tbuckley/cabot-search huggingface dataset:
A Randomised Study Comparing the Effects of Adjuvant Anastrozole (A), Letrozole (L) and Exemestane (E) on Lipid Metabolism.
Authors: F. McCaig, L. Renshaw, L. Williams, O. Young, J. Murray, E. Macaskill, M. McHugh, R. Riermersma, D. Evans, J. Dixon
Journal: Cancer Research (2009)

Abstract Background:Aromatase inhibitors (AIs) reduce circulating oestrogen which may have a detrimental effect on lipid metabolism and subsequently ↑ cardiovascular risk. This study compares the effects of adjuvant A, L and E on lipid metabolism.Patients and Methods:This was an open, randomised pharmacodynamic study. Plasma lipids were measured in 120 postmenopausal women with invasive ER +ve breast cancer. As part of their adjuvant hormone therapy, patients were randomized to receive either:• 4 months of A or• 4 months of L or• 4 months of EFasting blood and urine samples were collected at the same time of day on each of (a) the day of entry, (b) after 3 months and (c) after 4 months. Patients were then switched to tamoxifen (T) and further samples collected after 12 months.• Triglycerides, cholesterol, ApoB and cLDL were measured.↑ levels are associated with ↑ cardiovascular risk.• ApoA-1 and HDL were also measured.↑ levels are associated with ↓ cardiovascular risk.Analyses were performed using repeated measures or analysis of covariance.ResultsDifferences between A vs L vs ETriglycerides E significantly ↓ triglycerides. There was a borderline significant difference between the drugs (p=0.055).Cholesterol E significantly ↓ cholesterol (p=0.03).ApoB No significant changes were detected.cLDL No significant changes were detected.ApoA-1 There were no significant differences detected between A or L although the fall with E was less but not significantly different to A or L (p=0.08).HDL E significantly ↓ HDL (p=0.008).Differences between steroidal vs non-steroidal AIsTriglyceride and ApoA-1 levels fell significantly more with E compared to the non-steroidal A+L (p=0.02, p=0.045 respectively).Effects of tamoxifenChanges from baseline after treatment on AIs and subsequent treatment with TFollowing T there was no evidence to suggest that the changes from baseline were influenced by the type of AI that patients received.Changes from end of treatment on AIs and subsequent treatment with TT increased HDL by a statistically significant greater amount following E than it did after A or L (p=0.009). From the end of treatment with AIs, T produced significant rises in triglyceride (p=0.0001), HDL (p=0.006) and ApoA1 (p=0.0003), and significant falls in cholesterol (p=0.03) and cLDL (p&amp;lt;0.0001).Conclusions:There were no significant differences between letrozole, anastrozole and exemestane and their effects on cholesterol, HDL, cLDL or ApoB.There was a significant difference between steroidal and non-steroidal in their effect on triglycerides and ApoA1.Tamoxifen had significant effects on lipids lowering cholesterol and cLDL and increasing triglycerides HDL and ApoA-1. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4086.
Gastrin-Releasing Peptide Receptor-Mediated Autocrine Growth in Squamous Cell Carcinoma of the Head and Neck
Authors: M. N. Lango
Journal: JNCI Journal of the National Cancer Institute (2002)

Background: Gastrin-releasing peptide receptor (GRPR)-mediated autocrine growth appears to be an early marker of susceptibility to tobacco-related lung cancers. Because expression of GRPR, however, has not been reported in squamous cell carcinoma of the head and neck (SCCHN), we investigated its expression and that of its ligand GRP in normal mucosa and SCCHN tissues and the involvement of these proteins in the proliferation of SCCHN cells. Methods: We assessed GRPR messenger RNA (mRNA) expression in specimens from 25 patients with SCCHN, six control noncancer patients, and 14 SCCHN cell lines by use of quantitative reverse transcriptase–polymerase chain reaction. We used neutralizing GRP monoclonal antibody 2A11 to block the GRP–GRPR interaction in SCCHN cell lines and xenografts and assessed the antibody's effect on proliferation by counting cultured cells or measuring xenograft tumor volume in vivo. All statistical tests were two-sided. Results: Tumor and mucosa tissues, respectively, from SCCHN patients expressed sixfold and fourfold higher levels of GRPR mRNA than normal mucosa tissue from noncancer patients (P<.001). The levels of GRPR expression in the tumor and adjacent normal epithelium of individual patients with SCCHN were correlated (r = .652; P = .001), suggesting that increased GRPR expression is an early event in SCCHN formation. SCCHN cells expressed fivefold higher levels of GRPR mRNA than did cultured normal mucosal epithelial cells (P = .005). GRP stimulated proliferation of SCCHN cells in a dose-dependent fashion (P = .006). Neutralizing GRP monoclonal antibody 2A11 inhibited SCCHN cell proliferation in vitro and in vivo. Median survival was 54 months in patients with higher levels of GRPR mRNA and was not reached in those with lower levels. Conclusions: GRP and GRPR appear to participate in an autocrine regulatory pathway in SCCHN. Thus, strategies that specifically target GRP and/or GRPR may be effective therapeutic approaches for this disease.
Retrospective estimation of values for total lung capacity by plethysmography, helium gas dilution, and chest radiography in patients with cystic fibrosis.
Authors: R Cutrera, P Helms
Journal: Thorax (1988)

