tbuckley/cabot-search huggingface dataset:
Cognitive behavioural therapy can help chronic insomnia, review finds
Authors: J. Wise
Journal: BMJ (2015)

Cognitive behavioural therapy (CBT) can improve sleep in patients with chronic insomnia without the need for drugs, a systematic review and meta-analysis published in the Annals of Internal Medicine has found.[1]

Clinical chronic insomnia affects as many as 15% of adults and is linked to anxiety, depression, and type 2 diabetes. Hypnotics such as benzodiazepines are the most commonly used treatment for insomnia but are …
Osteoblast-secreted collagen upregulates paracrine Sonic hedgehog signaling by prostate cancer cells and enhances osteoblast differentiation
Authors: Samantha M Zunich, Maria Valdovinos, Taneka Douglas, David Walterhouse, Philip Iannaccone, Marilyn L G Lamm
Journal: Molecular Cancer (2012)

Induction of osteoblast differentiation by paracrine Sonic hedgehog (Shh) signaling may be a mechanism through which Shh-expressing prostate cancer cells initiate changes in the bone microenvironment and promote metastases. A hallmark of osteoblast differentiation is the formation of matrix whose predominant protein is type 1 collagen. We investigated the formation of a collagen matrix by osteoblasts cultured with prostate cancer cells, and its effects on interactions between prostate cancer cells and osteoblasts.In the presence of exogenous ascorbic acid (AA), a co-factor in collagen synthesis, mouse MC3T3 pre-osteoblasts in mixed cultures with human LNCaP prostate cancer cells or LNCaP cells modified to overexpress Shh (LNShh cells) formed collagen matrix with distinct fibril ultrastructural characteristics. AA increased the activity of alkaline phosphatase and the expression of the alkaline phosphatase gene Akp2, markers of osteoblast differentiation, in MC3T3 pre-osteoblasts cultured with LNCaP or LNShh cells. However, the AA-stimulated increase in Akp2 expression in MC3T3 pre-osteoblasts cultured with LNShh cells far exceeded the levels observed in MC3T3 cells cultured with either LNCaP cells with AA or LNShh cells without AA. Therefore, AA and Shh exert a synergistic effect on osteoblast differentiation. We determined whether the effect of AA on LNShh cell-induced osteoblast differentiation was mediated by Shh signaling. AA increased the expression of Gli1 and Ptc1, target genes of the Shh pathway, in MC3T3 pre-osteoblasts cultured with LNShh cells to at least twice their levels without AA. The ability of AA to upregulate Shh signaling and enhance alkaline phosphatase activity was blocked in MC3T3 cells that expressed a dominant negative form of the transcription factor GLI1. The AA-stimulated increase in Shh signaling and Shh-induced osteoblast differentiation was also inhibited by the specific collagen synthesis inhibitor 3,4-dehydro-L-proline.Matrix collagen, formed by osteoblasts in the presence of AA, potentiates Shh signaling between Shh-expressing prostate cancer cells and osteoblasts. Collagen and Shh signaling exert a synergistic effect on osteoblast differentiation, a defining event in prostate carcinoma bone metastasis. Investigations into paracrine interactions among prostate cancer cells, osteoblasts, and osteoblast-synthesized matrix proteins advance our understanding of mechanisms contributing to prostate cancer bone metastasis.
Prediction of Medium-Term Outcome by Cortisol Response to the Combined Dexamethasone-CRH Test in Patients With Remitted Depression
Authors: Astrid W. Zobel, Alexander Yassouridis, Ralf-Michael Frieboes, Florian Holsboer
Journal: American Journal of Psychiatry (1999)

Current hypotheses hold that mechanisms underlying abnormal hypothalamic-pituitary-adrenocortical (HPA) function are causal factors in the precipitation of depression. If this is the case, then normalization of initially disturbed HPA regulation should indicate a good prognosis and persistent HPA dysregulation should be associated with a greater likelihood of relapse or chronicity.The combined dexamethasone/corticotropin-releasing hormone test was administered twice to inpatients with major depression (N = 40), once after initiation of treatment and once after remission, shortly before discharge.Patients with a high cortisol response on both occasions or with a substantially increased cortisol response at discharge were at much higher risk for relapse within the next 6 months than those with low cortisol responses.An easy-to-administer neuroendocrine test allows the prediction of medium-term outcome in patients with remitted depression.
Suppression of arthritis by an inhibitor of nitric oxide synthase.
Authors: N McCartney-Francis, J B Allen, D E Mizel, J E Albina, Q W Xie, C F Nathan, S M Wahl
Journal: The Journal of Experimental Medicine (1993)

