tbuckley/cabot-search huggingface dataset:
Inhaled steroids are associated with cataracts
Authors: S Jain
Journal: Thorax (2003)

▴ Smeeth L, Boulis M, Hubbard R, et al . A population based case-control study of cataract and inhaled corticosteroids. Br J Ophthalmol2003;87:1247–51 [OpenUrl][1][Abstract/FREE Full Text][2] Exposure to systemic corticosteroids is known to be associated with a risk of cataract. This study was undertaken to determine the risk of cataract associated with the use of inhaled corticosteroids and to assess whether there is a dose-response relation. It was designed as a population based case-control study based on … [1]: {openurl}?query=rft.jtitle%253DBritish%2BJournal%2Bof%2BOphthalmology%26rft.stitle%253DBr%2BJ%2BOphthalmol%26rft.issn%253D0007-1161%26rft.aulast%253DSmeeth%26rft.auinit1%253DL%26rft.volume%253D87%26rft.issue%253D10%26rft.spage%253D1247%26rft.epage%253D1251%26rft.atitle%253DA%2Bpopulation%2Bbased%2Bcase-control%2Bstudy%2Bof%2Bcataract%2Band%2Binhaled%2Bcorticosteroids%26rft_id%253Dinfo%253Adoi%252F10.1136%252Fbjo.87.10.1247%26rft_id%253Dinfo%253Apmid%252F14507760%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=ABST&journalCode=bjophthalmol&resid=87/10/1247&atom=%2Fthoraxjnl%2F58%2F12%2F1026.atom
Interleukin-17A Is Dispensable for Myocarditis but Essential for the Progression to Dilated Cardiomyopathy
Authors: G. Christian Baldeviano, Jobert G. Barin, Monica V. Talor, Sachin Srinivasan, Djahida Bedja, Dongfeng Zheng, Kathleen Gabrielson, Yoichiro Iwakura, Noel R. Rose, Daniela Cihakova
Journal: Circulation Research (2010)

Rationale : One-third of myocarditis cases progresses to dilated cardiomyopathy (DCM), but the mechanisms controlling this process are largely unknown. CD4 + T helper (Th)17 cells have been implicated in the pathogenesis of autoimmune diseases, but the role of Th17-produced cytokines during inflammation-induced cardiac remodeling has not been previously studied. Objective : We examined the importance of interleukin (IL)-17A in the progression of myocarditis to DCM using a mouse model. Methods and Results : Immunization of mice with myocarditogenic peptide in complete Freund’s adjuvant induced the infiltration of IL-17A–producing Th17 cells into the inflamed heart. Unexpectedly, IL-17A–deficient mice developed myocarditis with similar incidence and severity compared to wild-type mice. Additionally, IL-17A deficiency did not ameliorate the severe myocarditis of interferon (IFN)γ-deficient mice, suggesting that IL-17A plays a minimal role during acute myocarditis. In contrast, IL-17A–deficient mice were protected from postmyocarditis remodeling and did not develop DCM. Flow cytometric and cytokine analysis revealed an important role for IL-17A in heart-specific upregulation of IL-6, TNFα, and IL-1β and the recruitment of CD11b + monocyte and Gr1 + granulocyte populations into the heart. Furthermore, IL-17A–deficient mice had reduced interstitial myocardial fibrosis, downregulated expression of matrix metalloproteinase-2 and -9 and decreased gelatinase activity. Treatment of BALB/c mice with anti–IL-17A monoclonal antibody administered after the onset of myocarditis abrogated myocarditis-induced cardiac fibrosis and preserved ventricular function. Conclusions : Our findings reveal a critical role for IL-17A in postmyocarditis cardiac remodeling and the progression to DCM. Targeting IL-17A may be an attractive therapy for patients with inflammatory dilated cardiomyopathy.
A STUDY OF THE DISTRIBUTION OF 2,4-DINITROBENZENE SENSITIZERS BETWEEN ISOLATED LYMPH NODE CELLS AND EXTRACELLULAR MEDIUM IN RELATION TO INDUCTION OF CONTACT SKIN SENSITIVITY
Authors: Herman N. Eisen, Milton Kern, William T. Newton, Ernst Helmreich
Journal: The Journal of Experimental Medicine (1959)

