tbuckley/cabot-search huggingface dataset:
Generalised ligament laxity and shoulder dislocations after sports injuries
Authors: M A Akhtar, C M Robinson
Journal: British Journal of Sports Medicine (2010)

This study was performed to assess the incidence of generalised ligament laxity in patients presented with shoulder dislocations. Prospective data were collected for patients presented with shoulder dislocations between August 2008 and August 2009 under the care of a specialist shoulder surgeon including demographic details, types of dislocation, mechanism of injury and generalised ligament laxity. Clinical examination was used to assess the ligament laxity using the Beighton score. Laxity is scored on a 0-9 scale. Scores of 4 or above are indicative of generalised ligament laxity. Brighton criteria is used to diagnose benign joint hypermobility syndrome (BJHS) and use signs and symptoms along with Beighton score. There were 82 patients with a mean age of 30 years. There were 77 male (94%) and 5 (6%) female patients. 34 patients (41%) attended after first time shoulder dislocation, 37 (45%) after recurrent shoulder dislocations and 11 (13%) for revision shoulder stabilisation. The most common cause of shoulder dislocation was sports related injuries in 48 patients (68%). The most common sports involved was rugby in 22 (46%) patients followed by football in 15 (31%) patients. 75 (91%) patients had anterior shoulder dislocations and 6 (7%) had multidirectional instability. The average Beighton score for these patients was 3.1 with a range from 0 to 9. 35 patients (43%) in this group had a Beighton score of 4 or more indicating generalised ligament laxity. 15 patients (18%) fulfilled the Brighton criteria for BJHS. 12 patients (15%) had a first degree relative with generalised ligament laxity. The authors found that there is a high incidence (43%) of generalised ligament laxity in patients with shoulder dislocations after sports injuries. Appropriate advice should be given about the risk of shoulder dislocations in patients with generalised ligament laxity.
miR-34a and miR-15a/16 are co-regulated in non-small cell lung cancer and control cell cycle progression in a synergistic and Rb-dependent manner
Authors: Nora Bandi, Erik Vassella
Journal: Molecular Cancer (2011)

microRNAs (miRNAs) are small non-coding RNAs that are frequently involved in carcinogenesis. Although many miRNAs form part of integrated networks, little information is available how they interact with each other to control cellular processes. miR-34a and miR-15a/16 are functionally related; they share common targets and control similar processes including G1-S cell cycle progression and apoptosis. The aim of this study was to investigate the combined action of miR-34a and miR-15a/16 in non-small cell lung cancer (NSCLC) cells. NSCLC cells were transfected with miR-34a and miR-15a/16 mimics and analysed for cell cycle arrest and apoptosis by flow cytometry. Expression of retinoblastoma and cyclin E1 was manipulated to investigate the role of these proteins in miRNA-induced cell cycle arrest. Expression of miRNA targets was assessed by real-time PCR. To investigate if both miRNAs are co-regulated in NSCLC cells, tumour tissue and matched normal lung tissue from 23 patients were collected by laser capture microdissection and compared for the expression of these miRNAs by real-time PCR. In the present study, we demonstrate that miR-34a and miR-15a/16 act synergistically to induce cell cycle arrest in a Rb-dependent manner. In contrast, no synergistic effect of these miRNAs was observed for apoptosis. The synergistic action on cell cycle arrest was not due to a more efficient down-regulation of targets common to both miRNAs. However, the synergistic effect was abrogated in cells in which cyclin E1, a target unique to miR-15a/16, was silenced by RNA interference. Thus, the synergistic effect was due to the fact that in concerted action both miRNAs are able to down-regulate more targets involved in cell cycle control than each miRNA alone. Both miRNAs were significantly co-regulated in adenocarcinomas of the lung suggesting a functional link between these miRNAs. In concerted action miRNAs are able to potentiate their impact on G1-S progression. Thus the combination of miRNAs of the same network rather than individual miRNAs should be considered for assessing a biological response. Since miR-34a and miR-15a/16 are frequently down-regulated in the same tumour tissue, administrating a combination of both miRNAs may also potentiate their therapeutic impact.
Overdiagnosis of malaria in patients with severe febrile illness in Tanzania: a prospective study
Authors: Hugh Reyburn, Redepmta Mbatia, Chris Drakeley, Ilona Carneiro, Emmanuel Mwakasungula, Ombeni Mwerinde, Kapalala Saganda, John Shao, Andrew Kitua, Raimos Olomi, Brian M Greenwood, Christopher J M Whitty
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objective</b> To study the diagnosis and outcomes in people admitted to hospital with a diagnosis of severe malaria in areas with differing intensities of malaria transmission. <b>Design</b> Prospective observational study of children and adults over the course a year. <b>Setting</b> 10 hospitals in north east Tanzania. <b>Participants</b> 17 313 patients were admitted to hospital; of these 4474 (2851 children aged under 5 years) fulfilled criteria for severe disease. <b>Main outcome measure</b> Details of the treatment given and outcome. Altitudes of residence (a proxy for transmission intensity) measured with a global positioning system. <b>Results</b> Blood film microscopy showed that 2062 (46.1%) of people treated for malaria had <i>Plasmodium falciparum</i> (slide positive). The proportion of slide positive cases fell with increasing age and increasing altitude of residence. Among 1086 patients aged ≥ 5 years who lived above 600 metres, only 338 (31.1%) were slide positive, while in children &lt; 5 years living in areas of intense transmission (&lt; 600 metres) most (958/1392, 68.8%) were slide positive. Among 2375 people who were slide negative, 1571 (66.1%) were not treated with antibiotics and of those, 120 (7.6%) died. The case fatality in slide negative patients was higher (292/2412, 12.1%) than for slide positive patients (142/2062, 6.9%) (P &lt; 0.001). Respiratory distress and altered consciousness were the strongest predictors of mortality in slide positive and slide negative patients and in adults as well as children. <b>Conclusions</b> In Tanzania, malaria is commonly overdiagnosed in people presenting with severe febrile illness, especially in those living in areas with low to moderate transmission and in adults. This is associated with a failure to treat alternative causes of severe infection. Diagnosis needs to be improved and syndromic treatment considered. Routine hospital data may overestimate mortality from malaria by over twofold.
PPARγ ligands inhibit cholangiocarcinoma cell growth through p53-dependent GADD45 and p21WAF1/Cip1 pathway
Authors: Chang Han, Jake A. Demetris, George K. Michalopoulos, Qimin Zhan, James H. Shelhamer, Tong Wu
Journal: Hepatology (2003)

