tbuckley/cabot-search huggingface dataset:
Assessment of impact of information booklets on use of healthcare services: randomised controlled trial Commentary: What's wrong with opting out? Commentary: Public opinion may force researchers to seek "opt in" consent for all
Authors: D. Heaney
Journal: BMJ (2001)

Objectives: To investigate the effect of patient information booklets on overall use of health services, on particular types of use, and on possible interactions between use, deprivation category of the area in which respondents live, and age. To investigate the possibility of a differential effect on health service use between two information booklets. Design: Randomised controlled trial of two patient information booklets (covering the management and treatment of minor illness). Setting: 20 general practices in Lothian, Scotland. Participants: Random sample of patients from the community health index (n=4878) and of those contacting out of hours services (n=4530) in the previous 12 months in each of the study general practices. Intervention: Booklets were posted to participants in intervention groups (3288 were sent What Should I Do? ; 3127 were sent Health Care Manual ). Patients randomised to control group (2993) did not receive a booklet. Main outcome measures: Use of health services audited from patients' general practice notes in 12 months after receipt of booklet. Results: Receipt of either booklet had no significant effect on health service use compared with a control group. However, nine out of ten matched practices allocated to receive Health Care Manual had reduced consultation rates compared with matched practices allocated to What Should I Do? Conclusion: Widespread distribution of information booklets about the management of minor illness is unlikely to reduce demand for health services. #### What is already known on this topic What is already known on this topic One view of help seeking behaviour is that increasing demand for health services is associated with a lack of knowledge in the self management of minor illness An alternative view sees individuals responding reflexively to symptoms on the basis of information and advice from a wide range of sources and using their own experiences #### What this study adds What this study adds The lack of effect on health service use indicates that widespread postal distribution of information booklets about the management of minor illness is unlikely to reduce demand for health services
Tolerogenic T cells, Th1/Th17 cytokines and TLR2/TLR4 expressing dendritic cells predominate the microenvironment within distinct oral mucosal sites
Authors: J.‐P. Allam, Y. Duan, J. Winter, G. Stojanovski, F. Fronhoffs, M. Wenghoefer, T. Bieber, W.‐M. Peng, N. Novak
Journal: Allergy (2010)

Most local oral vaccine strategies use the sublingual region for drug application. Only little is known about the cytokine micromilieu, the nature of T cell subtypes and expression of target structures for adjuvants at different oral mucosal regions (OMR). However, targeting the optimal OMR might ensure highest efficiency of drug uptake and lowest risk for adverse effects.Expression of TGF-β1, IL10 as well as Th1, Th2 and Th17 cytokines and transcription factors was investigated at different OMR and skin by quantitative real-time PCR, immunohistochemistry or flow cytometry.Highest number of T cells was located in vestibular/buccal region (VBR). In contrast to skin (SK), OMR T cells produced TGF-β1, IL-10, IFN-γ and IL-17. Significantly higher TGF-β1 mRNA expression in the VBR compared with the sublingual region (SLR) and skin could be detected, while equal transcripts of IL-10 and regulatory T cell-associated transcription factor FoxP3 could be demonstrated. Expression of Th17-associated IL-17A, IL-17F, IL-22 and IL-26 mRNA could be demonstrated in VBR and SLR but not in SK. Interestingly, compared to SK, significantly higher expression of TGF-β1 and IFN-γ could be detected in OMR. Moreover, expression of toll-like receptor (TLR) 2 and TLR4 was highest in VBR with significant expression on dendritic cells in OMR.From this data, we conclude that (i) VBR and SLR represent a protolerogenic micromilieu, (ii) both regions form a Th1 cytokine-predominated microenvironment, but also express mRNA for Th17 cytokines and (iii) TLRs detectable in VBR and SLR might serve as a target structures for adjuvants.
ABC of antithrombotic therapy: Anticoagulation in hospitals and general practice
Authors: A. D Blann
Journal: BMJ (2003)

Service requirements for warfarin management include phlebotomy or finger pricking, accurate measurement of the international normalised ratio (INR) by a coagulometer (with associated standards and quality control), interpretation of the result, and advice on the warfarin dose. Clinical management of the complications of treatment (predominantly overdose) are also required. Furthermore, almost any drug can interact with oral anticoagulants, and many (such as steroids and antibiotics) often increase the anticoagulant effect.



