tbuckley/cabot-search huggingface dataset:
Less is more, regularly: metronomic dosing of cytotoxic drugs can target tumor angiogenesis in mice
Authors: Douglas Hanahan, Gabriele Bergers, Emily Bergsland
Journal: Journal of Clinical Investigation (2000)

Chemotherapeutic drugs, long the mainstay of cancer treatment, cause DNA damage and disrupt DNA replication in proliferating cells. Drug regimens have been designed to kill as many tumor cells as possible by treating with “maximum tolerated doses” (MTDs) of these cytotoxic agents. Side effects such as neurotoxicity and damage to proliferating cells in healthy tissues pose serious constraints on the use of chemotherapy. In an effort to balance toxicity with efficacy, a conventional dosing schedule calls for episodic application of a cytotoxic drug at or near the MTD, followed by periods of rest to allow normal tissues to recover. Many such chemotherapy regimens are initially efficacious, resulting in tumor regression or stabilization and prolonged survival. In rare cases, cures are achieved. In general, however, responses are short-lived, with relapses often marked by aggressive cancers that are resistant to the cytotoxic drug. Furthermore, the standard MTD regimen as a rule seriously impairs quality of life.

The harsh side effects and the ultimate failures of most chemotherapies have fueled broad investigation of alternatives, including drugs that target not the transformed tumor cells themselves, but rather a genetically stable constituent cell type of tumors, the endothelial cells that form blood vessels. Angiogenesis, the process by which new blood vessels are formed, is a hallmark capability of cancer (1); a compelling body of evidence argues that tumor growth depends on the vasculature, and, in particular, on continuing angiogenesis (2, 3). More than two dozen new drugs that are in or soon to enter clinical trials appear to interfere with tumor angiogenesis (3, 4); there is considerable anticipation about their benefits in treating cancer. Now, two studies suggest a potentially complementary strategy of rescheduling the administration of classical cytotoxic drugs in order to target tumor endothelial cells.

It is well established that tumor-associated endothelial cells proliferate during chronic angiogenesis in tumors, albeit at lower frequencies than the tumor cells themselves. Apparently because of their lower rate of cell division, replication of these endothelial cells is only weakly disrupted by the episodic regimens of standard chemotherapeutic protocols. In these two new studies, however, cytotoxic drugs were administered routinely, to target the slowly proliferating tumor endothelial cells and abrogate their apparent capability to repair and recover during the usual rest periods. Both groups worked with mice bearing subcutaneous tumors, and each presents data suggesting that “metronomic” dosing regimens—either continuous infusion or frequent administration without extended rest periods—could have real value in the clinic. Both also demonstrated combinatorial effects of such altered cytotoxic drug regimens with newer, more specific angiogenesis inhibitors.
Cancer in thirty-nine nuclear industry workers: a preliminary report.
Authors: E D Richter, E Ben-Michael, T Tsafrir, R Laster
Journal: Environmental Health Perspectives (1997)

We constructed job-exposure profiles and assessed quality of health care in 39 of 47 current and former workers from a nuclear installation in the Negev whose files were referred to us for assessment of a possible work-related aspect of their tumors. The workers, all male except one, began employment at various times from the reactor construction and were engaged in different tasks in laboratory research, construction, maintenance, and service. Of those workers still living the average age was 57.9 years, with a range from 42 to 77 years of age. The average age at the time of death for the deceased workers was 57.3 years, with a range from 41 to 69 years of age, Information on past exposures to radiation and chemical agents came from employee records dosimetry, and interviews. Personal monitoring (urine assays) in 29 workers indicated the presence of various radionuclides, with higher levels found in persons with work histories in laboratory/research and development and technical/inspector job categories compared to those in administrative/service job categories. Among the 39 workers, latency between onset of exposure and first appearance of illness from tumor was 24.2 years, with a range of 5 to 34 years. Tumor distribution for these workers was as follows: hematolymphatic (n = 11 workers), gastrointestinal (n = 9), breast (n = 1 [male]), renal-urogenital (n = 8), skin (n = 1), and pulmonary (n = 8 [5 known smokers]). For all tumors except those of the respiratory tract, the first diagnosis was made more frequently in those patients under the age of 55. Observed/expected comparisons for tumor proportional incidence showed excess fractions of blood tumors in persons < 55 and > 55 years of age. Ratios were greater than unity for blood, breast (n = 1), gastrointestinal, and urogenital tumors in patients < 55 years of age and pulmonary tumors in persons > 55 years of age. The odds ratio for smoking history in patients with lung tumors compared to those with other tumors was 4.8. Nonmalignant conditions appeared at relatively younger ages. After the exposure episodes two children with major congenital anomalies were born to wives of the workers; one anomaly was fatal. Not all patients were first diagnosed for cancer following referral from the plant medical service, and delays between warning signs and symptoms and medical evaluation occurred in some. Although we lacked data on cancer incidence and population at risk, our findings suggest that earlier official assessments of risk should be reconsidered. There is a need for population-based monitoring of risk to nuclear industry workers, external quality control of their medical surveillance and care, and improvements in information delivery.
An appraisal of narrowband (TL-01) UVB phototherapy. British Photodermatology Group Workshop Report (April 1996)
Authors: D. BILSLAND, R. DAWE, B.L. DIFFEY, P. FARR, J. FERGUSON, S. GEORGE, N.K. GIBBS, C. GREEN, J. MCGREGOR, H. VAN WEELDEN, N.J. WAINWRIGHT, A.R. YOUNG
Journal: British Journal of Dermatology (1997)

