma found that they tended to …
Impaired diurnal adrenal rhythmicity restored by constant infusion of corticotropin-releasing hormone in corticotropin-releasing hormone-deficient mice.
Authors: L J Muglia, L Jacobson, S C Weninger, C E Luedke, D S Bae, K H Jeong, J A Majzoub
Journal: Journal of Clinical Investigation (1997)

The normal pattern of daily glucocorticoid production in mammals requires circadian modulation of hypothalamicpituitary-adrenal axis activity. To assess both the factors responsible for imparting this diurnal profile and its physiologic importance, we have exploited corticotropin-releasing hormone (CRH)-deficient mice generated by homologous recombination in embryonic stem cells. CRH-deficient mice have lost normal circadian variations in plasma ACTH and glucocorticoid while maintaining normal circadian locomotor activity. Constant peripheral infusion of CRH produced marked diurnal excursions of plasma glucocorticoid, indicating that CRH acts in part as a permissive factor for other circadian modulators of adrenocortical activity. The presence of atrophic adrenals in CRH-deficient mice without an overt deficit in basal plasma ACTH concentration suggests that the diurnal increase in ACTH is essential to maintain normal adrenal function.
Glucagon responses to intravenous arginine and oral glucose in insulin-dependent diabetic patients during six months conventional or continuous subcutaneous insulin infusion
Authors: K. Hermansen, O. Schmitz, N. Boye, C.K. Christensen, J.S. Christiansen, K.G.M.M. Alberti, H. Ørskov, C.E. Mogensen
Journal: Metabolism (1988)
Hyaluronan, CD44 and versican in epidermal keratinocyte tumours
Authors: S. Karvinen, V-M. Kosma, M.I. Tammi, R. Tammi
Journal: British Journal of Dermatology (2003)

The high molecular weight polysaccharide hyaluronan is a major component of the extracellular matrix between the vital cells of human skin epidermis. The levels of hyaluronan, and those of the hyaluronan receptor CD44 and the hyaluronan binding proteoglycan versican, correlate with the aggressiveness of different human carcinomas of epithelial origin.To study skin keratinocyte tumours for the expression of hyaluronan, the hyaluronan receptor CD44 and the hyaluronan binding proteoglycan versican.Paraffin-embedded sections of 114 basal cell carcinomas (BCC), 31 in situ carcinomas (ISC) and 35 squamous cell carcinomas (SCC) were stained with a hyaluronan specific probe, biotinylated hyaluronan binding complex, and with monoclonal antibodies against CD44 and versican.Compared with normal epidermis, ISC and well differentiated SCCs showed an enhanced hyaluronan signal on carcinoma cells while CD44 expression level resembled that of normal skin. Less differentiated SCCs showed reduced and irregular expression of both hyaluronan and CD44 on carcinoma cells. In BCCs, hyaluronan and CD44 signals were absent or very low on the surface of carcinoma cells. However, hyaluronan was frequently present on BCC cell nuclei, a feature completely absent in ISC, SCC and normal epidermis. An accumulation of hyaluronan in the connective tissue stroma around the tumour was more frequent in SCCs than BCCs. Versican staining was positive around hair follicles and dermal blood vessels of normal skin. Peritumoral versican signal was present in a part of the BCCs but not in other tumours.The completely different hyaluronan and CD44 expression patterns in BCC and SCC probably reflect the different origins of the tumours, with BCC an undifferentiated keratinocyte and SCC a keratinocyte at an early stage in the differentiation pathway. The difference in hyaluronan and CD44 expression between these tumours may also contribute to the difference in their capacity to metastasize.
Comparison of fluticasone propionate and beclomethasone dipropionate on direct and indirect measurements of bronchial hyperresponsiveness in patients with stable asthma.
Authors: G P Bootsma, P N Dekhuijzen, J Festen, P G Mulder, C L van Herwaarden
Journal: Thorax (1995)

BACKGROUND--Fluticasone propionate is a new inhaled corticosteroid with a 2:1 efficacy ratio compared with beclomethasone dipropionate with regard to lung function and symptom scores, without increased systemic activity. The aim of this study was to investigate whether this was also the case for bronchial hyperresponsiveness, assessed by both a direct (histamine) and an indirect (ultrasonically nebulised distilled water (UNDW)) provocation test. METHODS--Fluticasone propionate, 750 micrograms/day, and beclomethasone dipropionate, 1500 micrograms/day, were compared in a randomised, double blind, crossover study consisting of two six week treatment periods, each preceded by a three week single blind placebo period. Twenty one non-smoking asthmatics (mean forced expiratory volume in one second (FEV1) 74.7% predicted, mean PC20histamine 0.36 mg/ml) completed the study. RESULTS--Fluticasone propionate and beclomethasone dipropionate improved FEV1, peak flow rates, asthma symptoms, and bronchial hyperresponsiveness to the same extent. Both fluticasone propionate and beclomethasone dipropionate caused an increase in PC20histamine (mean 2.29 [95% confidence interval 1.45 to 3.13] and 1.95 [1.07 to 2.84] doubling doses, respectively) and in PD20UNDW (1.12 [0.55 to 1.70] and 1.28 [0.88 to 1.70] doubling doses, respectively). Neither treatment changed morning serum cortisol levels, but fluticasone propionate decreased the number of peripheral blood eosinophils less than beclomethasone dipropionate, indicating smaller systemic effects of fluticasone propionate. CONCLUSIONS--These findings show that fluticasone propionate is as effective as twice the dose of beclomethasone dipropionate on bronchial hyperresponsiveness, assessed by provocation with both histamine and UNDW, without increased systemic activity.
Gallstone pancreatitis: When is the optimal time for intervention?
Authors: Dan W. Elliott
Journal: Hepatology (1989)

