tbuckley/cabot-search huggingface dataset:
New European guidelines on atrial fibrillation
Authors: R. J. Hunter, R. J. Schilling
Journal: BMJ (2011)

Recommend key changes to management 

The European Society of Cardiology (ESC) has recently published guidelines for the management of atrial fibrillation.1 Key changes include the identification of more patients at risk of stroke and wider use of oral anticoagulants, a more pragmatic approach to rate control, and a lower threshold for catheter ablation of atrial fibrillation. The priorities in the management of atrial fibrillation (in order of their effect on prognosis) remain as stroke prevention, rate control, and rhythm control⇓.



Arno Massee/SPL

To incorporate new evidence for the role of oral anticoagulants, the simple and easily remembered CHADS2 scoring system has been modified. The age limit for stroke prevention has been lowered to 65, with an additional point in the scoring system given to those 75 years or more.2 An additional point is also now given for women and those with vascular disease. Table 1⇓ summarises the modified (CHA2DS2-VASc) system.

View this table:

Table 1 
Stroke risk assessment using the CHA2DS2-VASc system



Other changes are that no treatment is now recommended for a score of zero and oral anticoagulants are recommended over aspirin for a score of 1. Table 2⇓ shows the preferred anticoagulation strategy by CHA2DS2-VASc score. This revised strategy is the result of consistent evidence of the superiority of oral anticoagulants …
Spontaneous Hemorrhage within the Rectus Sheath
Authors: Harold Cohn, William Hoffman, Martin G. Goldner
Journal: New England Journal of Medicine (1953)

THE occurrence of hematomas within the rectus sheath, although relatively rare, has been sporadically described in the medical literature since the time of Hippocrates and Galen. Most of the reports1 2 3 4 emphasize the difficulty of accurate pre-operative diagnosis and state that this condition is rarely thought of in the differential diagnosis of painful abdominal tumors.Most of the reported cases have occurred as a result of direct trauma.1 Critical evaluation of those that were thought to be spontaneous revealed a coincidental occurrence of sudden stress or strain on the abdominal wall. These included coughing, sneezing, sudden turning in bed and coitus. . . .
Proguanil-resistance in Malayan Strains of Plasmodium Vivax
Authors: T. Wilson, D. S. Munro, D. R. Richard
Journal: BMJ (1952)

In a small number of patients tested by comparing maintenance-dosage requirements the effectiveness of cortisone (free alcohol) and cortisone acetate appeared to be about equal.The relative incidence of endocrine complications from the various preparations could not be determined from the short-term studies involved.However, the greater antirheumatic activity of hydrocortisone (free alcohol) did not seem to be accompanied by a corre- spondingly greater tendency to produce adverse physio- logical effects.In several patients signs of hormonal excess present while on maintenance doses of cortisone acetate actually diminished or disappeared after trans- fers were made to smaller, but equally effective, doses of hydrocortisone (free alcohol).The marked disparity in therapeutic effectiveness be- tween hydrocortisone (free alcohol) and hydrocortisone acetate when given by mouth may be accounted for, at least in part, by differences in solubility of the com- pounds.The low solubility of hydrocortisone acetate may substantially lessen its alimentary absorption.
Evidence for tissue-specific activation of renal angiotensinogen mRNA expression in chronic stable experimental heart failure.
Authors: H Schunkert, J R Ingelfinger, A T Hirsch, S S Tang, S E Litwin, C E Talsness, V J Dzau
Journal: Journal of Clinical Investigation (1992)