Warfarin tablets used routinely in the United Kingdom



When introducing a new drug, if the duration of treatment is short (less than five days), then adjustment of dose is often not essential. If, however, the treatment is to last more than five days, then the INR should be checked after starting treatment with the new drug and the warfarin dose adjusted on the basis of the results.

Once the indications for anticoagulation have been confirmed (for example, for suspected deep vein thrombosis do venography or D-dimer measurement), the initial dose of oral anticoagulant depends on a patient's coagulation status, age, clinical situation, and degree of heart failure (if present). In older patients, those with impaired liver function, and those with congestive heart failure oral anticoagulation should be started cautiously and the resulting INR checked often (every three to five days). The dose of warfarin needed to maintain an INR at 2.0-3.0, for example, falls with age and is greater in patients of Indo-Asian or African origin than Europeans. Where possible, take routine blood samples for prothrombin time and activated partial thromboplastin time (APTT), platelet count, and liver function tests before starting treatment. Oral anticoagulation with warfarin should be started on day one, preferably in conjunction with heparin because the initial period of treatment with warfarin may be associated with a procoagulant state caused by a rapid reduction in protein C …
Abstract 17176: Adiponectin, Metabolic Factors and CRP Changes with a Lifestyle Intervention for Weight Loss in Men and Women with Diabetes: Insights From the Look Ahead (Action for Health in Diabetes) Study
Authors: L. Maria Belalcazar, Wei Lang, Steven M Haffner, Ron C Hoogeveen, Russell P Tracy, Ashok Balasubramanyam, Dawn C Schwenke, F. Xavier Pi-Sunyer, Christie M Ballantyne
Journal: Circulation (2011)

Adiponectin (ADN) has anti-inflammatory effects. In obese diabetic persons, ADN levels are low and CRP levels are high. The associations of changes in total (T) ADN and its high molecular-weight oligomer (HMW-ADN) with CRP change (Δ) in response to an intensive lifestyle intervention for weight loss (ILI) have not been examined within a clinical trial. Little is known about the effects of metabolic changes by sex on these associations in diabetes. Methods: Using regression analyses, we examined whether T-ADN and HMW-ADN changes with a 1-year ILI would be associated with CRP Δ in a subset of 1,397 Look AHEAD participants with biomarker data, when compared to usual care, after accounting for weight, HbA1c, HDL-C and fitness changes. Look AHEAD is a randomized trial examining whether ILI, when compared to usual care, will reduce CV events in obese type 2 diabetic persons. Results: ILI resulted in greater CRP reductions and increases in T-ADN and HMW-ADN, when compared to usual care (p≤ 0.0001 for all). CRP Δ with ILI was similar in men and women (≈ -40%). The increases in T-ADN and HMW-ADN were greater in men (23.6 and 13.5%) than in women (6.2% and 14.8%), respectively. Change in T-ADN and HMW-ADN in men and in T-ADN in women were significantly associated with CRP Δ, independently of weight, HDL-C, fitness and HbA1c changes (See Table). Fitness change in men and weight change in women, but not HbA1c or HDL-C changes, were associated with CRP Δ after adjusting for T-ADN and HMW-ADN change in separate models. Conclusion: In obese diabetic subjects, T-ADN and HMW-ADN are associated with changes in CRP with differential effects in male and female participants, with weight playing a greater role in women and fitness a greater role in men.
More GPs will have new contract option
Authors: Linda Beecham
Journal: BMJ (2000)

Within the next year a quarter of GPs in England could be on new contracts, which will pay them on the basis of meeting quality standards and the particular needs of their local population, rather through a combination of capitation fees and item of service payments.

The personal medical services contract has been available since 1998, and last week the government announced that there had been 2000 applications for the third wave of personal medical services contracts, which are negotiated locally.