Journal Article An appraisal of narrowband (TL‐01) UVB phototherapy. British Photodermatology Group Workshop Report (April 1996) Get access BRITISH PHOTODERMATOLOGY GROUP, BRITISH PHOTODERMATOLOGY GROUP Search for other works by this author on: Oxford Academic Google Scholar D. BILSLAND, D. BILSLAND GLASGOW Search for other works by this author on: Oxford Academic Google Scholar R. DAWE, R. DAWE DUNDEE Search for other works by this author on: Oxford Academic Google Scholar B.L. DIFFEY, B.L. DIFFEY DURHAM Search for other works by this author on: Oxford Academic Google Scholar P. FARR, P. FARR NEWCASTLE Search for other works by this author on: Oxford Academic Google Scholar J. FERGUSON, J. FERGUSON DUNDEE Dr J. Ferguson, Photobiology Unit. Department of Dermatology, Ninewells Hospital and Medical School, Dundee DD1 9SY, Scotland, U.K. Search for other works by this author on: Oxford Academic Google Scholar S. GEORGE, S. GEORGE AMERSHAM Search for other works by this author on: Oxford Academic Google Scholar N.K. GIBBS, N.K. GIBBS DUNDEE Search for other works by this author on: Oxford Academic Google Scholar C. GREEN, C. GREEN DUNDEE Search for other works by this author on: Oxford Academic Google Scholar J. MCGREGOR, J. MCGREGOR LONDON Search for other works by this author on: Oxford Academic Google Scholar ... Show more H. VAN WEELDEN, H. VAN WEELDEN THE NETHERLANDS Search for other works by this author on: Oxford Academic Google Scholar N.J. WAINWRIGHT, N.J. WAINWRIGHT DUNDEE Search for other works by this author on: Oxford Academic Google Scholar A.R. YOUNG A.R. YOUNG LONDON Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 137, Issue 3, 1 September 1997, Pages 327–330, https://doi.org/10.1046/j.1365-2133.1997.18441939.x Published: 01 September 1997
Observational data insufficient to change treatment
Authors: R. I. Lindley, J. M. Wardlaw, P. A. G. Sandercock
Journal: BMJ (2011)

The paper by Mishra and colleagues suggests that age should not be a barrier to stroke thrombolysis,1 but caution is advised when using observational data to change clinical practice.

SITS is a voluntary register, so does not include all patients who receive recombinant tissue plasminogen activator (rt-PA), and those who have adverse events (such as haemorrhage and death) may be omitted. VISTA is a trials registry, so includes all patients without selective loss. Therefore a …
Usefulness and safety of a ready-to-use atopy patch test (APT) (Diallertest®) versus a reference test (Finn Chamber®) during cow's milk allergy in children
Authors: N. Kalach, P. Soulaines, D. De Boissieu, C. Dupont
Journal: Journal of Allergy and Clinical Immunology (2005)

