tbuckley/cabot-search huggingface dataset:
Two escalated followed by six standard BEACOPP in advanced-stage high-risk classical Hodgkin lymphoma: high cure rates but increased risk of aseptic osteonecrosis
Authors: A Fosså, I H Fiskvik, A Kolstad, G F Lauritzsen, E Aurlien, A K Blystad, K H Hole, I M Ikonomou, H Holte
Journal: Annals of Oncology (2011)
Incidence of insulin-dependent diabetes mellitus among Sardinianheritage children born in Lazio region, Italy
Authors: Sa Muntoni, MT Fonte, S Stoduto, G Marietti, C Bizzarri, A Crinò, P Ciampalini, G Multari, MA Suppa, MC Matteoli, L Lucentini, LM Sebastiani, N Visalli, P Pozzilli, B Boscherini, S Muntoni
Journal: The Lancet (1997)
GASTRIC CANCER IN PATIENTS WHO HAVE TAKEN CIMETIDINE
Authors: W.S.J. Ruddell, P.I. Reed, P.G. Cassell, C.L. Walters, M.J. Hill, T.V. Taylor, D. Lee, A.G. Howatson, J. Anderson, I.B. Macleod, Peter Rubin
Journal: The Lancet (1979)
Constitutive Activation of the DNA Damage Signaling Pathway in Acute Myeloid Leukemia with Complex Karyotype: Potential Importance for Checkpoint Targeting Therapy
Authors: Cindy Cavelier, Christine Didier, Naïs Prade, Véronique Mansat-De Mas, Stéphane Manenti, Christian Recher, Cécile Demur, Bernard Ducommun
Journal: Cancer Research (2009)

Genomic instability in solid tumors participates in the oncogenetic process and is associated with the activation of the DNA damage response pathway. Here, we report the activation of the constitutive DNA damage and checkpoint pathway associated with complex karyotypes in samples from patients with acute myeloid leukemia (AML). We show that antagonizing CHK1 kinase with a small inhibitory compound or by RNA interference strongly reduces the clonogenic properties of high-DNA damage level AML samples, particularly those with complex karyotypes. Moreover, we observe a beneficial effect of CHK1 inhibition in high-DNA damage level AML samples treated with 1-beta-d-arabinofuranosylcytosine. In contrast, CHK1 inhibition has no effect on the clonogenic properties of normal hematopoietic progenitors. All together, our results indicate that CHK1 inhibition may represent an attractive therapeutic opportunity in AML with complex karyotype.
A prospective open-label study of sirolimus for the treatment of anti-Hu associated paraneoplastic neurological syndromes
Authors: Adriaan H. de Jongste, Teun van Gelder, Jacoline E. Bromberg, Marieke T. de Graaf, Jan W. Gratama, Marco W. Schreurs, Herbert Hooijkaas, Peter A. Sillevis Smitt
Journal: Neuro-Oncology (2014)

Several lines of evidence suggest a T cell–mediated immune response in paraneoplastic neurological syndromes with anti-Hu antibodies (Hu-PNS). In order to investigate whether suppression of T cell–mediated immune responses in Hu-PNS patients improved their neurological outcome, we performed a prospective open-label, single-arm study on sirolimus. Seventeen progressive Hu-PNS patients were treated with sirolimus with an intended treatment duration of 8 weeks. Primary outcome measures were (i) functional improvement, defined as a decrease of one or more points on the modified Rankin Scale (mRS), and (ii) improvement of neurological impairment, defined as an increase of one or more points on the Edinburgh Functional Impairment Tests (EFIT). One patient showed improvement on both clinical scales (mRS and EFIT). This patient presented with limbic encephalitis and improved dramatically from an mRS score of 3 to mRS 1. Another patient, with subacute sensory neuronopathy, remained stable at mRS 2 and improved one point on the EFIT scale. The other patients showed no improvement on the primary outcome measures. Median survival was 21 months. We conclude that treatment of Hu-PNS patients with sirolimus may improve or stabilize their functional disabilities and neurological impairments. However, the effects of this T cell–targeted therapy were not better than reported in trials on other immunotherapies for Hu-PNS. Trial Registration https://www.clinicaltrialsregister.eu/ctr-search/trial/2008-000793-20/NL.
Cardiovascular diseases, diabetes mellitus, and cancer in the occupied Palestinian territory
Authors: Abdullatif Husseini, Niveen ME Abu-Rmeileh, Nahed Mikki, Tarik M Ramahi, Heidar Abu Ghosh, Nadim Barghuthi, Mohammad Khalili, Espen Bjertness, Gerd Holmboe-Ottesen, Jak Jervell
Journal: The Lancet (2009)
Lisinopril-Mediated Regression of Myocardial Fibrosis in Patients With Hypertensive Heart Disease
Authors: Christian G. Brilla, Reinhard C. Funck, Heinz Rupp
Journal: Circulation (2000)

