tbuckley/cabot-search huggingface dataset:
GP computerised summaries may not be accurate or complete
Authors: Pamela J F Smith
Journal: BMJ (2008)

Vitamin D deficiency is widespread in Scotland I agree with Holick 1 and Sievenpiper et al 2 about the urgent need to highlight the neglected subject of vitamin D deficiency in the United Kingdom.We have found in our general practice in Edinburgh a (to us) surprisingly high prevalence of gross vitamin D deficiency.The deficiency affects not only our South Asian patients but also a considerable number of those with white skin colour.Between 2005 and 2007, blood samples were taken from 99 patients aged 15-85.We included patients suspected of having a possible vitamin D deficiency: patients of South Asian origin or other ethnic minorities, patients with vague musculoskeletal symptoms or overweight, patients taking antiepileptic drugs, patients using sunscreen or make up, housebound patients, and patients with little exposure to sunlight.The figure shows our as yet unpublished results.According to the definitions of most vitamin D researchers, insufficient vitamin D concentrations are those below 75 nmol/l.In our sample only 2% had a sufficient vitamin D concentration.Measurements below 25 nmol/l are defined as severe deficiency; in our sample, the proportion was 47%.We select the letters for these pages from the rapid responses posted on bmj.com favouring those received within five days of publication of the article to which they refer.Letters are thus an early selection of rapid responses on a particular topic.
Azacytidine impairs NK cell activity in AML and MDS patients undergoing MRD-based pre-emptive treatment after allogeneic stem cell transplantation
Authors: C Schönefeldt, K Sockel, R Wehner, S Sopper, D Wolf, M Wermke, C Thiede, U Oelschlägel, G Ehninger, M Bornhäuser, U Platzbecker, M Schmitz
Journal: Blood Cancer Journal (2013)

We have recently demonstrated within a prospective trial (RELAZA1 study) that minimal residual disease (MRD)-triggered pre-emptive treatment with azacytidine (AZA) is able to prevent or at least delay hematologic relapse in patients with myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (HSCT). 1 Besides direct apoptotic effects at higher doses, AZA is considered to act as a hypomethylating agent at lower doses.Of note, hypomethylating effects not only affect cancer cells by inducing the re-expression of previously silenced tumor suppressor genes, but also influence gene expression in 'bystander' cells, such as T lymphocytes (T cells).In line with this hypothesis, several groups recently reported epigenetic regulation of the FOXP3 locus, the critical transcription factor, driving regulatory T-cell differentiation.AZA-induced demethylation induced upregulation of FOXP3 and expansion of T-regulatory cells (Tregs), which might also contribute to lower graft-versus-host disease rates in the setting of allogeneic HSCT. 2 Besides T cells, studies investigating the impact of AZA on other immune cell populations such as dendritic cells (DCs) or natural killer (NK) cells are rather limited.As AZA is currently explored in many clinical trials in the post-allograft setting, we aimed to study its impact on NK and DCs in vitro as well as in vivo when given as pre-emptive treatment within the RELAZA1 study. 1 For in vitro experiments we used AZA doses of 100 nM, 1 mM and 3 mM, based on the observation of peak plasma levels of 1 mM in humans after the application of the standard 75 mg/m 2 subcutaneous AZA dose.First we investigated the impact of AZA on DCs, which are professional antigen-presenting cells, involved in the activation of innate and adaptive antitumor responses.Functional data revealed that 6-sulfo LacNAc (slan) DCs represent a major subset of native human blood DCs, which produce various proinflammatory cytokines and contribute to antitumor immunity by activating NK and T cells. 3,4To explore how AZA modulates the secretion of proinflammatory cytokines by slanDCs in vitro, we isolated slanDCs immunomagnetically from peripheral blood of three healthy
Antigenic targets in tienilic acid hepatitis. Both cytochrome P450 2C11 and 2C11-tienilic acid adducts are transported to the plasma membrane of rat hepatocytes and recognized by human sera.
Authors: M A Robin, M Maratrat, M Le Roy, F P Le Breton, E Bonierbale, P Dansette, F Ballet, D Mansuy, D Pessayre
Journal: Journal of Clinical Investigation (1996)

