tbuckley/cabot-search huggingface dataset:
Immunoregulation in Sjögren's Syndrome
Authors: Haralampos M. Moutsopoulos, Anthony S. Fauci
Journal: Journal of Clinical Investigation (1980)

21 patients with Sjögren's syndrome (sicca syndrome) with either glandular or extraglandular involvement, but without other connective tissue diseases, were studied with regard to immunoregulatory T-cell subpopulations, B-cell function, and suppressor cell capabilities. Patients with isolated glandular disease as well as patients with extraglandular disease had normal absolute numbers of total lymphocytes, T cells, and B cells. However, 9 of 11 patients with extraglandular disease and only 3 of 10 patients with glandular disease had decreased relative proportions of T cells bearing receptors for the Fc portion of immunoglobulin (Ig)G (TG) which was explained by a factor that blocked the expression of the IgG Fc receptor on TG cells. This blockage was reversible since the factor could be removed by trypsinizing the T cells before TG determination. Serum from patients with abnormal proportions of TG cells, but not serum from patients with normal proportions of TG cells, blocked the expression of the IgG Fc receptor on normal T cells. The serum factor upon fractionation over Bio-Gel A 1.5 columns as well as over staphylococcal protein A-Sepharose 4B columns was found diffusely within the IgG fraction, and not in the IgM fraction.
GPs are disappointed at gaps in NHS Plan
Authors: Linda Beecham
Journal: BMJ (2000)

Representatives of the United Kingdom's 35 000 GPs have expressed their disappointment at some of the proposals in The NHS Plan for England (5 August, p 317).

At its meeting last week the General Practitioners Committee condemned the proposals for victimising singlehanded GPs—the government plans to introduce new contractual quality standards for singlehanded practices—and for resource allocation, which it believes will have a major impact on the distribution of doctors.

The committee has suggested that instead of abolition of the Medical Practices Committee, the …
Abstract 16937: Age at Genetic Testing is Negatively Correlated with the Number of Mutations Found in Five Cardiac Channelopathies and Cardiomyopathies
Authors: Benjamin A Salisbury, Thomas E Callis, Janet L Carr, Lisa Susswein, Guido D Pollevick
Journal: Circulation (2011)

INTRODUCTION: Although dominantly inherited diseases are defined as being caused by a single mutant gene copy, other factors can affect disease expression. Here we examined the relationship between mutation count and age at genetic testing across five autosomal dominant cardiac diseases. METHODS: We examined data for 2596 probands referred for genetic testing for arrhythmogenic right ventricular cardiomyopathy (ARVC), Brugada syndrome (BrS), catecholaminergic polymorphic ventricular tachycardia (CPVT), hypertrophic cardiomyopathy (HCM), or long QT syndrome (LQTS). Age at testing was used as a clinical correlate of age of onset. Mutations were categorized as either class I (definite or probable pathogenic) or class II (variant of uncertain significance). RESULTS: Among mutation-positive patients, 12% had two mutations and 1% had three; these two percentages were similar across all diseases, although the overall positive rate varied considerably. In all five diseases, age at testing was lower for positive than negative probands, and even lower for those with two mutations. In three out of the four diseases where at least one patient had three mutations, those patients were even younger. While differing by disease, the average age drop from 0 mutations to 1 was 3.5 years (p=0.00013) and from 1 mutation to 2 was 5.2 years (p=0.012). The patterns held when restricting to either class I or II mutations. CONCLUSIONS: This study found a remarkable 12% multiple-hit rate across five so-called autosomal dominant diseases and identified a correlation between mutation count and age at testing. This correlation may have multiple explanations: First, each mutation may contribute to disease severity or onset. Second, “more mutations” may reflect a higher probability that at least one is deleterious and that the patient indeed has the disease. Overall, the results point to a complexity that must continue to be explored as science and medicine grapple with the genetics of disease.
Abstract 1958: MicroRNA Mir-27b Rescues Impaired Angiogenic Function of Endothelial Progenitor Cells and Accelerates Wound Healing in Type 2 Diabetes
Authors: Jie-Mei Wang, Jun Tao, Alex F Chen
Journal: Circulation (2008)