In children with cystic fibrosis, total lung capacity was estimated by helium dilution, plethysmography, and radiography. None of these methods should be used interchangeably as the 95% confidence intervals for estimating were large at 58-144% for radiography and 45.3-100.4% for helium dilution.
Future of Food Standards Agency and other quangos is uncertain
Authors: A. O'Dowd
Journal: BMJ (2010)

The future of the Food Standards Agency and other arm’s length health bodies is still uncertain after this week’s health service white paper.

The agency, the UK watchdog that monitors food safety and standards, was rumoured to be a target for closure by the coalition government in its attempts to save money, but closure was not mentioned in the white paper published this week ( BMJ 2010;341:c3796, doi:10.1136/bmj.c3796).

The Department of Health in England is due to publish a review of arm’s length bodies within the next month, which …
Detection of engraftment and chimerism after bone marrow transplantation by in situ hybridization using a Y‐chromosome specific probe
Authors: Kazunaga Agematsu, Fuminori Kitahara, Yoshio Uehara, Hiroshi Kawai, Yukiaki Miyagawa, Atsushi Komiyama, Yutaka Nakahori, Yasuo Nakagome, Taro Akabane
Journal: American Journal of Hematology (1990)

Abstract After bone marrow transplantation (BMT), the recipient and donor cells must be distinguished from each other to document and characterize successful engraftment. In addition to dot blot and Southern blot analyses, we have performed in situ hybridization in two sex‐mismatched cases using a Y‐chormosome specific DNA probe (PHY10). In situ hybridization showed that &gt;95% of the peripheral mononculear cells had clusters of grains indicative of male cell origin in a recipient girl (case 1), and no cells had clusters of grains in another recipient boy (case 2) at the time of engraftment and 3 months after BMT. In situ hybridization using the PHY10 probe appears to facilitate identification of individual cells of male and female origin, and it requires only 20 hr to obtain the results. The technique provides a powerful new method for the documentation of engraftment and the detection of mixed hematopoietic chimerism in peripheral blood and bone marrow cell compartments after BMT.
Sperm banking and assisted reproduction treatment for couples following cancer treatment of the male partner
Authors: Amir Lass, Fidelis Akagbosu, Peter Brinsden
Journal: Human Reproduction Update (2001)

In recent years, the survival of young males suffering from cancer has been improved. Development of new techniques such as IVF and intracytoplasmic sperm injection enables even low quality spermatozoa to be used successfully. It is possible therefore to preserve fertility potential of cancer patients before embarking on adjuvant chemotherapy and radiotherapy. Recognizing the importance of protecting the fertility potential of these young males, we present our recommendations for sperm cryopreservation based on the 11 year experience of Bourn Hall and the British Joint Council for Clinical Oncology consultation report. This paper discusses the options available for patients who recover from cancer to become fathers. In many cases patients are concerned about possible abnormalities and teratogenic risks to their future children who have been conceived naturally or by fertility treatment. The data available in the literature may reassure the medical community that there is no such increased risk. However, due to the relatively small number of children born after such treatment, a long-term follow-up is required. There is an ongoing debate regarding the justification for the programme due to the small number of patients who make use of their banked spermatozoa. The authors believe in the importance of protecting the fertility potential of cancer patients, enabling them to father their genetic children in the future while fighting their illness.
Efficacy and safety of rifampicin for multiple system atrophy: a randomised, double-blind, placebo-controlled trial
Authors: Phillip A Low, David Robertson, Sid Gilman, Horacio Kaufmann, Wolfgang Singer, Italo Biaggioni, Roy Freeman, Susan Perlman, Robert A Hauser, William Cheshire, Stephanie Lessig, Steven Vernino, Jay Mandrekar, William D Dupont, Thomas Chelimsky, Wendy R Galpern
Journal: The Lancet Neurology (2014)
Topical Treatment with Inhibitors of the Phosphatidylinositol 3′-Kinase/Akt and Raf/Mitogen-Activated Protein Kinase Kinase/Extracellular Signal-Regulated Kinase Pathways Reduces Melanoma Development in Severe Combined Immunodeficient Mice
Authors: Barbara Bedogni, Melony S. O’Neill, Scott M. Welford, Donna M. Bouley, Amato J. Giaccia, Nicholas C. Denko, Marianne Broome Powell
Journal: Cancer Research (2004)

