tbuckley/cabot-search huggingface dataset:
Fetal Exposure to Altered Amniotic Fluid Glucose, Insulin, and Insulin-Like Growth Factor–Binding Protein 1 Occurs Before Screening for Gestational Diabetes Mellitus
Authors: Daniel K. Tisi, David H. Burns, Gary W. Luskey, Kristine G. Koski
Journal: Diabetes Care (2010)

OBJECTIVE We explored the possibility that perturbations in amniotic fluid glucose, insulin, and insulin-like growth factor–binding protein 1(IGFBP1) and/or metabolic acids exist before routine screening for GDM. RESEARCH DESIGN AND METHODS We selected consenting mother-infant pairs (n = 408) who met our inclusion criteria (singleton pregnancy, no genetic abnormalities, and no preexisting diabetes) and for whom sufficient amniotic fluid and appropriate medical information were available. We compared birth outcomes and second trimester amniotic fluid glucose, insulin, IGFBP1 concentrations, and amniotic fluid lactic, β-hydroxybutyric, and uric acids of mothers with gestational diabetes mellitus (GDM) (n = 52) with those of mothers with no diagnosis of GDM at &amp;gt;24 weeks (n = 356). RESULTS Higher amniotic fluid glucose, lactic acid, uric acid, and insulin and lower IGFBP1 concentrations were present by 15.1 ± 0.1 weeks in mothers in whom GDM was subsequently diagnosed. However, logistic regression showed that second trimester amniotic fluid glucose, but not insulin, IGFBP1, or metabolic acids was associated with an increased odds ratio (1.2 [95% CI 1.052–1.338]) for diagnosis of GDM at 24–28 weeks. In addition, probability contour maps that accounted for nonlinear relationships among the dynamically changing amniotic fluid constituents showed an increased risk for GDM with elevated second trimester amniotic fluid glucose in combination with either elevated amniotic fluid insulin or low amniotic fluid IGFBP1 CONCLUSIONS Fetuses are exposed to increased amniotic fluid glucose before 15 weeks of gestation, suggesting that metabolic perturbations are underway before diagnosis and that earlier screening and intervention may be warranted.
Phase III Randomized Trial of Weekly Cisplatin and Irradiation Versus Cisplatin and Tirapazamine and Irradiation in Stages IB2, IIA, IIB, IIIB, and IVA Cervical Carcinoma Limited to the Pelvis: A Gynecologic Oncology Group Study
Authors: Paul A. DiSilvestro, Shamshad Ali, Peter S. Craighead, Joseph A. Lucci, Yi-Chun Lee, David E. Cohn, Nicola M. Spirtos, Krishnasu S. Tewari, Carolyn Muller, Walter H. Gajewski, Margaret M. Steinhoff, Bradley J. Monk
Journal: Journal of Clinical Oncology (2014)

Purpose This prospective, randomized phase III intergroup trial of the Gynecologic Oncology Group and National Cancer Institute of Canada Clinical Trials Group was designed to test the effectiveness and safety of adding the hypoxic cell sensitizer tirapazamine (TPZ) to standard cisplatin (CIS) chemoradiotherapy in locally advanced cervix cancer. Patients and Methods Patients with locally advanced cervix cancer were randomly assigned to CIS chemoradiotherapy versus CIS/TPZ chemoradiotherapy. Primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS) and tolerability. Results PFS was evaluable in 387 of 402 patients randomly assigned over 36 months, with enrollment ending in September 2009. Because of the lack of TPZ supply, the study did not reach its original target accrual goal. At median follow-up of 28.3 months, PFS and OS were similar in both arms. Three-year PFS for the TPZ/CIS/RT and CIS/RT arms were 63.0% and 64.4%, respectively (log-rank P = .7869). Three-year OS for the TPZ/CIS/RT and CIS/RT arms were 70.5% and 70.6%, respectively (log-rank P = .8333). A scheduled interim safety analysis led to a reduction in the starting dose for the TPZ/CIS arm, with resulting tolerance in both treatment arms. Conclusion TPZ/CIS chemoradiotherapy was not superior to CIS chemoradiotherapy in either PFS or OS, although definitive commentary was limited by an inadequate number of events (progression or death). TPZ/CIS chemoradiotherapy was tolerable at a modified starting dose.
Sorafenib Has Potent Antitumor Activity against Multiple Myeloma <i>In Vitro</i>, <i>Ex Vivo</i>, and <i>In Vivo</i> in the 5T33MM Mouse Model
Authors: Pedram Kharaziha, Hendrik De Raeve, Charlotte Fristedt, Qiao Li, Astrid Gruber, Per Johnsson, Georgia Kokaraki, Maria Panzar, Edward Laane, Anders Österborg, Boris Zhivotovsky, Helena Jernberg-Wiklund, Dan Grandér, Fredrik Celsing, Magnus Björkholm, Karin Vanderkerken, Theocharis Panaretakis
Journal: Cancer Research (2012)

