tbuckley/cabot-search huggingface dataset:
Derivation of a needs based capitation formula for allocating prescribing budgets to health authorities and primary care groups in England: regression analysis Commentary: The emphasis on transparency weakens the formula
Authors: N. Rice
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objective</b>: To develop a weighted capitation formula for setting target allocations for prescribing expenditures for health authorities and primary care groups in England. <b>Design</b>: Regression analysis relating prescribing costs to the demographic, morbidity, and mortality composition of practice lists. <b>Setting</b>: 8500 general practices in England. <b>Subjects</b>: Data from the 1991 census were attributed to practice lists on the basis of the place of residence of the practice population. <b>Main outcome measures</b>: Variation in age, sex, and temporary resident originated prescribing units (ASTRO(97)-PUs) adjusted net ingredient cost of general practices in England for 1997–8 modelled for the impact of health and social needs after controlling for differences in supply. <b>Results</b>: A needs gradient based on the four variables: permanent sickness, percentage of dependants in no carer households, percentage of students, and percentage of births on practice lists. These, together with supply characteristics, explained 41% of variation in prescribing costs per ASTRO(97)-PU adjusted capita across practices. The latter alone explained about 35% of variation in total costs per head across practices <b>Conclusions</b>: The model has good statistical specification and contains intuitively plausible needs drivers of prescribing expenditure. Together with adjustments made for differences in ASTRO(97)-PUs the model is capable of explaining 62% (35%+0.65% (41%)) of variation in prescribing expenditure at practice level. The results of the study have formed the basis for setting target budgets for 1999–2000 allocations for prescribing expenditure for health authorities and primary care groups.
Ruxolitinib Treatment for Myelofibrosis: Efficacy and Tolerability in a Real-World Setting
Authors: Martin H. Ellis, Noa Lavi, Elena Mishchenko, Najib Dally, David Lavie, Anna Courevitch, Odit Gutwein, Shlomo Bulvik, Andrei Braester, Evgeni Chubar, Sigal Tavor, Adrian Duek, Ilya Kirgner, Maya Koren-Michowitz
Journal: Blood (2014)
Coating Stents With Antirestenotic Drugs: The Blunderbuss or the Magic Bullet?
Authors: Harry C. Lowe, Levon M. Khachigian
Journal: Circulation (2002)

Coating Stents With Antirestenotic Drugs: The Blunderbuss or the Magic Bullet?To the Editor:We read with interest a recent article in Circulation that reported that the binding protein (FK506BP12) for the drug sirolimus (rapamycin) is up-regulated in in-stent restenotic tissue. 1 This fact correlates with the observation that stents coated with sirolimus are associated with very low rates of neointima formation. 2These studies suggest a mechanism of action for this immunosuppressive, antineoplastic, and antifungal agent in the context of in-stent restenosis and provide proof-of-principle evidence that stent-based drug delivery can be achieved.Sirolimus therapy to date has been associated with a generally low incidence of side effects and toxicity.The mechanisms of action of sirolimus are not entirely understood, but are thought to involve inhibition of mitogeninduced downregulation of p27 Kip1 and p70 s6K phosphorylation.Recently, however, Sun et al 3 reported in Circulation that rapamycin inhibition of smooth muscle cell migration is both p27 Kip1 -and p70 s6K -dependent and independent.At the present time this drug, like Tranilast and Paclitaxel (taxol), which are also under investigation as antirestenotic agents, might be regarded as a "blunderbuss" because the mechanisms of action of these drugs do not appear to be gene-specific and are incompletely understood.The opposite approach, the "magic bullet," is to selectively target a specific gene or process that plays a pivotal role in the response to injury.One example is the immediate-early gene and zinc finger transcription factor, Egr-1.Using sequence-specific catalytic DNA molecules, or "DNAzymes," that selectively target and cleave a specific site in Egr-1 mRNA, we have demonstrated reduced neointima formation after balloon angioplasty to rat carotid arteries 4 and stenting in pig coronary arteries. 5Now, using human internal mammary arterial explants in an ex vivo model of intimal thickening, DzA (at 400 nmol/L final concentration), a DNAzyme targeting the 5Ј region of human EGR-1 mRNA, 5 could inhibit neointima formation in these segments compared with a non-cleaving DNAzyme (DzE) targeting the same gene.In this respect, neointima:media ratios (Ϯ SEM) were 0.06 (0.01) for DzA (PϽ0.05 using a Wilcoxen signed rank test for paired data compared with all other groups), 0.09 (0.03) for DzE, 0.08 (0.02) for the drug vehicle control, and 0.09 (0.02) for the control (no vehicle)(nϭ5 for each group).So far, in the short-term and in small patient numbers, the promise of inhibiting restenosis using what might be a blunderbuss approach is clearly encouraging.However, it may be clinically more appealing to locally deliver gene-specific magic bullets (such as DNAzymes) in efforts to inhibit intimal regrowth with potentially greater specificity, decreased toxicity, and fewer side effects.
Calcium homeostasis and body composition in patients with palmoplantar pustulosis: a case-control study
Authors: E. Hagforsen, I. Pihl-Lundin, K. Michaëlsson, G. Michaëlsson
Journal: British Journal of Dermatology (2011)