Endothelial progenitor cells (EPCs) play a key role in angiogenesis, which is dysfunctional in diabetes. MicroRNAs (miRNAs) are endogenous non-coding RNAs that regulate gene expression at the post-transcriptional level. However, whether miRNAs regulate EPC-mediated angiogenesis in diabetes is unknown. We tested the hypothesis that mir-27b rescues impaired EPC angiogenesis in vitro and in vivo via suppressing anti-angiogenic molecule thrombospondin-1 (TSP-1) in type 2 diabetes. Bone marrow-derived EPCs from adult male (C57BLKS/J, 9 weeks) type 2 diabetic db/db and their normal littermates db/+ mice (glucose 371.8±37.8 vs. 167.5±21.3 mg/dL, n=38, p&lt;0.05) were used. miRNA processing enzyme Dicer in EPCs was decreased by &gt;40% in db/db vs. db/+ mice (Western blot analysis, n=4 p&lt;0.01), paralleled with &gt;66% reduction of mir-27b expression (real-time PCR, n=4, p&lt;0.05). Both TSP-1 mRNA and protein in EPCs were significantly higher in db/db vs. db/+ mice (real-time PCR, 130.1%, n=4, p&lt;0.05, Western blot analysis, 127.4%, n=4 p&lt;0.05), which were suppressed upon mir-27b mimic transfection (by 75%, real-time PCR and 69%, Western blot analysis, n=4 – 6, p&lt;0.01). EPC-induced angiogenesis was decreased by &gt;70% in db/db vs. db/+ mice (Matrigel tube formation assay, n=4, p&lt;0.05), which was rescued upon mir-27b mimic transfection or silencing TSP-1 expression by its siRNA (both n=4, p&lt;0.05). Furthermore, inhibition of mir-27b in normal EPCs increased their TSP-1 protein by 117.5% (n=6, p&lt;0.05) and impaired their angiogenesis by 81.5% (n=4, p&lt;0.01), both were reversed by silencing TSP-1 expression by its siRNA. Finally, excisional wound closure was markedly delayed in db/db vs. db/+ mice (4-mm punch biopsy, n=4, p&lt;0.05), accompanied by impaired wound angiogenesis (perfusion index by Laser Doppler, n=4, p&lt;0.05). Cell therapy of diabetic EPCs (3×10 5 cells) transfected with mir-27b mimic onto diabetic wounds significantly accelerated their closure rates (n=4, p&lt;0.05 vs. diabetic EPCs alone), with a concomitant augmentation of in vivo wound angiogenesis (n=4, p&lt;0.05). Mir-27b rescues impaired EPC angiogenesis and accelerates wound healing in type 2 diabetic mice, at least in part, via suppressing TSP-1 expression. This research has received full or partial funding support from the American Heart Association, AHA Midwest Affiliate (Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, South Dakota &amp; Wisconsin).
New perspectives after the transition of EPIET to ECDC – the future of the programme
Authors: V Bremer, A Bosman, D Coulombier
Journal: Eurosurveillance (2009)

