tbuckley/cabot-search huggingface dataset:
The association between runners' lower limb alignment with running-related injuries: a systematic review
Authors: A C A Carvalho, L C Hespanhol Junior, L O P Costa, A D Lopes
Journal: British Journal of Sports Medicine (2011)

Background Although running is one of the most popular sports in the world, there are few studies that describe the relationships between anatomic characteristics of lower limb in this population. Objective To systematically review studies aimed at testing the association between lower limb alignment and running-related injuries. Design A systematic review. Setting The articles are related with long-distance runners without restriction of competitive level. Interventions We performed a search on MEDLINE, LILACS and SciELO. The keywords and operands used were: anatomical factors OR alignment OR Q angle OR foot structure OR lower limb injuries AND running. There was no restriction with regards to the year of publication. Main outcome measurements The lower limb alignment related with the musculoskeletal injuries in runners. Results Of the 1919 studies found, 973 were excluded by the title, 686 were excluded after reading the abstract and 287 were excluded after reading the original text. Eight articles were considered eligible and therefore were included. The main lower limb alignment characteristics related with the musculoskeletal injuries in runners found were: the Q angle greater than 20°, the navicular drop exceeding 5 mm, excessive pronation of the subtalar joint, the length discrepancy between the lower limbs (more than 10 mm), and the height of the medial longitudinal arch (dorsum foot height/truncated foot length ratio, high arch &gt;0.356 and low arch &lt;0.275). These variables as those most associated with the Patellar Tendinitis, Iliotibial Band Syndrome and the Plantar Fasciitis. Conclusion The main lower limb alignment characteristics related with running-related injuries found were: the Q angle greater than 20°, the navicular drop exceeding 5 mm, excessive pronation of the subtalar, the length discrepancy between the lower limbs, and the height of the medial longitudinal arch.
The perils and pitfalls of penile injections
Authors: None Porter, None Grabczynska, None Francis, None Staughton
Journal: British Journal of Dermatology (1999)

We describe a 45-year-old man who presented with an indurated penile nodule following self-injection of aciclovir tablets which he had dissolved in hydrogen peroxide solution. This is a hazardous procedure which may be complicated by permanent deformity and functional disability due to the irritant nature of the tablets' constituents and their propensity to cause foreign body reactions in the skin.
Luminal B Breast Cancer: Molecular Characterization, Clinical Management, and Future Perspectives
Authors: Felipe Ades, Dimitrios Zardavas, Ivana Bozovic-Spasojevic, Lina Pugliano, Debora Fumagalli, Evandro de Azambuja, Giuseppe Viale, Christos Sotiriou, Martine Piccart
Journal: Journal of Clinical Oncology (2014)

Gene expression profiling has reshaped our understanding of breast cancer by defining and characterizing four main intrinsic molecular subtypes: human epidermal growth factor receptor 2-enriched, basal-like, luminal A, and luminal B subtypes. Luminal B breast cancer has been reported to have lower expression of hormone receptors, higher expression of proliferation markers, and higher histologic grade than luminal A. It also exhibits worse prognosis and has a distinct profile of response to hormone therapy and chemotherapy. Although luminal cancers share similarities, the studies conducted in recent years using next-generation sequencing technology show that luminal A and B breast cancers should be perceived as distinct entities, with specific oncogenic drivers, rather than more proliferative varieties of luminal tumors. This review discusses the definition and molecular characterization of luminal B breast cancer and presents the available clinical evidence for chemotherapy and endocrine therapy patterns of response. It also provides an overview of ongoing research on molecularly targeted agents for this disease.
Mucin gene expression in Barrett's oesophagus: an in situ hybridisation and immunohistochemical study
Authors: G S Arul
Journal: Gut (2000)