The correct timing of surgery in cases of gallstone pancreatitis is debatable. To delineate more clearly the influence of the timing of surgery in the treatment of the disease, a prospective randomized clinical study of early surgery (less than 48 hours after admission) and delayed surgery (more than 48 hours after admission) was conducted in 165 patients. Ranson's prognostic signs of severity of disease were used to classify the patients into two risk groups: mild pancreatitis (three or fewer positive signs) and severe pancreatitis (more than three positive signs). In patients with three or fewer positive Ranson's signs, the time of surgery appeared to have little effect on the outcome, whereas in patients with more than three positive signs, early surgery resulted in a significant increase in rates of morbidity and mortality. Controlled randomization showed that in patients with gallstone pancreatitis, edematous or hemorrhagic necrotizing pancreatitis can develop, with or without impacted stones, early or late in the progression of the disease, during early or delayed surgery. These findings suggest that (1) although a gallstone initiates a bout of pancreatitis, it does not cause the progression of the disease; (2) the fate of the progression of pancreatitis is decided early by the amount of digestive enzymes being activated; (3) early removal of an impacted stone does not ameliorate the progression of pancreatitis; and (4)surgery should be performed during the initial hospital admission after the pancreatitis has subsided.
Pharmacogenomic Identification of Novel Determinants of Response to Chemotherapy in Colon Cancer
Authors: John Boyer, Wendy L. Allen, Estelle G. McLean, Peter M. Wilson, Andrea McCulla, Stephen Moore, Daniel B. Longley, Carlos Caldas, Patrick G. Johnston
Journal: Cancer Research (2006)

Abstract DNA microarray analysis was used to analyze the transcriptional profile of HCT116 colorectal cancer cells that were treated with 5-fluorouracil (5-FU) or oxaliplatin and selected for resistance to these agents. Bioinformatic analyses identified sets of genes that were constitutively dysregulated in drug-resistant cells and transiently altered following acute exposure of parental cells to drug. We propose that these genes may represent molecular signatures of sensitivity to 5-FU and oxaliplatin. Using real-time reverse transcription-PCR (RT-PCR), the robustness of our microarray data was shown with a strong overall concordance of expression trends for ≥82% (oxaliplatin) and ≥85% (5-FU) of a representative subset of genes. Furthermore, strong correlations between the microarray and real-time RT-PCR measurements of average fold changes in gene expression were observed for both the 5-FU (R2 ≥ 0.73) and oxaliplatin gene sets (R2 ≥ 0.63). Functional analysis of three genes identified in the microarray study [prostate-derived factor (PDF), calretinin, and spermidine/spermine N1-acetyl transferase (SSAT)] revealed their importance as novel regulators of cytotoxic drug response. These data show the power of this novel microarray-based approach to identify genes which may be important markers of response to treatment and/or targets for therapeutic intervention. (Cancer Res 2006; 66(5): 2765-77)
Medicine in Ulster in relation to the great famine and "the troubles"
Authors: P. Froggatt
Journal: BMJ (1999)

See pp 1609, 16483 Strangford Avenue, Belfast BT9 6PG

In the past two centuries doctors in Ulster, and in Ireland in general, have had to face unique challenges over and above the demands of their normal practice. In the 19th century they had to endure the nightmare of the great famine, which in five years (1846-51) accounted for at least a quarter of the country's population of eight and a half million through death or emigration. 1 2 This century they have had to deal with the consequences of the sectarian violence that has scarred Northern Ireland. Such tests have forged a profession whose integrity and clinical skills are second to none.

#### Summary points

In the past two centuries Ulster's doctors have had to face unique challenges over and above the demands of normal practice

In Ireland's great famine many Ulster doctors lost their lives to “famine fever” and cholera while treating patients at home and in fever hospitals

During “the troubles” in Northern Ireland, health professionals have again been in the front line helping, often quite literally, to pick up the pieces

Recognition of these extraordinary demands has often been sadly lacking, exemplified by the miserly five shillings a day paid to doctors for working in the fever hospitals during the great famine

These tests, and the underlying character of Ulster society, have produced an Ulster medical profession with great cohesion and coherence and, more importantly, strengthened the existing common cultural and historical identity between doctors and patients

In the great famine the cause of death was shared between diseases of nutritional deficiency (including the ultimate one of starvation) and “famine fever,” mainly typhus and relapsing fever, from which no one was immune—certainly not the 3500 physicians, surgeons, and apothecaries and the over 3000 “medical auxiliaries.” In 1849 these terrible twins …
Integrin-αvβ3 regulates thrombopoietin-mediated maintenance of hematopoietic stem cells
Authors: Terumasa Umemoto, Masayuki Yamato, Jun Ishihara, Yoshiko Shiratsuchi, Mika Utsumi, Yohei Morita, Hiroko Tsukui, Masao Terasawa, Takehiko Shibata, Kohji Nishida, Yoshiro Kobayashi, Brian G. Petrich, Hiromitsu Nakauchi, Koji Eto, Teruo Okano
Journal: Blood (2011)
Modern Surgical Pathology, vols 1 &amp; 2
Authors: L. I. Giltman
Journal: JAMA (2003)

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