Strengthening capacity in intervention epidemiology is key to the overall goal of responding to the challenge to detect and counter threats posed by outbreaks of infectious diseases in the European Union (EU). Since its founding in 1995, the European Programme for Intervention Epidemiology Training (EPIET) has become a core resource in training in intervention epidemiology in the EU. EPIET was integrated into the European Centre for Disease Prevention and Control (ECDC) on 1 November 2007 and this has resulted in an increased sustainability of the programme, allowing for long-term planning. Also, a new training programme, the European public health microbiology training (EUPHEM), was set up in 2008 to increase the response capacity for microbiology. Collaboration with EU Member States and other training programmes has been further intensified. Merging EPIET and other training activities in the ECDC training section has created the opportunity to develop an integrated multilevel approach to training in applied field epidemiology. An integrated approach to training activities on EU level, and increasing the number of EPIET and EPIET-associated fellows are essential to respond to the training needs of EU Member States, particularly new Member States. An external evaluation of EPIET in 2009 will provide guidance for a future strategy for the programme. This article examines the achievements of the EPIET programme after its transition to ECDC and provides an outlook on its future.
HPV Screening for Cervical Cancer in Rural India
Authors: Eric J. Suba, Edmund S. Cibas, Stephen S. Raab
Journal: New England Journal of Medicine (2009)

To the Editor: Sankaranarayanan et al. (April 2 issue)1 report no significant differences in rates of detection of high-risk cervical neoplasia among women who underwent screening by cytologic testing, testing for human papillomavirus (HPV) with the Hybrid Capture II assay, or visual inspection of the cervix with acetic acid (VIA). Reductions in mortality from cervical cancer were observed only among women screened by HPV testing. The unexpected lack of a correlation between detection rates reported for the screening tests and subsequent mortality rates requires careful consideration. Sankaranarayanan et al. acknowledge that unidentified differences in followup care, rather than differences in the performance of screening tests, account for differences in mortality between women screened by VIA in their current study and women screened by VIA in an earlier study.2 The same logic, applied to the current data, suggests that unidentified differences in follow-up care, rather than nonsignificant differences among screening-test detection rates, account for differences in mortality among the groups of women who underwent screening. Within the political structures of many developing countries, there is genuine lack of support for cervical-cancer prevention efforts,3 which may be further eroded by the questionable conclusion that only an unaffordable screening option is better than none at all.1 Eric J. Suba, M.D.
Abstract 17418: Vector Velocity Imaging: A Reliable Tool to Quantify Myocardial Function and Predict Clinical Outcomes in Single Ventricle Patients
Authors: Shawn C West, Christine H Saunders, Nicole Duncan, Kaimal A Jayakumar
Journal: Circulation (2011)

Background: Ventricular function is one of the factors that correlate with survival to second stage surgical palliation in single ventricle (SV) patients. Standard 2D echocardiography (2DE) has limitations in evaluating right ventricular function. Myocardial function can be reliably determined using Vector Velocity Imaging (VVI), which is an angle independent method of evaluating myocardial mechanics using conventional 2DE images. HYPOTHESIS: VVI provides a valid and reproducible measure of ventricular function in SV patients compared to standard 2DE with direct correlation to clinical outcomes. Methods: Medical records and 2DE's were retrospectively reviewed on 72 patients with SV's (37 systemic right ventricles, 35 systemic left ventricles. VVI analysis was performed offline using Siemens Syngo software. When feasible, 2D and Doppler parameters of ventricular function were performed. Using VVI on a 4 chamber image longitudinal velocity (LVel), strain (S), strain rate (SR) were obtained. Ventricular function was measured pre and post stage 1 palliation and compared to normals. Results: Fifty seven patients survived to stage 2 palliation (79%). Of the 15 deceased, 10 survived to hospital discharge; 10 had a single RV and 5 had single LV. Heterotaxy, post operative ECMO, sepsis, atrioventricular valve insufficiency and chylothorax were factors associated with death. Using 2DE, ventricular function was qualitatively normal in all but 3 patients pre-stage 1 and in 9 patients post stage 1. Other quantitative parameters were not consistently employed through the study period. LVel, S, and SR were depressed compared to normal hearts in all study patients. There was a statistical difference in the LVel between the survivors and non-survivors (p 0.017). Conclusions: Despite qualitatively normal ventricular function, VVI shows significantly decreased myocardial function in both single left and right ventricles when compared to normal hearts. In the absence of traditional quantitative measures of SV function, VVI is a reliable tool to evaluate myocardial mechanics and serves as an adjunct to prognosticate clinical outcomes.
Abstract #4400: Cdk3-mediated c-Jun phosphorylation at Ser63 and Ser73 enhances cell transformation
Authors: Yong-Yeon Cho, Faqing Tang, Ke Yao, Chengrong Lu, Feng Zhu, Duo Zheng, Angelo Pugliese, Ann Bode, Zigang Dong
Journal: Cancer Research (2009)