Mucin genes are expressed in a site specific manner throughout the gastrointestinal tract. Little is known about the expression pattern in the oesophagus. In this study we have investigated MUC gene expression in both the normal oesophagus and specialised intestinal metaplasia (Barrett's oesophagus).Archived paraffin embedded material from eight specimens of normal oesophagus, 18 Barrett's oesophagus, eight gastric metaplasia, six high grade dysplasia, and six cases of adenocarcinoma were examined for expression of the mucin genes MUC1-6.Mucin mRNA was detected by in situ hybridisation using [(35)S] dATP labelled oligonucleotide probes. Mucin core protein was detected by immunohistochemistry.Normal oesophagus expressed MUC5B in the submucosal glands and MUC1 and MUC4 in the stratified squamous epithelium. Barrett's oesophagus strongly expressed MUC5AC and MUC3 in the superficial columnar epithelium, MUC2 in the goblet cells, and MUC6 in the glands. In high grade dysplasia and adenocarcinoma there was downregulation of MUC2, MUC3, MUC5AC, and MUC6, but upregulation of MUC1 and MUC4 in half of the specimens examined.Normal oesophagus and Barrett's oesophagus have a novel pattern of mucin gene expression. Barrett's oesophagus expressed the mucins associated with normal gastric epithelium and normal intestinal epithelium. While most mucin genes were downregulated in severely dysplastic and neoplastic tissues, there was upregulation of the membrane bound mucins MUC1 and MUC4. This may prove useful in detecting early signs of progression to adenocarcinoma of the oesophagus.
Dignity Therapy: A Novel Psychotherapeutic Intervention for Patients Near the End of Life
Authors: Harvey Max Chochinov, Thomas Hack, Thomas Hassard, Linda J. Kristjanson, Susan McClement, Mike Harlos
Journal: Journal of Clinical Oncology (2005)

This study examined a novel intervention, dignity therapy, designed to address psychosocial and existential distress among terminally ill patients. Dignity therapy invites patients to discuss issues that matter most or that they would most want remembered. Sessions are transcribed and edited, with a returned final version that they can bequeath to a friend or family member. The objective of this study was to establish the feasibility of dignity therapy and determine its impact on various measures of psychosocial and existential distress.Terminally ill inpatients and those receiving home-based palliative care services in Winnipeg, Canada, and Perth, Australia, were asked to complete pre- and post-intervention measures of sense of dignity, depression, suffering, and hopelessness; sense of purpose, sense of meaning, desire for death, will to live, and suicidality; and a post-intervention satisfaction survey.Ninety-one percent of participants reported being satisfied with dignity therapy; 76% reported a heightened sense of dignity; 68% reported an increased sense of purpose; 67% reported a heightened sense of meaning; 47% reported an increased will to live; and 81% reported that it had been or would be of help to their family. Post-intervention measures of suffering showed significant improvement (P = .023) and reduced depressive symptoms (P = .05). Finding dignity therapy helpful to their family correlated with life feeling more meaningful (r = 0.480; P = .000) and having a sense of purpose (r = 0.562; P = .000), accompanied by a lessened sense of suffering (r = 0.327; P = .001) and increased will to live (r = 0.387; P = .000).Dignity therapy shows promise as a novel therapeutic intervention for suffering and distress at the end of life.
Predictors of therapy resistant asthma * Authors' reply
Authors: C F Everett
Journal: Thorax (2004)

We read with interest the report by Heaney et al 1 that the use of a systematic protocol for therapy resistant asthma resulted in control of asthma in 53% of patients who were previously poorly controlled. However, we suspect that a significant proportion of the remaining 47% of patients who were classified as having therapy resistant asthma actually had underlying gastro-oesophageal reflux disease which was either not adequately investigated (by 24 hour pH monitoring alone) or, once diagnosed, was not adequately treated (with standard dose proton pump inhibitor).

A large northern European study of 2661 subjects found that people with gastro-oesophageal reflux had a significantly higher rate of physician diagnosed current asthma and that those with reflux and asthma had more nocturnal cough, morning phlegm, sleep related symptoms, and more peak flow variability than those with asthma alone.2 Pathological gastro-oesophageal reflux, which is often clinically silent, has been found on pH monitoring in 53–65% of asthmatics3,4 and has been shown in various studies to cause increased capsaicin cough sensitivity,5 increased airway hyperresponsiveness,6 increased respiratory resistance,7 and increased respiratory symptoms.3,4 Certainly, in the case of chronic cough, gastro-oesophageal reflux has been found to be one of the most frequent underlying causes.8

Heaney et al state that 17 patients with positive oesophageal pH monitoring were classified as having therapy resistant asthma because their respiratory symptoms did not improve with standard dose proton pump inhibitors. However, proton pump inhibitors have only a minor effect on the reflux of gastric contents; they alter the pH of the refluxate. This mode of action is effective in diseases such as oesophagitis where acid plays a vital role in pathogenesis. However, in airways disease non-acid reflux may be a major …
Multidrug Transporter ABCG2 Prevents Tumor Cell Death Induced by the Epidermal Growth Factor Receptor Inhibitor Iressa (ZD1839, Gefitinib)
Authors: N. Barry Elkind, Zsófia Szentpétery, Ágota Apáti, Csilla Özvegy-Laczka, György Várady, Olga Ujhelly, Katalin Szabó, László Homolya, András Váradi, László Buday, György Kéri, Katalin Német, Balázs Sarkadi
Journal: Cancer Research (2005)