Patients with tienilic acid hepatitis exhibit autoantibodies that recognize unalkylated cytochrome P450 2C9 in humans but recognize 2C11 in rats. Our aim was to determine whether the immune reaction is also directed against neoantigens. Rats were treated with tienilic acid and hepatocytes were isolated. Immunoprecipitation, immunoblotting, and flow cytometry experiments were performed with an anti-tienilic acid or an anti-cytochrome P450 2C11 antibody. Cytochrome P450 2C11 was the main microsomal or plasma membrane protein that was alkylated by tienilic acid. Inhibitors of vesicular transport decreased flow cytometric recognition of both unalkylated and tienilic acid-alkylated cytochrome P450 2C11 on the plasma membrane of cultured hepatocytes. Tienilic acid hepatitis sera that were preadsorbed on microsomes from untreated rats (to remove autoantibodies), poorly recognized untreated hepatocytes in flow cytometry experiments, but better recognized tienilic acid-treated hepatocytes. This recognition was decreased by adsorption with tienilic acid or by preexposure to the anti-tienilic acid or the anti-cytochrome P450 2C11 antibody. We conclude that cytochrome P450 2C11 is alkylated by tienilic acid and follows a vesicular route to the plasma membrane. Tienilic acid hepatitis sera contain antibodies against this tienilic acid adduct, in addition to the previously described anticytochrome P450 autoantibodies.
Acetazolamide Effect on Vascular Response in Areas with Diaschisis as Measured by Tc-99m HMPAO Brain SPECT
Authors: HIROSHI MATSUDA, SHIRO TSUJI, HISASHI SUMIYA, SOTARO HOGASHI, KEIKO KINUYA, NORIHISA TONAMI, KINICHI HISADA, JUNKOH YAMASHITA
Journal: Clinical Nuclear Medicine (1992)

The effects of acetazolamide (Diamox®) on vascular response were investigated in areas with intrahemispheric thalamic diaschisis and crossed cerebellar diaschisis using consecutive Tc-99m HMPAO brain SPECT studies before and after Diamox administration. All six patients with thalamic diaschisis and five of eight patients with crossed cerebellar diaschisis at baseline showed significantly augmented perfusion after Diamox administration in the affected thalamus and cerebellum compared with that in the contralateral unaffected areas. These results suggest more dilatation of the arterioles in areas with diaschisis after Diamox administration than in areas without diaschisis. Diamox may produce relative luxury perfusion in areas with diaschisis.
CD59 protects rat kidney from complement mediated injury in collaboration with Crry
Authors: Midoriko Watanabe, Yoshiki Morita, Masashi Mizuno, Kazuhiro Nishikawa, Yukio Yuzawa, Nigishi Hotta, B. Paul Morgan, Noriko Okada, Hidechika Okada, Seiichi Matsuo
Journal: Kidney International (2000)
Fairer Pay for Consultants? — Clinical-Judgment Battle — Oriental Service
Authors: John Lister
Journal: New England Journal of Medicine (1978)

ONE of the most notable achievements of the earlier years of the National Health Service (NHS) was the upgrading of the nonteaching district hospitals. This advance was brought about by staffing them with well trained consultants who were enthusiastic in developing their departments and anxious to participate in the planning of new hospitals or in the modernization of old ones. Many of these consultants were also able to establish links between district hospitals and teaching hospitals by accepting students for elective periods and by arranging rotating internships and residency training programs. Others were active in organizing programs of continuing education . . .
Hb Iraq-Halabja ?10 (A7) Ala?Val (GCC?GTC): A new ?-chain silent variant in a family with multiple Hb disorders
Authors: S. Deutsch, R. Darbellay, R. Offord, A. Frutiger, J. Kister, H. Wajcman, Ph. Beris
Journal: American Journal of Hematology (1999)

A patient originating from Iraq was referred to our laboratory upon suspicion of a hemoglobinopathy. Routine hematological tests revealed a microcytic and slightly anemic phenotype with an elevated HbA2 suggestive of beta-thalassemia. Samples were obtained for several members of the family which upon examination revealed highly heterogeneous phenotypes that prompted us to investigate the case further. Sequencing of the beta-globin gene and alpha cluster mapping in the propositus and his brother showed a previously undescribed beta-globin variant:Hb Iraq-Halabja, beta10(A7) Ala-->Val (GCC-->GTC), associated with beta0-thalassemia IVS-2 nt1 G-->A and either alpha-thal-2-3.7 kb deletion (brother), or alpha-globin gene triplication anti-3.7 kb type (propositus). Detailed functional studies of the variant gave a normal oxygenation curve, a normal heterotopic action of 2,3 DPG, and normal heat stability and isopropanol precipitation tests. The variant shows a clear difference in migration properties compared to normal beta-chain only when run on PAGE urea Triton. As expected, alpha/beta-globin mRNA ratios were influenced by the concomitant presence of an alpha-globin gene pathology and the beta0 thalassemia and not by the presence of the beta-globin variant which apparently is clinically silent.
Occult Gastrointestinal Bleeding
Authors: Don C. Rockey
Journal: New England Journal of Medicine (1999)

