tbuckley/cabot-search huggingface dataset:
Efficacy and safety of bexarotene combined with psoralen-ultraviolet A (PUVA) compared with PUVA treatment alone in stage IB-IIA mycosis fungoides: final results from the EORTC Cutaneous Lymphoma Task Force phase III randomized clinical trial 21011 (NCT00
Authors: S. Whittaker, P. Ortiz, R. Dummer, A. Ranki, B. Hasan, B. Meulemans, S. Gellrich, R. Knobler, R. Stadler, M. Karrasch
Journal: British Journal of Dermatology (2012)

Background Psoralen plus ultraviolet A (PUVA) is the standard treatment for early stages of mycosis fungoides. There have been no adequate randomized controlled trials with sufficient power comparing this modality with other therapies. Objective To assess disease response and to compare the response rates of patients treated with PUVA alone or PUVA and bexarotene. Methods EORTC 21011 (NCT 00056056) was a randomized phase III study comparing combined bexarotene (Targretin®) and PUVA vs. PUVA alone in patients with stage IB and IIA mycosis fungoides (MF). The primary endpoint was the overall response rate [complete clinical response (CCR) plus partial response (PR)]. Results The study was prematurely closed due to low accrual after 93 of 145 required patients (65%) were randomized. Of the 93 randomized patients, 87 started treatment, 41 received PUVA and 46 received PUVA + bexarotene. Total UVA doses received were 107 J cm−2 (range 1·4–489·9) in the PUVA arm vs. 101·7 J cm−2 (0·2–529·9) in the combination arm. The safety profile was acceptable with few grade 3–4 toxicities observed in either arm. More drop‐outs due to toxicity were observed in the combination arm compared with the PUVA‐alone arm. The best overall response (CCR + PR) rate was 71% for PUVA alone and 77% for the combination arm (P =0·57). The median duration of response was 9·7 months for PUVA vs. 5·8 months for the combination arm (P =0·33). CCR was seen in 25 patients of whom 10 received PUVA alone (CCR 22%) and 15 received combination therapy (CCR 31%) (P =0·45). CCR was sustained in 25% of patients regardless of therapy. There was a trend towards fewer PUVA sessions needed to achieve CCR in the combination arm (median 22) compared with the PUVA arm (median 27·5) (P =0·11). Similarly, a trend towards lower UVA dose required to achieve CCR in the combination arm (median 55·8 J cm−2) compared with the PUVA arm alone (median 117·5 J cm−2) (P =0·5) was observed. Conclusions No significant difference in response rate or response duration was observed in this study. However, there was a trend towards fewer PUVA sessions and lower UVA dose required to achieve CCR in the combination arm (PUVA + bexarotene) but this did not achieve statistical significance due to insufficient power.
Vulvovaginal candidiasis in a Flemish patient population
Authors: M.M. De Vos, M. Cuenca-Estrella, T. Boekhout, B. Theelen, N. Matthijs, T. Bauters, H. Nailis, M.A. Dhont, J.L. Rodriguez-Tudela, H.J. Nelis
Journal: Clinical Microbiology and Infection (2005)
Prenatal Risk Factors for Childhood CKD
Authors: Christine W. Hsu, Kalani T. Yamamoto, Rohan K. Henry, Anneclaire J. De Roos, Joseph T. Flynn
Journal: Journal of the American Society of Nephrology (2014)

Development of CKD may be programmed prenatally. We sought to determine the association of childhood CKD with prenatal risk factors, including birth weight, maternal diabetes mellitus (DM), and maternal overweight/obesity. We conducted a population-based, case-control study with 1994 patients with childhood CKD (<21 years of age at diagnosis) and 20,032 controls in Washington state. We linked maternal and infant characteristics in birth records from 1987 to 2008 to hospital discharge data and used logistic regression analysis to assess the association of prenatal risk factors with childhood CKD. The prevalence of CKD was 126.7 cases per 100,000 births. High birth weight and maternal pregestational DM associated nominally with CKD, with respective crude odds ratios (ORs) of 1.17 (95% confidence interval [95% CI], 1.03 to 1.34) and 1.97 (95% CI, 1.15 to 3.37); however, adjustment for maternal confounders attenuated these associations to 0.97 (95% CI, 0.79 to 1.21) and 1.19 (95% CI, 0.51 to 2.81), respectively. The adjusted ORs for CKD associated with other prenatal factors were 2.88 (95% CI, 2.28 to 3.63) for low birth weight, 1.54 (95% CI, 1.13 to 2.09) for maternal gestational DM, 1.24 (95% CI, 1.05 to 1.48) for maternal overweight, and 1.26 (95% CI, 1.05 to 1.52) for maternal obesity. In subgroup analysis by CKD subtype, low birth weight and maternal pregestational DM associated significantly with increased risk of renal dysplasia/aplasia. Low birth weight, maternal gestational DM, and maternal overweight/obesity associated significantly with obstructive uropathy. These data suggest that prenatal factors may impact the risk of CKD. Future studies should aim to determine if modification of these factors could reduce the risk of childhood CKD.
Should a Diuretic Always Be the First Choice in Patients with Essential Hypertension? The Case for No
Authors: Alberto Morganti
Journal: Journal of the American Society of Nephrology (2005)

