tbuckley/cabot-search huggingface dataset:
Bone Mineral Measurements
Authors: Abtin Doroudinia, Patrick M Colletti
Journal: Clinical Nuclear Medicine (2015)

The accurate measurement of bone mineral density using noninvasive methods can be of value in the detection and evaluation of primary and secondary causes of decreased bone mass. This includes primary osteoporosis and secondary disorders, such as hyperparathyroidism, osteomalacia, multiple myeloma, diffuse metastases, and glucocorticoid therapy or intrinsic excess.By far, the largest patient population is that encompassed by primary osteoporosis with increased susceptibility to fractures in the absence of other recognizable causes of bone loss.Primary osteoporosis is a common clinical disorder and a major public health problem because of the significant number of related bone fractures occurring annually. Because the risk of vertebral and femoral neck fractures rises dramatically as bone mineral density falls, fracture risk in individual patients may be estimated. Furthermore, in estrogen-deficient women, bone mineral density values may be used to make rational decisions about hormone replacement therapy, or other bone mineral therapies, and as follow-up in assessing the success of such treatment.In this article, we discuss different methods of bone densitometry and will focus on dual-energy x-ray absorptiometry (DXA) with discussing the factors which should be considered for interpretation of DXA scan.
Down-Regulated Expression Of Protection Of Telomeres 1 (POT1) Gene In Bone Marrow Hematopoietic Progenitor Cell Compartment Has Prognostic Value In Myelodysplastic Syndromes (MDS)
Authors: Yue Wei, Yu Jia, Hong Zheng, Hui Yang, Zhihong Fang, Simona Colla, Guillermo Garcia-Manero
Journal: Blood (2013)
Identification of DNA Methylation–Independent Epigenetic Events Underlying Clear Cell Renal Cell Carcinoma
Authors: Elinne Becket, Sameer Chopra, Christopher E. Duymich, Justin J. Lin, Jueng Soo You, Kurinji Pandiyan, Peter W. Nichols, Kimberly D. Siegmund, Jessica Charlet, Daniel J. Weisenberger, Peter A. Jones, Gangning Liang
Journal: Cancer Research (2016)

Alterations in chromatin accessibility independent of DNA methylation can affect cancer-related gene expression, but are often overlooked in conventional epigenomic profiling approaches. In this study, we describe a cost-effective and computationally simple assay called AcceSssIble to simultaneously interrogate DNA methylation and chromatin accessibility alterations in primary human clear cell renal cell carcinomas (ccRCC). Our study revealed significant perturbations to the ccRCC epigenome and identified gene expression changes that were specifically attributed to the chromatin accessibility status whether or not DNA methylation was involved. Compared with commonly mutated genes in ccRCC, such as the von Hippel-Lindau (VHL) tumor suppressor, the genes identified by AcceSssIble comprised distinct pathways and more frequently underwent epigenetic changes, suggesting that genetic and epigenetic alterations could be independent events in ccRCC. Specifically, we found unique DNA methylation-independent promoter accessibility alterations in pathways mimicking VHL deficiency. Overall, this study provides a novel approach for identifying new epigenetic-based therapeutic targets, previously undetectable by DNA methylation studies alone, that may complement current genetic-based treatment strategies. Cancer Res; 76(7); 1954-64. ©2016 AACR.
Chronic Toxicity of Methotrexate in Rats: Partial to Complete Protection of the Liver by Choline: Brief Communication23
Authors: Marian Freeman-Narrod, Stuart A. Narrod, R. Philip Custer
Journal: JNCI Journal of the National Cancer Institute (1977)

Methotrexate (MTX) inhibits the enzyme dihydrofolate reductase, which in turn limits the body's ability to perform transmethylation reactions. This study examined the hypothesis that the consequent deficiency of an important methylated compound, choline, may have contributed to the MTX-induced fatty change in the liver of W rats. Groups of rats were given MTX alone or MTX plus choline in varying dose combinations. All groups but one receiving the combined treatment showed a significantly lower triglyceride concentration in their livers and much less visible hepatocytic fat on histologic examination than did those given MTX alone. The protective effect of choline on the liver was dose related, the unaffected group having received a very small amount. Growth rate, survival, and hematopoietic depression due to MTX were unaltered by choline administration.
Abstract 12308: Assessment of Liver Fibrosis Using Magnetic Resonance Elastography in Children Who Undergo the Fontan Procedure and Intracardiac Repair
Authors: Masaya Sugimoto, Hideharu Oka, Aya Kajihama, Kouichi Nakau, Hiroshi Azuma
Journal: Circulation (2014)

