tbuckley/cabot-search huggingface dataset:
Breast cancer in childhood cancer survivors not treated with chest-directed radiation in the Childhood Cancer Survivor Study (CCSS).
Authors: Tara O. Henderson, Chaya S. Moskowitz, Kenan Onel, Angela R. Bradbury, Danielle Novetsky Friedman, Joanne F. Chou, Smita Bhatia, Louise C. Strong, Joseph Philip Neglia, Marilyn Stovall, Wendy M. Leisenring, Leslie L. Robison, Gregory T. Armstrong, Lisa Diller, Kevin C. Oeffinger
Journal: Journal of Clinical Oncology (2014)

10009 Background: While chest radiation (CRT) is strongly associated with risk of breast cancer (BC) in childhood cancer survivors (CCS), there are BC cases among survivors not exposed to CRT. We sought to examine if BC risk is elevated in non-CRT exposed women to inform surveillance recommendations. Methods: Using the CCSS cohort, BC risk was assessed among 3,768 female 5-yr CCS (median follow-up 25.5 yr, range 8-39) not treated with CRT. Cumulative incidence was examined treating death as a competing risk. BC risk was assessed using standardized incidence ratios (SIR) and 95% confidence intervals (CI) using incidence from the Surveillance, Epidemiology, and End Results Program, and by calculation of absolute excess risk (AER) per 104person-yrs (py). Results: 47 CCS developed BC at a median age of 38 yrs (range 22-47) and median of 24 yrs (range 9.6-34.3) from primary diagnosis. Primary cancers included: 14 leukemia; 10 bone tumor; 10 soft tissue sarcoma; 6 Ewing’s sarcoma (EWS); 2 CNS; and, 1 each of neuroblastoma, Wilms, Hodgkin, NHL. Among non-CRT exposed survivors, the cumulative incidence of BC was 2.5% (CI 1.6-8.8) at 35 yrs from diagnosis and 1.6% (CI 1.0-2.3) by age 40 yrs. Non-CRT survivors had a 3.8-fold increased risk of BC (SIR=3.8, CI 2.8-5.0) with an AER of 4.8/104 py, CI 2.9-6.2. Survivors with potential Li-Fraumeni (LF)-associated malignancy (leukemia, CNS, sarcoma except EWS) had an SIR of 3.8 (CI 2.7-5.2) and AER of 5.1/104 py (CI 3.0-7.4). Leukemia and sarcoma survivors were at highest risk (SIR=3.9, CI 2.3-6.6 and AER=3.5/104 py, CI 1.0-5.9 and SIR 5.3, CI 3.6-7.8; AER=14.2/104 py, CI 7.5-20.9, respectively). Among sarcomas, EWS survivors had a significant risk (SIR=9.5, CI 4.3-21.7; AER=29.3/104 py, CI 3.2-55.3). Survivors of all other cancers (excluding EWS and LF cancer) did not have an elevated BC risk (SIR=2.2, CI 0.9-5.3; AER 1.5/104py, CI -0.8 – 2.3). Conclusions: Although overall incidence is low, CCS not treated with chest-directed radiation are at increased risk for BC. The elevated BC risk is predominantly among leukemia and sarcoma survivors, potentially due to a genetic risk, and support consideration of early BC surveillance and genetic risk assessment.
Copy number variation analysis identifies novel CAKUT candidate genes in children with a solitary functioning kidney
Authors: Rik Westland, Miguel Verbitsky, Katarina Vukojevic, Brittany J. Perry, David A. Fasel, Petra J.G. Zwijnenburg, Arend Bökenkamp, Johan J.P. Gille, Mirna Saraga-Babic, Gian Marco Ghiggeri, Vivette D. D'Agati, Michiel F. Schreuder, Ali G. Gharavi, Joanna A.E. van Wijk, Simone Sanna-Cherchi
Journal: Kidney International (2015)
Pioglitazone Attenuates Atherosclerotic Plaque Inflammation in Patients With Impaired Glucose Tolerance or Diabetes
Authors: Minori Mizoguchi, Nobuhiro Tahara, Atsuko Tahara, Yoshikazu Nitta, Norihiro Kodama, Toyoharu Oba, Kazutoshi Mawatari, Hideo Yasukawa, Hayato Kaida, Masatoshi Ishibashi, Naofumi Hayabuchi, Haruhito Harada, Hisao Ikeda, Sho-ichi Yamagishi, Tsutomu Imaizumi
Journal: JACC. Cardiovascular imaging (2011)
17p Deletion in Acute Myeloid Leukemia and Myelodysplastic Syndrome. Analysis of Breakpoints and Deleted Segments by Fluorescence In Situ
Authors: Valérie Soenen, Claude Preudhomme, Christophe Roumier, Agnès Daudignon, Jean Luc Laı̈, Pierre Fenaux
Journal: Blood (1998)
IMMUNOREACTANTS IN RHEUMATOID SYNOVIAL EFFUSIONS
Authors: Nathan J. Zvaifler
Journal: The Journal of Experimental Medicine (1971)