In arterial hypertension, left ventricular hypertrophy (LVH) includes myocyte hypertrophy and fibrosis, which leads to LV diastolic dysfunction and, finally, heart failure. In spontaneously hypertensive rats, myocardial fibrosis was regressed and LV diastolic function was improved by treatment with the angiotensin-converting enzyme inhibitor lisinopril. Whether this holds true for patients with hypertensive heart disease was addressed in this prospective, randomized, double-blind trial.A total of 35 patients with primary hypertension, LVH, and LV diastolic dysfunction were treated with either lisinopril (n=18) or hydrochlorothiazide (HCTZ; n=17). At baseline and after 6 months, LV catheterization with endomyocardial biopsy, Doppler echocardiography with measurements of LV peak flow velocities during early filling and atrial contraction and isovolumic relaxation time, and 24-hour blood pressure monitoring were performed. Myocardial fibrosis was measured by LV collagen volume fraction and myocardial hydroxyproline concentration. With lisinopril, collagen volume fraction decreased from 6.9+/-0.6% to 6. 3+/-0.6% (P:<0.05 versus HCTZ) and myocardial hydroxyproline concentration from 9.9+/-0.3 to 8.3+/-0.4 microg/mg of LV dry weight (P:<0.00001 versus HCTZ); this was associated with an increase in the early filling and atrial contraction LV peak flow velocity ratio from 0.72+/-0.04 to 0.91+/-0.06 (P:<0.05 versus HCTZ) and a decrease in isovolumic relaxation time from 123+/-9 to 81+/-5 ms (P:<0.00002 versus HCTZ). Normalized blood pressure did not significantly change in either group. No LVH regression occurred in lisinopril-treated patients, whereas with HCTZ, myocyte diameter was reduced from 22. 1+/-0.6 to 20.7+/-0.7 microm (P:<0.01 versus lisinopril).In patients with hypertensive heart disease, angiotensin-converting enzyme inhibition with lisinopril can regress myocardial fibrosis, irrespective of LVH regression, and it is accompanied by improved LV diastolic function.
p-Cresyl Sulfate Promotes Insulin Resistance Associated with CKD
Authors: Laetitia Koppe, Nicolas J. Pillon, Roxane E. Vella, Marine L. Croze, Caroline C. Pelletier, Stéphane Chambert, Ziad Massy, Griet Glorieux, Raymond Vanholder, Yann Dugenet, Hédi A. Soula, Denis Fouque, Christophe O. Soulage
Journal: Journal of the American Society of Nephrology (2012)

The mechanisms underlying the insulin resistance that frequently accompanies CKD are poorly understood, but the retention of renally excreted compounds may play a role. One such compound is p-cresyl sulfate (PCS), a protein-bound uremic toxin that originates from tyrosine metabolism by intestinal microbes. Here, we sought to determine whether PCS contributes to CKD-associated insulin resistance. Administering PCS to mice with normal kidney function for 4 weeks triggered insulin resistance, loss of fat mass, and ectopic redistribution of lipid in muscle and liver, mimicking features associated with CKD. Mice treated with PCS exhibited altered insulin signaling in skeletal muscle through ERK1/2 activation. In addition, exposing C2C12 myotubes to concentrations of PCS observed in CKD caused insulin resistance through direct activation of ERK1/2. Subtotal nephrectomy led to insulin resistance and dyslipidemia in mice, and treatment with the prebiotic arabino-xylo-oligosaccharide, which reduced serum PCS by decreasing intestinal production of p-cresol, prevented these metabolic derangements. Taken together, these data suggest that PCS contributes to insulin resistance and that targeting PCS may be a therapeutic strategy in CKD.
Genetic polymorphisms of EPHX1, Gsk3β, TNFSF8 and myeloma cell DKK-1 expression linked to bone disease in myeloma
Authors: B G M Durie, B Van Ness, C Ramos, O Stephens, M Haznadar, A Hoering, J Haessler, M S Katz, G R Mundy, R A Kyle, G J Morgan, J Crowley, B Barlogie, J Shaughnessy
Journal: Leukemia (2009)
Effect of the dual peroxisome proliferator-activated receptor-α/γ agonist aleglitazar on risk of cardiovascular disease in patients with type 2 diabetes (SYNCHRONY): a phase II, randomised, dose-ranging study
Authors: Robert R Henry, A Michael Lincoff, Sunder Mudaliar, Michael Rabbia, Cathy Chognot, Matthias Herz
Journal: The Lancet (2009)
Acute renal failure in patients with cirrhosis: Perspectives in the age of MELD
Authors: Richard Moreau, Didier Lebrec
Journal: Hepatology (2003)