Background: The incidence of late complications related to the liver such as fibrosis/cirrhosis is increasing in patients who have undergone the Fontan procedure and may contribute to morbidity and mortality. Recently, magnetic resonance elastography (MRE), a novel evaluation technique of liver fibrosis, has been attracting attention. However, few reports have described the use of MRE for evaluating liver fibrosis in children with congenital heart disease (CHD). Methods: Thirty-two children were examined and divided into 4 groups: 12 children with CHD who underwent intracardiac repair (ICR; median age, 13.0 years); 10 with CHD who underwent the Fontan procedure (Fontan; 15.3 years); 8 who were included in the control group (control; 15.8 years); and 2 children with cirrhosis (cirrhosis; 16.3 years). The liver stiffness (LS) was estimated by MRE. LS was measured 3 times consecutively, and the mean value was considered for further analysis. Central venous pressure (CVP) and cardiac index (C.I.) were determined by cardiac catheterization. The levels of cardiac biomarkers (NTproBNP and PIIIP) were determined at the same time. Results: Among the 4 groups, no significant differences were observed in age, C.I., and NTproBNP levels. The PIIIP levels in the cirrhosis group were significantly higher than those in the control, but no significant difference in PIIIP levels was found among the other groups (p &lt; 0.01). LS in the Fontan and cirrhosis group was significantly higher than that in the control group (5.6, 15.3 vs. 2.4 kPa, respectively; Fig. 1). Furthermore, there was a strong correlation between LS and CVP (r = 0.802; Fig. 2). Conclusions: This study showed that LS is a direct function of CVP, which should be considered when assessing the degree of liver fibrosis in children with CHD. In particular, in the case of children who undergo the Fontan procedure, the highly sensitive MRE can be used to evaluate liver fibrosis and help detect LS earlier than cardiac biomarkers do.
NOD2 and TLR2 ligands trigger the activation of basophils and eosinophils by interacting with dermal fibroblasts in atopic dermatitis-like skin inflammation
Authors: Delong Jiao, Chun-Kwok Wong, Huai-Na Qiu, Jie Dong, Zhe Cai, Man Chu, Kam-Lun Hon, Miranda Sin-Man Tsang, Christopher Wai-Kei Lam
Journal: Cellular and Molecular Immunology (2015)
Reduction of Circulating HLA-DR + T Cell Levels Correlates With Increased Carotid Intraplaque Neovascularization and Atherosclerotic Burden
Authors: Enrico Ammirati, Marco Magnoni, Francesco Moroni, Simona Di Terlizzi, Isabella Scotti, Chiara Villa, Federico Sizzano, Matteo Impellizzeri, Giovanna Fanelli, Gloria Esposito, Roberto Chiesa, Paolo G. Camici
Journal: JACC. Cardiovascular imaging (2016)
Effect of Pretreatment Renal Function on Treatment and Clinical Outcomes in the Adjuvant Treatment of Older Women With Breast Cancer: Alliance A171201, an Ancillary Study of CALGB/CTSU 49907
Authors: Stuart M. Lichtman, Constance T. Cirrincione, Arti Hurria, Aminah Jatoi, Maria Theodoulou, Antonio C. Wolff, Julie Gralow, Daniel E. Morganstern, Gustav Magrinat, Harvey Jay Cohen, Hyman B. Muss
Journal: Journal of Clinical Oncology (2016)