Abstract Multiple myeloma (MM) is a B-cell malignancy characterized by the expansion of clonal plasma blasts/plasma cells within the bone marrow that relies on multiple signaling cascades, including tyrosine kinase activated pathways, to proliferate and evade cell death. Despite emerging new treatment strategies, multiple myeloma remains at present incurable. Thus, novel approaches targeting several signaling cascades by using the multi-tyrosine kinase inhibitor (TKI), sorafenib, seem a promising treatment approach for multiple myeloma. Here, we show that sorafenib induces cell death in multiple myeloma cell lines and in CD138+-enriched primary multiple myeloma patient samples in a caspase-dependent and -independent manner. Furthermore, sorafenib has a strong antitumoral and -angiogenic activity in the 5T33MM mouse model leading to increased overall survival. Multiple myeloma cells undergo autophagy in response to sorafenib, and inhibition of this cytoprotective pathway potentiated the efficacy of this TKI. Mcl-1, a survival factor in multiple myeloma, is downregulated at the protein level by sorafenib allowing for the execution of cell death, as ectopic overexpression of this protein protects multiple myeloma cells. Concomitant targeting of Mcl-1 by sorafenib and of Bcl-2/Bcl-xL by the antagonist ABT737 improves the efficacy of sorafenib in multiple myeloma cell lines and CD138+-enriched primary cells in the presence of bone marrow stromal cells. Altogether, our data support the use of sorafenib as a novel therapeutic modality against human multiple myeloma, and its efficacy may be potentiated in combination with ABT737. Cancer Res; 72(20); 5348–62. ©2012 AACR.
Occupational Low Back Pain
Authors: J A D Anderson
Journal: Annals of the Rheumatic Diseases (1985)

In summary, in patients with Raynaud's syndrome, a 72-hour infusion of PGE1 failed to provide a more marked improvement than a 72-hour infusion of placebo.There was, however, a statistically significant improvement from preinfusion values in both placebo-and PGEI-treated patients.
Redefining the Role of Doxorubicin for the Treatment of Children With Hepatoblastoma
Authors: Marcio H. Malogolowkin, Howard M. Katzenstein, Mark Krailo, Zhengjia Chen, John J. Quinn, Marleta Reynolds, Jorge A. Ortega
Journal: Journal of Clinical Oncology (2008)

Systemic chemotherapy has improved the survival of patients with hepatoblastoma (HB). INT-0098 Intergroup Liver Tumor Study demonstrated that patients with HB treated with either cisplatin/fluorouracil/vincristine (CFV) or cisplatin/doxorubicin (CD) had a similar survival. The Children's Oncology Group adopted the less toxic CFV as the standard regimen for treating HB. However, international cooperative groups still favor the CD combination. We therefore decided to revisit the role of doxorubicin for the treatment of HB.Outcomes of patients with HB on the INT-0098 study were reviewed with an emphasis on the postevent survival time for both regimens to elucidate the role of doxorubicin in their retrieval.Sixty-four of the 173 randomly assigned patients had an event. Of these, 55 experienced progression or recurrence after initial treatment. Eleven (31%) of 36 patients treated with CFV were successfully retrieved with a doxorubicin-containing regimen and surgery and remain alive at last contact, whereas only one (6%) of 18 patients treated with CD was alive after retrieval therapy.CFV is effective for stage I or II HB. Doxorubicin can be omitted as part of initial therapy in the majority of these patients, potentially limiting the long-term cardiac toxicities, without compromising outcome. Doxorubicin is effective in rescuing patients with recurrent disease after CFV and should be incorporated as a means of intensifying initial therapy for advanced-stage, nonmetastatic HB. Outcome of patients with metastatic disease at diagnosis is poor, and improving their survival will require new therapeutic approaches.
Is There a Role for PGE2 in Urinary Concentration?
Authors: Emma T.B. Olesen, Robert A. Fenton
Journal: Journal of the American Society of Nephrology (2012)