In patients with cirrhosis, acute renal failure is mainly due to prerenal failure (caused by renal hypoperfusion) and tubular necrosis. The main causes of prerenal failure are “true hypovolemia” (induced by hemorrhage or gastrointestinal or renal fluid losses), sepsis, or type 1 hepatorenal syndrome (HRS). The frequency of prerenal failure due to the administration of nonsteroidal anti-inflammatory drugs or intravascular radiocontrast agents is unknown. Prerenal failure is rapidly reversible after restoration of renal blood flow. Treatment is directed to the cause of hypoperfusion, and fluid replacement is used to treat most cases of “non-HRS” prerenal failure. In patients with type 1 HRS with very low short-term survival rate, liver transplantation is the ideal treatment. Systemic vasoconstrictor therapy (with terlipressin, noradrenaline, or midodrine [combined with octreotide]) may improve renal function in patients with type 1 HRS waiting for liver transplantation. MARS (for molecular adsorbent recirculating system) and the transjugular intrahepatic portosystemic shunt may also improve renal function in these patients. In patients with cirrhosis, acute tubular necrosis is mainly due to an ischemic insult to the renal tubules. The most common condition leading to ischemic acute tubular necrosis is severe and sustained prerenal failure. Little is known about the natural course and treatment ( i.e. , renal replacement therapy) of cirrhosis-associated acute tubular necrosis.
Phase I clinical and laboratory evaluation of topotecan and cytarabine in patients with acute leukemia.
Authors: K Seiter, E J Feldman, H D Halicka, F Traganos, Z Darzynkiewicz, D Lake, T Ahmed
Journal: Journal of Clinical Oncology (1997)

To determine the maximal-tolerated dose (MTD) of topotecan with cytarabine in acute leukemia patients, and to evaluate leukemia cell apoptosis in these patients.Fifty-three patients with acute leukemia not responsive to standard therapy were treated at eight dose levels of topotecan (2.5 mg/m2/d to 7.75 mg/m2/d). Topotecan was given as a 30-minute infusion daily with cytarabine 1 g/m2/d, both for 5 days. Using a flow-cytometric technique, the percent apoptotic cells in blood and bone marrow samples was determined, and the cell cycle distribution of the leukemic cells studied.Oropharyngeal mucositis was dose-limiting. The MTD of topotecan was 4.75 mg/m2/d for 5 days in high-risk patients and 7.0 mg/m2/d for 5 days in low-risk patients. The mean percent apoptotic cells in the peripheral blood reached a peak of 18.8%, a median of 48 hours following the first dose of topotecan. Patients with higher S-phase fractions, either before treatment or following cytarabine, were more likely to achieve bone marrow aplasia than those with lower S-phase fractions (P = .01 and P < .05, respectively). Clinical responses were seen in four of 39 patients with acute myelogenous leukemia (AML; of whom 32 had received prior high-dose cytarabine), three of six with acute lymphoblastic leukemia (ALL), and one of eight with chronic myelogenous leukemia in blast phase (CML-BP).The recommended phase II dose of topotecan with intermediate-dose cytarabine is 4.75 mg/m2/d for high-risk patients and 7.0 mg/m2/d for low-risk patients. The percentage of cells in S phase was important in determining response to treatment.
Abstract P2-09-04: Measurements of advocate participation in and contributions to the Mayo Clinic breast cancer SPORE
Authors: Cynthia Chauhan, Wayland Eppard, Lori Denison, Debra Gearhart, Lawanna Holmes, Ruth Kraft, Linda Miller, Mary A Sitta, Mary L Smith, James Ingle, Matthew Goetz
Journal: Cancer Research (2015)