Palmoplantar pustulosis (PPP) is a common disease strongly associated with smoking, autoimmune comorbidities and a deranged calcium homeostasis. It is unclear whether these changes in calcium homeostasis are a consequence of vitamin D status, abnormal dermal vitamin D synthesis or whether they are substantiated in effects on bone mineral density (BMD).To study the vitamin D status and BMD in patients with PPP.In comparisons with two sets of controls (n=101 for serum analyses and n=5123 for BMD analyses), we therefore aimed to investigate whether PPP (59 cases) was associated with serum levels of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, whether patients with PPP had decreased BMD and finally if the dermal expression of 25-hydroxyvitamin D(3) -1α-hydroxylase (CYP27B1) and the vitamin D receptor (VDR) were affected in PPP skin lesions.We found no differences in mean serum 25-hydroxyvitamin D levels between cases and controls, whereas PPP cases displayed 17·8 pmol L(-1) lower (P=0·04) values in 1,25-dihydroxyvitamin D. BMD at the hip, lumbar spine or of total body did not differ substantially between cases and controls. Finally, patients with PPP had lower dermal expression of CYP27B1 and VDR in affected skin lesions.The increase in serum calcium levels and suppressed parathyroid hormone in patients with PPP were not attributable to derangements in vitamin D status and these patients did not have lower BMD.
Elevated levels of tumour necrosis factor (TNF)-α, interleukin (IL)-1β and IL-10 in hidradenitis suppurativa skin: a rationale for targeting TNF-α and IL-1β
Authors: H.H. van der Zee, L. de Ruiter, D.G. van den Broecke, W.A. Dik, J.D. Laman, E.P. Prens
Journal: British Journal of Dermatology (2011)

Journal Article Elevated levels of tumour necrosis factor (TNF)‐α, interleukin (IL)‐1β and IL‐10 in hidradenitis suppurativa skin: a rationale for targeting TNF‐α and IL‐1β Get access H.H. van der Zee, H.H. van der Zee Departments of DermatologyImmunology, Erasmus MC, University Medical Center, Dr Molewaterplein 50, 3015 GE Rotterdam, the Netherlands Hessel van der Zee. E‐mail: h.vanderzee@erasmusmc.nl Search for other works by this author on: Oxford Academic Google Scholar L. de Ruiter, L. de Ruiter Departments of DermatologyImmunology, Erasmus MC, University Medical Center, Dr Molewaterplein 50, 3015 GE Rotterdam, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar D.G. van den Broecke, D.G. van den Broecke Department of Plastic Surgery, Diaconessenhuis, Leiden, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar W.A. Dik, W.A. Dik Immunology, Erasmus MC, University Medical Center, Dr Molewaterplein 50, 3015 GE Rotterdam, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar J.D. Laman, J.D. Laman Immunology, Erasmus MC, University Medical Center, Dr Molewaterplein 50, 3015 GE Rotterdam, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar E.P. Prens E.P. Prens Departments of DermatologyImmunology, Erasmus MC, University Medical Center, Dr Molewaterplein 50, 3015 GE Rotterdam, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 164, Issue 6, 1 June 2011, Pages 1292–1298, https://doi.org/10.1111/j.1365-2133.2011.10254.x Published: 01 June 2011
HODGKIN'S SARCOMA SIMULATING VENTRICULAR ANEURYSM
Authors: J F HAMMARSTEN, W O SMITH, C D TOOL
Journal: Annals of Internal Medicine (1956)