Abstract Iressa (ZD1839, Gefitinib), used in clinics to treat non–small cell lung cancer patients, is a tyrosine kinase receptor inhibitor that leads to specific decoupling of epidermal growth factor receptor (EGFR) signaling. Recent data indicate that Iressa is especially effective in tumors with certain EGFR mutations; however, a subset of these tumors does not respond to Iressa. In addition, certain populations have an elevated risk of side effects during Iressa treatment. The human ABCG2 (BCRP/MXR/ABCP) transporter causes cancer drug resistance by actively extruding a variety of cytotoxic drugs, and it functions physiologically to protect our tissues from xenobiotics. Importantly, ABCG2 modifies absorption, distribution, and toxicity of several pharmacologic agents. Previously, we showed that ABCG2 displays a high-affinity interaction with several tyrosine kinase receptor inhibitors, including Iressa. Here, we show that the expression of ABCG2, but not its nonfunctional mutant, protects the EGFR signaling-dependent A431 tumor cells from death on exposure to Iressa. This protection is reversed by the ABCG2-specific inhibitor, Ko143. These data, reinforced with cell biology and biochemical experiments, strongly suggest that ABCG2 can actively pump Iressa. Therefore, variable expression and polymorphisms of ABCG2 may significantly modify the antitumor effect as well as the absorption and tissue distribution of Iressa.
Intraglomerular fibrin, platelet aggregation, and subendothelial deposits in lipoid nephrosis
Authors: John L. Duffy, Thomas Cinque, Edith Grishman, Jacob Churg
Journal: Journal of Clinical Investigation (1970)

We have investigated the formation of fibrin, platelet aggregates, and subendothelial deposits in lipoid nephrosis. Fibrin formation was found in 10 cases of active lipoid nephrosis. Platelet aggregates were found in eight cases and subendothelial deposits in nine. Fibrin and platelets were also found in cases of nephrotic syndrome due to other causes, and in glomerulonephritis. Fibrin was generally absent in lipoid nephrosis in remission and in benign recurrent hematuria. It is suggested that what seems to be a lower incidence in females is more apparent than real and that fibrin or related material may be present in a less easily identifiable form. Steroid therapy apparently had no effect on the presence or absence of fibrin. Most instances were associated with elevated serum cholesterol and alpha(2)-globulin. It is suggested that elevated serum lipids as well as the disease process in the kidney play a role in this phenomenon. It is further suggested that intraglomerular fibrin formation could lead to irreversible renal damage in lipoid nephrosis.
Refining the optimal chemotherapy regimen for good-risk metastatic nonseminomatous germ-cell tumors: a randomized trial of the Genito-Urinary Group of the French Federation of Cancer Centers (GETUG T93BP)
Authors: S. Culine, P. Kerbrat, A. Kramar, C. Théodore, C. Chevreau, L. Geoffrois, N.B. Bui, J. Pény, A. Caty, R. Delva, P. Biron, K. Fizazi, J. Bouzy, J.P. Droz
Journal: Annals of Oncology (2007)
The effect of coeliac disease upon bile salts
Authors: T. S. Low-Beer, K. W. Heaton, E. W. Pomare, A. E. Read
Journal: Gut (1973)

The size and composition of the bile salt pool has been measured in patients with untreated coeliac disease and in control subjects. The total bile salt pool was markedly increased in coeliac patients, the average being 9.2 grams compared with 3.1 grams in controls. Taurocholate synthesis was normal, consistent with its enlarged pool and prolonged half-life. Half-life and pool size were significantly correlated. The composition of the bile salt pool was virtually identical in the two groups. Our findings suggest that as the enterohepatic circulation is slowed by gallbladder inertia, so hepatic surveillance of pool size is diminished.
Tracheostomy in children: an ancient procedure still under debate
Authors: Angelo Barbato, Laura Bottecchia, Deborah Snijders
Journal: European Respiratory Journal (2012)

racheostomy is one of the oldest surgical procedures reported in ancient medicine books.It became widely used in the 19th century during the diphtheria epidemics in Europe, and then in the 20th century following a series of devastating poliomyelitis epidemics in the 1950s [1-3].Around the turn of the 20th century, JACKSON [4] standardised the indications for tracheostomy, the technique itself and the instruments used; he developed anatomically correct tracheostomy tubes and paved the way for further improvement of the technique.
A Randomized, Double-blind Evaluation of Buprenorphine Taper Duration in Primary Prescription Opioid Abusers
Authors: Stacey C. Sigmon, Kelly E. Dunn, Kathryn Saulsgiver, Mollie E. Patrick, Gary J. Badger, Sarah H. Heil, John R. Brooklyn, Stephen T. Higgins
Journal: JAMA Psychiatry (2013)