RATIONALE: A ready-to-use APT (Diallertest®) was compared to the reference one (Finn Chamber®) in pediatric cow's milk allergy. METHODS: A prospective study involved 49 children, 34.3 + 17 months (mean + SD), with cow milk allergy manifested by atopic dermatitis (10.2%), digestive manifestations (40.8%), and both (49%). All children underwent both APT techniques with a reading 72 hours after application, followed by a milk elimination diet for 4 to 6 weeks and by an open oral food challenge (OOFC). RESULTS: A positive result was seen in 22 (44.8%) vs 13 (26.5%), with the ready-to-use and the reference APTs, respectively. No side effect was recorded. Both techniques were concordant in 67.3% of cases. Of the total 41 OOFC, 60.9% were positive with 8 patients lost of follow up. The performances of the ready-to-use and the reference APTs were: sensitivity 76% (95% CI 59.2-92.7) vs 44% (24.5-63.4) vs, p 0.02, specificity 93.8% (81.9-100) vs 93.8% (81.9-100), positive predictive value 95% (85.4-100, 1 false positive) vs 91.7% (76-100, 1 false positive), negative predictive value 71.4% (52-90.7, 6 false negative) vs 51.7% (33.5-69.8, 14 false negative), and test accuracy 82.9% (71.3-94.5) vs 63.4% (48.6-78.1), p 0.05. CONCLUSIONS: The ready-to-use APT exhibited a good sensitivity and specificity with no side effects.
Abstract 636: Non-melanoma skin cancer and risk of second primary cancer
Authors: Fengju Song, Abrar Qureshi, Edward Giovannucci, Charlie Fuchs, Wendy Chen, Meir Stampfer, Jiali Han
Journal: Cancer Research (2012)

Abstract Objective: Previous studies suggest a positive association between history of non-melanoma skin cancer (NMSC) and risk of subsequent cancer development. We prospectively investigate this association in both men and women. Methods: In two large cohorts in the US, the Health Professionals Follow-up Study (HPFS) and the Nurses’ Health Study (NHS), we prospectively examined the risks of primary cancer according to history of NMSC. In the HPFS, 876,094 person-years were followed up from June 1986 to June 2008. In the NHS, 2,358,185 person-years were followed up from June 1984 to June 2008. We documented 30,636 cancer cases after ongoing NMSC diagnosis. The median time (and range) of diagnosis between NMSC and subsequent cancer was 156 (3 - 342) months in the NHS, and 116 (3 - 259) months in the HPFS. Cox proportional hazard models were used to calculate relative risks (RRs) and 95% confidence intervals (CIs), adjusting for major cancer risk factors (e.g. age, smoking, body mass index, physical activity, etc). Results: A history of NMSC was associated with a higher risk of other primary cancers in men (RR = 1.15; 95% CI: 1.08, 1.21; P &amp;lt; 0.0001), and in women (RR = 1.25; 95% CI: 1.20, 1.31; P &amp;lt; 0.0001). For individual cancer sites, in men, a history of NMSC was associated with an increased risk of prostate cancer, non-Hodgkin lymphoma, and melanoma. In women, a history of NMSC was associated with an increased risk of breast cancer, endometrial cancer, ovarian cancer, lung cancer, non-Hodgkin lymphoma, renal cancer, melanoma, and oral cancer. Conclusions: Our prospective-cohort study provides evidence for an association between a history of NMSC and an increased risk of subsequent malignancies. Further studies are warranted to identify the potential mechanism underlying this relationship. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 636. doi:1538-7445.AM2012-636
Abstract 5257: Preclinical evaluation of lestaurtinib (CEP-701) with the retinoids for neuroblastoma
Authors: Robin E. Norris, Jane E. Minturn, Garrett M. Brodeur, John M. Maris, Peter C. Adamson
Journal: Cancer Research (2010)