The intrarenal renin-angiotensin system (RAS) may contribute to the pathophysiology of heart failure by the generation of angiotensin II at local sites within the kidneys. Angiotensin II may directly influence renal hemodynamics, glomerular contractility, and tubular sodium reabsorption, thereby promoting sodium and fluid retention in this syndrome. In the present study, we examined components of the circulating RAS as well as the intrarenal expressions of renin and angiotensinogen mRNA in rats with stable compensated heart failure (HF) 12 wk after experimental myocardial infarction. Renal angiotensinogen mRNA level in vehicle-treated HF rats increased 47%, as compared with sham control rats (P = 0.001). The increase in angiotensinogen mRNA levels was more pronounced in animals with medium (46%, P < 0.05) and large (66%, P < 0.05) infarcts than in those with small infarcts (31%, P = NS). There were no differences in liver angiotensinogen mRNA, circulating angiotensinogen, angiotensin II, plasma renin concentration (PRC), kidney renin content (KRC), and renal renin mRNA level between sham and HFv. In addition, in a separate group of rats with heart failure, we demonstrated that renal angiotensin II concentration increased twofold (P < 0.05) as compared with that of age-matched sham operated controls. A parallel group of heart failure rats (HFe, n = 11) was treated with enalapril (25 mg/kg per d) in drinking water for 6 wk before these measurements. Blood pressure decreased significantly during treatment (91 vs. 103 mm Hg, P < 0.05). Enalapril treatment in HF rats increased renin mRNA level (2.5-fold, P < 0.005), KRC (5.6-fold, P = 0.005), and PRC (15.5-fold, P < 0.005). The increase in renal angiotensinogen mRNA level observed in HFv rats was markedly attenuated in enalapril treated HF rats (P < 0.001), suggesting a positive feedback of angiotensin II on renal angiotensinogen synthesis. These findings demonstrate an activation of intrarenal RAS, but no changes in the circulating counterpart in this model of experimental heart failure, and they support the concept that the intrinsic renal RAS may contribute to the pathophysiology in this syndrome.
3D-ECHOCARDIOGRAPHY DEMONSTRATES EXCELLENT CORRELATION WITH CARDIAC MAGNETIC RESONANCE FOR ASSESSMENT OF LEFT VENTRICULAR FUNCTION AND VOLUMES IN A MODEL OF MYOCARDIAL INFARCTION
Authors: Carlos Santos-Gallego, Torsten Vahl, Hans Gaebelt, Mar&iacute;a Lopez, Sara Ares-Carrasco, Javier Sanz, Martin Goldman, Roger Hajjar, Valentin Fuster, Juan Badimon
Journal: Journal of the American College of Cardiology (2012)
Economics notes: Converting international cost effectiveness data to UK prices
Authors: T. B Gosden
Journal: BMJ (2002)

To facilitate decision making the Department of Health commissioned a systematic review of all published economic evaluations (not just UK studies) with a view to constructing an economic evaluation database.1 This systematic approach has been influenced by the Cochrane style systematic review process of clinical evaluations and is a progression from the widely publicised “QALY league table” approach. A QALY (quality adjusted life year) league table ranks interventions according to the extra cost per extra quality adjusted life year gained. Ideally this approach should help direct health care resources to those interventions which produce the most QALYs for the least cost. However, economic data are often specific to time and place, and extrapolation of economic results between localities and especially between countries should be treated …
Fatness and fertility: which direction?
Authors: Stephanie B. Seminara
Journal: Journal of Clinical Investigation (2014)

Metabolic status has long been thought to determine reproductive status, with abnormal metabolic phenotypes altering reproductive cascades, such as the onset of puberty. In this issue of the JCI, Tolson and colleagues provide evidence that kisspeptin, a hormone that promotes sexual maturation, regulates metabolism. Female mice lacking the kisspeptin receptor (KISS1R) gained more weight than control animals, and this weight gain was caused not by increased food consumption, but by an overall decrease in energy and metabolism. While this study provides a direct link between the kisspeptin pathway and metabolic output, more work will need to be done to determine whether alterations in this pathway contribute to human obesity.
Dysregulation of microRNA-219 promotes neurodegeneration through post-transcriptional regulation of tau
Authors: Ismael Santa-Maria, Maria E. Alaniz, Neil Renwick, Carolina Cela, Tudor A. Fulga, David Van Vactor, Thomas Tuschl, Lorraine N. Clark, Michael L. Shelanski, Brian D. McCabe, John F. Crary
Journal: Journal of Clinical Investigation (2015)