Abstract [Background] Patient advocates bring a unique, valuable perspective and presence to SPOREs. However, although patient advocates are recommended members of SPORE grants, guidelines are not given on the role of advocates or on measurement of the performance of advocates. [Methods] The Mayo Clinic Breast Cancer SPORE Patient Advocate Advisory Committee has developed a participation measurement tool. This tool will underpin and augment evaluations of the individual advocate contributions by the program PI and the SPORE project leaders. The Advocate Advisory Committee Chair will review the evaluations with the individual advocates. Annually, the advocate committee will review the performance of the group by the standard of the metrics. [Results] Advocates kept a log of their SPORE activities for four months then worked with a statistician to discern patterns of measurable, evaluable behaviors. The determined evaluable areas are training, scientific activity, meeting attendance, communication. Currently, those metrics are being tracked. Advocates developed the metrics together and report activities at the monthly advocate meetings. Currently, activities are simply tracked and categorized. No minimum standards are set. This will be the third step in the development of the metrics. [Conclusions] This approach is the first step in the development of meaningful evaluation of advocate SPORE activities. It quantifies the participation of advocates in the SPORE and provides the basis for developing a qualitative performance evaluation. The SPORE PI and the Committee Chair will use the evaluations to interpret the involvement of advocates in SPORE research and activities and to plan interventions to strengthen the advocate contributions to the SPORE. Citation Format: Cynthia Chauhan, Wayland Eppard, Lori Denison, Debra Gearhart, Lawanna Holmes, Ruth Kraft, Linda Miller, Mary A Sitta, Mary L Smith, James Ingle, Matthew Goetz. Measurements of advocate participation in and contributions to the Mayo Clinic breast cancer SPORE [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-09-04.
Intermediate respiratory intensive care units in Europe: a European perspective
Authors: S. Nava, M. Confalonieri, C. Rampulla
Journal: Thorax (1998)

In the early 1950s an outbreak of poliomyelitis in Scandinavia highlighted for the first time the need for hospital units specialised in treating episodes of acute respiratory failure. The first intensive care units (ICUs), at that time utilising non-invasive techniques such as tank ventilators, were therefore built in Northern Europe. Later on positive pressure ventilation via an endotracheal tube or a tracheotomy became common and the modalities of non-invasive ventilation were progressively abandoned.1 Insertion of an endotracheal tube is usually performed after sedation and paralysis of the patient, and for this reason for many years mechanical ventilation was the exclusive field of anaesthetists so that in many European countries ICUs are still run mainly by anaesthetists rather than “organ specialists”. This clinical and management background has also conditioned respiratory medicine in Europe, and only a few European countries include specific training in emergency medicine and mechanical ventilation as part of the programme of the specialisation in respiratory medicine.2 This is not the case in North America where intensive care medicine has been closely linked to respiratory medicine for many years. In the middle of the 1960s, following the pioneering experience of Dr Petty,3 a growing number of specialised respiratory intensive care units (RICUs) started to spread all over the USA alongside, and not in competition with, “general” ICUs.4 The RICUs were designed to treat acute or acute-on-chronic respiratory failure due to any pulmonary disease with monitoring systems equal to those of the ICUs. These units necessitated a specialised environment and personnel, with increasing costs, so that in the 1980s a new class of “step down” or “intermediate” critical care units, the so-called non-invasive respiratory care units (NRCU) or high dependency units (HDU)5 were developed as a less costly option for patients receiving long term mechanical …
Whole-genome haplotyping approaches and genomic medicine
Authors: Gustavo Glusman, Hannah C Cox, Jared C Roach
Journal: Genome Medicine (2014)

Genomic information reported as haplotypes rather than genotypes will be increasingly important for personalized medicine. Current technologies generate diploid sequence data that is rarely resolved into its constituent haplotypes. Furthermore, paradigms for thinking about genomic information are based on interpreting genotypes rather than haplotypes. Nevertheless, haplotypes have historically been useful in contexts ranging from population genetics to disease-gene mapping efforts. The main approaches for phasing genomic sequence data are molecular haplotyping, genetic haplotyping, and population-based inference. Long-read sequencing technologies are enabling longer molecular haplotypes, and decreases in the cost of whole-genome sequencing are enabling the sequencing of whole-chromosome genetic haplotypes. Hybrid approaches combining high-throughput short-read assembly with strategic approaches that enable physical or virtual binning of reads into haplotypes are enabling multi-gene haplotypes to be generated from single individuals. These techniques can be further combined with genetic and population approaches. Here, we review advances in whole-genome haplotyping approaches and discuss the importance of haplotypes for genomic medicine. Clinical applications include diagnosis by recognition of compound heterozygosity and by phasing regulatory variation to coding variation. Haplotypes, which are more specific than less complex variants such as single nucleotide variants, also have applications in prognostics and diagnostics, in the analysis of tumors, and in typing tissue for transplantation. Future advances will include technological innovations, the application of standard metrics for evaluating haplotype quality, and the development of databases that link haplotypes to disease.
Phase III, Open-Label, Randomized Study Comparing Concurrent Gemcitabine Plus Cisplatin and Radiation Followed by Adjuvant Gemcitabine and Cisplatin Versus Concurrent Cisplatin and Radiation in Patients With Stage IIB to IVA Carcinoma of the Cervix
Authors: Alfonso Dueñas-González, Juan J. Zarbá, Firuza Patel, Juan C. Alcedo, Semir Beslija, Luis Casanova, Pittayapoom Pattaranutaporn, Shahid Hameed, Julie M. Blair, Helen Barraclough, Mauro Orlando
Journal: Journal of Clinical Oncology (2011)

