tbuckley/cabot-search huggingface dataset:
The effectiveness of prolotherapy for recalcitrant medial tibial stress syndrome: a prospective case series
Authors: N. Padhiar, P. R. Jones, M. Curtin, P. Malliaras, O. Chan, T. A. Crisp
Journal: British Journal of Sports Medicine (2011)

The aim was to evaluate whether ultrasound-guided injection of 15% dextrose for treatment of recalcitrant medial tibial stress syndrome (MTSS) decreases pain and facilitates a return to desired activity levels. This was a prospective case series. Participants were nine subjects: seven male and two female; (mean age=33.6 years) with MTSS, referred from sports injury clinics across the UK to a specialist centre at a London private hospital, having failed conservative treatment. An ultrasound-guided subperiosteal injection of 15% dextrose was administered by the same clinician (NP) along the length of the symptomatic area. Typically 1 ml of solution was injected per cm of symptomatic area. A second injection was subsequently administered at four weeks for 4 of the 9 subjects. Pain was assessed using a 10 cm visual analogue scale (VAS) at baseline, short-term, medium-term (mean 18 weeks) and at long-term (mean 1 year) follow-up. Symptom resolution and return to activity were measured using a Likert scale at medium-term and long-term follow-up. Subjects reported a significant (<i>p</i>&lt;0.01) reduction in median VAS pain score at medium-term follow-up compared to baseline. Median improvement per subject was 5/10. At long-term follow-up, median improvement was 4/10. Subjects rated their condition as ‘much improved9 at medium-term follow-up and ‘no change9 at long-term follow-up. Median return to sport score at medium-term follow-up was ‘returned to desired but not preinjury level9 and ‘returned to sport at an unsatisfactory level9 at long-term follow-up. There were no reported adverse events. Ultrasound-guided 15% dextrose prolotherapy injection has a significant medium-term effect on pain in MTSS. There is a suggestion that this benefit may be maintained long-term. More robust trials are required to validate these findings.
Endogenous and exogenous regulation of gamma-secretase
Authors: Yueming Li
Journal: Molecular Neurodegeneration (2013)

The gamma-secretase complex is an intramembrane aspartyl protease comprised of at least four known subunits: Presenilin (PS), Nicastrin (Nct), Aph, and Pen2. Presenilin is the catalytic subunit of the complex. Mutations in PS1 and PS2, which lead to familial early-onset Alzheimer disease, alter the activity and specificity of gamma-secretase. Investigation of gamma-secretase specificity and development of gamma-secretase based therapies have been a huge challenge because of its nature of intramembranal catalysis and macromolecular complex as well as cleavage of multiple substrates. We have developed an integrated approach of biochemistry, chemical biology and cell biology for the study of gamma-secretase structure and function. We will discuss how to apply this approach to elucidate the role endogenous and exogenous factors in regulation of gamma-secretase. We will focus on the development of chemical probes and utilize them to define the mechanism of action of gamma-secretase modulators.
The relevance of lung function tests in an intensive smoking cessation program
Authors: Ana Gonçalves, Miguel Guimarães, Joana Gomes, Julia Valério, Albertina Ferraz, Ivone Pacoal
Journal: European Respiratory Journal (2013)