Abstract Topical treatment with inhibitors of the phosphatidylinositol 3′-kinase/Akt and Raf/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathways inhibited the growth of TPras transgenic melanomas in severe combined immunodeficient mice, blocked invasive behavior, and reduced angiogenesis. The inhibitor Ly294002, which is specific for phosphatidylinositol 3′-kinase, effectively reduced melanoma cell growth both in vitro and in vivo. Both Ly294002 and U0126, a mitogen-activated protein kinase kinase 1/2 inhibitor, reduced invasion, which correlated with reduction of the metalloproteinase matrix metalloproteinase 2. Tumor angiogenesis was disrupted through inhibition of vascular endothelial growth factor production from the tumor cells and antiangiogenic effects on endothelial cells. Observations with TPras melanoma cells that express dominant negative Δp85 or kinase-inactive Raf301 supported the specificity of the phenomena observed with the chemical inhibitors. These studies demonstrate that topical treatment targeting Ras effectors is efficacious, without systemic toxicities, and may prove to be useful in treating and preventing the progression of cutaneous melanoma.
Investigation of the parallel conductor model of impedance cardiography by means of exchange transfusion with stroma free haemoglobin solution in the dog
Authors: K. R VISSER, R. LAMBERTS, W. G ZIJLSTRA
Journal: Cardiovascular Research (1987)

To test one of the assumptions underlying the calculation of stroke volume — namely, that the transthoracic impedance consists of a parallel connection of a tissue impedance and a blood resistance—experiments were carried out on four dogs in which blood was gradually replaced by a stroma free haemoglobin solution, with the purpose of changing the blood resistance while leaving the tissue impedance unchanged. This was accomplished by exchange transfusion in such a way that the volume of the circulating fluid remained constant and the distribution of fluid volume between the fluid compartments was not altered. During the exchange transfusions the mean decrease in resistivity of the circulating fluid was 54%. The packed cell volume and resistivity of every volume of removed circulating fluid were measured. Just before each exchange the real and imaginary parts of the transthoracic impedance were measured. The packed cell volume decreased exponentially with the number of exchanges. This indicates that the circulating fluid volume remained constant during the exchange transfusion. From the packed cell volumes an estimate of the circulating fluid volume was made. Because of the parallel connection all calculations were based on the use of admittance, which is the reciprocal value of impedance. The real and imaginary parts of the transthoracic admittance were calculated from the measured values of the real and imaginary parts of the transthoracic impedance. The real part (thoracic conductance) increased linearly with the conductivity of the circulating fluid whereas the imaginary part (thoracic susceptance) remained constant. This is in agreement with the model. The components of the model were estimated from the values of the thoracic conductance and susceptance. For a packed cell volume of 40% the mean values of the tissue impedance, the blood resistance, and the transthoracic impedance were 46, 712, and 43 Ω respectively. The mean values of the arguments (phase angles) of tissue impedance and thoracic impedance were 12.4° and 11.8° respectively.
Genetic Variant as a Selection Marker for Anti–Prostate Stem Cell Antigen Immunotherapy of Bladder Cancer
Authors: Indu Kohaar, Patricia Porter-Gill, Petra Lenz, Yi-Ping Fu, Adam Mumy, Wei Tang, Andrea B. Apolo, Nathaniel Rothman, Dalsu Baris, Alan R. Schned, Kris Ylaya, Molly Schwenn, Alison Johnson, Michael Jones, Masatoshi Kida, Debra T. Silverman, Stephen M. Hewitt, Lee E. Moore, Ludmila Prokunina-Olsson
Journal: JNCI Journal of the National Cancer Institute (2012)