Abstract Purpose Lestaurtinib (CEP-701), a selective and potent inhibitor of the Trk family of receptor tyrosine kinases, has undergone initial clinical evaluation in children with relapsed neuroblastoma. We studied the interaction of CEP-701 with 13-cis retinoic acid (13cRA) and fenretinide (4HPR), two retiniods that have been studied in children with high-risk neuroblastoma. Methods In a panel of 5 neuroblastoma cell lines (CHP-134, IMR-5, E6-NBLS, SH-SY5Y, and the SH-SY5Y-BR6 line that has been engineered to express high levels of functional TrkB receptors), in vitro cytotoxicity was assessed following a 72-hour drug exposure using the sulforhodamine B assay. When appropriate, the combination index (CI) of Chou-Talalay was used to characterize the interaction of 13cRA (non-constant ratio) or 4HPR (constant ratio) with CEP-701. Results The median (range) IC50 of single agent CEP-701 across all cell lines was 0.09 (0.08-0.17) μM. The combination of 13cRA and CEP-701 resulted in additive to synergistic interactions in 4 of the 5 cell lines studied. Addition of 1 and 5 µM of 13cRA decreased the median (range) CEP-701 IC50 1.5-fold (1.1 to 2.8-fold) and 1.7-fold (1.5 to 1.8-fold), respectively. With 10 µM 13cRA, less than 50% of cells survived when combined with various concentrations of CEP-701. The combination of 4HPR and CEP-701 trended toward being antagonistic, with a median (range) CI at the ED50 of 1.3 (1.1-1.5). Conclusions The combination of 13cRA and CEP-701 was additive or synergistic in a spectrum of neuroblastoma cell lines, suggesting that these agents can be used together to eliminate minimal residual disease following intensive chemoradiotherapy for high-risk neuroblastoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5257.
Teaching the teacher a lesson
Authors: Bruce McCormick
Journal: BMJ (2005)

decline and development of epilepsy (late spontaneous seizures) is increased.Mortality for refractory status epilepticus has been estimated to be as high as 48%, with only 29% of patients returning to their premorbid functional baseline. 20Morbidity associated with refractory status epilepticus usually consists of cognitive decline, but other neurological deficits, including persistent vegetative state and hemiparesis, have been described.
Concepts of Disease: A Textbook of Human Pathology
Authors: D. Murray Angevine
Journal: JAMA (1971)

The appearance of a new book that attempts to cover the entire field of pathology always elicits special interest among academic pathologists, and in this instance there is naturally considerable curiosity to see what such highly regarded and well-known pathologists as Gall and Brunson have been able to create. The authors justify the need for another textbook of pathology because "changing patterns and diverse forms of medical education dictate need for a somewhat different approach to the study of disease and its manifestations." They have attempted to accomplish their objective by interrelating cellular alterations with disease states, blending general and systemic pathology, liberally interspersed with clinically oriented information. In this manner they hope that students will be enabled to visualize more clearly the relation between structural and functional alterations and the signs and symptoms of disease. The editors have met their objective well. However, a few disjointed areas are apparent
Tandem mass spectrometry, but not T-cell receptor excision circle analysis, identifies newborns with late-onset adenosine deaminase deficiency
Authors: Giancarlo la Marca, Clementina Canessa, Elisa Giocaliere, Francesca Romano, Marzia Duse, Sabrina Malvagia, Francesca Lippi, Silvia Funghini, Leila Bianchi, Maria Luisa Della Bona, Claudia Valleriani, Daniela Ombrone, Maria Moriondo, Fabio Villanelli, Carsten Speckmann, Stuart Adams, Bobby H. Gaspar, Michael Hershfield, Ines Santisteban, Lynette Fairbanks, Giovanni Ragusa, Massimo Resti, Maurizio de Martino, Renzo Guerrini, Chiara Azzari
Journal: Journal of Allergy and Clinical Immunology (2012)
The Sanitarians: A History of American Public Health
Authors: Matthew J. Kleinerman
Journal: JAMA (1991)

With The Sanitarians: A History of American Public Health, historian John Duffy sets out to provide the definitive modern sourcebook on the subject. Tracing the evolution of efforts to improve populations' health from colonial times to the present, the book centers around the institutional forms and foci these efforts have taken: the formation of municipal boards of health in the 18th century, the establishment of health agencies as permanent parts of local and state governments in the 19th, the shifting emphasis of public health from contagious to chronic progressive diseases in the 20th, and its accompanying shift in administration from state and local to federal levels. Duffy organizes his book chronologically and thematically, dividing the history into well-justified trends. Exhaustively researched and copiously referenced, the book combines a diverse and enormous body of primary source material with a number of secondary source references and organizes them into a coherent whole.
Sterility and the State
Authors: A. Sharman
Journal: BMJ (1943)