Tau is a highly abundant and multifunctional brain protein that accumulates in neurofibrillary tangles (NFTs), most commonly in Alzheimer's disease (AD) and primary age-related tauopathy. Recently, microRNAs (miRNAs) have been linked to neurodegeneration; however, it is not clear whether miRNA dysregulation contributes to tau neurotoxicity. Here, we determined that the highly conserved brain miRNA miR-219 is downregulated in brain tissue taken at autopsy from patients with AD and from those with severe primary age-related tauopathy. In a Drosophila model that produces human tau, reduction of miR-219 exacerbated tau toxicity, while overexpression of miR-219 partially abrogated toxic effects. Moreover, we observed a bidirectional modulation of tau levels in the Drosophila model that was dependent on miR-219 expression or neutralization, demonstrating that miR-219 regulates tau in vivo. In mammalian cellular models, we found that miR-219 binds directly to the 3'-UTR of the tau mRNA and represses tau synthesis at the post-transcriptional level. Together, our data indicate that silencing of tau by miR-219 is an ancient regulatory mechanism that may become perturbed during neurofibrillary degeneration and suggest that this regulatory pathway may be useful for developing therapeutics for tauopathies.
Management of Patients with Traumatic Paraplegia
Authors: Donald Munro
Journal: New England Journal of Medicine (1964)

IT is assumed in the therapy of spinal-cord injuries that, because the paralyses all originated from a unified injury to the cord, the symptoms must also arise from a single source. Instead, it can be demonstrated that not only the cerebrospinal-fluid pathways and the somatic elements but the visceral or autonomic innervation there are all injuries, and that the symptoms arise from what amounts to a dual injury. Recent neurophysiologic discoveries in the field of spinal-axon repair and replacement related to the cause of spasticity serve as verification.It has thus been demonstrated that the mechanism that replaces the destroyed . . .
Accuracy of 68Ga DOTANOC PET/CT Imaging in Patients With Multiple Endocrine Neoplasia Syndromes
Authors: Punit Sharma, Anirban Mukherjee, Sellam Karunanithi, Niraj Naswa, Rakesh Kumar, Ariachery C. Ammini, Chandrasekhar Bal
Journal: Clinical Nuclear Medicine (2015)

The aim of this study was to evaluate the role of ⁶⁸Ga DOTANOC PET/CT imaging in patients with multiple endocrine neoplasia (MEN) syndromes.Data of 33 patients (age, 33.5 [13.8] years; male 14/female 19) with MEN syndromes (MEN 1, 9; MEN 2A, 19; MEN 2B, 5) who underwent 41 ⁶⁸Ga DOTANOC PET/CT studies were retrospectively analyzed. Twenty PET/CTs were done for staging and 21 for restating. PET/CT images were evaluated in consensus by 2 nuclear medicine physicians, qualitatively and semiquantitatively (SUV(max)). A combination of histopathology, clinical, and biomarker follow-up was taken as reference standard.Of the total 41 ⁶⁸Ga DOTANOC PET/CTs, 34 were interpreted as positive for neuroendocrine tumors (NETs) and 7 as negative. The patientwise sensitivity of PET/CT was 94% (95% confidence interval [CI], 80-99), specificity was 71% (95% CI, 29-96), positive predictive value was 94% (95% CI, 80-99), negative predictive value was 71% (95% CI, 29-96), and accuracy was 90%. A total of 74 disease sites were demonstrated on PET/CT, including 41 primary NETs (pancreas, 10; stomach, 2; pheochromocytoma, 10; medullary thyroid carcinoma, 19), 31 metastatic sites (lymph node, 15; liver, 10; bone, 4; lung, 1; breast, 1), and 2 parathyroid adenomas. Lesionwise sensitivity, positive predictive value, and accuracy of PET/CT were 93%, 96%, and 90% overall, 89%, 95%, and 85% for primary tumors, and 100%, 97%, and 97% for metastasis, respectively. Among primary tumors, the SUV(max) of medullary thyroid carcinoma was significantly lower than gastro pancreatic NETs (P = 0.003) and pheochromocytomas (P = 0.003). No site-specific difference was seen in SUV(max) of metastatic lesions.⁶⁸Ga DOTANOC PET/CT shows high diagnostic accuracy in MEN syndrome and can demonstrate both primary and metastatic NETs in these patients.
Effect of Starting Age of Physical Activity on Bone Mass in the Dominant Arm of Tennis and Squash Players
Authors: Pekka Kannus
Journal: Annals of Internal Medicine (1995)