Background : Smoking cessation is essential in preventing and in the prognosis of respiratory disease. Bronchial obstruction (BO) is often underdiagnosed even in symptomatic smokers.   Objectives:  Assess the role of Lung function tests (LFT) in early detection of respiratory pathology in smokers in an intensive smoking cessation program (ISCP).   Methods:  A questionnaire and LFT were performed to 247 smokers with no previous known respiratory pathology followed in an ISCP .  Data analyzed: demographic; smoking history; comorbidities; respiratory symptoms and LFT parameters.   Results:  185 (74,9%) men. Mean age 52,6 (+/- 11,6) years and mean pack-years of smoking of 50,4(+/-32,1). Most of the patients (113) were moderately dependent in the Fagerstrom test (mean: 5,25 (+/-2,3)). Co-morbidities: 73 (27,4%) dyslipidemia, 48 (19,4%) diabetes mellitus, 80 (32,4%) hypertension, 31 (12,6%) peripherical vascular disease, 37 (15%) ischemic heart disease, 19 (7,7%) malignancy 47 (19%) psychiatric pathology and 13 (5,3%) alcohol abuse. 170 (68,8%) had respiratory symptoms: 45,7% (113) cough; 38,9% (96) sputum; 36,4% (90) dyspnoea. 98 (39,7%) had respiratory symptoms with normal LFT. LFT: 157 (63,6%) normal, 57 (23,1%) BO, 11 (4.5%) restriction, 22 (8,9%) small airways obstruction. From those with BO, 44 (77,2%) showed no obstruction reversion with broncodilation. 13 (16,9%) of the asymptomatic had BO. DLCO was decrease in 81 (32,8%) of the cases.   Conclusion:  LFT integrated in an ISCP may be an excellent opportunity for diagnosis of respiratory disease especially COPD (17,8%) even in asymptomatic smokers (5,2%).
Circulating osteopontin: a dual marker of bone destruction and angiogenesis in patients with multiple myeloma
Authors: Aikaterini Sfiridaki, Spiros Miyakis, Constantina Pappa, George Tsirakis, Athanasios Alegakis, Vasileios Kotsis, Efstathios Stathopoulos, Michael Alexandrakis
Journal: Journal of Hematology & Oncology (2011)

The matrix protein osteopontin has been shown to be a marker of osteoclastic activity in multiple myeloma patients, as well as a regulator of angiogenesis. We measured serum levels of osteopontin in 50 untreated multiple myeloma patients (in 25, also after treatment) and examined the relation to markers of osteolytic and angiogenic activity. The median (range) of serum osteopontin was 85 (5-232) in the patient group vs. 36 (2-190) ng/ml in the control group. Serum osteopontin levels were significantly higher in patients with advanced stage or grade of myeloma disease. All patients with serum osteopontin levels >100 ng/ml had advanced stage (II or III) or high grade bone disease, whereas stage I or low grade patients had serum osteopontin levels <100ng/ml. Serum osteopontin levels significantly decreased after treatment. There was a positive correlation of osteopontin with the bone turnover marker N-terminal propeptide of procollagen type I (NTx) and the angiogenic markers vascular endothelial growth factor (VEGF) and bone marrow microvessel density (r: 0.35, 0.47 and 0.30 respectively, p < 0.05). These results support osteopontin as a dual marker of bone destruction and angiogenic activity in myeloma patients. Osteopontin represents a useful biomarker for monitoring myeloma disease activity.
Characterizing the Clinical Relevance of an Embryonic Stem Cell Phenotype in Lung Adenocarcinoma
Authors: Marvaretta Stevenson, William Mostertz, Chaitanya Acharya, William Kim, Kelli Walters, William Barry, Kristin Higgins, Sascha A. Tuchman, Jeffrey Crawford, Gordana Vlahovic, Neal Ready, Mark Onaitis, Anil Potti
Journal: Clinical Cancer Research (2009)