Many countries have applied lockdown that helped suppress COVID-19, but with devastating economic consequences. Here we propose exit strategies from lockdown that provide sustainable, albeit reduced, economic activity. We use mathematical models to show that a cyclic schedule of 4-day work and 10-day lockdown, or similar variants, can prevent resurgence of the epidemic while providing part-time employment. The cycle pushes the reproduction number R below one by reduced exposure time and by exploiting the virus latent period: those infected during work days reach peak infectiousness during lockdown days. The number of work days can be adapted in response to observations. Throughout, full epidemiological measures need to continue including hygiene, physical distancing, compartmentalization, testing and contact tracing. This conceptual framework, when combined with other interventions to control the epidemic, can offer the beginnings of predictability to many economic sectors.
Profiting from the NHS
Authors: C. Ham
Journal: BMJ (1995)

<h3>Objective</h3> Healthcare providers (HCPs) often overestimate the quality and quantity of information they provide to patients. This study aimed to find out inpatients’ satisfaction towards information about medicines provided during inpatient stay. <h3>Methods</h3> This cross-sectional study was conducted at Lewisham Hospital and Queen Elizabeth Hospital in June 2017. Patients’ satisfaction with information about medicines provided during inpatient stay was assessed using a 17-item Satisfaction with Information about Medicines Scale (SIMS). <h3>Results</h3> 71 patients completed the questionnaire. The average percentage of patients being satisfied with the information provided in the nine-item ‘action and usage’ subscale of SIMS was 74.4%, compared with the eight-item ‘potential problems’ subscale with an average percentage of 56%. Patients aged 45–64 were more likely to be satisfied with information on ‘how the medicines work’ than the 65 and above as well as the 18–44 age groups (p=0.045). Patients who attended secondary school and below were more likely to be satisfied than those attending college and above towards this information (p=0.002). Patients of white or mixed white and black ethnicity were less satisfied than other ethnic groups of information regarding the impact of medication on sex life (p=0.019). Black or black British were more likely to be satisfied towards information on unwanted medication side effects compared with other ethnic groups (p=0.025). <h3>Conclusions</h3> HCPs could improve on the provision of information on potential problems that patients might experience with their medicines. Patients’ age, educational level and ethnicity should be taken into consideration when providing information about medicines.
THE ART OF PREVENTION
Authors: Erbest L. Wynder
Journal: JAMA (1962)

The emphasis of today's medical education rests principally on the diagnosis and treatment of disease. The majority of medical students view with considerable disinterest the instruction they receive in the community control of infectious disease, sanitary measures, and other environmental factors in which they see no immediacy and which they cannot directly relate to the individual practice of medicine. Furthermore, many medical schools do not adequately emphasize the important role that preventive medicine can also play in the field of noncommunicable diseases. If one further considers that man is always more concerned about a problem at hand than one that may occur at some distant future, it is understandable that many practicing physicians are relatively uninformed about what preventive measures can do in the field of cancer, one of the major noninfectious diseases, as is well demonstrated by Dr. Samp's article in this issue ofThe Journal, p. 1001.  After
PROGNOSTIC SIGNIFICANCE OF CARBOHYDRATE ANTIGEN 125 IN PATIENTS WITH HEART FAILURE AND PRESERVED EJECTION FRACTION
Authors: Sirikarn Napan, Taweewat Aussawapokee, Erol Nargileci, Ataul Qureshi, Suhail Khadra, John H. Stroger
Journal: Journal of the American College of Cardiology (2010)
Sunlight Interference with Wireless Capsule Endoscopy
Authors: S.-J. Tang, S. Zanati, E. Dubcenco, M. Cirocco, G. Kandel, G. B. Haber, N. F. Marcon, P. Kortan
Journal: Endoscopy (2004)

A 30-year-old woman underwent capsule endoscopy (Given® M2A, Given Imaging Ltd., Yoqneam, Israel) to investigate melena. Her medical history was significant for neurofibromatosis, portal and mesenteric vein thrombosis, portorenal shunt surgery, and antrectomy. On examination, her abdomen was slightly protuberant, with multiple surgical scars. A reducible, golf ball-sized, ventral hernia in the epigastric region was noted when performing a Valsalva maneuver. After swallowing the capsule, the patient left the clinic wearing a white T-shirt covering the capsule endoscopy (CE) belt pack. The next 7 h were uneventful, and no discomfort was experienced.