Nitric oxide (NO), a toxic radical gas produced during the metabolism of L-arginine by NO synthase (NOS), has been implicated as a mediator of immune and inflammatory responses. A single injection of streptococcal cell wall fragments (SCW) induces the accumulation of inflammatory cells within the synovial tissue and a cell-mediated immune response that leads destructive lesions. We show here that NO production is elevated in the inflamed joints of SCW-treated rats. Administration of NG-monomethyl-L-arginine, an inhibitor of NOS, profoundly reduced the synovial inflammation and tissue damage as measured by an articular index and reflected in the histopathology. These studies implicate the NO pathway in the pathogenesis of an inflammatory arthritis and demonstrate the ability of a NOS inhibitor to modulate the disease.
The use of LH activity to drive folliculogenesis: exploring uncharted territories in ovulation induction
Authors: M. Filicori
Journal: Human Reproduction Update (2002)

LH plays critical roles in the control of folliculogenesis and ovarian function in humans. LH activity administration during gonadotrophin ovulation induction can enhance ovarian response and optimise treatment. More specifically, LH activity (both LH and low-dose hCG) can support the growth and stimulate the maturation of larger ovarian follicles as a result of specific granulosa cell receptors that develop after a few days of FSH priming. This action of LH is independent of FSH, and it has been shown recently that the last stages of follicular development can be supported by sole administration of LH activity in the form of low-dose hCG, without causing premature luteinization. Reproductively competent oocytes and pregnancy can be obtained with this regimen. Furthermore, LH activity is capable of reducing the development of small ovarian follicles (<10 mm) that may predispose patients to developing complications such as the ovarian hyperstimulation syndrome. Thus, better understanding of the dynamics and mechanisms that control human folliculogenesis and a more rational and selective use of LH activity administration may allow a reduction in cost and increased safety, while maintaining a high efficacy of the ovulation induction regimens used in assisted reproduction.
Enzymes of collagen synthesis and type III procollagen aminopropeptide in the evaluation of D-penicillamine and medroxyprogesterone treatments of primary biliary cirrhosis.
Authors: E R Savolainen, T A Miettinen, P Pikkarainen, M P Salaspuro, K I Kivirikko
Journal: Gut (1983)

Changes in serum immunoreactive prolyl hydroxylase protein (IRPH), galactosylhydroxylysyl glucosyltransferase activity (GGT) and the aminoterminal propeptide of type III procollagen [Pro(III)-N-P] were studied in 21 patients with primary biliary cirrhosis during a follow-up period of up to three years. The patients received either D-penicillamine (600 mg/day), medroxyprogesterone acetate (5 mg/day), or a placebo, or no treatment after the D-penicillamine or medroxyprogesterone medication, each period lasting from nine to 15 months. The individual serum IRPH, GGT, and Pro(III)-N-P concentrations exceeded the upper normal limit in most patients. No significant changes were found in any of these three serum markers during any of the five different periods, nor was there any evidence for a decrease in the raised prolyl 4-hydroxylase activity in the hepatic biopsy specimens in response to any of the treatments. Galactosylhydroxylysyl glucosyltransferase activity decreased significantly in these specimens during medroxyprogesterone therapy, but the interpretation of this, the only positive change, remains unclear. The data suggest that D-penicillamine or medroxyprogesterone therapy may have no favourable effect on the increased hepatic collagen formation involved in primary biliary cirrhosis.
Expression Signature of <i>E2F1</i> and Its Associated Genes Predict Superficial to Invasive Progression of Bladder Tumors
Authors: Ju-Seog Lee, Sun-Hee Leem, Sang-Yeop Lee, Sang-Cheol Kim, Eun-Sung Park, Sang-Bae Kim, Seon-Kyu Kim, Yong-June Kim, Wun-Jae Kim, In-Sun Chu
Journal: Journal of Clinical Oncology (2010)