Ligands of peroxisome proliferator-activated receptor-gamma (PPARgamma) induce differentiation and growth inhibition in several human cancers. However, the role of PPARgamma ligands in the growth control of human cholangiocarcinoma cells remains unknown. This study was designed to investigate the biological functions and molecular mechanisms of PPARgamma ligands in the growth regulation of human cholangiocarcinoma cells. Western blot analysis showed that PPARgamma is expressed in all of the three human cholangiocarcinoma cell lines used in this study (SG231, CC-LP-1, and HuCCT1). Transient transfection assays using a peroxisome proliferator response element (PPRE) reporter construct showed that the PPARgamma expressed in human cholangiocarcinoma cells is functional as a transcription activator. Exposure of SG231, CC-LP-1, and HuCCT1 cells to PPARgamma ligands 15-deoxy-delta12, 14-prostaglandin J(2) (15d-PGJ(2)) and troglitazone for 24 to 96 hours resulted in a dose-dependent inhibition of cell growth. Flow cytometry analysis showed that 15d-PGJ(2) and troglitazone-induced cell cycle arrest at the G2/M checkpoint. Consistent with these findings, both 15d-PGJ(2) and troglitazone significantly inhibited the G2/M cyclin-dependent kinase (CDK) Cdc2 activity. Furthermore, cells treated with 15d-PGJ(2) and troglitazone showed elevated expression of p53 and two p53-controlled downstream genes, GADD45 and p21(WAF1/Cip1). Dominant negative inhibition of p53 in SG231 cells significantly blocked the 15d-PGJ(2) and troglitazone-induced growth inhibition, G2/M arrest, and GADD45/p21 induction. 15d-PGJ(2) and troglitazone failed to directly inhibit Cdc2 activity in a cell-free system in spite of direct association between GADD45 and PPARgamma proteins. In conclusion, these results show a novel p53-dependent mechanism in the PPARgamma ligand-mediated inhibition of cholangiocarcinoma growth and suggest a potential therapeutic role of PPARgamma ligands in the treatment of human cholangiocarcinoma.
Adjuvant Chemotherapy for Resected Adenocarcinoma of the Esophagus, Gastro-Esophageal Junction, and Cardia: Phase II Trial (E8296) of the Eastern Cooperative Oncology Group
Authors: Mary Armanios, Ronghui Xu, Arlene A. Forastiere, Daniel G. Haller, John W. Kugler, Al B. Benson
Journal: Journal of Clinical Oncology (2004)