Cancer cells possess traits reminiscent of those ascribed to normal stem cells. It is unclear whether these phenotypic similarities are the result of a common biological phenotype, such as regulatory pathways.Lung cancer cell lines with corresponding gene expression data and genes associated with an embryonic stem cell identity were used to develop a signature of embryonic stemness (ES) activity specific to lung adenocarcinoma. Biological characteristics were elucidated as a function of cancer biology/oncogenic pathway dysregulation. The ES signature was applied to three independent early-stage (I-IIIa) lung adenocarcinoma data sets with clinically annotated gene expression data. The relationship between the ES phenotype and cisplatin (current standard of care) sensitivity was evaluated.Pathway analysis identified specific regulatory networks [Ras (P = 0.0005), Myc (P = 0.0224), wound healing (P < 0.0001), chromosomal instability (P < 0.0001), and invasiveness (P < 0.0001)] associated with the ES phenotype. The prognostic relevance of the ES signature, as related to patient survival, was characterized in three cohorts [CALGB 9761 (n = 82; P = 0.0001), National Cancer Institute Director's Challenge Consortium (n = 442; P = 0.0002), and Duke (n = 45; P = 0.06)]. The ES signature was not prognostic in prostate, breast, or ovarian adenocarcinomas. Lung tumors (n = 569) and adenocarcinoma cell lines (n = 31) expressing the ES phenotype were more likely to be resistant to cisplatin (P < 0.0001 and P = 0.006, respectively).Lung adenocarcinomas that share a common gene expression pattern with normal human embryonic stem cells were associated with decreased survival, increased biological complexity, and increased likelihood of resistance to cisplatin. This indicates the aggressiveness of these tumors.
A randomized controlled trial (volunteer study) of sitafloxacin, enoxacin, levofloxacin and sparfloxacin phototoxicity
Authors: R.S. Dawe, S.H. Ibbotson, J.B. Sanderson, E.M. Thomson, J. Ferguson
Journal: British Journal of Dermatology (2003)

Background Fluoroquinolone antibiotics (FQs) are associated with phototoxic skin reactions following exposure to sunlight. Objectives We aimed to compare the phototoxic potential of sitafloxacin, a novel FQ with three others: sparfloxacin, enoxacin, levofloxacin and placebo in Caucasian volunteers. In a second study, two dosage regimens of sitafloxacin were compared with placebo in Oriental subjects. Methods Randomized, placebo‐controlled, assessor‐blinded clinical trial. In 40 healthy Caucasians, sitafloxacin 100 mg twice a day (n = 8), sparfloxacin 200 mg day−1 (n = 8), enoxacin 200 mg three times a day (n = 8), levofloxacin 100 mg three times a day (n = 8) and placebo (n = 8) were given in oral doses for 6 days. In the second study, sitafloxacin 50 mg and 100 mg, both twice daily, were compared with placebo in 17 healthy Oriental subjects. Using an established monochromator technique, baseline threshold erythema levels were established pre‐drug and on‐drug. The phototoxic index (PI) baseline, minimal erythema dose (MED) divided by on‐drug MED for each medication at each wavelength was determined and related to sitafloxacin peak plasma levels. The duration of susceptibility to phototoxicity was assessed by repeat phototesting daily after stopping medication. Results In the Caucasian study, sitafloxacin 100 mg twice a day produced mild ultraviolet (UV) A‐dependent phototoxicity (median PI = 1·45) at 365 ± 30 nm (half‐maximum bandwidth), maximal at 24 h with normalization by 24 h postdrug cessation. The sparfloxacin group experienced severe phototoxicity maximal at 24 h and, unusually for an FQ, extended in the visible region (430 ± 30 nm), maximal at 400 ± 30 nm (median PI = 12·35) with abnormal pigmentation at on‐drug phototest sites lasting, although fading, for up to 1 year. Enoxacin showed UVA‐dependent phototoxicity (335–365 ± 30 nm) median PI 3·94 (at 365 ± 30 nm) returning to normal 48 h after stopping the drug. Fading pigmentation at phototoxic sites also lasted up to 1 year. Phototoxicity was not detected in the levofloxacin or placebo groups. In the Oriental study, no clinically relevant phototoxicity was seen with either sitafloxacin or placebo groups. Conclusions We conclude that 100 mg twice a day sitafloxacin in Caucasians is associated with a mild degree of cutaneous phototoxicity. Enoxacin 200 mg three times a day and sparfloxacin 200 mg day−1 are much more photoactive. Sparfloxacin phototoxicity is induced by UVA and visible wavelengths. Levofloxacin and placebo failed to show a phototoxic effect. In the Oriental study, sitafloxacin 50 mg twice a day and 100 mg twice a day failed to demonstrate a clinically significant phototoxic effect.
Genetic Dissection of a Blood Pressure Quantitative Trait Locus on Rat Chromosome 1 and Gene Expression Analysis Identifies <i>SPON1</i> As a Novel Candidate Hypertension Gene
Authors: Jenny-Rebecca Clemitson, Richard J. Dixon, Steve Haines, Andrew J. Bingham, Bhakti R. Patel, Laurence Hall, Ming Lo, Jean Sassard, Fadi J. Charchar, Nilesh J. Samani
Journal: Circulation Research (2007)