In approximately 20% of patients with superficial bladder tumors, the tumors progress to invasive tumors after treatment. Current methods of predicting the clinical behavior of these tumors prospectively are unreliable. We aim to identify a molecular signature that can reliably identify patients with high-risk superficial tumors that are likely to progress to invasive tumors.Gene expression data were collected from tumor specimens from 165 patients with bladder cancer. Various statistical methods, including leave-one-out cross-validation methods, were applied to identify a gene expression signature that could predict the likelihood of progression to invasive tumors and to test the robustness of the expression signature in an independent cohort. The robustness of the gene expression signature was validated in an independent (n = 353) cohort.Supervised analysis of gene expression data revealed a gene expression signature that is strongly associated with invasive bladder tumors. A molecular classifier based on this gene expression signature correctly predicted the likelihood of progression of superficial tumor to invasive tumor.We present a molecular signature that can predict, at diagnosis, the likelihood of bladder cancer progression and, possibly, lead to improvements in patient therapy.
Disruption of Sarcolemmal ATP-Sensitive Potassium Channel Activity Impairs the Cardiac Response to Systolic Overload
Authors: Xinli Hu, Xin Xu, Yimin Huang, John Fassett, Thomas P. Flagg, Ying Zhang, Colin G. Nichols, Robert J. Bache, Yingjie Chen
Journal: Circulation Research (2008)

Sarcolemmal ATP-sensitive potassium channels (K ATP ) act as metabolic sensors that facilitate adaptation of the left ventricle to changes in energy requirements. This study examined the mechanism by which K ATP dysfunction impairs the left ventricular response to stress using transgenic mouse strains with cardiac-specific disruption of K ATP activity (SUR1-tg mice) or Kir6.2 gene deficiency (Kir6.2 KO). Both SUR1-tg and Kir6.2 KO mice had normal left ventricular mass and function under unstressed conditions. Following chronic transverse aortic constriction, both SUR1-tg and Kir6.2 KO mice developed more severe left ventricular hypertrophy and dysfunction as compared with their corresponding WT controls. Both SUR1-tg and Kir6.2 KO mice had significantly decreased expression of peroxisome proliferator-activated receptor γ coactivator (PGC)-1α and a group of energy metabolism related genes at both protein and mRNA levels. Furthermore, disruption of K ATP repressed expression and promoter activity of PGC-1α in cultured rat neonatal cardiac myocytes in response to hypoxia, indicating that K ATP activity is required to maintain PGC-1α expression under stress conditions. PGC-1α gene deficiency also exacerbated chronic transverse aortic constriction–induced ventricular hypertrophy and dysfunction, suggesting that depletion of PGC-1α can worsen systolic overload induced ventricular dysfunction. Both SUR1-tg and Kir6.2 KO mice had decreased FOXO1 after transverse aortic constriction, in agreement with the reports that a decrease of FOXO1 can repress PGC-1α expression. Furthermore, inhibition of K ATP caused a decrease of FOXO1 associated with PGC-1α promoter. These data indicate that K ATP channels facilitate the cardiac response to stress by regulating PGC-1α and its target genes, at least partially through the FOXO1 pathway.
Effects of biphasic positive airway pressure in patients with chronic obstructive pulmonary disease
Authors: E Katz-Papatheophilou, W Heindl, H Gelbmann, P Hollaus, M Neumann
Journal: European Respiratory Journal (2000)

Biphasic positive airway pressure (BiPAP) is a ventilatory mode in which two pressure levels (higher (Phigh) and lower (Plow)) acting as continuous positive airway pressure (CPAP) alternate at preset time intervals. BiPAP combines pressure-controlled ventilation with unrestricted spontaneous breathing. BiPAP has not yet been evaluated in patients with chronic obstructive pulmonary disease (COPD). Therefore, the effects of BiPAP (15 cmH2O Phigh and 5 cmH2O Plow) pressure support (PS; 15 cmH2O and positive end-expiratory pressure (PEEP) 5 cmH2O) and CPAP (5 cmH2O) on respiratory mechanics in COPD patients were compared. Twenty-one COPD patients were supported in randomized order with BiPAP, PS and CPAP. Pressure-time product (PTP), work of breathing (WOB), change in oesophageal pressure (deltaPoes), mouth occlusion pressure (P0.1), intrinsic PEEP (PEEPi), tension time index (TTI), respiratory frequency, and tidal volume (VT) were measured. During BiPAP, the COPD patients showed a significantly higher PTP, WOB, deltaPoes, P0.1, TTI and PEEPi than during PS. Comparing the Plow phases of BiPAP and CPAP, the breaths during the Plow phases of BiPAP had a lower VT and a greater WOB and PTP due to a higher PEEPi than on CPAP alone. In conclusion, biphasic positive airway pressure carries the risk of increased work of breathing in spontaneously breathing chronic obstructive pulmonary disease patients. Pressure support is superior for reducing their respiratory muscle effort.
Randomized Phase IIB Trial of BLP25 Liposome Vaccine in Stage IIIB and IV Non–Small-Cell Lung Cancer
Authors: Charles Butts, Nevin Murray, Andrew Maksymiuk, Glenwood Goss, Ernie Marshall, Denis Soulières, Yvon Cormier, Peter Ellis, Allan Price, Ravinder Sawhney, Mary Davis, Janine Mansi, Colum Smith, Dimitrios Vergidis, Paul Ellis, Mary MacNeil, Martin Palmer
Journal: Journal of Clinical Oncology (2005)