<h3>Importance</h3> Although abuse of prescription opioids (POs) is a significant public health problem, few experimental studies have investigated the treatment needs of this growing population. <h3>Objective</h3> To evaluate, following brief stabilization with a combination of buprenorphine hydrochloride and naloxone hydrochloride dihydrate, the relative efficacy of 1-, 2-, and 4-week buprenorphine tapering regimens and subsequent naltrexone hydrochloride therapy in PO-dependent outpatients. <h3>Design, Setting, and Participants</h3> A double-blind, 12-week randomized clinical trial was conducted in an outpatient research clinic. Following a brief period of buprenorphine stabilization, 70 PO-dependent adults were randomized to receive 1-, 2-, or 4-week tapers followed by naltrexone therapy. <h3>Intervention</h3> During phase 1 (weeks 1-5 after randomization), participants visited the clinic daily; during phase 2 (weeks 6-12), visits were reduced to thrice weekly. Participants received behavioral therapy and urine toxicology testing throughout the trial. <h3>Main Outcomes and Measures</h3> The percentage of participants negative for illicit opioid use, retention, naltrexone ingestion, and favorable treatment response (ie, retained in treatment, opioid abstinent, and receiving naltrexone at the end of the study). <h3>Results</h3> Opioid abstinence at the end of phase 1 was greater in the 4-week compared with the 2- and 1-week taper conditions (<i>P</i> = .02), with 63% (n = 14), 29% (n = 7), and 29% (n = 7) of participants abstinent in the 4-, 2-, and 1-week conditions, respectively. Abstinence at the end of phase 2 was also greater in the 4-week compared with the 2- and 1-week conditions (<i>P</i> = .03), with 50% (n = 11), 16% (n = 4), and 20% (n = 5) of participants abstinent in the 4-, 2-, and 1-week conditions, respectively. There were more treatment responders in the 4-week condition (<i>P</i> = .03), with 50% (n = 11), 17% (n = 4), and 21% (n = 5) of participants in the 4-, 2-, and 1-week groups considered responders at the end of treatment, respectively. Retention and naltrexone ingestion also were superior in the 4-week vs briefer tapers (both<i>P</i> = .04). Experimental condition (ie, taper duration) was the strongest predictor of treatment response, followed by buprenorphine stabilization dose. <h3>Conclusions and Relevance</h3> This study represents a rigorous experimental evaluation of outpatient buprenorphine stabilization, brief taper, and naltrexone maintenance for treatment of PO dependence. Results suggest that a meaningful subset of PO-dependent outpatients may respond positively to a 4-week taper plus naltrexone maintenance intervention. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT00719095
Expression of the cathelicidin LL-37 is modulated by short chain fatty acids in colonocytes: relevance of signalling pathways
Authors: J Schauber
Journal: Gut (2003)

Short chain fatty acids (SCFA) exert profound effects on the colonic mucosa. In particular, SCFA modulate mucosal immune functions. The antimicrobial cathelicidin LL-37 is expressed by colon epithelial cells. In the present study the effect of SCFA on LL-37 expression was investigated.LL-37 expression in vivo was assessed by immunohistochemistry. Real time quantitative reverse transcription-polymerase chain reaction was employed to determine LL-37 expression in colonocytes in vitro after treatment with various cytokines, SCFA, or flavone. LL-37 levels were correlated to cell differentiation which was determined by alkaline phosphatase (AP) activity. In addition, intracellular signalling pathways such as MEK-ERK (mitogen/extracellular signal protein kinase (MEK)/extracellular signal regulated protein kinase (ERK)) and p38/mitogen activated protein (MAP) kinase were explored.In vivo, LL-37 expression in healthy mucosa was restricted to differentiated epithelial cells in human colon and ileum. In colonocytes, increased LL-37 expression associated with cell differentiation was detected in vitro following treatment with butyrate, isobutyrate, propionate, and trichostatin A. Flavone induced LL-37 transcription but did not affect AP activity while cytokines had no effect. To dissect pathways mediating differentiation and LL-37 expression, specific inhibitors were applied. Inhibition of the protein kinase MEK enhanced butyrate induced AP activity while LL-37 expression in colon epithelial cells was blocked. In contrast, inhibition of p38/MAP kinase blocked cell differentiation without inhibiting LL-37 expression.Expression of the cathelicidin LL-37 in colonocytes and cellular differentiation are separately modulated by SCFA via distinct signalling pathways. These data may provide a rationale for dietary modulation of mucosal defence mechanisms.
Involvement of dendritic cells in sarcoidosis
Authors: M Ota
Journal: Thorax (2004)