A region with a major effect on blood pressure (BP) is located on rat chromosome 1. We have previously isolated this region in reciprocal congenic strains (WKY.SHR-Sa and SHR.WKY-Sa) derived from a cross of the spontaneously hypertensive rat (SHR) with the Wistar-Kyoto rat (WKY) and shown that there are 2 distinct BP quantitative trait loci, BP1 and BP2, in this region. Sisa1, a congenic substrain from the SHR.WKY-Sa animals carrying an introgressed segment of 4.3Mb, contains BP1. Here, we report further dissection of BP1 by the creation of 2 new mutually exclusive congenic substrains (Sisa1a and Sisa1b) and interrogation of candidate genes by expression profiling and targeted transcript sequencing. Only 1 of the substrains (Sisa1a) continued to demonstrate a BP difference but with a reduced introgressed segment of 3Mb. Exonic sequencing of the 20 genes located in the Sisa1a region did not identify any major differences between SHR and WKY. However, microarray expression profiling of whole kidney samples and subsequent quantitative RT-PCR identified a single gene, Spon1 that exhibited significant differential expression between the WKY and SHR genotypes at both 6 and 24 weeks of age. Western blot analysis confirmed an increased level of the Spon1 gene product in SHR kidneys. Spon1 belongs to a family of genes with antiangiogenic properties. These findings justify further investigation of this novel positional candidate gene in BP control in hypertensive rat models and humans.
Health Care Needs of Gay Men and Lesbians in the United States
Authors: Ronald M. Davis
Journal: JAMA (1996)

IN 1981 the House of Delegates of the American Medical Association (AMA) adopted a report from the Council on Scientific Affairs entitled<i>Health Care Needs of the Homosexual Population</i>. A substantial number of studies involving gay men and lesbians have subsequently appeared in the medical literature that provide a better understanding of health issues related to sexual orientation and behavior. For this reason, the original recommendations were reviewed, including that of reversal of sexual orientation in selected cases.<sup>1</sup> <h3>DEFINITION AND DEMOGRAPHICS</h3> In this report,<i>sexual orientation</i>refers to an individual's self-perception as gay, lesbian, bisexual, or heterosexual. Sexual behavior may or may not correlate with sexual orientation. Furthermore, an individual's sexual behavior and orientation may vary over time. The scientific literature indicates that homosexual feelings are more frequent than homosexual behavior and that same-sex behavior is more frequent than lasting homosexual identification.<sup>2-11</sup>According to researchers from RAND,<sup>10(p145)</sup>
THE VACCINATION QUESTION
Authors: T. G. Horder
Journal: BMJ (1903)