Measurements were made of the IgG in synovial fluid which is synthesized by the intact rheumatoid synovium. In five rheumatoid subjects 12–24% of the IgG present in their synovial fluid was derived from local production. No evidence for local production was found in patients with degenerative arthritis or Reiter's syndrome. It was estimated that as much as 95 mg of IgG was produced by the synovium of a single knee joint daily. Rheumatoid inflammation is associated with the presence of large numbers of white blood cells, predominantly polymorphonuclear, in the articular cavity. Each day as many as one billion white cells enter the articular cavity to participate in this inflammatory response. Factors causing the directed migration of polymorphonuclear leukocytes were found in the majority of rheumatoid effusions studied. The chemotactic activity is, in large part, related to the fifth (C5) and sixth (C6) components of human complement. Physical-chemical techniques indicate that the activity is attributable to C 567 and C5a, a cleavage product of C5. In addition to the presence of preformed chemotactic factors, more than half of the rheumatoid fluids contain an enzyme capable of generating chemotactic activity from the fifth component (C5) of human complement. This information supports the concept that rheumatoid joint inflammation is an example of immune complex disease in which a significant proportion of the immunoreactants are derived from local production.
Commentary: "Fetal pain" is a misnomer
Authors: S. W G Derbyshire, A. Furedi
Journal: BMJ (1996)

For DebateDo fetuses feel pan?The past decade has seen a profound change in anaesthetists'attitudes and practice regarding the question of whether neonates and infants feel pain (p 787).Until recently, however, whetherfetuses felt pain has attracted little attention.In the context of late abortions and fetal surgery it becomes a question worth answering.We therefore asked a range ofspecialists for their opinions.
Paget disease and osteosarcoma of the calcaneus.
Authors: SOPHIE DE WAELE, MAX LONNEUX, BRUNO VANDE BERG, ADRIEN NZEUSSEU, JEAN-PIERRE BRASSEUR, FREDERIC LECOUVET
Journal: Clinical Nuclear Medicine (2001)

DE WAELE, SOPHIE M.D.,*; LONNEUX, MAX M.D.,*; VANDE BERG, BRUNO M.D., Ph.D.,†; NZEUSSEU, ADRIEN M.D.,‡; BRASSEUR, JEAN-PIERRE M.D.‡; LECOUVET, FRÉDÉRIC E. M.D., Ph.D.† Author Information
An evaluation of image quality and accuracy of eye bank measurement of donor cornea endothelial cell density in the Specular Microscopy Ancillary Study
Authors: Jonathan H Lass, Robin L Gal, Katrina J Ruedy, Beth Ann Benetz, Roy W Beck, Keith H Baratz, Edward J Holland, Andrea Kalajian, Craig Kollman, Francis J Manning, Mark J Mannis, Kristen McCoy, Monty Montoya, Doyle Stulting, Dongyuan Xing
Journal: Ophthalmology (2005)
Abstract 3343: Podophyllotoxin acetate (PA) enhancing γ-ionizing radiation-induced apoptosis via the ROS/p38/caspase pathway
Authors: Jae Yeon Choi, Sang-Gu Hwang, Hong-Duck Um, Jong Kuk Park
Journal: Cancer Research (2015)