Prostanoids are prominent, yet complex, components in the maintenance of body water homeostasis. Recent functional and molecular studies have revealed that the local lipid mediator PGE2 is involved both in water excretion and absorption. The biologic actions of PGE2 are exerted through four different G-protein-coupled receptors; designated EP1-4, which couple to separate intracellular signaling pathways. Here, we discuss new developments in our understanding of the actions of PGE2 that have been uncovered utilizing receptor specific agonists and antagonists, EP receptor and PG synthase knockout mice, polyuric animal models, and the new understanding of the molecular regulation of collecting duct water permeability. The role of PGE2 in urinary concentration comprises a variety of mechanisms, which are not fully understood and likely depend on which receptor is activated under a particular physiologic condition. EP3 and microsomal PG synthase type 1 play a role in decreasing collecting duct water permeability and increasing water excretion, whereas EP2 and EP4 can bypass vasopressin signaling and increase water reabsorption through two different intracellular signaling pathways. PGE2 has an intricate role in urinary concentration, and we now suggest how targeting specific prostanoid receptor signaling pathways could be exploited for the treatment of disorders in water balance.
Basic Mechanisms of Arsenic Trioxide (ATO)-Induced Apoptosis in Human Leukemia (HL-60) Cells
Authors: Clement Yedjou, Paul Tchounwou, John Jenkins, Robert McMurray
Journal: Journal of Hematology & Oncology (2010)

Acute promyelocytic leukemia (APL) is a blood cancer that affects people of all ages and strikes about 1,500 patients in the United States each year. The standard treatment of APL has been based on the combined administration of all-trans retinoic acid and chemotherapy including anthracyclins and cytarabine. However, 10-20% of patients relapse, with their disease becoming resistant to conventional treatment. Recently the Food and Drug Administration has approved the use of arsenic trioxide (ATO) or Trisenox for the treatment of APL, based on clinical studies showing a complete remission, especially in relapsed patients. In a recently published study we demonstrated that ATO pharmacology as an anti-cancer drug is associated with its cytotoxic and genotoxic effects in human leukemia cells.In the present study, we further investigated the apoptotic mechanisms of ATO toxicity using the HL-60 cell line as a test model. Apoptosis was measured by flow cytometry analysis of phosphatidylserine externalization (Annexin V assay) and caspase 3 activity, and by DNA laddering assay.Flow cytometry data showed a strong dose-response relationship between ATO exposure and Annexin-V positive HL-60 cells. Similarly, a statistically significant and dose-dependent increase (p <0.05) was recorded with regard to caspase 3 activity in HL60 cells undergoing late apoptosis. These results were confirmed by data of DNA laddering assay showing a clear evidence of nucleosomal DNA fragmentation in ATO-treated cells.Taken together, our research demonstrated that ATO represents an apoptosis-inducing agent and its apoptotic mechanisms involve phosphatidylserine externalization, caspase 3 activation and nucleosomal DNA fragmentation.
FDA Finding May Curb Mentholated Cigarette Availability
Authors: Merrill Goozner
Journal: JNCI Journal of the National Cancer Institute (2011)