<h3>Objective</h3> Although asthma has been linked to psychological morbidity, this relationship may be confounded by poor asthma control. We aimed to compare the prevalence of anxiety, depression and low level of self-esteem in children with well-controlled asthma with that of healthy peers. <h3>Setting</h3> Dedicated asthma clinic in a general hospital. <h3>Patients</h3> 70 patients with mostly well-controlled asthma and 70 matched healthy controls. <h3>Interventions</h3> Comprehensive asthma education, management and follow-up for asthma patients. <h3>Main outcome measures</h3> Validated Dutch versions of the Childhood Depression inventory (CDI), Revised Fear Survey for Children (RFSC), Self Perception Profile for Children (SPC-C) and Adolescents (SPC-A) and State-Trait Anxiety Inventory for Children (STAIC). Asthma control assessed by asthma control questionnaire. <h3>Results</h3> No significant differences were found in total scores between asthmatics and controls (95% CI for difference −0.2 to 2.9 for CDI, −5.9 to 11.2 for RFSC, −19.9 to 6.3 for SPC-C, −24.1 to 5.0 for SPC-A and −2.7 to 0.01 for STAIC). There were also no significant differences between asthmatics and controls in the prevalence of scores exceeding cut-off levels for clinically relevant anxiety (13.3 vs 13.0%, p=0.605), depression (12.9 vs 5.7%, p=0.243) or low self-esteem (21.4 vs 12.9%, p=0.175). A significant correlation was found between poorer asthma control and CDI (p=0.012) and anxiety trait symptoms (p&lt;0.001). <h3>Conclusions</h3> <i>C</i>hildren with well-controlled asthma enrolled in a comprehensive asthma management programme do not have an increased risk of anxiety, depression and poor self-esteem. Earlier reports of psychological comorbidity in asthma may have been related to inadequately controlled asthma.
Simvastatin inhibits the pro-inflammatory and pro-thrombotic effects of IL-17 and TNF-α on endothelial cells
Authors: Arnaud Hot, Fabien Lavocat, Vanina Lenief, Pierre Miossec
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objectives</h3> Statins are widely used for primary and secondary prevention of coronary atherosclerosis. Simvastatin, besides its lipid lowering properties, has various anti-inflammatory effects. The aim of this study was to assess whether simvastatin modulates the vascular effects of interleukin (IL)-17, an emerging actor in atherosclerosis. <h3>Methods</h3> The effect of simvastatin was assessed in human umbilical vein endothelial cells treated by IL-17 alone or combined with tumour necrosis factor (TNF)-α, with or without mevalonate, an inhibitor of simvastatin. Its effects on IL-17-induced cytokine or chemokine expression were assessed at the mRNA level using qRT-PCR or protein level by ELISA. Its effect on the IL-17-induced pro-thrombotic state and cell invasion was assessed using a lumi-aggregometer and a Matrigel assay, respectively. <h3>Results</h3> Simvastatin decreased IL-17-induced IL-6, IL-8, CX3CL-1, RANTES mRNA and CX3CL-1 and CCL20 production. Simvastatin restored the level of IL-33 mRNA which was decreased by IL-17. It reduced the expression of IL-17-induced pro-thrombotic genes such as tissue factor. Simvastatin restored the level of platelet aggregation to normal levels. Simvastatin enhanced the expression of CD39 and thrombomodulin mRNA initially reduced by IL-17 and TNF-α combination. Simvastatin suppressed IL-17-induced endothelial cells invasion. All these effects were reversed by the addition of mevalonate. Finally, simvastatin had an additive effect with infliximab to decrease the effect of the combination of IL-17 and TNF-α on IL-6 mRNA expression. Similar conclusion was obtained with rosuvastatin. <h3>Conclusions</h3> Statins inhibit the pro-inflammatory, thrombotic and pro-aggregation effects of IL-17 on vessels. This provides a new understanding of the beneficial effects of statins in blood vessel inflammation.
Multiple Roles of Cyclin-Dependent Kinase 4/6 Inhibitors in Cancer Therapy
Authors: Patrick J. Roberts, John E. Bisi, Jay C. Strum, Austin J. Combest, David B. Darr, Jerry E. Usary, William C. Zamboni, Kwok-Kin Wong, Charles M. Perou, Norman E. Sharpless
Journal: JNCI Journal of the National Cancer Institute (2012)

BackgroundCyclin-dependent kinases (CDKs) regulate cell proliferation and coordinate the cell cycle checkpoint response to DNA damage. Although inhibitors with varying selectivity to specific CDK family members have been developed, selective CDK4/6 inhibitors have emerged as the most attractive antineoplastic agents because of the importance of CDK4/6 activity in regulating cell proliferation and the toxic effects associated with inhibition of other CDKs (eg, CDK1 and CDK2).
Science, medicine, and the future: Leishmaniasis
Authors: L. J Roberts
Journal: BMJ (2000)