To evaluate the effect of BLP25 liposome vaccine (L-BLP25) on survival and toxicity in patients with stage IIIB and IV non-small-cell lung cancer (NSCLC). Secondary objectives included health-related quality of life (QOL) and immune responses elicited by L-BLP25.Patients with an Eastern Cooperative Oncology Group performance status of 0 to 2 and stable or responding stage IIIB or IV NSCLC after any first-line chemotherapy were prestratified by stage and randomly assigned to either L-BLP25 plus best supportive care (BSC) or BSC alone. Patients in the L-BLP25 arm received a single intravenous dose of cyclophosphamide 300 mg/m2 followed by eight weekly subcutaneous immunizations with L-BLP25 (1,000 microg). Subsequent immunizations were administered at 6-week intervals.The survival results indicate a median survival time of 4.4 months longer for patients randomly assigned to the L-BLP25 arm (88 patients) compared with patients assigned to the BSC arm (83 patients; adjusted hazard ratio [HR] = 0.739; 95% CI, 0.509 to 1.073; P = .112). The greatest effect was observed in stage IIIB locoregional (LR) patients, for whom the median survival time for the L-BLP25 arm has not yet been reached compared with 13.3 months for the BSC arm (adjusted HR = 0.524; 95% CI, 0.261 to 1.052; P = .069). No significant toxicity was observed. QOL was maintained longer in patients on the L-BLP25 arm.L-BLP25 maintenance therapy in patients with advanced NSCLC is feasible with minimal toxicity. The survival difference of 4.4 months observed with the vaccine did not reach statistical significance. In the subgroup of patients with stage IIIB LR disease, a strong trend in 2-year survival in favor of L-BLP25 was observed.
Targeting γδ T Lymphocytes for Cancer Immunotherapy: From Novel Mechanistic Insight to Clinical Application
Authors: Anita Q. Gomes, Duarte S. Martins, Bruno Silva-Santos
Journal: Cancer Research (2010)

Abstract Abundant interferon-γ secretion, potent cytotoxicity, and major histocompatibility complex–independent targeting of a large spectrum of tumors make γδ T cells attractive mediators of cancer immunotherapy. However, a better understanding of the molecular mechanisms involved in tumor cell recognition and γδ T-cell activation is required to improve the limited success of γδ T-cell–mediated treatments. Here, we review key advances in basic knowledge made over the past 3 years, and summarize the results of γδ T-cell–based clinical trials concluded to date. We also highlight new research directions on the basis of the modulation of receptors that control the function of γδ T cells. Cancer Res; 70(24); 10024–7. ©2010 AACR.
A swollen right eye in a child
Authors: M. S. Harris, G. Chawdhary
Journal: BMJ (2015)

A 9 year old boy presented to the emergency department with a one day history of generalised swelling of the right eye, conjunctival oedema, and difficulty opening the eye (fig 1⇓). In the preceding two weeks he had experienced coryzal symptoms.



Fig 1 Periorbital swelling of the right eye





### 1. What is the diagnosis?

#### Short answer

Periorbital (preseptal) or orbital (post-septal) cellulitis.

#### Long answer

The terminology used in the literature is often ambiguous, with the terms “periorbital” and “preseptal” cellulitis used interchangeably. Similarly, the terms “orbital” cellulitis and “post-septal” cellulitis are also used interchangeably.

The orbital septum is a tough fibrous membrane that forms the scaffold for the eyelids. It also provides a barrier to infection between the superficial tissues of the face and the deep tissues within the orbits.1 2 Infection superficial to this layer (preseptal) is termed periorbital cellulitis, whereas infection deep to the orbital septum (post-septal) is termed orbital cellulitis.

### 2. What is the likely infective source?

#### Short answer

Infection of the paranasal sinuses (most commonly ethmoid sinusitis). Causative organisms tend to reflect the underlying involvement of sinus disease, with Streptococcus pneumoniae , Streptococcus pyogenes , Staphylococcus aureus , and Haemophilus species most commonly being cultured.3

#### Long answer

Periorbital and orbital cellulitis can have a sinugenic or non-sinugenic cause. Given the history of coryzal symptoms, this patient’s infection probably originated from the paranasal sinuses (maxillary, ethmoid, frontal, or sphenoid sinusitis).