A more extensive use of diuretics as first-line drug for the treatment of hypertensive patients has been recommended on the basis of the results of the recent Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial, yet diuretics have numerous drawbacks that may limit their undisputed ability to lower BP. These include the stimulation of the renin-angiotensin-aldosterone system with the attending negative cardiovascular effects that ensue from this activation and several metabolic alterations, namely those in glucose, lipid, and potassium metabolism. Numerous mechanistic as well as interventional trials indicate that these limitations of diuretics can adversely affect the clinical outcome of patients and their compliance to treatment and consequently the cost of therapy. In addition, there are a number of clinical conditions in which the diuretics are admittedly contraindicated as first-line drugs. Thus, the emphasis should be on obtaining optimal BP control rather on the drug used to achieve it.
Effects of Age and Human Papilloma Viral Load on Colposcopy Triage: Data From the Randomized Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study (ALTS)
Authors: M. E. Sherman, M. Schiffman, J. T. Cox
Journal: JNCI Journal of the National Cancer Institute (2002)

Background: Testing for oncogenic human papillomavirus (HPV) DNA at a 1.0-pg/mL threshold represents a promising approach for colposcopy triage of atypical squamous cells of undetermined significance (ASCUS), but not for low-grade squamous intraepithelial lesions (LSIL). Considering age or viral load could improve colposcopy triage. Methods: We determined the sensitivity for detecting Cervical Intraepithelial Neoplasia 3 (CIN3) and cancer and the percentage of referrals for colposcopy using HPV testing and repeat thin-layer cytopathology in 2198 women with ASCUS and in 848 women with LSIL enrolled in ALTS from November 1996 through December 1998. We analyzed results by age and at two thresholds for HPV load and repeat cytopathology. Results: For ASCUS, the overall sensitivity of HPV testing at 1.0 pg/mL was 96.1% (95% confidence interval [CI] = 92.8 to 99.5%) and varied minimally with age (range, 93.9% to 97.8%). HPV testing at this threshold would refer 31.2% (95% CI = 28.0% to 34.3%) of women aged 29 years or older as compared with more than 65% of younger women. Among women aged 29 years or older with ASCUS, referral for repeat cytopathology of ASCUS had a sensitivity of 90.9% (95% CI = 81.1% to 100.0%) and would refer 50.1% (95% CI = 46.7 to 53.5%). Among all ASCUS, HPV testing using a 10.0-pg/mL threshold decreased sensitivity to 91.5% and referrals to 41.7%. More than 63% of LSIL would have been referred using any strategy achieving 90% sensitivity. Conclusion: For women with ASCUS, HPV testing was highly sensitive for detecting CIN3 and cancer with dramatically fewer referrals of older women. Neither a single HPV test nor repeat cytopathology provides useful triage for women with LSIL.
Systemic juvenile idiopathic arthritis presenting in a young child with long term disability as an adolescent
Authors: K M Bailey
Journal: Annals of the Rheumatic Diseases (2004)

A young man now aged 19 years presented, aged 2½ years, with an 8 week history of being unwell with high swinging fevers, a “measles”-type rash, anorexia, and weight loss. He complained throughout this time of a painful right knee, and subsequently, pain in his left wrist and ankle, neck, and elbows. Initial assessment confirmed synovitis in his left ankle, right hip, neck, and some small joints of his hands. He had a quotidian fever pattern, intermittent macular rash, lymphadenopathy but no splenomegaly, and a cardiovascular examination was normal. Inflammatory markers were high (erythrocyte sedimentation rate (ESR) 129 mm/1st h; C reactive protein (CRP) 226 mg/l; platelets 594×109/l—peak 1360×109/l), haemoglobin 92 g/l; white blood cell count 9.6×109/l (neutrophils 6.6, lymphocytes 1.9), and albumin 24 g/l. The differential diagnosis included systemic arthritis, infections, inflammatory bowel disease, and malignancy.