T he availability of menthol cigarettes increases the likelihood that youths and African Americans will become habitual smokers, making menthols a greater public-health hazard than regular brands, the U.S. Food and Drug Administration’s Tobacco Products Scientific Advisory Committee (TPSAC) said at its mid-March meeting. “The availability of menthol cigarettes has an adverse impact on public health by increasing the number of smokers and increasing the number of avoidable deaths and premature mortality,” said committee member Mark Stuart Clanton, M.D., chief medical officer of the American Cancer Society’s High Plains Division. However, the committee found insuffi cient evidence to conclude that smoking menthols increases the likelihood of addiction among all adults. Nor did evidence indicate that mentholated brands are more dangerous than regular cigarettes, which increase lung and other cancers, heart disease, emphysema, and other chronic conditions. The TPSAC’s conclusions came after a year-long review of epidemiological and physiological studies of menthol smokers in the past decade. The committee’s fi ndings could lead to stepped-up FDA regulation of mentholated brands, which could go as far as a ban. The FDA has until mid-June to issue its fi nal review of the evidence. Agency officials were noncommittal about what actions they might take in response to the TPSAC report. “We do recognize the strong interest in this issue,” said Lawrence Deyton, M.D., director of the Center for Tobacco Products at FDA. “Now it’s up to us to do our job.” The 2009 Tobacco Control Act, which created TPSAC and gave the FDA the authority to regulate tobacco, targeted menthol cigarettes as the fi rst product for heightened scrutiny because of mounting evidence that mentholated brands ultimately lead to lifelong smoking by youths and minorities. The consensus statement of the eight-member panel (three industry representatives on the committee were not allowed to vote on the fi nal recommendations) said the evidence was suffi cient to reach that conclusion. The committee found that menthol brands increase experimentation and regular smoking, as well as increase the likelihood of addiction in young smokers and African-Americans, 80% of whom prefer menthols. It also found that smoking menthols makes the success of smokingcessation programs less likely. “Youths who initiate with menthol cigarettes are more likely to become daily, regular smokers than those who initiate with nonmenthol cigarettes, [and] adolescent menthol smokers have a higher prevalence of addiction than those who smoke nonmenthol cigarettes,” Clanton said. Also, “the availability of menthol cigarettes results in lower likelihood of smoking cessation in AfricanAmericans [than that for] nonmenthol cigarettes.”
Prevention and treatment of hepatitis C in injection drug users
Authors: Brian R. Edlin
Journal: Hepatology (2002)

Injection drug users constitute the largest group of persons infected with the hepatitis C virus (HCV) in the United States, and most new infections occur in drug users. Controlling hepatitis C in the U.S. population, therefore, will require developing, testing, and implementing effective prevention and treatment strategies for persons who inject drugs. Fortunately, a substantial body of research and clinical experience exists on the prevention and management of chronic viral diseases among injection drug users. The need to implement interventions to stop the spread of HCV among drug users is critical. The capacity of substance-use treatment programs need to be expanded to accommodate all who want and need treatment. Physicians and pharmacists should be educated in how to provide access to sterile syringes and to teach safe injection techniques, both of which are lifesaving interventions. The treatment of hepatitis C in drug users requires an interdisciplinary approach that brings together expertise in treating hepatitis and caring for drug users. Treatment decisions should be made individually by patients with their physicians, based on a balanced assessment of risks and benefits and the patient’s personal values. Physicians should carefully assess, monitor, and support adherence and mental health in all patients, regardless of whether drug use is known or suspected. Research is needed to better understand how best to prevent and treat hepatitis C in substance users. In the meantime, substantial progress can be made if existing knowledge and resources are brought to bear.
Tests of Glycemia in Diabetes
Authors: David E Goldstein, Randie R Little, Rodney A Lorenz, John I Malone, David Nathan, Charles M Peterson, David B Sacks
Journal: Diabetes Care (2003)

Monitoring of glycemic status, as performed by patients and health care providers, is considered a cornerstone of diabetes care.Results of monitoring are used to assess the efficacy of therapy and to guide adjustments in medical nutrition therapy (MNT), exercise, and medications to achieve the best possible blood glucose control.This position statement presents the recommendations of the American Diabetes Association on the tests used most widely in monitoring the glycemic status of people with diabetes and addresses both patient and physician/laboratorybased testing.It does not address tests for diabetes screening and diagnosis.The recommendations are based on the American Diabetes Association's technical review on the subject, which should be consulted for further information (1). BLOOD GLUCOSE TESTINGBY PATIENTS -Within only a few years, self-monitoring of blood glucose (SMBG) by patients has revolutionized management of diabetes.Using SMBG, patients with diabetes can work to achieve and maintain specific glycemic goals.Given the results of the Diabetes Control and Complications Trial (DCCT) and other studies, there is broad consensus on the health benefits of normal or nearnormal blood glucose levels and on the importance, especially in insulin-treated patients, of SMBG in treatment efforts designed to achieve such glycemic goals.The subject of SMBG has been addressed extensively by two American Diabetes Association Consensus Conferences, which provide a comprehensive review of the subject (2,3).
Characterization of GMP-140 (P-selectin) as a circulating plasma protein.
Authors: L C Dunlop, M P Skinner, L J Bendall, E J Favaloro, P A Castaldi, J J Gorman, J R Gamble, M A Vadas, M C Berndt
Journal: The Journal of Experimental Medicine (1992)