c-Jun is a component of the activator protein-1 (AP-1) complex, which plays a crucial role in the regulation of gene expression, cell proliferation and transformation, as well as cancer development. Herein, we found that Cdk3, but not Cdk2 or JNK, is a novel kinase of c-Jun induced by stimulation with growth factors such as epidermal growth factor (EGF). Cdk3 was shown to phosphorylate c-Jun at Ser63 and Ser73 in vitro and ex vivo. EGF-induced Cdk3 activation caused c-Jun phosphorylation at Ser63 and Ser73, resulting in increased AP-1 transactivation. Ectopic expression of Cdk3 resulted in anchorage-independent cell transformation of JB6 Cl41 cells induced by EGF and foci formation stimulated by constitutively active Ras (RasG12V), which was mediated by AP-1 in NIH3T3 cells. These results demonstrated that the Cdk3/c-Jun signaling axis plays an important role in EGF-stimulated cell proliferation and cell transformation.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4400.
Drug points: Potentiation of warfarin anticoagulant activity by miconazole oral gel
Authors: S Ariyaratnam, N S Thakker, P Sloan, M. Thornhill
Journal: BMJ (1997)

Objective: To evaluate the immunogenicity and reactogenicity of a new triple S recombinant hepatitis B vaccine in a cohort of healthy people in whom currently licensed hepatitis B vaccines had persistently not induced an immune response.Design: Single centre, randomised, double blind, dose-response study.Setting: Research vaccine evaluation centre at a teaching hospital.Subjects: 100 healthcare workers aged 18-70 years with a history of failure to seroconvert after at least four doses of a licensed hepatitis B vaccine containing the S component.Intervention: Each subject was randomly allocated two doses of 5, 10, 20, or 40 g of a new hepatitis B vaccine two months apart.Main outcome measures: Immunogenicity of the four doses.Seroconversion and seroprotection were defined as an antibody titre > 10 IU/l and > 100 IU/l respectively against an international antibody standard.Results: 69 subjects seroconverted after a single dose of the vaccine.After the booster vaccination one other subject seroconverted, bringing the overall seroconversion rate to 70%.Fifteen subjects given 5 g of vaccine, 19 given 10 g, 16 given 20 g, and 20 given 40 g seroconverted.Seroconversion rates in the four antigen dose groups were 60% (15/25), 76% (19/25), 64% (16/25), and 80% (20/25).After the booster dose there was no significant dose-response effect on the overall seroconversion rate, although the small sample size meant that a clinically important dose-response could not be ruled out. Conclusion:A single dose of 20 g of the vaccine was as effective as two doses of either 40 g or 20 g of this vaccine formulation in terms of seroconversion, seroprotection, and geometric mean titres.
Postnatal dexamethasone in preterm infants
Authors: W. Tarnow-Mordi, A. Mitra
Journal: BMJ (1999)

Clinical research must determine whether treatments enhance lives, make little difference, cause significant harm, or do several of these things. This is well illustrated by the epidemic of blindness due to retrolental fibroplasia that affected thousands of preterm babies in the 1950s.1 Although oxygen was accepted as lifesaving in severe respiratory distress syndrome, randomised controlled trials showed that its unrestricted use could also cause permanent visual impairment. The risk is minimised with modern oxygen therapy, which is strictly controlled. The lesson is that new treatments need to be tested with randomised trials that are large enough and with follow ups long enough to provide robust data on all clinically important endpoints 12 Dexamethasone for chronic lung disease in preterm infants may be a similar case where we need better data from larger trials with longer follow up.