After exclusion of these diseases, a diagnosis of systemic juvenile idiopathic arthritis (SJIA) was made, and treatment was started with high dose non-steroidal anti-inflammatory drugs and oral prednisolone. Many treatments were subsequently used in the following years, including penicillamine, rifampicin with isoniazid, methotrexate (introduced 4 years into his disease and continued for 7 years), ciclosporin in combination with methotrexate, intravenous immunoglobulin; he is currently receiving etanercept (started after 15 years of disease, maximum dose 0.8 mg/kg twice weekly). These treatments have been complemented with intermittent multiple intra-articular steroids. Despite this treatment he continues to have active disease—ESR 42 mm/1st h, CRP 38 mg/l (ESR <20 mm/1st h on only two occasions in 17 years)—and has remained dependent on steroids (average daily dose 5–10 mg prednisolone).

There have been many consequences of a lifetime of inflammatory disease. Growth restriction (130 cm tall at the time of transfer to adult care, with only a 35 cm gain in height …
Physical inactivity as a risk factor for metabolic syndrome in retired elite male athletes
Authors: M I Tudor, E I Iconaru, C Ciucurel, L Georgescu
Journal: British Journal of Sports Medicine (2010)

The protective role of intense physical activity (PA) on chronic diseases is sustained by the high aerobic capacity, muscle strength and also the low evidence of metabolic alteration in elite athletes. Studies on detrained athletes have demonstrated the risk of metabolic syndrome (MS) onset, physical inactivity in retired athletes being associated with changes in insulin sensitivity, plasma lipids and body composition. To study the impact of physical inactivity on MS onset in retired elite male athletes, the authors completed a longitudinal retrospective case-control study, using two samples of retired top male athletes, who were involved in contact sports: an experimental group, with low level of PA (N=50, average age: 52 years) and a control one, with normal level of PA (N=50, average age: 54 years). The assessed variables were: body mass index (BMI), diagnostic parameters of MS and PA level (evaluated using the Romanian PA Questionnaire). Reporting to the tested parameters, the experimental group subjects, not involved in regular PA, had a higher risk for MS comparing to the control group subjects (p=0.001, RA=94.11%, OR=17). Retired athletes who renounce all forms of PA expose themselves to greater risks for weight gain, glucose intolerance and induction of MS than their correspondents with an active lifestyle. Remaining physically active may be helpful in protecting against much of the deterioration in health status in middle age.
Longtime Recirculating Tumor Cells in Breast Cancer Patients
Authors: Katharina Pachmann
Journal: Clinical Cancer Research (2005)

To the Editor: In their article (Clin Cancer Res 2004;10, 8152–62), Meng et al. report on the detection of circulating tumor cells in blood of breast cancer patients even in long-term remission. In a somewhat different approach ([1][1]),[1][2] using only RBC lysis and no other enrichment apart
Molecular Pathways: Targeting Phosphoinositide 3-Kinase p110-Delta in Chronic Lymphocytic Leukemia
Authors: Sarah E.M. Herman, Amy J. Johnson
Journal: Clinical Cancer Research (2012)

The advent of targeted therapy, specifically to the B-cell receptor (BCR), has changed the convention for the treatment of chronic lymphocytic leukemia (CLL). The phosphoinositide 3-kinase (PI3K) pathway, activated upstream by the BCR, receptor tyrosine kinases, and cytokine receptors, has been a potential target for a multitude of cancers, but until the recent introduction of isoform-specific inhibitors has not been widely used. In this review, we focus on describing the intricate upstream and downstream signaling, leading to cell survival mediated by PI3K in B cells with a specific focus on the impact and importance of the p110δ isoform (which is localized to hematopoietic cells and regulates distinct cellular functions in B cells). In addition, the clinical advances from targeting p110δ are described, with a focus on clinical outcome, toxicities, and rational combination therapies. The experiences with p110δ in CLL have led to a more fundamental understanding of CLL signaling defects and may be predictive of other BCR-directed therapeutics.
Evaluating the Effects of Metformin Use on Height in Children and Adolescents
Authors: Nicholas Kuzik, Étienne Myette-Côté, Valerie Carson, Linda Slater, Normand G. Boulé
Journal: JAMA Pediatrics (2015)