Abstract To develop a new radiosensitizer candidate capable of increasing the efficiency of radiotherapy and to investigate the underlying molecular mechanisms in vitro and in vivo. To develop a new radiosensitizer against non-small cell lung cancer cells, we screened a natural product library for growth-inhibitory compounds. Podophyllotoxin acetate (PA) was found to be cytotoxic toward NCI-H460 cells, and its IC50 value was determined. The radiosensitizer effects of PA were tested at its IC50 value in clonogenic and cell-counting assays. The intracellular mechanism underlying this effect was determined by immunoblotting and by measuring propidium iodide uptake and ROS generation. The radiosensitizer activity of PA in vivo was tested in nude mice by treating with PA and IR, and measuring tumor volume and assessing apoptosis. PA, tested at its experimentally determined IC50 value (12 nM), enhanced γ-ionizing radiation (IR)-induced death of NCI-H460 cells by increasing apoptosis, yielding a mean calculated dose-enhancement ratio of 3.8. Combination with PA and IR also increased the production of reactive oxygen species (ROS), which subsequently induced phosphorylation of p38, suppressed phosphorylation of ERK, and activated caspase-3, -8, and -9. Notably, inhibition of ROS production prevented p38 phosphorylation, and inhibition of ROS production or p38 activation blocked caspase activation and apoptosis. In a xenograft assay, combination with PA and IR delayed tumor growth by 11.4 days compared with controls, yielding an enhancement factor of 1.48. Collectively, these results indicate that PA functions as a radiosensitizer by enhancing apoptosis through activation of a ROS/p38/caspase pathway and suppression of ERK. Citation Format: Jae Yeon Choi, Sang-Gu Hwang, Hong-Duck Um, Jong Kuk Park. Podophyllotoxin acetate (PA) enhancing γ-ionizing radiation-induced apoptosis via the ROS/p38/caspase pathway. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3343. doi:10.1158/1538-7445.AM2015-3343
Patient-reported symptoms after primary therapy for early prostate cancer: results of a prospective cohort study.
Authors: J A Talcott, P Rieker, J A Clark, K J Propert, J C Weeks, C J Beard, K I Wishnow, I Kaplan, K R Loughlin, J P Richie, P W Kantoff
Journal: Journal of Clinical Oncology (1998)

PURPOSE To assess complications of therapy for early (nonmetastatic) prostate cancer. PATIENTS AND METHODS A prospective study of a cohort of 279 men who sought treatment advice and completed required pretreatment forms. The measures were self-reported patient symptoms and other measures of quality of life before therapy and at 3 and 12 months afterward. RESULTS Bowel and bladder symptoms were uncommon pretreatment. Patients frequently reported irritative bowel and bladder symptoms at 3 months after radiotherapy, although these subsided somewhat at 12 months. Substantial ("a lot") urinary incontinence and wearing of absorptive pads were reported by 11% and 35% at 12 months after surgery and varied little by age. Incontinence occurred after radiotherapy infrequently, and only in men more than 65 years old. Inadequate erections, present in one third of men pretreatment, were nearly universal at 3 months after surgery, although some improvement, primarily in men under 65 years of age, was evident at 12 months. Sexual dysfunction after radiotherapy increased less but continually through 12 months, suggesting that observed treatment-related differences would decline with further follow-up. CONCLUSION External-beam radiotherapy of early prostate cancer is followed by bowel and bladder irritability, by increasingly severe sexual dysfunction and, in men aged more than 65 years, occasional urinary incontinence. Greater sexual dysfunction and urinary incontinence occur in the year following radical prostatectomy. These postsurgical complication rates from patient questionnaires are greater than have been reported in other treatment series and confirm the results of two retrospective studies of patient-reported complications.
P16 as a marker to differentiate atypical lipomatous tumor/well-differentiated liposarcoma from deep seated lipoma: An immunohistochemical analysis of 51 cases
Authors: M. He, S. Aisner, J. Benevenia, F. Patterson, H. Aviv, M. Hameed
Journal: Journal of Clinical Oncology (2007)

