tbuckley/cabot-search huggingface dataset:
PSA doubling time (PSA-DT) during the “off treatment” interval in men with biochemical relapse of prostate cancer treated with intermittent androgen suppression (IAS)
Authors: N. Howlander, S. Tam, R. Etzioni, C. S. Higano
Journal: Journal of Clinical Oncology (2005)

4670 Background: PSA-DT has been shown to be a surrogate marker for mortality in patients who have biochemical relapse after either RP or XRT (D’Amico, J Urol 172 2004). These men are often treated with IAS. The significance of PSA-DT during the “off treatment” period has not been described. Methods: Eugonadal men with biochemical relapse of prostate cancer were treated with IAS. One cycle consists of 9 mos of LHRH analog plus anti-androgen followed by an “off treatment” interval determined by the rise in PSA to an arbitrary value of 1 or 4 ng/ml for RP or XRT patients respectively. A new cycle is then started. PSA-DTs were calculated for patients while “off” therapy for the first cycle and for the last cycle prior to becoming “hormone refractory” (HRPC) or prior to analysis for hormone sensitive patients. Time to HRPC, defined as 2 rising PSAs on hormonal therapy, was determined relative to PSA-DT. Results: Of 48 patients with median age of 64.5 yrs (range 51–78), 34 had RP and 14 had XRT as primary therapy. The subjects were divided into tertiles based on PSA-DT. For the first cycle, the average time to HRPC in the low, intermediate and high tertiles was 6.2 yrs, 7 yrs, and 10.5 yrs respectively. Using Kaplan-Meier cumulative hazard analysis, the first cycle of IAS therapy demonstrated shorter time to hormone refractoriness with shorter PSA-DT. During the last cycle of IAS, the average time to HRPC for low, intermediate and high PSA-DT tertiles was 1.8 yrs, 7.6 yrs, and 13.2 yrs respectively. Conclusions: Shorter PSA-DT during the first or last “off treatment” cycle of IAS appears to be associated with a shorter time to develop HRPC in patients who were treated for biochemical relapse after primary therapy. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Cell Therapuetics Corixa, Cougar Biotechnology, Icos, Nordic Biotech, Novartis, Sanofi-Synthelabo Cell Therapuetics Abbott, Abgenix, Amgen, Aventis, Cell Genesys, Cell Pathways, Dendreon, Lilly Oncology, Medarex, Novacea, Novartis, Sanofi-Synthelabo, Transgene, Xycte
Case 20-2002
Authors: Anne C. Moore, Edward T. Ryan, Mary Ann Waldron
Journal: New England Journal of Medicine (2002)

Presentation of CaseA 37-year-old man was admitted to the Tropical and Geographic Medicine Center of this hospital because of fever and an inflamed foot.The patient had been in vigorous health three months earlier, when he and his wife began a trip around the world. Initially they traveled throughout Brazil, including the Amazonian basin, up to the border of Peru. During this portion of the trip, the patient and his wife had an episode of fever and diarrhea, all of which resolved within days. They then spent three days in Buenos Aires, Argentina, before flying to the Republic of . . .
Retinoid X Receptor Heterodimers in the Metabolic Syndrome
Authors: Robert A. Hegele
Journal: New England Journal of Medicine (2005)

To the Editor: The excellent review of nuclear receptors by Shulman and Mangelsdorf (Aug. 11 issue)1 mentioned that the study of patients with mutations in PPARγ, the gene encoding peroxisome-proliferator–activated receptor γ (PPARγ), which is rare, can yield corroborating and new insights into the metabolic syndrome. However, it is important to acknowledge that all reported cases of the metabolic syndrome involving heterozygous germ-line loss-of-function PPARγ mutations2–5 concurrently have familial partial lipodystrophy type 3 (FPLD3). Given the role of PPARγ in adipogenesis, it seems reasonable that adipose tissue is repartitioned from peripheral to central stores in patients with . . .
Medical Facts vs. Value Judgments
Authors: Robert W Carlson, Joan S McClure
Journal: New England Journal of Medicine (2015)