<h3>Importance</h3> Metformin hydrochloride use is increasing in children and adolescents. Previous meta-analyses have identified a large variability in the effects of metformin use on body mass index changes but have not considered height changes as a confounder, to our knowledge. <h3>Objective</h3> To conduct a systematic review and meta-analysis of the effects of metformin use on height in children and adolescents. <h3>Data Sources</h3> Computerized databases, including MEDLINE and EMBASE, were searched up to September 9, 2014, for terms related to metformin and childhood or adolescence. <h3>Study Selection</h3> Randomized clinical trials examining the effects of metformin use on height of participants younger than 19 years were considered eligible. Trials with cointerventions other than lifestyle changes were excluded. <h3>Data Extraction and Synthesis</h3> Height, weight, body mass index, age, sex, metformin dosage, and study duration were independently extracted by 2 reviewers. The weighted mean differences for changes in height, weight, and body mass index were compared between the metformin and control groups using random-effects models. <h3>Main Outcome and Measure</h3> Height changes. <h3>Results</h3> Ten studies were included, with a total of 562 participants, 330 (58.7%) of whom were female. The mean age within the studies ranged from 7.9 to 16.1 years, with a high variability in most studies. The duration of metformin interventions lasted from 3 to 48 months. Overall, height changes were not significantly different between the metformin and control groups. However, stratified analyses according to the cumulative metformin dose (in milligrams per day times the number of days of treatment) showed a greater increase in height with metformin use in the 5 studies providing the largest cumulative metformin doses (weighted mean difference, 1.0; 95% CI, 0.0 to 2.0 cm) but not in the 5 studies providing the lowest doses (weighted mean difference, −0.1; 95% CI, −0.7 to 1.0 cm) compared with the control group. <h3>Conclusions and Relevance</h3> Preliminary evidence suggests a dose-response relationship between metformin use and increases in height in children and adolescents compared with a control group. While an approximate 1-cm increase in height may appear small, it is likely underestimated given that many studies were of short duration and included older adolescents, potentially after epiphyseal growth plate closure.
Prognostic Value of Translocation t(11;18) in Tumoral Response of Low-Grade Gastric Lymphoma of Mucosa-Associated Lymphoid Tissue Type to Oral Chemotherapy
Authors: Michaël Lévy, Christiane Copie-Bergman, Christine Gameiro, Marie-Thérèse Chaumette, Marie-Hélène Delfau-Larue, Corinne Haioun, Antoine Charachon, François Hemery, Philippe Gaulard, Karen Leroy, Jean-Charles Delchier
Journal: Journal of Clinical Oncology (2005)

To determine the impact of translocation t(11;18) on response to oral alkylating agents in gastric mucosa-associated lymphoid tissue lymphoma (GML).Fifty-three patients with a GML were studied. Helicobacter pylori-positive patients (n = 34) received anti-H pylori treatment and H pylori-negative patients (n = 19) or patients who failed to respond to anti-H pylori treatment received oral alkylating agents. t(11;18) was detected by reverse transcription polymerase chain reaction from frozen gastric biopsies.t(11;18) was detected in 32% of patients. It was more prevalent in H pylori-negative as compared with H pylori-positive patients (12 of 19 v five of 34 patients; P = .0005). Among 31 H pylori-eradicated patients, t(11;18) was detected in three patients, all of whom experienced treatment failure, and it was absent in 28 patients: 21 patients (75%) were in remission and seven patients (25%) experienced treatment failure (P = .03). Among 21 patients who received an alkylating agent, t(11;18) was detected in 12 patients: five patients (42%) were in remission and seven patients (58%) experienced treatment failure. t(11;18) was absent in nine patients: eight patients (89%) were in remission and one patient (11%) experienced treatment failure by the end of treatment. Four patients in remission relapsed during follow-up (median, 7 years): they all had t(11;18). Durable remission was obtained in eight (89%) of the nine patients without t(11;18) versus one of the 12 patients (8%) with t(11;18) (P = .0003).Presence of t(11;18) in GML is predictive of resistance to oral alkylating agents, with less than 10% of durable remission at long-term follow-up.
Cellular immunity to P. acnes in the normal population and patients with acne vulgaris
Authors: G. GOWLAND, R. M. WARD, K. T. HOLLAND, W. J. CUNLIFFE
Journal: British Journal of Dermatology (1978)