10070 Background: Atypical lipomatous tumor (ALT)/well-differentiated (WD) liposarcoma is a locally aggressive malignant mesenchymal neoplasm characterized by supernumerary ring and giant marker chromosomes with amplification of MDM2 gene. These cytogenetic characteristics can be very helpful to distinguish ALT from deep-seated lipomas. As ALTs have only rare presence of lipoblasts, they can resemble benign lipomas rendering difficulty in morphological diagnosis. P16INK4 is a specific inhibitor of CDK4/CDK6. CDK6 gene is often found co-amplified with MDM2 gene in ALTs. P16 overexpression is a hallmark of cervical dysplasia. Our study investigates the value of p16 expression in cytogenetically confirmed ALTs and deep-seated lipomas. Design: Fifty-one (51) cases of lipomatous neoplasms, with cytogenetic results, from forty-three (43) patients were collected for the study from the archives in department of pathology, UMDNJ/NJMS during 1998 - 2005. These include 18 cases of deep-seated lipoma, one hibernoma, and 32 cases of ALT / well-differentiated liposarcoma (24 patients, five patients with recurrence, and four cases with de-differentiation). Immunohistochemical staining for p16 was performed on representative paraffin blocks. Staining results were scored according to intensity (negative 0, weak 1+, intermediate 2+, and strong 3+) and percentage of positive cells. Results: Twenty-eight cases (28/32, 87.5%) of ALT/WD liposarcoma, including all four cases of dedifferentiated liposarcoma, showed strong nuclear p16 expression. In cases of recurrence, the primary and recurrent tumor showed the same pattern of p16 staining. Four cases (4/32, 12.5%) of ALT/WD liposarcoma showed negative p16 expression. All cases of deep-seated lipoma (18/18, 100%) and single hibernoma showed negative p16 staining except focal positivity in areas of fat necrosis in two cases (p16 positivity, 87.5 vs. 0%, P &lt;0.00001, Fisher's exact test). Conclusion: 1). P16 appears to be a valuable marker to differentiate ALT and deep-seated lipomas. 2). P16 expression remains unchanged in progression and transformation of ALT. 3). P16 related signal transduction pathway most likely is an early event in tumorogenesis of ALT. No significant financial relationships to disclose.
Metastatic malignant melanoma treated with combined bolus and continuous infusion interleukin-2 and lymphokine-activated killer cells.
Authors: M H Bar, M Sznol, M B Atkins, N Ciobanu, K C Micetich, D H Boldt, K A Margolin, F R Aronson, A A Rayner, M J Hawkins
Journal: Journal of Clinical Oncology (1990)