View this table:

Hospital mortality, and morbidity after 12 months, in randomised studies of postnatal …
A comparison of unipolar and bipolar depressive illness
Authors: R Abrams, M A Taylor
Journal: American Journal of Psychiatry (1980)

In a study of 40 consecutively hospitalized patients with research diagnoses of endogenous depression, the authors found no difference between unipolar and bipolar depressive patients in the risk for affective disorder in first-degree relatives, proportion of EEG or neuropsychological abnormalities, clinical evidence of the depressive syndrome, or response to doctor's choice of treatment. Bipolar patients had an earlier age of onset and displayed more manic symptoms that did unipolar patients. The authors conclude that the two forms of depressive illness are clinically and genetically homogeneous, are without identifying EEG or cognitive differences, and have an equally good response to somatic treatments.
Abstract 3176: Differerential Impact Of Acute Myocardial Risk Factors And Chronic Comorbidities On Use Of Guideline-recommended Therapies In Patients Presenting With Acute Coronary Syndromes
Authors: Karen E Joynt, Luan Huynh, John Amarena, David Brieger, Steven Coverdale, Jamie Rankin, Ashish Soman, Derek P Chew
Journal: Circulation (2008)

Background: Prior investigations show that patients presenting with ACS with high-risk features are less likely to receive evidence-based therapies (EBT). Current risk stratification tools combine acute and chronic risk factors (RF); these may contribute differently to receipt of proven therapies. Methods: Using data from a prospective audit of 2600 patients in Australia, the impact of acute myocardial RF (biomarker elevation, ECG changes, cardiac arrest, Killip class ≥ 2), chronic co-morbid RF (prior CHF, chronic lung disease, malignancy, prior CVA, GFR &lt; 60, age &gt; 75), and traditional RF on patient management were examined using logistic regression. Results: the best predictor of receipt of EBT was the number of myocardial RF; the best predictor of a low likelihood of receipt was the number of co-morbid RF (Table ). The presence of three or more myocardial RF conferred an OR of 2.21 for receiving clopidogrel and 4.3 for undergoing angiography, while the presence of four or more co-morbid RF lowered the OR to 0.47 for clopidogrel and 0.09 for angiography (Figure 1a /b ). Conclusions: High-risk patients may be less likely to receive EBT than low-risk patients, but this is driven by comorbid conditions rather than markers of severity of illness. Research is needed to validate these therapies in high-risk patients, and ongoing efforts at quality improvement should focus on high-risk populations. Figure 1a. Odds of receiving clopidogrel during hospitalization Figure 1b. Odds of receiving angiography during hospitalization Application of management recommendations within 24 hours of admission and at discharge, adjusted for cardiovascular risk factors and prior coronary artery bypass grafting.
Abstract 5327: Opposing Influences Of Serca2a Gene Transfer Upon Catecholamine-induced Ventricular Arrhythmias In Normal And Failing Hearts
Authors: Alexander R Lyon, Ken T Macleod, Sukhpreet Dubb, Amir Sepehripour, Philip A Poole-Wilson, Nicholas S Peters, Sian E Harding
Journal: Circulation (2008)