A monoclonal antibody against prostate stem cell antigen (PSCA) has emerged as a novel cancer therapy currently being tested in clinical trials for prostate and pancreatic cancers, but this treatment is likely to be efficient only in patients with PSCA-expressing tumors. The present study demonstrates that a genetic variant (rs2294008) discovered by bladder cancer genome-wide association studies is a strong predictor of PSCA protein expression in bladder tumors, as measured by two-sided multivariable linear regression (P = 6.46×10(-11); n = 278). The association pattern is similar in non-muscle-invasive tumors, stages Ta (P = 3.10×10(-5); n = 173) and T1 (P = 2.64×10(-5); n = 60), and muscle-invasive tumors, stages T2 (P =.01; n = 23) and T3/4 (P =.03; n = 22). The study suggests that anti-PSCA immunotherapy might be beneficial for bladder cancer patients with high tumor PSCA expression, which is statistically significantly associated with the presence of CT and TT genotypes of a common genetic variant, rs2294008. Future clinical studies will be needed to validate PSCA as a therapeutic target for bladder cancer.
Indian group seeks ban on use of electroconvulsive therapy without anaesthesia
Authors: G. Mudur
Journal: BMJ (2002)

A voluntary medical organisation in India has urged the Indian Supreme Court to ban the use of electroconvulsive therapy without anaesthesia in mentally ill patients, a practice that some Indian psychiatrists say is sometimes unavoidable.

The request, which also seeks to make informed consent mandatory in all electroconvulsive therapy procedures, comes after nearly a decade of concern among doctors that electroconvulsive therapy is overused in India and often administered without anaesthesia.

“All we're asking for is that all psychiatrists should follow good practice guidelines,” said Dr Achal Bhagat, …
Genetic control of alpha-fetoprotein synthesis in the mouse.
Authors: M Olsson, G Lindahl, E Ruoslahti
Journal: The Journal of Experimental Medicine (1977)

To approach the genetic mechanism that turns off the synthesis of alpha-fetoprotein (AFP) after birth, we assumed that a change in this mechanism might affect the low basal level of AFP that can be detected in the adult organism. The concentration of AFP was therefore determined for serum from adult mice of 27 different inbred strains. With one exception, this basal level was between 34 and 173 ng/ml, which is about 10(5)-fold less than the serum concentration at birth. In one strain, BALB/c/J, the AFP level was found to be considerably increased; it was about 10-fold higher than in other strains at 9-10 wk of age. Two other substrains of BALF/c mice showed normally low AFP levels. Kinetic studies show that the rate with which AFP disappears from serum after birth is reduced in BALB/c/J mice as compared to other strains. The increased AFP level of BALB/c/J mice appears to be due to an increased rate of synthesis of AFP, since the rate of catabolism of AFP was found to be normal in these mice. Genetic analysis was performed by crossing BALB/c/J mice with mice having an ordinary AFP level, followed by determination of AFP levels in mice of the F1 and F2 generations as well as in back-cross mice. The results clearly indicate that the increased AFP level in BALB/c/J mice is controlled by a single recessive Mendelian gene, which has been named Raf (for regulation of alphafetoprotein). The Raf gene could be directly involved in the regulation of AFP synthesis, but it may also control AFP levels only indirectly, e.g., by regulating the synthesis of a hormone that controls AFP synthesis.
Different Selective Pressures Shape the Molecular Evolution of Color Vision in Chimpanzee and Human Populations
Authors: B. C. Verrelli, C. M. Lewis, A. C. Stone, G. H. Perry
Journal: Molecular Biology and Evolution (2008)

A population genetic analysis of the long-wavelength opsin (OPN1LW, "red") color vision gene in a global sample of 236 human nucleotide sequences had previously discovered nine amino acid replacement single nucleotide polymorphisms, which were found at high frequencies in both African and non-African populations and associated with an unusual haplotype diversity. Although this pattern of nucleotide diversity is consistent with balancing selection, it has been argued that a recombination "hot spot" or gene conversion within and between X-linked color vision genes alone may explain these patterns. The current analysis investigates a closely related primate with trichromatism to determine whether color vision gene amino acid polymorphism and signatures of adaptive evolution are characteristic of humans alone. Our population sample of 56 chimpanzee (Pan troglodytes) OPN1LW sequences shows three singleton amino acid polymorphisms and no unusual recombination or linkage disequilibrium patterns across the ∼5.5-kb region analyzed. Our comparative population genetic approach shows that the patterns of OPN1LW variation in humans and chimpanzees are consistent with positive and purifying selection within the two lineages, respectively. Although the complex role of color vision has been greatly documented in primate evolution in general, it is surprising that trichromatism has followed very different selective trajectories even between humans and our closest relatives.
Residual Venous Thrombosis as a Predictive Factor of Recurrent Venous Thromboembolism
Authors: Paolo Prandoni
Journal: Annals of Internal Medicine (2002)