Fifty patients with advanced melanoma received high-dose bolus and continuous infusion interleukin-2 (IL-2) with lymphokine-activated killer (LAK) cells in an attempt to improve the therapeutic index of this active but toxic therapy. Treatment began with up to nine bolus doses of IL-2 administered over 3 days. After 1 day of rest, patients underwent daily leukapheresis for 4 days, and the leukocytes were cultured with IL-2 in vitro to prepare LAK cells. Continuous infusion IL-2 was begun 1 day after the last leukapheresis and continued for up to 148 hours; LAK cells were administered on days 1, 2, and 4 of the infusion. Responding patients were eligible to receive up to two additional cycles of therapy at 3-month intervals. Most patients completed each cycle without dose reduction. One patient had a complete response and six patients had partial responses (14% response rate). The complete responder and three of the partial responders (8%) remain free from disease progression with follow-up of 21 to 24 months. Of these four patients with durable remissions, one had extensive liver and lymph node metastases, one had lymph node, pleural, and parenchymal lung metastases, and two had disease limited to lymph nodes or subcutaneous tissues. Seventeen patients (34%) required pressors for hypotension, three patients (6%) developed hemodynamically significant arrhythmias, and six patients (12%) developed dyspnea at rest, but none required intubation and there were no treatment-related deaths. Unacceptable toxicity developed in two patients during bolus IL-2 administration and therapy was aborted; both returned to baseline status within 4 days of discontinuing IL-2. Fever, oliguria, and elevated creatinine or transaminase levels occurred frequently but were also transient. Despite less frequent severe toxicity with this modified regimen, these results confirm the ability of IL-2 and LAK cell therapy to induce durable remissions in some patients with advanced melanoma.
Developing Guidelines for Cervical Cancer Prevention in the Face of Diagnostic Complexity
Authors: L. Stewart Massad
Journal: Journal of the National Comprehensive Cancer Network (2014)

Adoption of new cervical cancer screening guidelines by the American Cancer Society and others in 2012 required new guidelines for the management of abnormal screening and follow-up tests. The American Society for Colposcopy and Cervical Pathology led a consensus conference including 26 professional organizations and agencies that developed new management guidelines. These guidelines are risk-based and derive from analysis of approximately 1.4 million women screened by the Kaiser Permanente Northern California medical group, with risk assessment in collaboration with NCI. New guidelines provide guidance for the conservative management of young women, for women with unsatisfactory Papanicolaou (Pap) tests and tests with limited transformation zone component, for women with discordant Pap and human papillomavirus (HPV) cotesting results, and for the incorporation of HPV 16/18 genotyping results into management decisions. The increasing number of available tests and the increasingly nuanced understanding of risk mean that clinicians will need to offset the complexity of diagnostic and treatment algorithms with technology and specialization.
A Prognostic Gene Expression Signature in the Molecular Classification of Chemotherapy-naïve Urothelial Cancer is Predictive of Clinical Outcomes from Neoadjuvant Chemotherapy: A Phase 2 Trial of Dose-dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin with Bevacizumab in Urothelial Cancer
Authors: David J. McConkey, Woonyoung Choi, Yu Shen, I.-Ling Lee, Sima Porten, Surena F. Matin, Ashish M. Kamat, Paul Corn, Randall E. Millikan, Colin Dinney, Bogdan Czerniak, Arlene O. Siefker-Radtke
Journal: European Urology (2015)
Abstract 238: Toll-Like Receptor 4-Deficiency Improves Ischemic Cardiomyocytes Contractile Dysfunction via Augmentation of AMPK Activation
Authors: Peng Zhao, Leilei He, Heng Ma, Jing Li, Jingying Wang, Xinglei Zhu, Jun Ren, Ji Li
Journal: Circulation (2008)