Case Reports1 December 1956HODGKIN'S SARCOMA SIMULATING VENTRICULAR ANEURYSMWILLIAM O. SMITH, CHARLES D. TOOL, JAMES F. HAMMARSTENWILLIAM O. SMITHSearch for more papers by this author, CHARLES D. TOOLSearch for more papers by this author, JAMES F. HAMMARSTENSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-45-6-1222 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAccording to a number of reported autopsy series, infiltration of the myocardium by nests of malignant cells is not rare in Hodgkin's sarcoma, nor are small nodules on the pericardium.1 However, large tumor nodules involving the heart are uncommon. Rottino and Hoffmann2 reviewed the world literature in 1952 and were able to find only five cases of tumor involvement of the heart in Hodgkin's disease, and they reported a sixth case. All of these cases showed a tumor mass in the right auricle, usually occluding the orifice of the inferior vena cava.The present case appears to be unique in...Bibliography1. CohenPeeryEvans GULMJM: Neoplastic invasion of the heart and pericardium, Ann. Int. Med. 42: 1238, 1955. LinkGoogle Scholar2. RottinoHoffmann AGL: Cardiac involvement in Hodgkin's disease, Am. Heart J. 43: 115, 1952. CrossrefMedlineGoogle Scholar3. Nabarro JD: Cardiac involvement in malignant lymphoma, Arch. Int. Med. 92: 258, 1953. CrossrefGoogle Scholar4. ChevallierBernardChristolBoiron PJDM: Maladie de Hodgkin avec granulomatose du myocarde et granulomatose pulmonaire a forme cavitaire, Le Sang Biol. et Path. (Paris) 23: 704, 1952. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Oklahoma City, Oklahoma*Received for publication August 3, 1955.From the Departments of Medicine and Pathology, University of Oklahoma School of Medicine, and the Veterans Administration Hospital, Oklahoma City, Oklahoma.Requests for reprints should be addressed to James F. Hammarsten, M.D., Chief, Medical Service, Veterans Administration Hospital, 921 Northeast Thirteenth Street, Oklahoma City, Oklahoma. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byHerz- und Perikardtumoren 1 December 1956Volume 45, Issue 6Page: 1222-1228KeywordsCardiovascular therapyCellsEdemaElectrocardiographyHeartHodgkin lymphomaHospital medicineInferior vena cavaMyocardiumSarcoma ePublished: 1 December 2008 Issue Published: 1 December 1956 PDF downloadLoading ...
Abstract 15915: Gender Matters in the Risk for Sudden Death in Young Competitive Athletes
Authors: Aneesha Ahluwalia, Tammy S Haas, Ross F Garberich, Barry J Maron
Journal: Circulation (2014)