Occult gastrointestinal bleeding typically refers to bleeding that is not apparent to the patient. The potential for occult bleeding is emphasized by the finding that for melena to be produced consistently, 150 to 200 ml of blood must be present in the stomach.1 Moreover, patients with gastroduodenal blood loss of 100 ml per day may have stools that appear normal.2 Thus, occult bleeding is usually identified only by tests that detect fecal blood or, if bleeding is sufficient, when it becomes manifest as iron deficiency. Occult gastrointestinal bleeding can also refer to bleeding that is clinically evident but from an . . .
Skin Tearing During Corticosteroid Therapy
Authors: James H. Penoff
Journal: JAMA (1980)

To the Editor.—  Referring to the article by Gottlieb and Penneys, the ease of skin tearing in patients receiving long-term corticosteroid therapy has been well documented in the literature, and clinically I have seen a number of these cases. I would seriously doubt the spontaneous tearing of the skin as described in this particular article but would instead attribute this to extremely thin skin that responded to minimal trauma and therefore resulted in the defect. I doubt that the skin would split of its own accord, but certainly the minimal trauma of even brushing against a bed could cause this to occur.  I have found the most effective method of treating this is to unfold all of the skin and steri-strip it. The skin that tears is usually extremely thin, almost having the appearance of wet tissue paper, but all the elements are there. This can be unfolded with a
Abstract 2296: Identification of novel nuclear receptor targets in estrogen receptor negative breast cancer
Authors: Kyle R. Covington, Guowei Gu, Anna Tsimelzon, Susan Hilsenbeck, Powel Brown, Jenny Change, C Kent Osborne, Jianming Xu, Bert O'Malley, David Mangelsdorf, John Minna, Suzanne Fuqua
Journal: Cancer Research (2011)

Abstract Introduction: Estrogen receptor (ER)-negative breast cancer has a particularly poor prognosis, and there are limited targeted agents for this subtype. Aims and Methods: To identify nuclear receptor (NR) targets, we did microarray analysis of 227 ER-negative tumors as assessed by immunohistochemistry, and performed hierarchical clustering using 41 NRs, and prediction analysis of microarrays (PAM) across the clustered groups. Cell lines were matched to identified groups using previously published data. Clinical correlations were made using previously published breast cancer datasets. Results and Conclusion: The 41 NRs clustered the tumors into 5 distinct groups. We found that the androgen receptor (AR) was the highest ranked discriminator of these groups followed by ERα. Group 1 (14% of the tumors) was characterized by elevated ERRα and RXR expression. Group 2 (9%) was characterized by higher expression of the orphan receptor NURR1. Group 3 was the largest group (37%), and showed high level expression of PPARα. Group 4 (16%) expressed higher levels of PPARγ. Group 5 (24%) demonstrated particularly high relative expression of AR, and also showed higher expression of ERα and ERRα. We used previously published microarray data to match cell lines to the NR groups using the scoring matrix developed in the PAM analysis. These cell lines are currently being tested for response to NR agonists and antagonists in growth (MTT, soft-agar, mammosphere) and apoptotic assays. We used a previously published microarray data set with long-term follow up information to identify potential differences in outcomes for the different NR subtypes. While we found no significant differences between the groups, the sample size was quite low for each subtype (n∼15 per group). In summary, we have identified several novel ER-negative tumor groups by different expression level of NRs which may contribute to the prediction of breast cancer molecular subtypes. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2296. doi:10.1158/1538-7445.AM2011-2296
Financial incentives of subregional RAWP.
Authors: G Bevan, J Brazier
Journal: BMJ (1987)

Accounting for the cross boundary flows of residents from one health authority treated by another has been considered by the review of the Resource Allocation Working Party (RAWP) formula by the National Health Service Management Board. A common concern is that the approximate costs used are unfair to those authorities (typically those with teaching hospitals) that are likely to treat more complex cases. This paper argues that when spending exceeds the target allowance for acute services this is more likely to be due to district residents using services at a high rate than to inadequate compensation for inflows. Districts where residents make a high use of services are often those where there are large flows across district boundaries. Since authorities cannot control outflows there is little they can do to reduce their residents9 high use of services. Furthermore, curious financial incentives can be inferred for clinicians in these districts if they were to take effective action to bring their district9s spending to target levels. These problems are discussed to illuminate problems of accounting for cross boundary flows that alternatives to current practice must resolve.
The Management of Mitral Valve Prolapse
Authors: Larry E. Alves
Journal: JAMA (1986)