Purpose CALGB 49907 showed the superiority of standard therapy, which included either cyclophosphamide/doxorubicin (AC) or cyclophosphamide/methotrexate/fluorouracil over single-agent capecitabine in the treatment of patients age ≥ 65 with early-stage breast cancer. The treatment allowed dosing adjustments of methotrexate and capecitabine for pretreatment renal function. The purpose of the current analysis was to assess the relationship between pretreatment renal function and five end points: toxicity, dose modification, therapy completion, relapse-free survival, and overall survival. Methods Pretreatment renal function was defined as creatinine clearance (CrCl) using the Cockcroft-Gault equation. Multivariable logistic and proportional hazards regression were used to model separately for each regimen the relationship between CrCl and the first three binary end points and the last two time-to-event end points, respectively, after adjusting for variables of prognostic importance. Results Six hundred nineteen assessable patients were analyzed. The incidence of stage III (moderate) or stage IV (severe) renal dysfunction was 72%, 64%, and 75% for treatment with cyclophosphamide/methotrexate/fluorouracil, AC, and capecitabine, respectively. There was no relationship for any regimen between pretreatment renal function and the five end points. For AC, as CrCl increased, the odds of nonhematologic toxicity decreased (P = .008), whereas for capecitabine, as CrCl increased, the odds of experiencing toxicity of any type also increased (P = .035). Patients with renal insufficiency who received dose modifications were not at increased risk for complications compared with those who did not have renal insufficiency and received a full dose. Conclusion Excluding from clinical trials patients with renal insufficiency but good performance status on the basis of concern of excessive hematologic toxicity or poor outcomes may not be justified with appropriate dosing modifications. Results should be considered in the design of clinical trials for older patients.
CNS-Leukaemia Prophylaxis in Adult Acute Lymphoblastic Leukaemia
Authors: R. Willemze, A. M. Drenthe-Schonk, J. van Rossum, C. Haanen
Journal: Neuro-Oncology (1980)

The prognosis for children with acute lymphoblastic leukaemia (ALL) has improved considerably since the introduction of CNS leukaemia prophylaxis by cranial irradiation and intrathecal administration of methotrexate (Mauer and Simone, 1976; Pinkel, 1979). The incidence of CNS-relapses dropped from 50% to approximately 5% of the children. Little is known about the efficacy of this treatment in adults, in whom CNS relapses are also frequent (Willemze et al., 1975; 1979; Gee et al., 1976; Lister et al., 1978.,Pavlovsky et al 1973).
Radiation-Induced Loss of Salivary Gland Function Is Driven by Cellular Senescence and Prevented by IL6 Modulation
Authors: Yitzhak Marmary, Revital Adar, Svetlana Gaska, Annette Wygoda, Alexander Maly, Jonathan Cohen, Ron Eliashar, Lina Mizrachi, Carmit Orfaig-Geva, Bruce J. Baum, Stefan Rose-John, Eithan Galun, Jonathan H. Axelrod
Journal: Cancer Research (2016)

Abstract Head and neck cancer patients treated by radiation commonly suffer from a devastating side effect known as dry-mouth syndrome, which results from the irreversible loss of salivary gland function via mechanisms that are not completely understood. In this study, we used a mouse model of radiation-induced salivary hypofunction to investigate the outcomes of DNA damage in the head and neck region. We demonstrate that the loss of salivary function was closely accompanied by cellular senescence, as evidenced by a persistent DNA damage response (γH2AX and 53BP1) and the expression of senescence-associated markers (SA-βgal, p19ARF, and DcR2) and secretory phenotype (SASP) factors (PAI-1 and IL6). Notably, profound apoptosis or necrosis was not observed in irradiated regions. Signs of cellular senescence were also apparent in irradiated salivary glands surgically resected from human patients who underwent radiotherapy. Importantly, using IL6 knockout mice, we found that sustained expression of IL6 in the salivary gland long after initiation of radiation-induced DNA damage was required for both senescence and hypofunction. Additionally, we demonstrate that IL6 pretreatment prevented both senescence and salivary gland hypofunction via a mechanism involving enhanced DNA damage repair. Collectively, these results indicate that cellular senescence is a fundamental mechanism driving radiation-induced damage in the salivary gland and suggest that IL6 pretreatment may represent a promising therapeutic strategy to preserve salivary gland function in head and neck cancer patients undergoing radiotherapy. Cancer Res; 76(5); 1170–80. ©2016 AACR.
Long-Term Stenting for Benign Ureteric Disease
Authors: Andrew Wedderburn, Mark Harrison
Journal: Journal of the Royal Society of Medicine (1999)