Background: Sudden deaths in young competitive athletes are highly visible and tragic events, which receive much public visibility. However, little is known regarding the specific impact of gender on these events. Methods and Results: The U.S. National Registry of Sudden Death in Athletes was accessed to identify the causes, frequency and epidemiology of sudden deaths in U.S. competitive athletes by gender. A total of 2,408 deaths (2155 male; 253 female) were identified in athletes engaged in 41 diverse organized sports from 1980 to 2011. Most sudden deaths occurred with physical exertion during competition/training (66%), and were predominantly due to cardiovascular disease (54%). In high school and college athletes, accounting for participation rates, the ratio of male to female deaths was 5.4:1. Males were somewhat older than females (19±6 vs. 17.8±6; P=0.003), and were more commonly black (30% vs. 17%; P&lt;0.001). Of the male athletes, the highest rate of cardiovascular sudden death was in blacks (65% vs. 49% in whites; P&lt;0.001). The most frequent sports were football (n=725) and basketball (n=437) in males, and basketball (n=47) and cross country/track (n=41) in females. Most common cardiovascular cause of death was hypertrophic cardiomyopathy (HCM), which accounted for a greater proportion of confirmed cardiovascular deaths in males (47%) vs. females (14%; P&lt;0.001); a 19:1 male:female ratio in high school and college athletes. In contrast, females experienced greater frequency of death due to congenital coronary artery anomalies (30% vs. 14%; P&lt;0.001), arrhythmogenic right ventricular dysplasia (12% vs. 4%; P=0.018), and long-QT syndrome (7% vs. 1%; P&lt;0.001). Blunt trauma, including commotio cordis, occurred more frequently in males (24% vs. 15% in females; P=0.001). Conclusions: Female athletes have a 5-fold lower risk for sudden death, compared to males, and were almost 20-times less likely to die of HCM. Black males had the highest rate of sudden death due to cardiovascular disease, with HCM most common.
Management of High-Risk Pregnancy.
Authors: John T. Queenan, Catherine Y. Spong, Charles J. Lockwood
Journal: Annals of Internal Medicine (1986)

Sectional Contents: Factors of High-Risk Pregnancy - Procedures - Genetics - Monitoring, Biochemical and Biophysical - Maternal Disease - Pregnancy Complications - Complications of Labor and Delivery - Neonatal Considerations.
Jüvenil başlangıçlı behçet hastalığının demografik ve klinik özellikleri: Kontrollü çok merkezli bir çalışma
Authors: Yelda Karincaoglu, Murat Borlu, Semra Cikman Toker, Ayse Akman, Meltem Onder, Suhan Gunasti, Aysegul Usta, Basak Kandi, Cicek Durusoy, Muammer Seyhan, Serap Utas, Hayriye Saricaoglu, Muge Guler Ozden, Sonern, Umit Tursen, Demet Cicek, Levent Donmez veErkan Alpsoy Malatya, Kayseri, Bursa, Antalya, Ankara, Adana, Mersin, Elazig, and Alanya
Journal: Journal of the American Academy of Dermatology (2008)
Abstract 421: Aldose Reductase Protects Against the Early Atherosclerotic Lesion Formation InApoe-null Mice
Authors: Sanjay Srivastava, Oleg Barski, Aruni Bhatnagar
Journal: Circulation (2008)