Although induction of contact skin sensitivity by low molecular weight 2,4-dinitrobenzenes requires the formation in vivo of 2,4-dinitrophenyl-proteins, analogous protein conjugates prepared in vitro are unable to induce this hypersensitive state. Low molecular weight 2,4-dinitrobenzenes are concentrated by isolated lymph node cells, but a representative 2,4-dinitrophenyl-protein conjugate (2,4-dinitrophenyl-bovine serum albumin) was not taken up to a detectable extent by these cells. It is inferred that there exist large quantitative differences in the extent to which dinitrophenyl-proteins are localized within cells following the administration to an intact animal of (a) those simple dinitrobenzenes which are both concentrated by lymph node cells and have the capacity to form protein conjugates in vivo, and (b) 2,4-dinitrophenyl-protein conjugates prepared in vitro. It is suggested that this difference could account for the fact that a varietyof 2,4-dinitrophenyl-proteins prepared in vitro are unable to induce contact skin sensitivity.
Pilot study of epothilone B analog (BMS-247550) and estramustine phosphate in patients with progressive metastatic prostate cancer following castration
Authors: O. Smaletz, M. Galsky, H.I. Scher, A. DeLaCruz, S.F. Slovin, M.J. Morris, D.B. Solit, U. Davar, L. Schwartz, W.K. Kelly
Journal: Annals of Oncology (2003)
Addition of gemtuzumab ozogamicin to induction chemotherapy in adult patients with acute myeloid leukaemia: a meta-analysis of individual patient data from randomised controlled trials
Authors: Robert K Hills, Sylvie Castaigne, Frederick R Appelbaum, Jacques Delaunay, Stephen Petersdorf, Megan Othus, Elihu H Estey, Hervé Dombret, Sylvie Chevret, Norbert Ifrah, Jean-Yves Cahn, Christian Récher, Lucy Chilton, Anthony V Moorman, Alan K Burnett
Journal: The Lancet Oncology (2014)
Outcomes of Elderly Patients after Predialysis Vascular Access Creation
Authors: Timmy Lee, Mae Thamer, Yi Zhang, Qian Zhang, Michael Allon
Journal: Journal of the American Society of Nephrology (2015)

Uniform vascular access guidelines for elderly patients may be inappropriate because of the competing risk of death, high rate of arteriovenous fistula (AVF) maturation failure, and poor vascular access outcomes in this population. However, the outcomes in elderly patients with advanced CKD who receive permanent vascular access before dialysis initiation are unclear. We identified a large nationally representative cohort of 3418 elderly patients (aged ≥ 70 years) with CKD undergoing predialysis AVF or arteriovenous graft (AVG) creation from 2004 to 2009, and assessed the frequencies of dialysis initiation, death before dialysis initiation, and dialysis-free survival for 2 years after vascular access creation. In all, 67% of patients with predialysis AVF and 71% of patients with predialysis AVG creation initiated dialysis within 2 years of access placement, but the overall risk of dialysis initiation was modified by patient age and race. Only one half of patients initiated dialysis with a functioning AVF or AVG; 46.8% of AVFs were created <90 days before dialysis initiation. Catheter dependence at dialysis initiation was more common in patients receiving predialysis AVF than in patients receiving AVG (46.0% versus 28.5%; P<0.001). In conclusion, most elderly patients with advanced CKD who received predialysis vascular access creation initiated dialysis within 2 years. As a consequence of late predialysis placement or maturation failure, almost one half of patients receiving AVFs initiated dialysis with a catheter. Insertion of an AVG closer to dialysis initiation may serve as a "catheter-sparing" approach and allow delay of permanent access placement in selected elderly patients with CKD.
Rituximab in Combination With Fludarabine Chemotherapy in Low-Grade or Follicular Lymphoma
Authors: M.S. Czuczman, A. Koryzna, A. Mohr, C. Stewart, K. Donohue, L. Blumenson, Z.P. Bernstein, P. McCarthy, A. Alam, F. Hernandez-Ilizaliturri, M. Skipper, K. Brown, A. Chanan-Khan, D. Klippenstein, P. Loud, M.K. Rock, M. Benyunes, A. Grillo-Lopez, S.H. Bernstein
Journal: Journal of Clinical Oncology (2005)