To the Editor: In his Perspective article (June 25 issue),1 Ubel contends that the National Comprehensive Cancer Network (NCCN) guidelines fail to consider patient preferences and values. Clinical practice guidelines are designed to assist physicians and patients in decision making in specific clinical circumstances and do not remove the physician's or patient's autonomy in decision making, nor do they eliminate the need for shared decision making between patient and physician. The NCCN guidelines were the first in oncology to incorporate patient preference in decision making. Patient advocates with full voice and vote serve on many NCCN guidelines panels, transparency procedures . . .
Vaccination during myeloid cell depletion by cancer chemotherapy fosters robust T cell responses
Authors: Marij J. Welters, Tetje C. van der Sluis, Hélène van Meir, Nikki M. Loof, Vanessa J. van Ham, Suzanne van Duikeren, Saskia J. Santegoets, Ramon Arens, Marieke L. de Kam, Adam F. Cohen, Mariette I. van Poelgeest, Gemma G. Kenter, Judith R. Kroep, Jacobus Burggraaf, Cornelis J. Melief, Sjoerd H. van der Burg
Journal: Science Translational Medicine (2016)

Therapeutic vaccination against HPV16 is effective with chemotherapy for advanced cervical cancer patients.
Abstract 3764: Modeling tumors in their environment
Authors: Juan Delgado, James Yates
Journal: Cancer Research (2015)

Abstract Tumour microenvironment plays an important role in tumour growth. However, the composition and architecture of the tumour stroma varies dramatically across animal models and the clinic. In these animal models, not only the tumour formation, but the whole environment (stroma, mechanical stress…) is very different to the clinical tumour “context”. Nevertheless, explant models show a conserved stroma-tumour architecture. Keeping this in mind, we developed a mathematical model that not only captures tumour growth in animals, but may in the future also translate to patients. We propose a multiscale model to mimic tumour microenvironment and tumour cell co-development. The model is an agent-based model. The agents (epithelial clusters) represent 10 cells each with 5 transit states (G1, S, G2M, Hypoxic and Necrotic). Also, stromal cells may be recruited, can migrate and deliver blood to the tumour. The transitioning probabilities across the cell cycle are characterised by a pure time delay, followed by an exponential decrease. Further, profiles of chemokines and oxygen are computed as an approximation of the Fick Diffusion equations. These profiles trigger cell recruitment and proliferation. Additionally, cells may undergo hypoxia and become necrotic. All this computed by the Gillespie algorithm method in a 3D lattice in matlab 13b. The model successfully predicts tumour growth for a number of xenografted cell lines and explants of different cell origin. The patterns of the stromal architecture have been validated against IHC images from explant tumours at the end of study. For the validation, we developed an advanced imaging method to score tumour heterogeneity spatially from different immunostains. By interrogating the model, we can demonstrate that explant tumours - unlike xenografts - are not completely out of the clinical “context”. Our model being able to mimic the different phenotypes of heterogeneity observed across explants of diverse tissue origins (or patients), demonstrates that this method is potentially very broad. In future versions, the model will include more characteristics of the stroma, which would help us understand reasons why patterns of the stromal complexity form and affect tumour development and its treatment; both in animal studies and the clinic. The model will be contrasted with clinical data. Citation Format: Juan Delgado, James Yates. Modeling tumors in their environment. [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 3764. doi:10.1158/1538-7445.AM2015-3764
Type 1 wild poliovirus and putative enterovirus 109 in an outbreak of acute flaccid paralysis in Congo, October-November 2010
Authors: G Grard, J F Drexler, S Lekana-Douki, M Caron, A Lukashev, D Nkoghe, J P Gonzalez, C Drosten, E Leroy
Journal: Eurosurveillance (2010)

An outbreak of flaccid paralysis syndrome in adults is ongoing in Congo. Molecular analysis of faecal, throat and cerebrospinal samples identified wildtype 1 poliovirus and an additional enterovirus C strain related to enterovirus 109 as the cause. As of 22 November, the cumulative number of cases was 409, of which 169 (41.3%) were fatal. This is one of the largest wild type 1 poliovirus outbreaks ever described associated with an unusually high case fatality rate.
Prevalence of Clinical Mitral-Valve Prolapse in 1169 Young Women
Authors: P.M. Procacci, Stephen V. Savran, Spencer L. Schreiter, A. Laird Bryson
Journal: New England Journal of Medicine (1976)