Leishmaniasis constitutes a diverse collection of human diseases ranging in severity from a spontaneously healing skin ulcer to overwhelming visceral disease. Worldwide, two million new cases occur each year, and a 10th of the world's population is at risk of infection.1 Although the disease is highly endemic throughout northern Africa, the Middle East, parts of Europe, and Central and South America, epidemics are well recognised. For example, in southern Sudan more than 10% of the population died from visceral leishmaniasis over the past five years.

Outcome of infection is determined by interactions between the host and parasite, which are governed by the genomes of the host and parasite. It is therefore exciting to see that both host and parasite genomes have been targeted for sequence analysis.2 The leishmania genome project began as a large scale attempt to sequence part of each of the transcripts of all the genes of the organism, and the plan is now to sequence its entire genome. The genetic information from both human and parasite and the emergence of new tools such as microarray technologies will allow us to gain an understanding of the interaction between parasite virulence factors and host response factors. Molecular knowledge of the host-parasite interaction will facilitate targeting of new treatments.

We chose topics for this article to convey the impact that current research will have on the pathophysiology and treatment of leishmaniasis. We used a variety of sources for the topics, including published original articles and reviews, the internet, and personal communications.

### Epidemiology

Leishmaniasis results from an infection with the protozoan parasite Leishmania spp. The organism is transmitted to humans by the bite of the sandfly.1 Humans are usually accidental hosts of these 2 mm long flies; natural hosts include a variety of rodents, small mammals, and dogs. Disease …
Human Granulocyte Colony-Stimulating Factor in Children With High-Risk Acute Lymphoblastic Leukemia: A Children’s Cancer Group Study
Authors: John A. Heath, Peter G. Steinherz, Arnold Altman, Harland Sather, Suresh Jhanwar, Steven Halpern, Richard Pieters, Narayan Shah, Laurel Steinherz, Raymond Tannous, William Terry, Michael E. Trigg
Journal: Journal of Clinical Oncology (2003)

Purpose: To investigate the effect of granulocyte colony-stimulating factor (G-CSF) on hematopoietic toxicities, supportive care requirements, time to complete intensive therapy, and event-free survival (EFS) and overall survival (OS) in children with high-risk acute lymphoblastic leukemia (HR-ALL). Patients and Methods: A total of 287 children with HR-ALL were randomly assigned to intensive chemotherapy regimens (New York I [NY I] or NY II) as part of the Children’s Cancer Group (CCG)-1901 protocol. The induction phases consisted of five drugs (vincristine, prednisone, l-asparaginase, daunorubicin, and cyclophosphamide). Initial consolidation comprised six-agent chemotherapy combined with 18 Gy of total-brain irradiation. Patients were randomly assigned to receive G-CSF (5 μg/kg/day) during either induction or initial consolidation. A crossover study analysis was done on the 259 patients who completed both phases of therapy. Results: The mean time to neutrophil recovery (≥ 0.5 × 10 9 /L) was reduced with G-CSF (16.7 v 19.1 days, P = .0003); however, patients who received G-CSF did not have significantly reduced episodes of febrile neutropenia (149 v 164, P = .41), positive blood cultures (57 v 61, P = .66), or serious infections (75 v 79, P = .62). Hospitalization (14.0 v 13.9 days, P = .87) and induction therapy completion times (NY I, 30.3 v 31.3 days, P = .11; NY II, 33.4 v 32.3 days, P = .40) were not significantly altered. There were no differences in 6-year EFS (P = .24) or OS (P = .54) between patients receiving or not receiving G-CSF on CCG-1901, NY I and NY II. Conclusion: Children with high-risk ALL do not appear to benefit from prophylactic G-CSF.