They will allow GPs, health authorities, and primary care trusts to develop a specific range of …
MRI guided iron assessment and oral chelator use improve iron status in thalassemia major patients
Authors: Diana X. Nichols‐Vinueza, Matthew T. White, Andrew J. Powell, Puja Banka, Ellis J. Neufeld
Journal: American Journal of Hematology (2014)

Oral iron chelators and magnetic resonance imaging (MRI) assessment of heart and liver iron burden have become widely available since the mid 2000s, allowing for improved patient compliance with chelation and noninvasive monitoring of iron levels for titration of therapy. We evaluated the impact of these changes in our center for patients with thalassemia major and transfusional iron overload. This single center, retrospective observational study covered the period from 2005 through 2012. Liver iron content (LIC) was estimated both by a T2* method and by R2 (Ferriscan® ) technique. Cardiac iron was assessed as cT2*. Forty-two patients (55% male) with transfused thalassemia and at least two MRIs were included (median age at first MRI, 17.5 y). Over a mean follow-up period of 5.2 ± 1.9 y, 190 MRIs were performed (median 4.5 per patient). Comparing baseline to last MRI, 63% of patients remained within target ranges for cT2* and LIC, and 13% improved from high values to the target range. Both the median LIC and cT2* (cR2* = 1000/cT2*) status improved over time: LIC 7.3 to 4.5 mg/g dry weight, P = 0.0004; cR2* 33.4 to 28.3 Hz, P = 0.01. Individual responses varied widely. Two patients died of heart failure during the study period. Annual MRI iron assessments and availability of oral chelators both facilitate changes in chelation dose and strategies to optimize care.
Subcutaneous T-cell lymphoma in a child with eosinophilia
Authors: S. Taniguchi, T. Kono
Journal: British Journal of Dermatology (2000)

Journal Article Subcutaneous T‐cell lymphoma in a child with eosinophilia Get access S. Taniguchi, S. Taniguchi Department of Dermatology, Osaka General Hospital of West Japan Railway Company, 1‐3‐5, Tennoji‐cho‐minami, Abeno‐ku, Osaka 545‐0002, Japan E‐mail: shojitan@msic.med.osaka‐cu.ac.jp Search for other works by this author on: Oxford Academic Google Scholar T. Kono T. Kono Department of Dermatology, Osaka General Hospital of West Japan Railway Company, 1‐3‐5, Tennoji‐cho‐minami, Abeno‐ku, Osaka 545‐0002, Japan E‐mail: shojitan@msic.med.osaka‐cu.ac.jp Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 142, Issue 1, 1 January 2000, Pages 183–184, https://doi.org/10.1046/j.1365-2133.2000.03269.x Published: 01 January 2000
Prioritisation of infectious diseases in public health - call for comments
Authors: G Krause, Collective the working group on prioritisation
Journal: Eurosurveillance (2008)

In order to allocate rationally resources for research and surveillance of infectious diseases at the level of the German public health institute (RKI), we prioritised pathogens by public health criteria. After screening the relevant literature we developed a standardised methodology including a three-tiered scoring system for selected pathogens. The pathogens were rated in four categories containing a total of 12 criteria: burden of disease including incidence, severity, mortality; epidemiologic dynamic including outbreak potential, trend, emerging potential; information need including evidence on risk factors/groups, validity of epidemiologic information, evidence for pathogenesis; international duties and public attention; health gain opportunity including preventability, treatability. For each criterion a numerical score of +1, 0 or -1 was given and each criterion received a weight by which the numerical score of each criterion was to be multiplied. The total weighted scores ranged from +22.7 (influenza) to - 64.4 (cholera) with the median being -22.9 (rubella). Relevant changes were observed between weighted and unweighted scores. The chosen approach proved to be feasible and the result plausible. However, in order to further improve the methodology we invite experts to give feedback on the methodology via a structured web-based questionnaire at www.rki.de/EN > Prevention of infection > Infectious Disease Surveillance > Pathogen prioritization. Results of this survey will be included in a modification of the methodology. .
CXCR4-activated astrocyte glutamate release via TNFα: amplification by microglia triggers neurotoxicity
Authors: Paola Bezzi, Maria Domercq, Liliana Brambilla, Rossella Galli, Dominique Schols, Erik De Clercq, Angelo Vescovi, Giacinto Bagetta, George Kollias, Jacopo Meldolesi, Andrea Volterra
Journal: Nature Neuroscience (2001)
Press: The steady drip of biased reporting
Authors: N. Goodman
Journal: BMJ (2000)