To evaluate the safety and efficacy of fludarabine plus rituximab in treatment-naive or relapsed patients with low-grade and/or follicular non-Hodgkin's lymphoma.This was an open-label, single-arm, single-center phase II study enrolling 40 patients. During the first week of the study, patients received two infusions of rituximab 375 mg/m2 administered 4 days apart. Seventy-two hours after the second infusion of rituximab, patients received the first of six cycles of fludarabine chemotherapy (25 mg/m2/d for 5 days on a 28-day cycle). Single infusions of rituximab were administered 72 hours before the second, fourth, and sixth cycles of fludarabine, and two infusions of rituximab were given 4 weeks after the last cycle of fludarabine. Treatment duration was 26 weeks.An overall response rate of 90% (80% complete response rate) was achieved in the intent-to-treat population. Similar response rates were seen in treatment-naive and previously treated patients. The median duration of response has not been reached at 40+ months. The median follow-up time in this study is 44 months (range, 15 to 66 months). In patients positive for the 14;18 translocation in blood and/or marrow at enrollment, molecular remission was achieved in 88% of cases, with patients remaining negative for up to 4 years to date. Hematologic toxicity was manageable, and except for a 15% incidence of herpes simplex/zoster infections, infectious complications were rare. Nonhematologic toxicities were minimal.Rituximab plus fludarabine was well tolerated and associated with an excellent complete response rate, including molecular remissions, in patients with low-grade or follicular lymphoma.
Syndrome of congenital ventricular diverticulum and midline thoraco-abdominal defects.
Authors: G Gula, M Yacoub
Journal: Thorax (1977)

The long-term follow-up of a 30-year-old patient who had a correction of the syndrome of left ventricular diverticulum and thoraco-abdominal defects is presented. The main features of the syndrome include a diverticulum of the left ventricle, a ventricular septal defect, and sometimes other cardiac anomalies. The thoraco-abdominal defects consist of foreshortened sternum, pericardial and diaphragmatic defects, and umbilical hernia. The association of these anomalies is thought to be due to a developmental failure of the primitive paramidline mesoderm. The diagnosis can be made clinically by the presence of a pulsatile, epigastric mass associated with signs of cardiac septal defects and dextrocardia. The prognosis of patients with this syndrome depends mainly on the associated abnormalities although rupture of the diverticulum can be a fatal complication. The treatment of choice is resection of the diverticulum combined with repair of associated anomalies which can give good early and late results.
End-of-Life Care for Older Patients With Ovarian Cancer Is Intensive Despite High Rates of Hospice Use
Authors: Alexi A. Wright, Laura A. Hatfield, Craig C. Earle, Nancy L. Keating
Journal: Journal of Clinical Oncology (2014)

To date, few studies have examined end-of-life care for patients with ovarian cancer. One study documented increased hospice use among older patients with ovarian cancer from 2000 to 2005. We sought to determine whether increased hospice use was associated with less-intensive end-of-life medical care.We identified 6,956 individuals age ≥ 66 years living in SEER areas who were enrolled in fee-for-service Medicare, diagnosed with epithelial ovarian cancer between 1997 and 2007, and died as a result of ovarian cancer by December 2007. We examined changes in medical care during patients' last month of life over time.Between 1997 and 2007, hospice use increased significantly, and terminal hospitalizations decreased (both P < .001). However, during this time, we also observed statistically significant increases in intensive care unit admissions, hospitalizations, repeated emergency department visits, and health care transitions (all P ≤ .01). In addition, the proportion of patients referred to hospice from inpatient settings rose over time (P = .001). Inpatients referred to hospice were more likely to enroll in hospice within 3 days of death than outpatients (adjusted odds ratio, 1.36; 95% CI, 1.12 to 1.66).Older women with ovarian cancer were more likely to receive hospice services near death and less likely to die in a hospital in 2007 compared with earlier years. Despite this, use of hospital-based services increased over time, and patients underwent more transitions among health care settings near death, suggesting that the increasing use of hospice did not offset intensive end-of-life care.
Developmental and oncogenic effects of Insulin-like Growth Factor-I in Ptc1+/- mouse cerebellum
Authors: Mirella Tanori, Melissa Santone, Mariateresa Mancuso, Emanuela Pasquali, Simona Leonardi, Vincenzo Di Majo, Simonetta Rebessi, Anna Saran, Simonetta Pazzaglia
Journal: Molecular Cancer (2010)