To evaluate the effect of postoperative paclitaxel and cisplatin on 2-year survival in patients with completely resected adenocarcinoma of the distal esophagus, gastro-esophageal (GE) junction, and cardia.We conducted a multicenter phase II trial. Patients had pathologically staged T2 node-positive to T3-4, any node status adenocarcinoma of the distal esophagus, GE junction, or gastric cardia with negative margins (R0). Treatment consisted of four cycles of paclitaxel 175 mg/m2 intravenously (i.v.) over 3 hours followed by cisplatin 75 mg/m2 i.v. every 21 days. A positive outcome was considered to be an improvement in 2-year survival rate by > or = 20% compared to historic controls.Fifty-nine patients were recruited from 20 centers. Of 55 eligible patients, 49 (89%) had lymph node involvement. Forty-six patients (84%) completed all four cycles. Of the total 59 patients, 31 (56%) developed grade 3 or 4 toxicity with leukopenia/neutropenia, nausea/vomiting, and metabolic toxicities were most common. The median follow-up for surviving patients was 4 years. At 2 years, 33 patients were alive and 22 were dead, with a survival rate of 60% (95% CI, 46% to 73%; one-sided P = .0008 compared with the historic controls).Our data suggest that adjuvant paclitaxel and cisplatin may improve survival in R0 resected patients with locally advanced adenocarcinoma of the distal esophagus, GE junction, and cardia. These results warrant further testing in randomized trials.
Tissue engineering of aortic tissue: dire consequence of suboptimal elastic fiber synthesis in vivo
Authors: F OPITZ
Journal: Cardiovascular Research (2004)

To study autologous tissue engineered blood vessels (TEBV) in the descending aorta of juvenile sheep.Autologous vascular smooth muscle cells (vSMC) and endothelial cells were obtained from ovine carotid arteries. vSMC were seeded on bioresorbable scaffolds and dynamically cultured for 14 days. Following endothelialization an additional external ovine small intestinal submucosa wrapping was applied. Constructs were implanted in the descending aorta of juvenile sheep and removed after 1, 3, 6, 12 and 24 weeks for evaluation with histological, microscopical and biochemical techniques.Up to 3 months after implantation, grafts were fully patent, without any signs of dilatation, occlusion or intimal thickening. Scanning electron microscopy revealed a confluent luminal endothelial cell layer. In contrast, the 6 months graft displayed significant dilatation and partial thrombus formation. Histology displayed layered tissue formation resembling native aorta. Extracellular matrix (ECM) stains, immunostaining and Transmission Electron Microscopy (TEM) revealed alternating layers of vSMC and extracellular matrix consisting of collagen, elastin and glycosaminogycans. Compared to native aorta, the elastin content of the TE grafts was significantly reduced.In this study, we report for the first time, the implantation of a TEBV in the descending aorta in a large animal model. TEBV were fully functional for up to 3 months. At 6 months the graft remained functional but significantly dilated, most likely caused by an insufficient elastic fiber synthesis. Hence, future studies need to focus on the stimulation of elastin synthesis in TEBV.
PRO: confronting resistance to rule-based medicine is essential to improving outcomes
Authors: John D Blakey, Michael Brown, James Pinchin, Mark Barley, Sarah Sharples
Journal: Thorax (2014)

The past 20 years have seen two great changes in the practice of medicine: the widespread adoption of evidence-based medicine, and the increasing challenge of managing complex multimorbid patients. Both these developments have resulted in clinical rules and protocols becoming ever more abundant and increasingly critical to delivering safe and effective patient care. These evidence-based clinical rules perform at least as well as expert opinion, and the increasing volume and quality of available clinical data suggests their performance could continue to improve. This article considers why clinicians deviate from effective rules, highlighting key issues such as the persisting culture of heroism, institutional inertia, deference to authority and personal heuristics. We argue that better rules can be created, and that clinical improvements will follow if there is a 'common knowledge' of these rules. Furthermore, we argue that there is a ceiling to the effectiveness of any rule, even one as simple as ensuring hand hygiene, unless individuals are held accountable for transgressions.
PROSPECTIVE RANDOMISED TRIAL OF METRONIDAZOLE VERSUS VANCOMYCIN FOR CLOSTRIDIUM-DIFFICILE-ASSOCIATED DIARRHOEA AND COLITIS
Authors: DavidG. Teasley, MaryM. Olson, RogerL. Gebhard, DaleN. Gerding, LanceR. Peterson, MichaelJ. Schwartz, JamesT. Lee
Journal: The Lancet (1983)
Pulmonary ventilation imaged by magnetic resonance: at the doorstep of clinical application
Authors: H.U. Kauczor, X.J. Chen, E.J.R. van Beek, W.G. Schreiber
Journal: European Respiratory Journal (2001)