<h3>To the Editor.—</h3> I read with interest the recent article on the mitral valve prolapse syndrome.<sup>1</sup>One aspect of the syndrome that was not addressed was the use of antiplatelet therapy in patients using the birth control pill. The transient ischemic attacks that I have seen in patients without other forms of organic heart disease have been associated with mitral valve prolapses. In view of this I have recommended antiplatelet therapy in any women using oral contraceptive agents. Since my practice is devoted primarily to cardiology, I am undoubtedly seeing a biased population. However, the unresolved questions are these: should the patients who are being seen by our gynecologic colleagues and beginning use of oral contraceptive agents be screened for mitral valve prolapses, and, if they are found, should they then begin using antiplatelet agents?
Release of Active Tissue Factor by Human Arterial Smooth Muscle Cells
Authors: Alison D. Schecter, Benjamin Spirn, Maria Rossikhina, Peter L. A. Giesen, Vladimir Bogdanov, John T. Fallon, Edward A. Fisher, Lynn M. Schnapp, Yale Nemerson, Mark B. Taubman
Journal: Circulation Research (2000)

Abstract —Tissue factor (TF), the initiator of coagulation, is thought to function predominantly at the cell surface. Recent data have suggested that active TF is present extracellularly in atherosclerotic plaques, the arterial wall, and the blood. This study was conducted to determine whether smooth muscle cells (SMCs), a major source of arterial TF, could generate extracellular TF. Active TF accumulated in the medium of cultured human SMCs, representing ≈10% of that measured in the underlying cells at 24 hours. Platelet-derived growth factor, phorbol ester, and tumor necrosis factor-α caused ≈3-fold increases in TF activity in the medium. Release of TF into the medium was dependent on the presence of the TF transmembrane domain but not the cytoplasmic domain. Antibodies to TF precipitated most of the activity from the culture medium, whereas antibodies to the β 1 -integrin subunit precipitated ≈33% of the activity. Treatment with detergent or phosphatidylserine:phosphatidylcholine did not increase activity, suggesting that all TF released by SMCs was in the appropriate lipid milieu and not encrypted. Western blotting showed that the medium contained full-length TF protein. Fluorescent cytometry showed that extracellular TF was present largely in particles ≤200 nm, which had a density of 1.10 g/mL. We hypothesize that active extracellular TF found in the injured arterial wall and atherosclerotic plaques derives, in part, from SMC microparticles. (Circ Res. 2000;87:126-132.)
Quantification of Incomplete Revascularization and its Association With Five-Year Mortality in the Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) Trial Validation of the Residual SYNTAX Score
Authors: Vasim Farooq, Patrick W. Serruys, Christos V. Bourantas, Yaojun Zhang, Takashi Muramatsu, Ted Feldman, David R. Holmes, Michael Mack, Marie Claude Morice, Elisabeth Ståhle, Antonio Colombo, Ton de Vries, Marie-angèle Morel, Keith D. Dawkins, Arie-Pieter Kappetein, Friedrich W. Mohr
Journal: Circulation (2013)

The residual Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) Score is an objective measure of the degree and complexity of residual stenosis after percutaneous coronary intervention (PCI).In the randomized PCI cohort of the SYNTAX Trial (n=903), the baseline and residual SYNTAX Scores were calculated. Subjects with a residual SYNTAX Score of 0 were defined as having undergone complete revascularization (CR), and a residual SYNTAX Score >0 as incomplete revascularization (ICR). Five-year clinical outcomes were stratified by CR and ICR (tertiles of the residual SYNTAX Score: >0-4, >4-8, and >8). In the PCI cohort, the mean baseline and residual SYNTAX Scores were 28.4±11.5 and 4.5±6.9, respectively. The mean Δ SYNTAX Score (representative of the burden of disease removed by PCI) was 23.8±10.9. The residual SYNTAX Score was distributed as follows: CR, 0 (n=386, 42.7%); ICR, >0 to 4 (n=184, 20.4%), >4 to 8 (n=167, 18.5%), >8 (n=153, 16.9%). A progressively higher residual SYNTAX Score was shown to be a surrogate marker of increasing clinical comorbidity and anatomic complexity. Subjects with CR or residual SYNTAX Scores ≤8 had comparable 5-year mortality (CR, 8.5%; residual SYNTAX Score >0-4, 8.7%; >4-8, 11.4%; P=0.60). A residual SYNTAX Score >8 was associated with 35.3% all-cause mortality at 5-years (P<0.001). Stratified analyses in the predefined medical treated diabetic and left main subgroups yielded similar results.The residual SYNTAX Score was shown to be a powerful indicator of 5-year mortality in the SYNTAX Trial. The residual SYNTAX Score may aid in determining a reasonable level of revascularization.
Controlled trial of supervised exercise training in chronic bronchitis.
Authors: D J Sinclair, C G Ingram
Journal: BMJ (1980)