Abstract Background Medulloblastoma is amongst the most common malignant brain tumors in childhood, arising from neoplastic transformation of granule neuron precursors (GNPs) of the cerebellum via deregulation of pathways involved in cerebellar development. Deregulation of the Sonic hedgehog/Patched1 (Shh/Ptc1) signaling pathway predisposes humans and mice to medulloblastoma. In the brain, insulin-like growth factor (IGF-I) plays a critical role during development as a neurotrophic and neuroprotective factor, and in tumorigenesis, as IGF-I receptor is often activated in medulloblastomas. Results To investigate the mechanisms of genetic interactions between Shh and IGF signaling in the cerebellum, we crossed nestin/IGF-I transgenic (IGF-I Tg) mice, in which transgene expression occurs in neuron precursors, with Ptc1 +/- knockout mice, a model of medulloblastoma in which cancer develops in a multistage process. The IGF-I transgene produced a marked brain overgrowth, and significantly accelerated tumor development, increasing the frequency of pre-neoplastic lesions as well as full medulloblastomas in Ptc1 +/- /IGF-I Tg mice. Mechanistically, tumor promotion by IGF-I mainly affected preneoplastic stages through de novo formation of lesions, while not influencing progression rate to full tumors. We also identified a marked increase in survival and proliferation, and a strong suppression of differentiation in neural precursors. Conclusions As a whole, our findings indicate that IGF-I overexpression in neural precursors leads to brain overgrowth and fosters external granular layer (EGL) proliferative lesions through a mechanism favoring proliferation over terminal differentiation, acting as a landscape for tumor growth. Understanding the molecular events responsible for cerebellum development and their alterations in tumorigenesis is critical for the identification of potential therapeutic targets.
A Transcription-Independent Function of FOXO1 in Inhibition of Androgen-Independent Activation of the Androgen Receptor in Prostate Cancer Cells
Authors: Ping Liu, Shangwei Li, Lu Gan, Timothy P. Kao, Haojie Huang
Journal: Cancer Research (2008)

Abstract Increasing evidence suggests that aberrant activation of the androgen receptor (AR) plays a pivotal role in the development and progression of androgen depletion–independent prostate cancer (PCa) after androgen deprivation therapy. Here, we show that loss of the PTEN tumor suppressor gene is associated with hyperactivation of the AR in human PCa cell lines. This effect is mediated primarily by its downstream effector FOXO1. In addition to the inhibition of androgenic activation of the AR, forced expression of FOXO1 in PTEN-negative PCa cells also inhibits androgen-independent activation of the AR in a manner independent of FOXO1 transcriptional function. In contrast, silencing of FOXO1 in PTEN-positive cells not only increases the basal activity of the AR in the absence of androgens, it also markedly sensitizes the AR activation by low levels of androgens or nonandrogenic factors such as interleukin-6. FOXO1-mediated inhibition of the AR is partially attenuated by the histone deacetylase (HDAC) inhibitor trichostatin A. Accordingly, FOXO1 interacts with HDAC3 as shown by coimmunoprecipitation assays, and cotransfection of cells with FOXO1 and HDAC3, but not HDAC1 and HDAC2, results in a greater inhibition of AR activity than in cells transfected with FOXO1 or HDAC3 individually. Together, our findings define a novel corepressor function of FOXO1 in inhibition of androgen-independent activation of the AR. [Cancer Res 2008;68(24):10290–9]
Endocannabinoids as biomarkers of human reproduction
Authors: Cinzia Rapino, Natalia Battista, Monica Bari, Mauro Maccarrone
Journal: Human Reproduction Update (2014)

Infertility is a condition of the reproductive system that affects ∼10–15% of couples attempting to conceive a baby. More than half of all cases of infertility are a result of female conditions, while the remaining cases can be attributed to male factors, or to a combination of both. The search for suitable biomarkers of pregnancy outcome is a challenging issue in human reproduction, aimed at identifying molecules with predictive significance of the reproductive potential of male and female gametes. Among the various candidates, endocannabinoids (eCBs), and in particular anandamide (AEA), represent potential biomarkers of human fertility disturbances. Any perturbation of the balance between synthesis and degradation of eCBs will result in local changes of their tone in human female and male reproductive tracts, which in turn regulates various pathophysiological processes, oocyte and sperm maturation included. PubMed and Web of Science databases were searched for papers using relevant keywords like 'biomarker', 'endocannabinoid', 'infertility', 'pregnancy' and 'reproduction'. In this review, we discuss different studies on the measurements of AEA and related eCBs in human reproductive cells, tissues and fluids, where the local contribution of these bioactive lipids could be critical in ensuring normal sperm fertilizing ability and pregnancy. Based on the available data, we suggest that the AEA tone has the potential to be exploited as a novel diagnostic biomarker of infertility, to be used in association with assays of conventional hormones (e.g. progesterone, β-chorionic gonadotrophin) and semen analysis. However further quantitative research of its predictive capacity is required.
Milk intake and risk of mortality and fractures in women and men: cohort studies
Authors: K. Michaelsson, A. Wolk, S. Langenskiold, S. Basu, E. Warensjo Lemming, H. Melhus, L. Byberg
Journal: BMJ (2014)