To determine whether addition of gemcitabine to concurrent cisplatin chemoradiotherapy and as adjuvant chemotherapy with cisplatin improves progression-free survival (PFS) at 3 years compared with current standard of care in locally advanced cervical cancer.Eligible chemotherapy- and radiotherapy-naive patients with stage IIB to IVA disease and Karnofsky performance score ≥ 70 were randomly assigned to arm A (cisplatin 40 mg/m(2) and gemcitabine 125 mg/m(2) weekly for 6 weeks with concurrent external-beam radiotherapy [XRT] 50.4 Gy in 28 fractions, followed by brachytherapy [BCT] 30 to 35 Gy in 96 hours, and then two adjuvant 21-day cycles of cisplatin, 50 mg/m(2) on day 1, plus gemcitabine, 1,000 mg/m(2) on days 1 and 8) or to arm B (cisplatin and concurrent XRT followed by BCT only; dosing same as for arm A).Between May 2002 and March 2004, 515 patients were enrolled (arm A, n = 259; arm B, n = 256). PFS at 3 years was significantly improved in arm A versus arm B (74.4% v 65.0%, respectively; P = .029), as were overall PFS (log-rank P = .0227; hazard ratio [HR], 0.68; 95% CI, 0.49 to 0.95), overall survival (log-rank P = .0224; HR, 0.68; 95% CI, 0.49 to 0.95), and time to progressive disease (log-rank P = .0012; HR, 0.54; 95% CI, 0.37 to 0.79). Grade 3 and 4 toxicities were more frequent in arm A than in arm B (86.5% v 46.3%, respectively; P < .001), including two deaths possibly related to treatment toxicity in arm A.Gemcitabine plus cisplatin chemoradiotherapy followed by BCT and adjuvant gemcitabine/cisplatin chemotherapy improved survival outcomes with increased but clinically manageable toxicity when compared with standard treatment.
The Fluorescent Properties of Maturing Arterial Elastin
Authors: J. Blomfield, J. F. Farrar
Journal: Cardiovascular Research (1969)

Two fluorescent peaks resembling dityrosine have been found in arterial elastin. The high intensity of fluorescence in neonatal elastin residues suggests an early cross-linking role. Increases of wavelength with age follow differing patterns for the two peaks. Pulmonary artery elastin fluorescence changes more slowly with age than aortic elastin, except in children with pulmonary hypertension.
Dietary phytochemicals regulate whole-body CYP1A1 expression through an arylhydrocarbon receptor nuclear translocator–dependent system in gut
Authors: Shinji Ito, Chi Chen, Junko Satoh, SunHee Yim, Frank J. Gonzalez
Journal: Journal of Clinical Investigation (2007)

Cytochrome P450 1A1 (CYP1A1) is one of the most important detoxification enzymes due to its broad substrate specificity and wide distribution throughout the body. On the other hand, CYP1A1 can also produce highly carcinogenic intermediate metabolites through oxidation of polycyclic aromatic hydrocarbons. We describe what we believe to be a novel regulatory system for whole-body CYP1A1 expression by a factor originating in the gut. A mutant mouse was generated in which the arylhydrocarbon receptor nuclear translocator (Arnt) gene is disrupted predominantly in the gut epithelium. Surprisingly, CYP1A1 mRNA expression and enzymatic activities were markedly elevated in almost all non-gut tissues in this mouse line. The induction was even observed in early-stage embryos in pregnant mutant females. Interestingly, the upregulation was CYP1A1 selective and lost upon administration of a synthetic purified diet. Moreover, the increase was recovered by addition of the natural phytochemical indole-3-carbinol to the purified diet. These results suggest that an Arnt-dependent pathway in gut has an important role in regulation of the metabolism of dietary CYP1A1 inducers and whole-body CYP1A1 expression. This machinery might be involved in naturally occurring carcinogenic processes and/or other numerous biological responses mediated by CYP1A1 activity.