GMP-140 is a 140-kD granule membrane protein, found in the alpha granules of platelets and the Weibel-Palade bodies of endothelial cells, that is surface expressed on cell activation and mediates neutrophil attachment. Cloning data for GMP-140 from an endothelial library predict a soluble form of the protein, the transcription message for which is also found in platelets. In this study, we report the detection by enzyme-linked immunosorbent assay of soluble GMP-140 in plasma centrifuged for 3 h at 100,000 g (to remove platelet microparticles) and confirm its identity by purification from plasma. Plasma concentrations were found to be 0.251 +/- 0.043 micrograms/ml (means +/- SD, n = 10) in normal male controls and 0.175 +/- 0.063 micrograms/ml (means +/- SD, n = 10) in normal female controls. The purified protein had an identical molecular mass (nonreduced) to platelet membrane GMP-140 (approximately 3 kD lower, reduced) and was immunoblotted by polyclonal anti-GMP-140, and the anti-GMP-140 monoclonal antibodies AK4 and AK6. Analytical gel filtration studies indicated that the plasma GMP-140 eluted as a monomer whereas detergent-free, platelet membrane GMP-140 eluted as a tetramer consistent with plasma GMP-140 lacking a transmembrane domain. Purified plasma GMP-140 bound to the same neutrophil receptor as the membrane-bound form, and when immobilized on plastic, bound neutrophils equivalently to immobilized platelet membrane GMP-140. Since it has been shown that fluid-phase GMP-140 is antiinflammatory and downregulates CD18-dependent neutrophil adhesion and respiratory burst, its presence in plasma may be of major importance in preventing the inadvertent activation of neutrophils in the circulation.
Domiciliary nasal intermittent positive pressure ventilation in severe COPD: effects on lung function and quality of life
Authors: C Perrin, Y El Far, F Vandenbos, R Tamisier, MC Dumon, F Lemoigne, J Mouroux, B Blaive
Journal: European Respiratory Journal (1997)

The aim of this study was to determine the effect of domiciliary nasal intermittent positive pressure ventilation (NIPPV) on lung function and quality of life in hypercapnic patients with chronic obstructive pulmonary disease (COPD). Fourteen hypercapnic COPD patients in a stable clinical condition were evaluated in a prospective study of domiciliary NIPPV plus long-term oxygen therapy. Baseline data obtained during a 4 week run-in period were compared with measurements at the end of the 6 month study period. Spirometric parameters, arterial blood gas tensions, and quality of life were assessed. Quality of life was measured using the St George's Respiratory Questionnaire (SGRQ) and the French version of the Nottingham Health Profile (FVNHP). All patients completed 6 months of domiciliary NIPPV. Gastro-intestinal inflation was reported by eight patients. Daytime arterial oxygen tension and arterial carbon dioxide tension, improved after therapy. During the NIPPV study period, the total SGRQ score and impacts score both improved significantly; significant improvements were also noted in the total FVNHP score and the physical mobility, emotional reactions, and energy component scores. Domiciliary nasal intermittent positive pressure ventilation combined with long-term oxygen therapy has been found to improve blood gases in spontaneous ventilation, as well as the quality of life of patients with chronic obstructive pulmonary disease.
Autografting for Chronic Granulocytic Leukemia in Transformation&lt;xref ref-type="fn" rid="FN1"&gt;1&lt;/xref&gt;
Authors: J Reiffers, N C Gorin, M Michallet, D Maraninchi, P Herve
Journal: JNCI Journal of the National Cancer Institute (1986)

Forty-five patients were treated for chronic granulocytic leukemia (CGL) in transformation by intensive chemotherapy (23 patients) or radiochemotherapy (22 patients) followed by autologous transplantation of bone marrow (17 patients) or blood-derived hematopoietic stem cells (28 patients). Hematopoiesis was reestablished in most evaluable patients and was significantly more rapid in previously splenectomized patients or in those receiving more than 10 X 10(8) nucleated cells/kg. However, partial or complete failure of engraftment was observed in 11 patients, in most cases after autografting with marrow cells. The median survival of all patients was 4.5 months. The major cause of death was the rapid recurrence of the blast cells not eradicated by the conditioning regimen. However, 4 of the 11 patients treated during the accelerated phase are still alive in the chronic phase, 17, 23, 35, and 54 months after autografting. These results and the restoration of hematopoiesis without the Philadelphia chromosome in 5 patients suggest that autografting could be used in CGL before the onset of the blast crisis.