<h3>Abstract</h3> Cancer treatments targeting DNA repair deficiencies often encounter drug resistance, possibly due to alternative metabolic pathways that counteract the most damaging effects. To identify such alternative pathways, we screened for metabolic pathways exhibiting synthetic lethality with inhibition of the DNA damage response kinase ATM using a metabolism-centered CRISPR/Cas9 library. Our data revealed Kelch-like ECH-associated protein 1 (KEAP1) as a key factor involved in desensitizing cancer cells to ATM inhibition both <i>in vitro</i> and <i>in vivo</i>. Cells depleted of KEAP1 exhibited an aberrant overexpression of the cystine transporter SLC7A11, robustly accumulated cystine inducing disulfide stress, and became hypersensitive to ATM inhibition. These hallmarks were reversed in a reducing cellular environment indicating that disulfide stress was a crucial factor. In the TCGA pan-cancer datasets, we found that ATM levels strongly correlated with KEAP1 levels across multiple solid malignancies. Together, our results unveil ATM and KEAP1 as new targetable vulnerabilities in solid tumors.
Minimally-Invasive Implantation of Living Tissue Engineered Heart Valves
Authors: Dörthe Schmidt, Petra E. Dijkman, Anita Driessen-Mol, Rene Stenger, Christine Mariani, Arja Puolakka, Marja Rissanen, Thorsten Deichmann, Bernhard Odermatt, Benedikt Weber, Maximilian Y. Emmert, Gregor Zund, Frank P.T. Baaijens, Simon P. Hoerstrup
Journal: Journal of the American College of Cardiology (2010)
Death and Dying—a Muslim Perspective
Authors: Aziz Sheikh
Journal: Journal of the Royal Society of Medicine (1998)

Islamic law (Shariah) defines expected behaviors at the time of death.  Since these expectations are followed by most of the 2 million Muslims in the UK it is important for British health professionals to be familiar with them.  For Muslims death marks the transition from one state of existence to the next and is therefore not resisted.  Ideally Muslims wish to die at home.  When this is not feasible certain changes in hospital routine are recommended including not restricting the number of friends and relatives who come for daily prayers provisions for ablution before prayer and positioning the bed of the dying person in the direction of Mecca.  Since it is a religious requirement that the dead be buried as soon as possible family stress can be avoided by timely production of the death certificate.  Both postmortem examinations and organ donations are generally prohibited.
Abstract 18112: SIRT3-AMPK Activation by Nitrite and Metformin Improves Hyperglycemia and Normalizes PH-HFpEF
Authors: Yen-Chun Lai, Diana M Tabima, John J Dube, Dmitry A Goncharov, Elena A Goncharova, Stevan P Tofovic, Ana L Mora, Mark T Gladwin
Journal: Circulation (2014)

Background: Pulmonary hypertension in heart failure with preserved ejection fraction (PH-HFpEF) is an increasingly common cause of PH and a newly recognized clinical complication of metabolic syndrome. To date, no animal model of PH-HFpEF associated with metabolic syndrome has been developed and no specific therapy has yet been shown to favorably affect patients with PH-HFpEF.

Methods and Results: We first developed a relevant animal model of PH-HFpEF by injecting the VEGF receptor blocker, SU5416, in a genetic model of obese, diabetic, insulin-resistant, and spontaneously hypertensive rats (ZSF1). Our data showed that SU5416/ZSF1 rats resulted in enhanced RVPSP and was accompanied by elevated LVEDP, preserved LV EF, and both LV and RV enlargement. Next, the therapeutic and mechanistic effects of nitrite and an anti-diabetic drug, metformin, on metabolic syndrome and PH-HFpEF were explored. We found that chronic nitrite treatment significantly improved hyperglycemia in obese ZSF1 rats. Nitrite administration had no effect on plasma insulin levels and the insulin-dependent signaling pathway, but it significantly increased AMPK phosphorylation and membrane translocation of GLUT4, the key regulators of glucose uptake in skeletal muscle. In addition, sirtuin-3 (SIRT3), a major mitochondrial deacetylase, was also upregulated and activated by nitrite in rat skeletal muscles. Moreover, knockdown of SIRT3 expression in human skeletal muscle cells resulted in impaired AMPK activation and glucose uptake. Finally, in our newly developed PH-HFpEF model (SU5416/ZSF1), we found that both oral nitrite and oral metformin therapies normalize PH-HFpEF in terms of hemodynamic benefits, reduced pulmonary vascular remodeling, and improved hyperglycemia via SIRT3-AMPK activation.