Eleven hundred and sixty-nine young women were prospectively examined for the presence of mitral-valve prolapse as manifested by midsystolic non-ejection click or late systolic murmur (or both). Of the 1169 women 74 (6.3%) had physical findings consistent with mitral-valve prolapse. Sixty-eight of the 74 (92%) had midsystolic non-ejection click, and in 57 the click was accompanied by a late systolic murmur. In six (8%) only a late systolic murmur was heard. Echocardiography on all patients with clinical diagnosis of mitral-valve prolapse showed patterns of prolapse in 60 of 74 (81%). Fourteen (19%) had negative echocardiograms. We conclude that mitral-valve prolapse is clinically present in approximately 6.3% of otherwise healthy young women.
Cardiovascular Complications of Cocaine Use
Authors: Richard A. Lange, L. David Hillis
Journal: New England Journal of Medicine (2001)

The deaths of several celebrities in recent years in association with the nontherapeutic use of cocaine have focused widespread attention on the problem of cocaine abuse. In 1999, an estimated 25 million Americans admitted that they had used cocaine at least once; 3.7 million had used it within the previous year; and 1.5 million were current users. During the same year, cocaine was mentioned in 30 percent of all drug-related visits to emergency departments.1 Cocaine is the most commonly used illicit drug among subjects seeking care in hospital emergency departments or drug-treatment centers. In addition, it is the most frequent . . .
Open access as a requirement for research ethics committee approval
Authors: Wendy Rogers
Journal: BMJ (2015)

Restoring Study 329 has important implications for research ethics.1 Whether clinical trials are considered ethical depends on risk to participants, merit and integrity of the research, potential benefits, whether and how potential participants are respected and offered informed choices, and how justice requirements are met.2 The merit and integrity of the research are linked to potential benefits: high quality research produces valid and reliable results to …
Pregnancy during Residency
Authors: Maureen Sayres, Grace Wyshak, Geraldine Denterlein, Roberta Apfel, Eleanor Shore, Daniel Federman
Journal: New England Journal of Medicine (1986)

Abstract To identify possible barriers to women physicians who wish to combine parenting with medical careers, we studied 56 of 64 pregnancies from the past 10 years in 63 of 66 Harvard-affiliated residency programs. Pregnancies during residency were common (one in eight married women in 1983) and were usually planned (77 percent). Most institutions were unprepared for pregnancies among members of the house staff; four fifths of the programs had no maternity-leave policy. No one quit a residency program because of pregnancy, and pregnancy rarely affected achievement of board certification. Whether the pregnant women found pregnancy during residency a "pleasant" experience was determined largely by whether the program director was supportive, whether the issue of pregnancy was openly discussed within the program, and whether the woman was permitted to return to work on a part-time basis for the first weeks after maternity leave. We conclude that pregnancy within residency programs should be expected and planned for and that if proper arrangements are made, it need not be a major problem for either the training program or the pregnant resident. (N Engl J Med 1986; 314:418–23.)
PTPS-18APPARENT DIFFUSION COEFFICIENT MEASUREMENT IN PATIENTS WITH DIFFUSE INTRINSIC PONTINE GLIIOMA (DIPG): WORK-IN-PROGRESS
Authors: Shamseldeen Mahmoud, Tanya Tekautz, Erin Murphy, Aman Wadhwa, Johannes Wolff, Paul Ruggieri, Stephen Jones
Journal: Neuro-Oncology (2015)

BACKGROUND: Pediatric diffuse intrinsic pontine gliomas (DIPG) are pediatric brain tumors with an extremely poor prognosis. Diagnosis has historically been based on magnetic resonance (MR) imaging appearance of the lesion, which demonstrates an expansile pontine lesion; T1 hypo-/T2 hyperintense and without significant contrast enhancement. These imaging findings change during the course of treatment. Efforts have focused on identifying prognostically significant, quantifiable MR characteristics. PURPOSE: Measure the apparent diffusion coefficient (ADC) on serial MR examinations in patients with DIPG. SUBJECTS/METHODS: Medical records of 7 subjects, (2.11 -54.6 years), with the diagnosis of pontine glioma and diffusion imaging were reviewed. MR studies were retrieved from the online Agfa archives. After reviewing the MRIs, images with the most significant enhancing tumor/disease were identified from each patient's most recent/last imaging series. Regions of interest (ROIs) were drawn on the corresponding slices on the ADC maps. Similar ROIs were drawn on the same slices from prior examinations for each patient. Control ROI was obtained from measurements on normal appearing cerebellar white matter bilaterally. ADC values were recorded. Right and left values were combined for the pontine and cerebellar ROIs. Adjusted values were calculated for time points by dividing the pontine by the cerebellar value compensating for differences in the diffusion B-Value and scanner to scanner imaging parameter variability. Adjusted ADC values were plotted against the patient's age at the time of each MRI. A graph with ADC value vs. the number days remaining before patient's death (or last imaging study) was generated, reflecting patient's survival. RESULTS: We identified different patterns of change in the ADC over time for each patient. ADC values were higher than normal in all patients though interpatient variability was noted. Clinical significance of these differences is unclear at present. Correlation with clinical parameters, treatments and survival time is a work-in-progress.
Case 20-1992
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, S.J. Spechler, F.M. Graeme-Cook
Journal: New England Journal of Medicine (1992)