Objective: To determine in female tennis and squash players the effect of biological age (that is, the starting age of playing relative to the age at menarche) at which tennis or squash playing was started on the difference in bone mineral content between the playing and nonplaying arms. Design: Cross-sectional study. Setting: Finnish tennis and squash federations. Participants: 105 female Finnish national-level players and 50 healthy female controls. Main Outcome Measures: Differences in bone mineral content in playing and nonplaying (dominant to nondominant) arms (proximal humerus, humeral shaft, radial shaft, and distal radius) were compared in the players and controls and among six groups of players. Players were divided into groups according to the biological age (years before or after menarche) at which their playing careers began: more than 5 years before; 3 to 5 years before; 2 to 0 years before; 1 to 5 years after; 6 to 15 years after; and more than 15 years after. Results: Compared with controls (whose mean ±SD differences in bone mineral content were 4.6% ±4.6%, 3.2% ±2.3%, 3.2% ±3.8%, and 3.9% ±4.3% at the previously noted anatomical sites), the players had a significantly (P < 0.001) larger side-to-side difference in every measured site (15.5% ±8.4%, 16.2% ±9.8%, 8.5% ±6.6, and 12.5% ±7.1%). Among players, the group differences in bone mineral content were significant (P < 0.001 to P = 0.005), with the group means clearly decreasing with increasing starting biological age of playing. The difference was two to four times greater in the players who had started their playing careers before or at menarche (lowest mean difference in bone mineral content, 10.5% ±7.2%; highest difference, 23.5% ±7.2%) than in those who started more than 15 years after menarche (lowest difference, 2.4% ±4.8%; highest difference, 9.6% ±4.9%). Adjustment for potential confounding factors (age and height) did not change these trends. Conclusions: Bones of the playing extremity clearly benefit from active tennis and squash training, which increases their mineral mass. The benefit of playing is about two times greater if females start playing at or before menarche rather than after it. The minimal level and minimum number of years of activity necessary to produce these results, the extent to which this benefit is sustained after cessation of intensive training, and the degree to which these results can be extended to other forms of physical activity and other bone sites should be studied further.
Evidence of dynamic airway compression during cough in tetraplegic patients.
Authors: M Estenne, A Van Muylem, M Gorini, W Kinnear, A Heilporn, A De Troyer
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Although all the well-recognized muscles of expiration are paralyzed after traumatic transection of the lower cervical cord, tetraplegic subjects can still empty their lungs actively by contracting the clavicular portion of the pectoralis major. It is not known, however, whether contraction of this muscle bundle may raise pleural pressure enough to cause dynamic compression of the intrathoracic airways, which is critical for the production of an effective cough. To investigate this question, we measured expiratory flow rate and esophageal pressure during a series of forced expiratory vital capacity (VC) maneuvers in twelve subjects with C5-8 traumatic tetraplegia and constructed isovolume-pressure flow (IVPF) curves. The curves were interpretable with certainty in nine patients. Three of them did not show any plateau of flow. On the other hand, six patients had clearcut plateaus of flow on all IVPF curves between 80-60 and 20% VC, suggesting they had dynamic airway compression. Videoendoscopic recordings in two patients confirmed trachea and main bronchi collapse during forced expiration and cough. We conclude, therefore, that contraction of the pectoralis major causes dynamic airway compression during expiratory efforts in a substantial proportion of tetraplegic subjects. Increasing the pressure-generating capacity of this muscle might thus improve the effectiveness of cough and reduce the prevalence of bronchopulmonary infections.
Nutrition Intervention in the Community — The WIC Program
Authors: Janet Berkenfield, Janet B. Schwartz
Journal: New England Journal of Medicine (1980)

Studies of the effects of nutrition on pregnancy and early childhood growth and development have shown that proper nutritional intake results in a marked improvement in health.1 , 2 Both the course of pregnancy and the condition of the infant at birth are affected by the mother's diet, and normal growth and development of young children are also dependent upon the quantity and quality of their diet.In recognition of the important role that nutrition has in the health of young children and pregnant women, Congress in 1972 enacted legislation creating a major nutritional intervention program. The Supplemental Food Program for Women, . . .
Abstract 393: The chemokine receptor, CXCR2/IL8RB, contributes to the survival of pancreatic adenocarcinoma, and may play a role in stroma-tumor communication
Authors: Carolyn V. Ustach, Aprill Watanabe, Meraj Aziz, Caroline Diep, Galen Hostetter, Demeure Michael, Haiyong Han, Daniel D. Von Hoff
Journal: Cancer Research (2011)