Over the past few years, magnetic resonance imaging (MRI) has emerged as an important instrument for functional ventilation imaging. The aim of this review is to summarize established clinical methods and emerging techniques for research and clinical arenas. Before the advent of MRI, chest radiography and computed tomography (CT) dominated morphological lung imaging, while functional ventilation imaging was accomplished with scintigraphy. Initially, MRI was not used for morphological lung imaging often, due to technical and physical limitations. However, recent developments have considerably improved anatomical MRI, as well as advanced new techniques in functional ventilation imaging, such as inhaled contrast aerosols, oxygen, hyperpolarized noble gases (Helium‐3, Xenon‐129), and fluorinated gases (sulphur­hexafluoride). Straightforward images demonstrating homogeneity of ventilation and determining ventilated lung volumes can be obtained. Furthermore, new image­derived functional parameters are measurable, such as airspace size, regional oxygen partial pressure, and analysis of ventilation distribution and ventilation/perfusion ratios. There are several advantages to using MRI: lack of radiation, high spatial and temporal resolution and a broad range of functional information. The MRI technique applied in patients with chronic obstructive pulmonary disease, emphysema, cystic fibrosis, asthma, and bronchiolitis obliterans, may yield a higher sensitivity in the detection of ventilation defects than ventilation scintigraphy, CT or standard pulmonary function tests. The next step will be to define the threshold between physiological variation and pathological defects. Using complementary strategies, radiologists will have the tools to characterize the impairment of lung function and to improve specificity.
157 CAN RAPID TESTS BE APPLIED FOR HEPATITIS C VIRUS DIAGNOSIS IN DEVELOPING COUNTRIES?
Authors: L.M. Villar, H.M. Cruz, L.P. Scalioni, V.S. de Paula, J.C. Miguel, E.F. da Silva, J.C. Oliveira, V.A. Marques, M.M. Portilho, B.L.C. Marques, C.A. Villela-Nogueira, F.A.P. Milagres, L.L. Lewis-Ximenez, E. Lampe
Journal: Journal of Hepatology (2012)
Experimental methods of ethanol administration
Authors: Charles S. Lieber, Leonore M. Decarli, Michael F. Sorrell
Journal: Hepatology (1989)

Techniques are reviewed for the experimental feeding of alcohol, including a liquid diet procedure invented 25 years ago. This technique results in much higher ethanol intake than with other approaches. As a consequence, various complications observed in alcoholics can be reproduced in animal models. These include fatty liver, hyperlipemia, various metabolic and endocrine disorders, tolerance to ethanol and other drugs, physical dependence and withdrawal and, in the baboon, liver fibrosis and cirrhosis. Variations of the liquid diet formulation are compared, and adequacy of nutrition in terms of minerals, vitamins, lipotropes, carbohydrates and proteins is discussed. The importance of selecting proper controls is emphasized. The respective advantages of three standardized basic rat formulas are reviewed: (i) an all-purpose (35% fat) diet, comparable to the diet previously referred to as the “Lieber-DeCarli formula” and suitable for most experimental applications, particularly those intended to mimic the clinical situation in which the various effects of alcohol occur in the setting of hepatic changes characterized by a fatty liver; (ii) a low-fat diet comparable in all respects to the preceding diet but with a lower fat content, intended to minimize the hepatic changes, and (iii) a high-protein formula particularly useful in those circumstances in which an oversupply of dietary protein might be recommended ( i.e. pregnancy). Variations of this technique, including continuous intragastric infusion, are also discussed. It is concluded that, for most experimental studies of chronic alcohol consumption, the liquid diet technique provides one of the most efficient tools to study the effects of ethanol under controlled nutritional conditions because it allows for alcohol consumption of clinical relevance and offers flexibility to adjust to special experimental or physiologic needs by allowing for various substitutions required for a particular experimental design, including changes in lipids, proteins or other dietary constituents. The technique also facilitates the comparison with controls by simplifying the pair feeding and is the best procedure available for the study of the toxic effects of alcohol and their interactions with deficiency or excess of various nutrients.
Urinary Albumin Excretion Predicts Cardiovascular and Noncardiovascular Mortality in General Population
Authors: Hans L. Hillege, Vaclav Fidler, Gilles F.H. Diercks, Wiek H. van Gilst, Dick de Zeeuw, Dirk J. van Veldhuisen, Rijk O.B. Gans, Wilbert M.T. Janssen, Diederick E. Grobbee, Paul E. de Jong
Journal: Circulation (2002)