All three patients had undergone extensive abdominal and pelvic surgery, and further abdominal and retroperitoneal surgery would have carried a substantial risk (see Table 1 for details). Figure 1 is the anterior nephrostogram from patient 1, showing obstruction where the ureter passes over his aorto-bifemoral graft. In Figure 2, from patient 2, the soft-tissue mass encasing the ureter is due to endometriosis (unchanged over 4 years). All patients had their first stent inserted antegradely after nephrostomy placement. Thereafter, stent changes were performed retrogradely under general anaesthesia. The only proven complication was one lower urinary tract infection. Urinary frequency, loin pain on micturition, and stent calcification have not been observed. Table 1 Patient details
Role of Vitamin C As an Adjuvant Therapy with Different Iron Chelators in Young β-Thalassemia Major Patients: Safety and Efficacy in Relation to Tissue Iron Overload
Authors: Mohsen Saleh Elalfy, Maha Saber, Amira Adly, Eman Ismail, Mohamed Tarif, Fatma Ibrahim, Omar Elalfy
Journal: Blood (2014)
The Medicare System of Prospective Payment: Implications for Medical Education and Practice.
Authors: Mohan L. Garg, Barbara M. Barzansky
Journal: Annals of Internal Medicine (1986)

The financing of graduate medical education is likely to change significantly in the near future as third party payers are already pressuring hospitals to discontinue paying for graduate medical education through patient care. The Medicare System of Prospective Payment Implications for Medical Education and Practice isolates significant implications of prospective payment systems, and deals with each one in detail. Besides providing a theoretical base, it identifies various alternatives and provides guidelines for dealing with them.
A phase I trial of high-dose diaziquone and autologous bone marrow transplantation: an Illinois Cancer Council study.
Authors: P J Stiff, R S McKenzie, L D Potempa, K Albain, D Koch, E Braud, V K Bansal, M K Weidner, V J Lanzotti, H G Chun
Journal: Journal of Clinical Oncology (1991)

Diaziquone (AZQ), a synthetic quinone with demonstrated activity against acute nonlymphocytic leukemia (ANLL), primary CNS tumors, and non-Hodgkin's lymphoma (NHL), is virtually devoid of nonhematopoietic toxicity at conventional doses. As a prelude to its inclusion into bone marrow transplant (BMT) preparative regimens, a phase I study of high-dose AZQ with autologous BMT (ABMT) was performed. Patients with refractory solid tumors and lymphomas were treated with a single 24-hour infusion of AZQ at 50 to 355 mg/m2 in dose escalations of 20%. Fifty-six patients received 69 courses. Those receiving greater than 60 mg/m2 had nadir granulocyte and platelet counts less than 500/microL and 20,000/microL, respectively. Nausea, vomiting, stomatitis, and diarrhea were mild, transient, and not dose-related. Transient minimal elevations of liver function tests were seen in five patients and were also not dose-related. The maximally tolerated dose (MTD) of high-dose AZQ was found to be 245 mg/m2, with nephrotoxicity being dose-limiting. Significant azotemia was seen in four of 12 patients treated at 295 and 355 mg/m2, including fatal anuric renal failure in three of these patients. Reversible proteinuria also occurred in 24 of 26 courses above 150 mg/m2, including nephrotic range proteinuria in eight courses, all at doses of 205 to 355 mg/m2. The proteinuria was also associated with multiple proximal tubular defects including generalized aminoaciduria and proximal renal tubular acidosis. There were six early deaths including two of early renal failure (295 and 355 mg/m2), two of sepsis (205 and 245 mg/m2), one of a pulmonary embolus (85 mg/m2), and one of progressive disease (60 mg/m2). Of 50 patients who were assessable for response, there were seven responses including two of 10 with primary CNS tumors, one of 12 with malignant melanoma, one of five with non-small-cell lung carcinoma, two of two with breast carcinoma, and one of one with ovarian carcinoma. Because of its activity in ANLL and NHL and its unique toxicity spectrum, high-dose AZQ may improve the efficacy of current BMT preparative regimens without significantly increasing their nonhematopoietic toxicity.
PD2-3-4: Prognostic and predictive value of apoptosis related factors Fas, FasL and survivin in non small cell lung carcinoma patients enrolled in the IALT Trial
Authors: Elisabeth Brambilla, Jean-Charles Soria, Vincent Haddad, Sylvie Lantuejoul, Fabrice Andre, Martin Filipits, Helmut Popper, Robert Pirker, Thierry Le Chevalier, Ariane Dunant
Journal: Journal of Thoracic Oncology (2007)
A Biparatopic HER2-Targeting Antibody-Drug Conjugate Induces Tumor Regression in Primary Models Refractory to or Ineligible for HER2-Targeted Therapy
Authors: John Y. Li, Samuel R. Perry, Vanessa Muniz-Medina, Xinzhong Wang, Leslie K. Wetzel, Marlon C. Rebelatto, Mary Jane Masson Hinrichs, Binyam Z. Bezabeh, Ryan L. Fleming, Nazzareno Dimasi, Hui Feng, Dorin Toader, Andy Q. Yuan, Lan Xu, Jia Lin, Changshou Gao, Herren Wu, Rakesh Dixit, Jane K. Osbourn, Steven R. Coats
Journal: Cancer Cell (2016)
Assessment of competence to complete advance directives
Authors: S. Teunise, S. Eagger, J. Warner, S. Fazel, T. Hope, R. Jacoby
Journal: BMJ (1999)