Anatomically, the ethmoid sinuses lie directly medial to the orbits and are separated from the orbital cavities by a ‘paper thin’ layer of bone called the lamina papyracea. This makes the orbital cavities vulnerable to direct spread of infection from the nose.1 2

Non-sinugenic causes of infection are less common but …
Guidelines for management of Bowen's disease
Authors: None Cox, None Eedy, None Morton
Journal: British Journal of Dermatology (1999)

These guidelines for management of Bowen's disease have been prepared for dermatologists on behalf of the British Association of Dermatologists. They present evidence‐based guidance for treatment, with identification of the strength of evidence available at the time of preparation of the guidelines, and a brief overview of epidemiological aspects, diagnosis and investigation.
Serum Vitamin D Levels and Markers of Severity of Childhood Asthma in Costa Rica
Authors: John M. Brehm, Juan C. Celedón, Manuel E. Soto-Quiros, Lydiana Avila, Gary M. Hunninghake, Erick Forno, Daniel Laskey, Jody S. Sylvia, Bruce W. Hollis, Scott T. Weiss, Augusto A. Litonjua
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Maternal vitamin D intake during pregnancy has been inversely associated with asthma symptoms in early childhood. However, no study has examined the relationship between measured vitamin D levels and markers of asthma severity in childhood.To determine the relationship between measured vitamin D levels and both markers of asthma severity and allergy in childhood.We examined the relation between 25-hydroxyvitamin D levels (the major circulating form of vitamin D) and markers of allergy and asthma severity in a cross-sectional study of 616 Costa Rican children between the ages of 6 and 14 years. Linear, logistic, and negative binomial regressions were used for the univariate and multivariate analyses.Of the 616 children with asthma, 175 (28%) had insufficient levels of vitamin D (<30 ng/ml). In multivariate linear regression models, vitamin D levels were significantly and inversely associated with total IgE and eosinophil count. In multivariate logistic regression models, a log(10) unit increase in vitamin D levels was associated with reduced odds of any hospitalization in the previous year (odds ratio [OR], 0.05; 95% confidence interval [CI], 0.004-0.71; P = 0.03), any use of antiinflammatory medications in the previous year (OR, 0.18; 95% CI, 0.05-0.67; P = 0.01), and increased airway responsiveness (a < or =8.58-mumol provocative dose of methacholine producing a 20% fall in baseline FEV(1) [OR, 0.15; 95% CI, 0.024-0.97; P = 0.05]).Our results suggest that vitamin D insufficiency is relatively frequent in an equatorial population of children with asthma. In these children, lower vitamin D levels are associated with increased markers of allergy and asthma severity.
Chronic respiratory symptoms and airway responsiveness to methacholine are associated with eosinophilia in older men: the Normative Aging Study
Authors: JT Annema, D Sparrow, GT O'Connor, B Rijcken, GH Koeter, DS Postma, ST Weiss
Journal: European Respiratory Journal (1995)

Identification of subsets of patients with chronic obstructive lung disease (COLD) in order to determine disease outcomes and, possibly, the effects of treatment is an area of clinical interest. At present, it remains unclear which patients with COLD are most likely to benefit from anti-inflammatory therapy. We investigated this question in a community-dwelling sample of men. In this study, the relationship of chronic respiratory symptoms, airway responsiveness to methacholine, and skin test reactivity to peripheral-blood eosinophil and neutrophil counts was examined among 894 male participants in the Normative Aging Study (mean age 60 yrs; range 41-90 yrs). The symptoms considered were asthma, persistent wheeze, dyspnoea, chronic cough and phlegm. Responsiveness to methacholine was defined as a provocative dose producing a 20% fall in forced expiratory volume in one second (PD20FEV1) of &lt; or = 8.6 mumol, a positive skin test as a wheal diameter of &gt; or = 5 mm after subtraction of the diameter of any wheal reaction to a glycerin control, and eosinophilia as an eosinophil count of &gt; or = 275 cells.mm-3 in peripheral blood. Chronic symptoms (odds ratio (OR) 2.0; 95% confidence interval (CI) 1.4-2.7), airway responsiveness (OR 1.7; CI 1.1-2.7), and the combination of symptoms and airway responsiveness (OR 3.4; CI 2.0-5.6) were positively and significantly related to peripheral-blood eosinophil counts. These relationships remained significant after adjustment for the effects of age and smoking, and after exclusion of asthmatic subjects. Symptoms and airway responsiveness combined were not significantly related to neutrophil counts.(ABSTRACT TRUNCATED AT 250 WORDS)