Background: The optimum duration of anticoagulant therapy after an episode of deep venous thrombosis (DVT) is controversial. Contributing to the controversy is uncertainty about whether residual venous thrombosis, as assessed by repeated ultrasonography over time, increases the risk for recurrent thromboembolism. Objective: To determine the risk for recurrent thromboembolism in patients who have persistent residual thrombosis compared with patients who have early vein recanalization. Design: Prospective cohort study. Setting: A university hospital in Padua, Italy. Patients: 313 consecutive symptomatic outpatients with proximal DVT who received conventional short-term anticoagulation. Measurements: Ultrasonographic assessment of the common femoral and popliteal veins was performed 3 months after acute DVT in all patients and at 6, 12, 24, and 36 months in patients found to have residual venous thrombosis. Veins were considered recanalized if they were 2.0 mm or less in diameter on a single test or 3.0 mm or less in diameter on two consecutive tests. Recurrent thromboembolism was assessed during a 6-year period. Results: The cumulative incidence of normal results on ultrasonography was 38.8% at 6 months, 58.1% at 12 months, 69.3% at 24 months, and 73.8% at 36 months. Of 58 recurrent episodes, 41 occurred while the patient had residual thrombosis. The hazard ratio for recurrent thromboembolism was 2.4 (95% CI, 1.3 to 4.4; P = 0.004) for patients with persistent residual thrombosis versus those with early vein recanalization. Conclusions: Residual venous thrombosis is an important risk factor for recurrent thromboembolism. Ultrasonographic assessment of residual venous thrombosis may help clinicians modify the duration of anticoagulation in patients with DVT.
Ustekinumab improves health-related quality of life in patients with moderate-to-severe psoriasis: results from the PHOENIX 1 trial
Authors: M. Lebwohl, K. Papp, C. Han, B. Schenkel, N. Yeilding, Y. Wang, G.G. Krueger
Journal: British Journal of Dermatology (2009)

Journal Article Ustekinumab improves health‐related quality of life in patients with moderate‐to‐severe psoriasis: results from the PHOENIX 1 trial Get access M. Lebwohl, M. Lebwohl Mount Sinai School of Medicine, New York, NY, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar K. Papp, K. Papp Probity Medical Research, Waterloo and University of Western Ontario, London, ON, Canada Search for other works by this author on: Oxford Academic Google Scholar C. Han, C. Han Worldwide Health Economics, Johnson & Johnson Pharmaceutical Services, LLC, Horsham, PA, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar B. Schenkel, B. Schenkel Worldwide Health Economics, Johnson & Johnson Pharmaceutical Services, LLC, Horsham, PA, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar N. Yeilding, N. Yeilding Centocor Research & Development, Inc., Malvern, PA, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar Y. Wang, Y. Wang Centocor Research & Development, Inc., Malvern, PA, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar G.G. Krueger G.G. Krueger University of Utah, 30 N. 1900 East, Suite 4A‐330, Salt Lake City, UT 84132, U.S.A. Gerald G. Krueger. E‐mail: gerald.krueger@derm.med.utah.edu Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 162, Issue 1, 1 January 2010, Pages 137–146, https://doi.org/10.1111/j.1365-2133.2009.09491.x Published: 01 January 2010
Occult Para-Aortic Lymph Node Metastasis After Negative Positron Emission Tomography/Computed Tomography Scan
Authors: Sokbom Kang, Sang Soo Seo, Sang Yoon Park
Journal: Journal of Clinical Oncology (2008)

concerning our recently published article.Kang et al add interesting data, reporting their own experience about the correlation between histology and positron emission tomography combined with computed tomography (PET-CT) in advanced stage cervical carcinoma.Among 24 patients reported with negative PET-CT imaging in the para-aortic area, two patients (8.3%) had histologically involved para-aortic nodes.This result is similar to those reported in our series, and seems to suggest that the false-negative rate of PET-CT imaging should be close to 10%. 1 As suggested by Kang et al and in our study, such results would justify including surgical staging in the para-aortic area to precisely define the level of chemoradiotherapy fields. 2,3Furthermore, a recent article seems to demonstrate that this staging surgery improves the survival of patients with advanced-stage