<b>Background:</b> Sarcoidosis is a systemic granulomatous disease of unknown aetiology. It has been suggested that T helper type 1 (Th1) polarisation is associated with the pathophysiology of sarcoidosis, but the mechanism of skewing towards Th1 has not been elucidated. Dendritic cells (DCs) are known to regulate immune responses. This study was performed to determine whether DCs are involved in the aetiology of sarcoidosis. <b>Methods:</b> The numbers of peripheral blood DCs in 24 patients with sarcoidosis were analysed and biopsy specimens from four patients were stained immunohistochemically using monoclonal antibodies. <b>Results:</b> The numbers of both myeloid and lymphoid DC subsets were significantly decreased in the blood and mature DCs were found in the granulomas of patients with sarcoidosis. A number of interferon-γ (IFN-γ) producing T cells were also detected in the sarcoid granuloma, as well as many interleukin (IL)-4 producing T cells. Double staining of the biopsy specimen using anti-fascin and anti-CD3 antibodies showed an anatomical interaction between DCs and T cells. <b>Conclusions:</b> These findings suggest that the blood DC subsets may migrate into the affected tissues, contributing to the formation of the granulomas in sarcoidosis. It is hypothesised that the migrating DCs may regulate the T cell response in sarcoidosis, at least in the granulomatous lesions.
GW25-e3178 Tissue kallikrein 1 gene overexpression improves ventricular remodeling and upregulates the expression of p27kip1 and p2lCip1 protein in post-myocardial infarct rats
Authors: Yu Huizhen, Shujie Huang, Hong Xiang, Feng Li, Weiping Zheng, Pengli Zhu
Journal: Journal of the American College of Cardiology (2014)
Paving the way to metastasis
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2005)

Tumors must invade lymph nodes to become metastatic, but how the tumor cells make this trip is not completely clear. On page 1089, Hirakawa and colleagues show that a tumor-derived growth factor stimulates the formation of new lymphatic vessels in the nearby lymph node, even before any tumor cells arrive. This suggests that the tumor may instruct the lymph node to prepare for its arrival.

Stimulation of lymphatic growth has for some time played second fiddle to angiogenesis. During angiogenesis, tumors produce factors such as vascular endothelial growth factor-A (VEGF-A) that induce vessel growth and thus greater nutrient supply. Recently, however, two relatives of VEGF-A, VEGF-C and VEGF-D, have been shown to induce lymphangiogenesis within tumors. Although earlier studies suggested that VEGF-A could also induce lymphangiogenesis, this had never been shown in a tumor model and remained controversial.






Figure 

Even before metastasis, VEGF-A induces growth of new lymphatic vessels (red) in the draining lymph node.




Hirakawa et al. now show that expression of VEGF-A by skin cells causes mice to develop cancer more rapidly in response to a chemical carcinogen. Both blood vessel and lymphatic vessel growth were increased in VEGF-A–expressing skin tumors, a result that was consistent with their earlier observations that VEGF-A could induce the proliferation of lymphatic endothelial cells in culture.

VEGF-A induced active lymphatic proliferation both within the tumor and in the nearby lymph node, possibly explaining the increased metastasis of VEGF-A–expressing tumors. Lymphatic growth in the lymph node began—to the authors' surprise—before tumor cells arrived on the scene, suggesting that VEGF-A expression may help initiate tumor metastasis.

The angiogenic activity of VEGF-A was previously thought to be restricted to the immediate tumor vicinity. The authors now suggest that VEGF-A is drained from the tumor through both preexisting lymphatic vessels and the lymphatic vessels it helped construct. They are now investigating relative timing to see if tumor-localized lymphangiogenesis might be a prerequisite for node-localized lymphangiogenesis.