Presentation of CaseA 24-year-old man was admitted to the hospital because of nausea and epigastric pain that were unrelieved after a posterior gastropexy for a hiatal hernia.There was a history of adrenocorticosteroid-dependent asthma since childhood, which was controlled with difficulty; anaphylaxis occurred on one occasion after the ingestion of nuts. The total eosinophil count in recent years ranged between 17 and 528 per cubic millimeter. The α1-antitrypsin was normal. Except for intermittent exacerbations of asthma the patient was well until six years before admission, when he began to experience substernal pain with nausea and vomiting; the . . .
Parental Origin of the Extra Chromosome in Trisomy 21 as Indicated by Analysis of DNA Polymorphisms
Authors: S E Antonarakis
Journal: New England Journal of Medicine (1991)

Over the past 20 years, the parental origin of the extra chromosome in children with trisomy 21 has been investigated with cytogenetic methods of identifying morphologic variations in chromosome 21. These studies have concluded that the origin of the extra chromosome 21 was maternal in approximately 80 percent of cases and paternal in about 20 percent.We studied 200 families, each with a single child with trisomy 21, using DNA polymorphisms as markers to determine the parental origin of the nondisjunction causing the extra chromosome 21. These polymorphisms spanned a region of about 120 centimorgans on the long arm of chromosome 21, from the D21S13 locus (the most centromeric) to the COL6A1 gene (the most telomeric).The parental origin of nondisjunction could be determined for all but 7 of the 200 children. It was maternal in 184 children (proportion [+/- SE], 95.3 +/- 1.5 percent) and paternal in 9 (4.7 +/- 1.5 percent). In a subgroup of 31 families, we compared the results of DNA analysis with those of traditional cytogenetic analysis. According to the cytogenetic analyses, nondisjunction originated in the mother in 26 cases (84 percent) and in the father in 5 (16 percent). DNA analysis demonstrated the origin as maternal in 29 (94 percent) and paternal in 2 (6 percent). With the cytogenetic analyses, there were three false determinations of paternal origin.In trisomy 21 the extra chromosome 21 is maternal in origin in about 95 percent of the cases, and paternal in only about 5 percent--considerably less than has been reported with cytogenetic methods. DNA polymorphic analysis is now the method of choice for establishing the parental origin of nondisjunction.
P0641 : Excellent 5-year survival in caucasian chronic hepatitis B (CHB) patients with or without cirrhosis under long-term entecavir (ETV) or tenofovir (TDF) therapy and the impact of hepatocellular carcinoma (HCC)
Authors: G. Papatheodoridis, G. Dalekos, C. Yurdaydin, M. Buti, V. Sypsa, J. Goulis, J.L Calleja, H. Chi, S. Manolakopoulos, G. Mangia, N. Gatselis, O. Keskın, S. Savvidou, J. De La Revilla, B.E. Hansen, I. Vlachogiannakos, K. Galanis, R. Idılman, M. Colombo, R. Esteban, H.L. Janssen, P. Lampertico
Journal: Journal of Hepatology (2015)
An Outbreak of Community-Acquired<i>Pneumocystis carinii</i>Pneumonia
Authors: Henry Masur, Mary Ann Michelis, Jeffrey B. Greene, Ida Onorato, Robert A. Vande Stouwe, Robert S. Holzman, Gary Wormser, Lee Brettman, Michael Lange, Henry W. Murray, Susanna Cunningham-Rundles
Journal: New England Journal of Medicine (1981)