Atherosclerotic lesion formation is associated with extensive oxidation of unsaturated lipids and the accumulation of lipid oxidation products. Products of lipid oxidation, particularly aldehydes, stimulate cytokine production and enhance monocyte adhesion. Aldehydes generated by oxidized lipids are metabolized by several biochemical pathways, of which aldose reductase (AR)-catalyzed reduction represents a metabolic fate common to both free and phospholipid esterified aldehydes. Herein, we tested the hypothesis that inhibition of AR could aggravate atherosclerotic lesion formation by preventing the removal and the detoxification of aldehydes generated by oxidized lipids. In atherosclerotic lesions of apoE-null mice, AR protein was associated with macrophage-rich regions and its abundance increased with lesion progression. Treatment of 8 week old apoE-null mice with AR inhibitors sorbinil or tolrestat for 4 weeks increased lesion formation in the aortic arch (P&lt;0.01) and the aortic sinus (P&lt;0.01). No change in lesion formation was observed when 24 week old mice were fed AR inhibitors for 12 weeks. To probe the role of AR in atherogenesis further, we generated AR −/− /apoE −/− mice. Lesions of 8 week old AR −/− /apoE −/− mice maintained on high fat diet for 4 or 12 weeks were significantly larger throughout the aortic tree (P&lt;0.01 for both the groups) when compared with age-matched AR +/+ /apoE −/− mice. Lesions in AR −/− /apoE −/− mice exhibited increased collagen (P&lt;0.01) and macrophage content (P&lt;0.01) and a decrease in smooth muscle cells (P&lt;0.01). GC-MS analysis showed that the concentration of AR substrates HNE and hexanal was increased by 2.5–3 fold (P&lt;0.01) in the plasma of AR −/− /apoE −/− mice as compared with AR +/+ /apoE −/− mice. Immunohistochemical analysis showed greater accumulation of protein-HNE adducts in arterial lesions of AR −/− /apoE −/− mice. These observations suggest that AR is up regulated during atherosclerosis and that this protein protects against early stages of atherosclerotic lesion formation by removing aldehydes generated by lipid oxidation.
Identification of immunologically high-risk individuals of stomach cancer and application to cancer prevention
Authors: Tomonori Hayashi, Kazue Imai, Yoichiro Kusunoki, Eiichi Tahara, Kei Nakachi
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4603 

Immunological host defense system is thought to play an important role not only in virus-related cancers but also in most cancers. The objectives of this study are to elucidate individual variability in cancer susceptibility via genetic polymorphisms involving immunological host defense and to assess the gene-environment interaction, which provides useful information for cancer prevention. In this study, we first investigated the association between polymorphisms of IL-10 , an immune-suppressive/anti-inflammatory cytokine gene, and risk of stomach cancer, in terms of a case-control study within the Adult Health Study cohort of atomic-bomb survivors. Second, we studied the influence of past exposure to atomic-bomb radiation on stomach cancer risk estimated by IL-10 haplotyping. Finally, we examined plasma IL-10 levels by IL-10 haplotype and evaluated the functional significance of these haplotypes. This case-control study comprised 238 stomach cancer cases (149 and 89 individuals exposed and not exposed to atomic radiation, respectively) and 1,757 controls (1,008 and 749 individuals exposed and not exposed to radiation, respectively). We found haplotype blocks ( IL10-GGCG , IL10-ATTA ) consisting of four htSNPs located in the IL-10 gene region containing its promoter; the odds ratio of stomach cancer among non-exposed individuals having the IL10-ATTA/IL10-GGCG or IL10-GGCG/IL10-GGCG haplotype was 1.71 (95% CI: 1.03-2.84) or 2.46 (1.28-4.70), respectively, compared to those having IL10-ATTA/IL10-ATTA . A further increased risk of stomach cancer was also observed among individuals exposed to atomic-bomb radiation, although the degree of increase varied depending on the haplotype: The odds ratio for IL10-ATTA/IL10-ATTA, IL10-ATTA/IL10-GGCG or IL10-GGCG/IL10-GGCG among exposed individuals was 1.50 (0.92-2.45), 2.16 (1.35-3.45) or 2.46 (1.31-4.60), respectively, adopting as reference the risk of non-exposed individuals with IL10-ATTA/IL10-ATTA . Plasma IL-10 levels in control subjects with IL10-ATTA/IL10-GGCG and those with IL10-GGCG/IL10-GGCG were approximately 1.1 and 1.4 times higher, respectively, than those with IL10-ATTA/IL10-ATTA ( P = 0.005 for trend); IL-10 level also increased with increased radiation dose ( P = 0.03 for trend). Thus, plasma IL-10 level was closely associated with the risk of stomach cancer, implying that IL-10 may be a promising surrogate marker for prevention of stomach cancer.
Abstract 409: Regulation of chromatin remodeling in leukemia by Ikzf1 and Casein Kinase II
Authors: Jonathon L. Payne, Carlos M. Casiano, Kimberly J. Payne, Justin Sloane, Elanora Dovat, Chunhua Song, Sinisa Dovat
Journal: Cancer Research (2014)