Caring for and about acute general medicine Expansion in consultant numbers is neededEditor-Forgacs's review provides an excellent picture of the unpleasant reality of acute medicine, as practised at present. 1 The Royal College of Physicians is well aware of the need to cost future improvements in increasing the number of hospital doctors and to provide evidence of the likely benefits.The latter will be a difficult task but must be tackled.Indeed, a working group of the three Royal Colleges of Physicians is currently reviewing all aspects of the problems regarding acute medicine.As chairman of the group which produced the document "Consultant physicians working for patients" and main author, 2 I (JDW) can assure readers that I have had experience, on many occasions, of handling more than 20 acutely ill patients during a 24 hour period of acute medicine as a general physician in Sheffield.Our working group realises that hundreds more consultants tomorrow and much smaller numbers of "take patients" is unrealistic.We do know from several sources that doctors are working 14-16 sessions per week and close to a 60 hour week.We know that consultation times in outpatient departments have been pared to the bone.We know that clinical governance in all its guises will place further demands on consultants.If we do not state our requirements now for an expansion in the number of consultants we will never achieve improvements.
Sixty seconds on . . . alcohol guidelines
Authors: Nigel Hawkes
Journal: BMJ (2016)

Not at all! We’re being told how much we can drink before we increase our lifetime risk of premature death by 1%.

Yes. It’s now 14 units of alcohol a week for men and women, lower than the old guideline of 2-3 units a day for women and 3-4 for men.1

A much exaggerated benefit, …
Abstract 15259: Sex Differences in Left Atrial Electroanatomical Remodeling and Their Relationship to Left Ventricular Diastolic Function in Patients with Atrial Fibrillation
Authors: Chi Young Shim, Jae Sun Uhm, Jaemin Shim, Boyoung Joung, Gue-Ru Hong, Jong-Won Ha, Moon-Hyoung Lee, Hui-Nam Pak
Journal: Circulation (2012)

Background It has been reported that women are more susceptible to the preserved ejection fraction heart failure and diastolic dysfunction than men, and determined as a risk factor in CHA2DS2-VAS s...
Trends in the Management and Outcomes of Acute Pulmonary Embolism
Authors: David Jiménez, Javier de Miguel-Díez, Ricardo Guijarro, Javier Trujillo-Santos, Remedios Otero, Raquel Barba, Alfonso Muriel, Guy Meyer, Roger D. Yusen, Manuel Monreal
Journal: Journal of the American College of Cardiology (2016)
IL-7 and IL-10 Serum Levels Are Potential Immune Biomarkers for Acute Graft-Versus-Host Disease Following Unrelated Hematopoietic Stem Cell Transplantation
Authors: Rita I Azevedo, Antonio S Soares, Eduardo Espada, Nadia Camacho, Carlos V Martins, Fernanda Lourenco, Clara Juncal, Raul Moreno, Jose A Carmo, Joao F Lacerda
Journal: Blood (2014)
Three Italian hospitals where women died in labour are criticised in report
Authors: Michael Day
Journal: BMJ (2016)

The effect of the funding crisis on hospital services, and on obstetrics in particular, is in the spotlight in Italy, after a series of deaths during labour has resulted in government inspectors declaring major deficiencies in three hospitals.

Three of four hospitals where four women died in childbirth in December had “critical” problems in terms of their management, clinical standards, and emergency care, a health ministry taskforce said in a preliminary report this week. 

Hospitals in Brescia, in Lombardy, and in Bassano Del Grappa and San Bonifacio, in Veneto, were found lacking. Turin’s Sant’Anna Hospital, which is considered to have one of Italy’s top obstetrics and gynaecology departments, was not censured by the taskforce, however.

In one of the …