Eleven cases of community-acquired Pneumocystis carinii pneumonia occurred between 1979 and 1981 and prompted clinical and immunologic evaluation of the patients. Young men who were drug abusers (seven patients), homosexuals (six), or both (two) presented with pneumonia. Immunologic testing revealed that absolute lymphocyte counts, T-cell counts, and lymphocyte proliferation were depressed, and that humoral immunity was intact. Of the 11 patients, one was found to have Kaposi's sarcoma, and another had angioimmunoblastic lymphadenopathy. Eight patients died. In the remaining three, no diagnosis of an immunosuppressive disease was established, despite persistence of immune defects. These cases of pneumocystosis suggest the importance of cell-mediated immune function in the defense against P. carinii. The occurrence of this infection among drug abusers and homosexuals indicates that these groups may be at high risk for this infection. (N Engl J Med. 1981; 305:1431–8.)
Deep enteroscopy diagnosis of obscure overt gastrointestinal bleeding due to intravascular endothelial hyperplasia missed by capsule endoscopy
Authors: Mingming Zhang, Yanbo Yu, Xiuli Zuo, Wenwen Zheng, Yanqing Li
Journal: Endoscopy (2016)

A 56-year-old woman was referred to our hospital with a 3-day history of melena. She reported a 3-year history of dull pain in the left iliac region and intermittent melena. She had no history of drug use, fever, nausea, vomiting, or weight loss. Her vital signs were stable. She appeared pale and was tender in the left iliac region, but without guarding or rebound tenderness. Rectal examination confirmed melena. Laboratory investigation showed a red cell count of 3.16 × 1012/L and hemoglobin of 85.0 g/L. Other laboratory values were normal.
Thiazide Effect on the Mineral Content of Bone
Authors: Richard D. Wasnich, Richard J. Benfante, Katsuhiko Yano, Lance Heilbrun, John M. Vogel
Journal: New England Journal of Medicine (1983)

The thiazide diuretics are known to cause calcium retention. In order to study the effect of thiazides on bone mineralization, we have measured the mineral content of bone at five sites (the distal radius, the distal ulna, the proximal radius, the proximal ulna, and the os calcis) in 1368 men with a mean age of 68 years, including 323 who were taking thiazides for hypertension. The results were adjusted for age and body-mass index. Thiazide users had significantly more bone mineral content at all five sites than did non-users. Untreated hypertensive patients and persons without hypertension had comparable bone mineral content, indicating that the higher mineral content found among thiazide users is related to the drug and not to the underlying hypertension. These findings suggest the possibility of a preventive or therapeutic role for thiazides in osteoporosis. (N Engl J Med 1983; 309:344–7.)
The Natural History of Initially Untreated Low-Grade Non-Hodgkin's Lymphomas
Authors: Sandra J. Horning, Saul A. Rosenberg
Journal: New England Journal of Medicine (1984)

To learn more about the natural history of low-grade non-Hodgkin's lymphoma, we have studied 83 patients in whom the advanced disease was initially managed without therapy. Actuarial survival was 82 per cent at 5 years and 73 per cent at 10 years. The median time until therapy was required was three years. Spontaneous regressions occurred in 19 untreated patients (23 per cent), including 30 per cent of patients with nodular, poorly differentiated lymphocytic lymphoma. Histologic transformation to an Intermediate-Grade or high-grade lymphoma occurred both before and after primary therapy. The actuarial risk of transformation among the initially untreated patients was similar to that in a group of patients treated at this institution immediately after diagnosis. Neither the time to histologic transformation nor the incidence of transformation was influenced by when therapy was started. (N Engl J Med 1984; 311:1471–5.)
Nonsegmental vitiligo disease duration and female sex are associated with comorbidity and disease extent: a retrospective analysis in 1307 patients aged ≥ 50 years
Authors: H.E. Teulings, E. Ceylan, M. Overkamp, C. Vrijman, J.D. Bos, T.E. Nijsten, A. Wolkerstorfer, R.M. Luiten, J.P.W. van der Veen
Journal: British Journal of Dermatology (2016)

The disease course of nonsegmental vitiligo is relatively unstudied. Clinical and epidemiological differences have been described in early- versus later-onset vitiligo but duration of disease has not been taken into account. Also, the prevalence of auto-immune comorbidities in patients with vitiligo has been mostly studied in young vitiligo patient populations while autoimmune comorbidity may manifest later in life. The aim of this study was to retrospectively assess factors associated with disease extent and the life-time prevalence of autoimmune comorbidities in a large cohort of older-aged patients with nonsegmental vitiligo. This article is protected by copyright. All rights reserved