Abstract Ikzf1 (Ikaros) encodes a zinc finger protein that binds DNA and regulates gene expression via chromatin remodeling. The loss of Ikaros activity due to genetic or functional inactivation results in leukemia with a poor prognosis. The goal of our project is to determine the mechanism by which Ikaros regulates chromatin remodeling in human leukemia. Previous studies showed that Ikaros function in leukemia is controlled through its direct phosphorylation by Casein Kinase II (CK2). Treatment of leukemia cells with CK2 inhibitors results in enhanced Ikaros activity, which leads to cessation of cell growth. We have studied the mechanism by which inhibition of CK2 regulates Ikaros-induced epigenetic changes in leukemia. The human Nalm6 pre-B cell leukemia was treated with CK2 inhibitor, and the epigenetic signature of the histone modifications H3K9ac and H3K9me3 were determined using chromatin immunoprecipitation coupled with next generation sequencing (ChIP-SEQ). H3K9ac histone modification is associated with positive regulation of gene expression, while H3K9me3 is associated with the formation of heterochromatin and repression. The enrichment of particular histone modifications was confirmed by quantitative chromatin immunoprecipitation (qChIP). The results demonstrated that the inhibition of CK2 activity in leukemia results in a marked alteration in the epigenetic signature of both H3K9ac and H3K9me3 compared to untreated cells. This is associated with altered Ikaros binding to its target genes following CK2 inhibition. Current bioinformatics analysis is directed toward establishing a link between epigenetic modifications and Ikaros binding in leukemia. These results suggest that CK2 and Ikaros regulate gene transcription via epigenetic modifications and chromatin remodeling in leukemia. Citation Format: Jonathon L. Payne, Carlos M. Casiano, Kimberly J. Payne, Justin Sloane, Elanora Dovat, Chunhua Song, Sinisa Dovat. Regulation of chromatin remodeling in leukemia by Ikzf1 and Casein Kinase II. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 409. doi:10.1158/1538-7445.AM2014-409
Contribution of clinical pulmonary infection score in the diagnosis of hospital acquired pneumonia
Authors: Burcu Basarik, Pelin Ozdemir, Mehmet Sezai Tasbakan, Ozen Kacmaz Basoglu, Alev Gurgun, Feza Bacakoglu
Journal: European Respiratory Journal (2011)

Introduction and aim: Clinical pulmonary infection score (CPIS) is a scoring system calculated by symptoms and signs of pneumonia, that is used in the diagnosis and management of hospital acquired pneumonia (HAP). In this study, the contribution of CPIS for diagnosis of HAP was investigated in intensive care unit (ICU) patients.

Methods: The ICU patients followed-up between February 2008 and September 2010 were assessed retrospectively. Hospital acquired pneumonia was diagnosed by quantitative endotracheal aspirate (ETA). CPIS was calculated on 3rd and 7th days of ICU admission. The correlations of CPIS with concurrent ETA cultures and laboratory markers of infection were assessed.

Results: Out of 240 patients (165 men, mean age 58.2±16.6 yrs) included in the study, ETA cultures were positive in 61 patients (25.4%) on 3rd day, and in 59 patients (24.6%) on 7th day. CPIS was found higher in patients with ETA culture positive (5.0±2.3 vs. 3.5±2.1 on 3rd day, p<0.0001; 5.2±2.6 vs. 3.6±2.9 on 7th day, p<0.0001). Sensitivity and specificity ratios of CPIS with a threshold level of 6.5 in diagnosis of HAP were 26.2% and 92.3% for 3rd day; 30.5% and 91.9% for 7th day, respectively. On 3rd and 7th days, there were positive correlations between CPIS and C-reactive protein (CRP) levels (p=0.002 and p=0.001, respectively); and also between CPIS and procalcitonin (PCT) levels (p=0.012 and p<0.0001, respectively).

Conclusion: Clinical pulmonary infection score can be used instead of infection markers like CRP and PCT in the diagnosis of hospital acquired pneumonia.