Abstract The failure of most chemotherapeutic agents to treat pancreatic cancer could be related to poor delivery of drug due to the physical barrier of dense fibrosis surrounding the tumor. Targeting and attenuating the fibrotic stroma may result in better access of drug to tumor. Our current studies show that CXCR2/IL8RB is over-expressed in the surrounding stroma of pancreatic ductal adenocarcinoma tumors. CXCR2/IL8RB and its ligands are well known to be involved in fibrosis, and recently published papers suggest a role for CXCR2 in tumor proliferation, as well. Therefore, CXCR2 is a good target for pancreatic cancer therapy, because it has the potential to target both the stroma surrounding the tumor, as well as the tumor itself. When comparing matched samples of patient tumor and adjacent normal tissue, the mean IHC score of stroma surrounding normal pancreatic ducts is 0.61 (95% CI 0.38-0.84), while the mean IHC score of stroma surrounding ductal adenocarcinoma is 1.6 (95% CI: 1.3-1.9; Mann-Whitney test p&amp;lt;.0001; n=31). We previously reported that a CXCR2 ligand, CXCL5, was highly expressed in patient tumor samples, but not in the stroma. Interestingly, our present data shows CXCR2 is also expressed in tumor cells, therefore, CXCR2 may be involved in both autocrine and paracrine signaling inducing tumor proliferation, as well as induction of fibrosis in the stroma. Supporting CXCR2's role in pancreatic tumor proliferation, specific knockdown of CXCR2 expression by siRNA reduces cell growth by approximately 50%. Additionally, drug dose response curve experiments show pancreatic cancer cell lines which express CXCR2 are more sensitive to the CXCR2 antagonist, SB225002, than cells which do not express CXCR2. For example, the CXCR2 expressing cell line PANC-1 is approximately 7 times more sensitive to SB225002 than the CXCR2 negative cell line BxPC-3 (0.12uM vs. 0.88uM in IC50). We are currently assessing the mechanism of death induced by CXCR2 inhibition in the cancer cells. CXCR2's role in tumor cell proliferation, as well as its over-expression in the stroma surrounding tumors, make it a good target for both weakening the protective stroma surrounding the tumor, and reducing tumor cell survival. This work was supported by NIH P01 Grant CA109552. 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 393. doi:10.1158/1538-7445.AM2011-393
A Novel Cancer Therapy by Skin Delivery of Indoleamine 2,3-Dioxygenase siRNA
Authors: Meng-Chi Yen, Chi-Chen Lin, Yi-Ling Chen, Shih-Shien Huang, Huei-Jiun Yang, Chih-Peng Chang, Huan-Yao Lei, Ming-Derg Lai
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Indoleamine 2,3-dioxygenase (IDO), an enzyme that degrades tryptophan, is a negative immune regulatory molecule of dendritic cells. IDO-expressing dendritic cells suppress T cell responses and may be immunosuppressive in vivo. We hypothesized that silencing the IDO expression in skin dendritic cells in vivo could elicit antitumor activity in tumor-draining lymph nodes. Experimental Design: The efficiency of IDO-specific small interfering RNA (siRNA) was evaluated in vitro and in vivo. The therapeutic effect was evaluated in MBT-2 murine bladder tumor model and CT-26 colon tumor models. Results: IDO expression was down-regulated in CD11c-positive lymphocytes after IDO siRNA treatment. In vivo skin administration of IDO siRNA inhibited tumor growth and prolonged survival in both tumor models. The number of infiltrated T cells and neutrophils increased at tumor sites, which are correlated with therapeutic efficacy. The T cells may be mainly responsible for the immunologic rejection because the effect was abolished by depletion of CD8-positive T cells. Adoptive transfer of CD11c-positive dendritic cells from vaccinated mice delayed tumor progression. The cancer therapeutic effect was reproducibly observed with another IDO siRNA targeting at different site, suggesting the effect was not due to off-target effect. In a neu-overexpressing MBT-2 tumor model, IDO siRNA enhanced the therapeutic efficacy of Her2/Neu DNA vaccine. Down-regulation of IDO2, an IDO homologue, with siRNA also generated antitumor immunity in vivo. Conclusions: Antitumor immunity can be effectively elicited by physical delivery of siRNAs targeting immunoregulatory genes in skin dendritic cells in vivo, as shown by IDO and IDO2 in this report.