In a controlled trial of exercise retraining in patients with severe chronic bronchitis, 33 subjects were followed for a mean period of 10.3 months. The exercise programme was supervised once a week, and daily training comprised a 12-minute walk and simple stair climbing exercises. The subjects in the exercise group showed a highly significant improvement in their walking distance, attaining a maximum increase of 24% after eight to 12 months. There was also considerable subjective improvement. The control group did not improve. No significant changes in cardiorespiratory function or muscle strength were seen. Simple exercise rehabilitation is of benefit to patients with disabling obstructive lung disease.
5-Fluorocytosine Therapy
Authors: William C. Weese, Ronald W. Schope
Journal: Annals of Internal Medicine (1972)

Letters, Comments, and Corrections1 December 19725-Fluorocytosine TherapyWILLIAM C. WEESE, M.D., RONALD W. SCHOPE, M.D.WILLIAM C. WEESE, M.D.Search for more papers by this author, RONALD W. SCHOPE, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-77-6-1003 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Recent articles in the ANNALS OF INTERNAL MEDICINE have emphasized clinical usefulness of 5-fluorocytosine in the treatment of fungal diseases. In two, therapeutic failure due to drug resistance in cryptococcal meningitis was suggested, although not documented (1, 2). A third paper (3) reported resistant strains of Cryptococcus neoformans mainly in patients receiving less than 100 mg/kg body weight of 5-fluorocytosine daily. None observed thrombocytopenia. We wish to report a patient with cryptococcal meningitis in whom both drug resistance and thrombocytopenia developed during 5-fluorocytosine therapy.A 43-year-old white man with chronic glomerulonephritis had undergone splenectomy, bilateral nephrectomy, and...References1. STEERMARKSKLITE PMP: 5-Fluorocytosine: an oral antifungal compound. Ann Intern Med 76:15-22, 1972 LinkGoogle Scholar2. VANDEVELDEMAUCERIJOHNSON AAJ: 5-Fluorocytosine in the treatment of mycotic infections. Ann Intern Med 77:43-51, 1972 LinkGoogle Scholar3. FASSPERKINS RR: 5-Fluorocytosine in the treatment of cryptococcal and Candida mycoses. Ann Intern Med 74:535-539, 1971 LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByPyrimidinones as biodynamic agentsAntifungal agentsAntifungal drugsCombination antifungal therapy for cryptococcal meningitisTherapy of Deep-Seated Fungal Infections with 5-Fluorocytosine 1 December 1972Volume 77, Issue 6Page: 1003-1004KeywordsBody weightCryptococcal meningitisCryptococcus neoformansDrug therapyDrugsFungal diseasesGlomerulonephritisNephrectomySplenectomy Issue Published: 1 December 1972 PDF DownloadLoading ...
Guidelines can harm patients too
Authors: G. Hutchison
Journal: BMJ (2012)

The clinical entity of guideline fatigue syndrome has already been described in the BMJ : “a debilitating condition characterised by irritability and overwhelming lethargy in the presence of guidelines.”1 My own chronic guideline fatigue syndrome underwent an acute exacerbation recently, with the arrival of another set of guidelines in my email inbox. On reviewing the level of evidence provided for the various recommendations being offered, I was struck by the fact that no relevant clinical trials had been carried out in the population of interest. Eleven out of 25 of the recommendations made were supported only by the lowest levels of published evidence (case reports and case series, or inference from studies not directly applicable to the relevant population). A further seven out of 25 were derived only from the expert opinion of members of the guidelines committee, in the absence of any guidance to be gleaned from the published literature.

Quite deliberately, I’m not naming the particular set of …