Myocardial ischemia/reperfusion injury involves a robust inflammatory response especially activation of toll-like receptor 4 (TLR4), a proximal signaling receptor in innate immune responses to lipopolysaccharide of Gram-negative pathogens. TLR4 is expressed in the heart and vasculature, the deficiency of which was shown to protect the heart against ischemia/reperfusion injury. However, the molecular mechanisms behind TLR4 deficiency-induced cardioprotection against ischemic damage remain unclear. The AMP-activated protein kinase (AMPK), an intracellular energy gauge, plays an important role in limiting cardiac damage following by ischemia, thus we hypothesized that AMPK maybe a mediator of TLR4-deficiency cardioprotection against ischemic injury. To test this hypothesis, In vivo regional ischemia was induced by occlusion of the left anterior descending (LAD) coronary artery in wild type (WT) C3H/HeN and TLR4-deficient C3H/HeJ mice, which carry a natural mutation of TLR4. Immunoblotting analysis was performed to assess the activation of AMPK and TLR4 downstream signal, the mitogen-activated protein kinase (MAPK). The endoplasmic reticulum (ER) chaperons, Grp78/BiP and Gadd153/CHOP, and ER integral membrane protein IRE1α were also monitored. The results demonstrated that C3H/HeJ hearts had impaired ischemic MAPK and AMPK activation compared to WT C3H/HeN hearts, i.e. activation of p38 MAPK and JNK was blunted, while ERK and AMPK signaling pathways were augmented during ischemia in C3H/HeJ hearts. Intriguingly, ischemia-stimulated ER stress was higher in WT C3H/HeN hearts than that in C3H/HeJ as demonstrated by up-regulation of Grp78/BiP, Gadd153/CHOP and IRE1α. Caspase-3 activity and TUNEL staining results showed that WT C3H/HeN hearts have more damages than those of C3H/HeJ hearts. Moreover, isolated cardiomyocytes from C3H/HeJ hearts showed resistance to ischemia-induced contractile dysfunction compared to WT C3H/HeN hearts. These findings suggest that the cardioprotective effects against ischemic injury of TLR4-deficient hearts may mediated through augmentation of AMPK and ERK while alleviation of p38 MAPK and JNK inflammatory signaling pathways. This research has received full or partial funding support from the American Heart Association, AHA National Center.
Using real patients in professional medical exams
Authors: D. I Newble
Journal: BMJ (2002)

Editor—The paper by Sayer et al raises important issues for those responsible for developing and delivering undergraduate and postgraduate clinical examinations.1 Clearly most would want to include real patients, often alongside simulated patients, to enhance the validity of the examination, although obtaining suitable real patients has become harder recently.

No one would argue about the need to obtain informed consent or to ensure confidentiality of patient data. The issue of the available level of medical care, however, needs further consideration. If the source of patients includes inpatients then the environment in which the examination is conducted should offer nursing and medical support that would be available elsewhere in the hospital, and to a level appropriate to clinical need. Obviously the permission of the responsible doctor must be sought, and this should be granted only if the care available is adequate.

In many examinations, however, the patients may be outpatients, and this situation is quite different. There is no reason to believe that attending the examination is more likely to cause an adverse effect than would spending the day doing something else. In fact, should the patients be taken ill or their condition become unstable one could argue that it was their good fortune to be at the examination, where medical attention was more likely to be readily available than elsewhere.

The traditional places in which clinical examinations are conducted, such as wards and outpatient clinics, are becoming less likely to be made available by hospital trusts. Increasingly, purpose built clinical skills centres and other venues are being used, which may not be located on the same site as a hospital. I cannot see any reason why properly informed outpatients are at an increased risk through attending the examination or are much different from simulated patients, who may also be examined, in their need for complex medical facilities.

Common sense would dictate that first aid and resuscitation equipment should be available; that only patients whose condition was stable should be recruited; that patients should be instructed to bring their normal drugs with them; and that nursing and medical staff should be available during the examination. To go to some of the extremes suggested in the paper might make it impractical to continue clinical examinations using real patients, to the detriment of our attempts to ensure high quality assessment procedures.
Role of Ultrasound in the Management of Ovarian Carcinoma
Authors: O Khan, E Wiltshaw, V R McCready, D O Cosgrove, C Bland
Journal: Journal of the Royal Society of Medicine (1983)

The ultrasound findings of the pelvis, upper abdomen and peritoneal cavity were correlated with second-look laparotomy in 85 patients with Stage III or Stage IV ovarian carcinoma. High values of accuracy were obtained for the pelvis (90%) and liver (91%) but ultrasound was insensitive to peritoneal disease unless ascites was present.