<b>Objective</b> To examine whether high milk consumption is associated with mortality and fractures in women and men. <b>Design</b> Cohort studies. <b>Setting</b> Three counties in central Sweden. <b>Participants</b> Two large Swedish cohorts, one with 61 433 women (39-74 years at baseline 1987-90) and one with 45 339 men (45-79 years at baseline 1997), were administered food frequency questionnaires. The women responded to a second food frequency questionnaire in 1997. <b>Main outcome measure</b> Multivariable survival models were applied to determine the association between milk consumption and time to mortality or fracture. <b>Results</b> During a mean follow-up of 20.1 years, 15 541 women died and 17 252 had a fracture, of whom 4259 had a hip fracture. In the male cohort with a mean follow-up of 11.2 years, 10 112 men died and 5066 had a fracture, with 1166 hip fracture cases. In women the adjusted mortality hazard ratio for three or more glasses of milk a day compared with less than one glass a day was 1.93 (95% confidence interval 1.80 to 2.06). For every glass of milk, the adjusted hazard ratio of all cause mortality was 1.15 (1.13 to 1.17) in women and 1.03 (1.01 to 1.04) in men. For every glass of milk in women no reduction was observed in fracture risk with higher milk consumption for any fracture (1.02, 1.00 to 1.04) or for hip fracture (1.09, 1.05 to 1.13). The corresponding adjusted hazard ratios in men were 1.01 (0.99 to 1.03) and 1.03 (0.99 to 1.07). In subsamples of two additional cohorts, one in males and one in females, a positive association was seen between milk intake and both urine 8-iso-PGF2α (a biomarker of oxidative stress) and serum interleukin 6 (a main inflammatory biomarker). <b>Conclusions</b> High milk intake was associated with higher mortality in one cohort of women and in another cohort of men, and with higher fracture incidence in women. Given the observational study designs with the inherent possibility of residual confounding and reverse causation phenomena, a cautious interpretation of the results is recommended.
A–Z of nutritional supplements: dietary supplements, sports nutrition foods and ergogenic aids for health and performance – Part 28
Authors: K Currell, D R Moore, P Peeling, L M Burke, S J Stear, L M Castell
Journal: British Journal of Sports Medicine (2011)

Part 28 includes a supplement purported to combat fatigue and enhance growth hormone (ornithine); a well-known ingredient (phenylalanine) of a well-known sweetener (aspartame); a possible energy enhancer via 2,3 diphosphoglycerate (phosphate); and a rather dubious supplement purported in the early 1940s to have a wide range of medicinal effects (pangamic acid). Of these, only phosphate appears to have some credible evidence to support the claims of an ergogenic effect.

### K Currell

Ornithine is an amino acid which plays a key role in the urea cycle, facilitating the disposal of ammonia. Ammonia is produced during intense exercise and may be one of the causes of fatigue. There is some evidence that L-ornithine hydrochloride supplementation prior to high-intensity exercise may prevent fatigue and improve performance by modulating the metabolism of ammonia.1 At present, the evidence is far from conclusive with a need to conduct more research using valid measures of performance.

It has been suggested that ornithine supplementation will promote the secretion of growth hormone within humans.2 However, research has not been conducted to show whether this may enhance the adaptation to training and ultimately lead to an improvement in the performance.

One potential avenue of future research is ornithine-α-ketoglutarate. This has been shown to improve the recovery of individuals from burns, trauma and in the postoperative state. It may also be a precursor of nitric oxide.2 At present, there is not enough evidence to support the use of ornithine in sport performance. However, further research should be conducted to investigate its use.

### DR Moore

Phenylalanine is …
A common NKCC2 mutation in Costa Rican Bartter's syndrome patients
Authors: C L Kurtz, L Karolyi, H W Seyberth, M C Koch, R Vargas, D Feldmann, M Vollmer, N V Knoers, G Madrigal, L M Guay-Woodford
Journal: Journal of the American Society of Nephrology (1997)

Bartter's syndrome involves an overlapping set of closely related renal tubular disorders that can be subdivided into at least three clinical phenotypes: (1) the hypercalciuric antenatal Bartter variant; (2) the classic Bartter variant; and (3) the hypocalciuric-hypomagnesemic Gitelman variant. Recent data demonstrate that in several phenotypically indistinguishable cohorts, antenatal Bartter's syndrome is genetically heterogeneous. In these patients, mutations in the genes encoding either the bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2) or the ATP-regulated potassium channel ROMK (KCNJI) have been identified. A cohort of 20 Costa Rican patients with a congenital syndrome that bears strong similarities to antenatal Bartter's syndrome but also has several distinct features has recently been described. In this cohort, we have identified a predominant mutation that introduces a premature stop in codon W625 of the NKCC2 gene (SCL12A1). This mutant allele is contained on a single common haplotype, suggesting that the majority of antenatal Bartter's syndrome patients in Costa Rica share a single common ancestor.