Patients with varying degrees of acne, acne-free adult controls and samples of cord blood were investigated for cell mediated immunity to P. acnes using a leukocyte migration inhibition test. Despite the fact that the mean migration index tended to decrease with acne severity, only the patients with severe acne showed cell-mediated immunity. It is suggested that when cellular immunity arises it is a late event which may contribute to inflammation but is probably not a factor in its initiation.
JOURNEES INTERNATIONALES D’ENDOCRINOLOGIE CLINIQUE
Authors: Henri-Pierre Klotz
Journal: Endocrine Reviews (2007)

its role in blunting glucocorticoid action at physiological levels of substrate. Endocrinology 146:2657–2664 29. Colombe L, Fostier A, Bury N, Pakdel F, Guiguen Y 2000 A mineralocorticoidlike receptor in the rainbow trout, Oncorhynchus mykiss: cloning and characterization of its steroid binding domain. Steroid 65:319–328 30. Balm PHM, Lambert JDG, Wendelaar Bonga SE 1989 Corticosteroid biosynthesis in the interrenal cells of the teleost fish, Oreochromis mossambicus. Gen Comp Endocrinol 76:53–62 31. Jiang JQ, Young G, Kobayashi T, Nagahama 1998 Eel (Anguilla japonica) testis 11 -hydroxylase gene is expressed in interrenal tissue and its product lacks aldosterone synthesizing activity. Mol Cell Endocrinol 146:207–211 32. Tetsuka M, Thomas FJ, Thomas MJ, Anderson RA, Mason JI, Hillier SG 1997 Differential expression of messenger ribonucleic acids encoding 11 -hydroxysteroid dehydrogenase type 1 and 2 in human granulose cells. J Clin Endocrinol Metab 82:2006–2009 33. Tetsuka M, Milne M, Simpson GE, Hillier SG 1999 Expression of 11 hydroxysteroid dehydrogenase, glucocorticoid receptor, and mineralocorticoid receptor genes in rat ovary. Biol Reprod 60:330–335 34. Gao HB, Ge RS, Lakshmi V, Marandici A, Hardy MP 1997 Hormonal regulation of oxidative and reductive activities of 11 -hydroxysteroid dehydrogenase in rat Leydig cells. Endocrinology 138:156–161 35. Gomez JM, Weil C, Ollitrault M, Le Bail PY, Breton B, Le Gac F 1999 Growth hormone (GH) and gonadotropin subunit gene expression and pituitary and plasma changes during spermatogenesis and oogenesis in rainbow trout (Oncorhynchus mykiss). Gen Comp Endocrinol 113:413–428
Bronchodilation by pituitary adenylate cyclase-activating peptide and related peptides
Authors: A Lindén, L-O Cardell, S Yoshihara, J.a Nadel
Journal: European Respiratory Journal (1999)

That endothelin-1(ET-1) plays a mediator role in asthma is consistent with reports of ET-1-induced potentiation of cholinergic nerve-mediated contraction in airways from various animal species. This study examined the effect of ET-1 on cholinergic contractions in human isolated bronchus. Macroscopically nondiseased human bronchial tissue was obtained from 23 patients with respiratory tumours. An electrical field stimulation (EFS) frequency that produced one third of the contraction at 30 Hz (EFS30) was estimated. The effect of ET-1 on these EFS-evoked contractions was assessed. EFS-evoked contractions were frequency-dependent and abolished by either atropine or tetrodotoxin. Thus, EFS-induced contractions were mediated by acetylcholine from cholinergic nerves. ET-1 (3 nM) potentiated EFS-evoked contractions by 10+/-2% EFS30 (p&lt;0.05) without any significant effect on contractions induced by exogenous acetylcholine. Neither the ET(A) receptor-selective antagonist BQ-123 (3 microM) nor the ET(B) receptor-selective antagonist BQ-788 (10 microM) alone significantly altered ET-1-induced potentiation of EFS-evoked contractions. However, in the combined presence of both BQ-123 and BQ-788, ET-1-induced potentiation of EFS-evoked contractions was abolished. Thus, prejunctional endothelinA and endothelinB receptors appear to mediate endothelin-1-induced potentiation of electrical field stimulation-evoked cholinergic contractions in human bronchus. This suggests another potentially important mechanism through which endothelin-1 could increase bronchial tone in asthma.