Conclusions: Our “two-hit” model of PH-HFpEF provides evidence for an interaction between metabolic syndrome and pulmonary endothelial injury to the subsequent development of PH-

HFpEF: Our observations also indicate that chronic oral nitrite and metformin therapies limited PH-HFpEF through SIRT3-AMPK-mediated signaling events, providing new therapeutic strategies in the treatment of patients with PH-HFpEF.
Abstract #5122: \#945;-TEA sensitizes human breast cancer cells to Doxorubicin-induced apoptosis via death receptor dependent and independent mechanisms
Authors: Richa Tiwary, Weiping Yu, Bob Sanders, Kimberly Kline
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

The apoptotic-inducing properties of the combination of RRR-\#945;-tocopherol derivative \#945;-TEA (RRR-\#945;-tocopherol ether-linked acetic acid analog) and doxorubicin were investigated in human MCF-7 breast cancer cells. Sub-apoptotic levels of \#945;-TEA + doxorubicin, in comparison to single agents (i) significantly enhanced apoptosis as measured by Annexin V-FITC/PI staining, cleavage of PARP, and activation of caspases 8 and 9, (ii) activated both pJNK1/2 and pc-Jun, and (iii) enhanced Fas and Fas Ligand protein levels. siRNA knockdown of JNK and c-Jun as well as Fas and Fas Ligand reduced \#945;-TEA + doxorubicin-induced apoptosis. Doxorubicin significantly increased levels of DR5 protein expression. Combinations of \#945;-TEA + doxorubicin did not further increase protein levels of DR5 protein in comparison to doxorubicin alone. Knockdown of DR5 using siRNA blocked \#945;-TEA + doxorubicin-induced apoptosis. Treatment of the breast cancer cells with sub-apoptotic levels of doxorubicin enhanced protein levels of survival factors pAkt, pERK, pmTOR and their downstream mediators pBad (Ser 136 and Ser 112), and cFLIP; whereas, \#945;-TEA in combination with doxorubicin reduced the expression of these survival factors. Inhibitors of PI-3K/Akt, MEK/ERK and mTOR as well as siRNA to cFLIP enhanced the ability of sub-apoptotic levels of doxorubicin to induce apoptosis, suggesting that \#945;-TEA's ability to prevent doxorubicin-induced pro-survival factors (i.e. pAkt, pERK and pmTOR, cFLIP) plays a role in enhanced sensitivity to the combinations of \#945;-TEA + doxorubicin. In summary, data show enhanced apoptosis in cells treated with \#945;-TEA + doxorubicin is due to activation of JNK, Fas and DR5 apoptotic signaling pathways and down-regulation of doxorubicin-induced survival factors Akt, ERK, mTOR, and c-FLIP. T32 ES007247, Training in Molecular Toxicology/Environmental Disease, Public Health Services Grant CA59739 and The Clayton Foundation For Research.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5122.
Phylogenetic variation and polymorphism at the Toll-like receptor 4 locus (TLR4)
Authors: Irina Smirnova, Alexander Poltorak, Edward KL Chan, Colleen McBride, Bruce Beutler
Journal: Genome biology (2000)

Differences in responses to bacterial surface lipopolysaccharides (LPSs) are apparent between and within mammalian species. It has been shown in mice that resistance to LPS is caused by defects in the Toll-like receptor 4 gene (Tlr4), the product of which is thought to bind LPS and mediate LPS signal transduction in immune system cells. We have sequenced the Toll-like receptor 4 gene of humans (TLR4; 19.0 kilobases, kb) and mice (Tlr4; 91.7 kb), as well as the coding region and splice junctions of Tlr4 from 35 mouse (Mus musculus) strains, from the chimpanzee and from the baboon. No other discernible genes or regions of interspecies conservation lies close to Tlr4 and, in both humans and mice, flanking sequences and introns are rich in repeats of retroviral origin. Interstrain analyses reveal that Tlr4 is a polymorphic protein and that the extracellular domain is far more variable than the cytoplasmic domain, both among strains and among species. The cytoplasmic domain of the Tlr4 protein is highly variable at the carboxy-terminal end. We suggest that selective evolutionary pressure exerted by microbes expressing structurally distinguishable LPS molecules has produced the high level of variability in the Tlr4 extracellular domain. The highly variable carboxy-terminal region of the cytoplasmic domain is likely to determine the magnitude of the response to LPS within a species.