For the general population, the clinical relevance of an increased urinary albumin excretion rate is still debated. Therefore, we examined the relationship between urinary albumin excretion and all-cause mortality and mortality caused by cardiovascular (CV) disease and non-CV disease in the general population.In the period 1997 to 1998, all inhabitants of the city of Groningen, the Netherlands, aged between 28 and 75 years (n=85 421) were sent a postal questionnaire collecting information about risk factors for CV disease and CV morbidity and a vial to collect an early morning urine sample for measurement of urinary albumin concentration (UAC). The vital status of the cohort was subsequently obtained from the municipal register, and the cause of death was obtained from the Central Bureau of Statistics. Of these 85 421 subjects, 40 856 (47.8%) responded, and 40 548 could be included in the analysis. During a median follow-up period of 961 days (maximum 1139 days), 516 deaths with known cause were recorded. We found a positive dose-response relationship between increasing UAC and mortality. A higher UAC increased the risk of both CV and non-CV death after adjustment for other well-recognized CV risk factors, with the increase being significantly higher for CV mortality than for non-CV mortality (P=0.014). A 2-fold increase in UAC was associated with a relative risk of 1.29 for CV mortality (95% CI 1.18 to 1.40) and 1.12 (95% CI 1.04 to 1.21) for non-CV mortality.Urinary albumin excretion is a predictor of all-cause mortality in the general population. The excess risk was more attributable to death from CV causes, independent of the effects of other CV risk factors, and the relationship was already apparent at levels of albuminuria currently considered to be normal.
The balancing act: endogenous modulation of pain in functional gastrointestinal disorders
Authors: C. H. Wilder-Smith
Journal: Gut (2011)

Functional gastrointestinal disorders (FGIDs) are characterised by visceral pain or discomfort with an unknown cause. There is increasing evidence for abnormal processing of sensory input in FGIDs. Modulation of sensory input occurs at all levels of the nervous system, with a dynamic balance between facilitation and inhibition and close integration with the body's wider homoeostatic control. Cognitive, emotional, autonomic and spinal reflex pathways effectively orchestrate supraspinal and spinal pain modulation, as demonstrated in neurophysiological and brain imaging studies. Endogenous pain modulation has been studied in visceral pain conditions and abnormal regulation has been shown in irritable bowel syndrome (IBS) and functional dyspepsia, as well as other chronic pain syndromes. A majority of patients with IBS have diminished pain inhibition or even pain facilitation compared with healthy controls. Brain imaging during specific activation of endogenous pain modulation demonstrates a fairly consistent functional hub of mainly frontal, limbic and brainstem modulatory regions in healthy humans. Patients with IBS have a different pattern of activation and a correlation between the imaging and sensory changes. Because the modulatory balance of inhibition and facilitation appears to be distributed within the same functional network, future imaging studies of modulation mechanisms should include conditions allowing quantification of inhibitory and facilitatory components. An altered modulatory balance may well be a unifying pathophysiological mechanism in FGID as it can be driven by both top-down (ie, CNS pathology) and bottom-up (ie, peripheral immune activation) influences, but further validation in diverse FGID groups over time is required. Therapeutic manipulation of the modulatory system is possible by both pharmacological and non-pharmacological means.
Mortality in Selected Cities with Fluoridated and Non-Fluoridated Water Supplies
Authors: J. David Erickson
Journal: New England Journal of Medicine (1978)

Mortality rates (for blacks and whites only) in 24 cities with fluoridated and 22 with non-fluoridated water supplies in the United States were compared for the years 1969–1971. During these three years 570,671 deaths occurred in the cities with fluoridated water; the 1970 reference population in those cities was 15,972,817. The figures for the cities with non-fluoridated water were 351,053 and 11,106,746 respectively, so that the crude death rates for all causes were 1190.9 (fluoridated) and 1053.6 (non-fluoridated) per 100,000 person-years. Adjustments for age, sex and race reduced differences for some causes and removed them for others. Further correction, using analyses of covariance for city characteristics that influence mortality, gave adjusted death rates for all causes of 1123.9 and 1137.1, and for malignant neoplasms 195.3 and 196.9, in the cities with fluoridated and non-fluoridated water respectively. I found no evidence of a harmful effect of fluoridation. (N Engl J Med 298:1112–1116, 1978)