Sarcoplasmic Reticulum (SR) calcium levels may influence ventricular arrhythmogenesis during catecholamine stimulation. The role of SR Calcium-ATPase 2a (SERCA2a) in modulating isoproterenol (ISO)-induced arrhythmia was evaluated in normal and failing intact hearts. SERCA2a gene transfer was achieved via direct myocardial injection of 3.75×10 9  Ad.SERCA2a.GFP particles into the normal rat heart (N+SERCA) and the chronically infarcted failing rat heart (HF+SERCA) characterised by reduced SERCA2a levels and increased SR calcium leak. Ad.GFP gene transfer into normal, failing and sham ligated animals plus unoperated cases served as controls (N+GFP, HF+GFP, SHAM+GFP and UNOP). In vivo ventricular arrhythmia (VA) generation was recorded after intraperitoneal ISO injection using ECG telemetry transmitters. HF cases were studied at baseline (HF) and post gene transfer. Hearts were explanted and ventricular arrhythmia thresholds studied ex vivo during perfusion with 100nM ISO. In normal hearts heterogeneous SERCA2a overexpression increased the number of ISO-induced sustained VAs: N+SERCA 3.0 (1.4), N+GFP 0.25 (0.16), UNOP 1.13 (0.44) p
Abstract 2308: A Novel Method for Automatic Detection of Atrial Fibrillation Episode for Extremely Long Period of Daily Life Using Pulse Oximetry
Authors: Yasumasa Tsukamoto, Takahisa Yamada, Takanao Mine, Takashi Morita, Shunsuke Tamaki, Masaharu Masuda, Keiji Okuda, Yusuke Iwasaki, Kazumi Kitajima, Yoshiro Nagai, Koji Yamamoto, Masatake Fukunami
Journal: Circulation (2006)
Abstract 11413: TNF-α Receptor 1 Antagonist Treatment Attenuates Arterial Inflammation and Intimal Hyperplasia in Interleukin-1 Receptor Antagonist Deficient Mice
Authors: Kikuo Isoda, Manabu Kitagaki, Haruhiko Kamada, Shinichi Tsunoda, Yasuo Tsutsumi, Tomiharu Niida, Norio Ishigami, Miya Ishihara, Makoto Kikuchi, Fumitaka Ohsuzu
Journal: Circulation (2010)

Background:  Tumor necrosis factor (TNF)-α plays a key role in arterial inflammation. We have shown that TNF-α participates importantly in the development of aortitis and intimal hyperplasia in IL-1 receptor antagonist-deficient (IL-1Ra−/−) mice. However it remains undetermined whether a selective TNF receptor 1 (TNFR1) antagonist inhibits arterial inflammation and intimal hyperplasia. This study aimed to determine the effect and mechanism of a novel TNFR1 antagonist (PEG-R1antTNF) in the suppression of arterial inflammation.   Methods and Results:  We investigated intimal hyperplasia in IL-1Ra−/− mice two weeks after inducing femoral artery injury with an external vascular cuff model. We injected mice intraperitoneally with a PEG-R1antTNF or normal saline twice daily for 14days. PEG-R1antTNF treatment yielded no adverse systemic effects, and we observed no significant differences in serum cholesterol or blood pressure in either group. Compared to saline injection, however, selective PEG-R1antTNF treatment significantly reduced intimal hyperplasia (11,440 ± 3,292 vs. 19,671 ± 1,625μm 2 ; P=0.011) and intima/media ration (1.34 ± 0.14 vs. 1.86 ± 0.16 ; P=0.029). Immunostaining revealed that inhibition of NF-κB activation by PEG-R1antTNF suppressed smooth muscle cell (SMC) proliferation and decreased expression of chemokine and adhesion molecules. Furthermore, immunostaining also revealed fewer macrophages in the intima of PEG-R1antTNF treated mice compared with controls. These results showed that PEG-R1antTNF decreased inflammation and intimal hyperplasia in the injured artery of IL-1Ra−/− mice.   Conclusions:  Our data suggest that PEG-R1antTNF suppresses SMC proliferation and inflammation by inhibiting NF-κB. This study highlights the potential therapeutic benefit of selective TNFR1 antagonist therapy in preventing intimal hyperplasia and arterial inflammation. Furthermore, PEG-R1antTNF therapy may have a lower risk for infection compared with nonselective anti-TNF therapy, because previous study suggested that TNFR2-facilitated programmed necrosis may have a crucial role in regulating immune responses against bacterial and viral infection.