tbuckley/cabot-search huggingface dataset:
Combining xenoestrogens at levels below individual no-observed-effect concentrations dramatically enhances steroid hormone action.
Authors: Nissanka Rajapakse, Elisabete Silva, Andreas Kortenkamp
Journal: Environmental Health Perspectives (2002)

The low potency of many man-made estrogenic chemicals, so-called xenoestrogens, has been used to suggest that risks arising from exposure to individual chemicals are negligible. Another argument used to dismiss concerns of health effects is that endogenous steroidal estrogens are too potent for xenoestrogens to contribute significantly to estrogenic effects. Using a yeast reporter gene assay with the human estrogen receptoralpha, we tested these ideas experimentally by assessing the ability of a combination of 11 xenoestrogens to affect the actions of 17ss-estradiol. Significantly, each xenoestrogen was present at a level well below its no-observed-effect concentration (NOEC). To derive accurate descriptions of low effects, we recorded concentration-response relationships for each xenoestrogen and for 17ss-estradiol. We used these data to predict entire concentration-response curves of mixtures of xenoestrogens with 17ss-estradiol, assuming additive combination effects. Over a large range of concentrations, the experimentally observed responses decisively confirmed the model predictions. The combined additive effect of the 11 xenoestrogens led to a dramatic enhancement of the hormone's action, even when each single agent was present below its NOEC. Our results show that not even sub-NOEC levels of xenoestrogens can be considered to be without effect on potent steroidal estrogens when they act in concert with a large number of similarly acting chemicals. It remains to be seen to what degree these effects can be neutralized by environmental chemicals with antiestrogenic activity. Nevertheless, potential human and wildlife responses induced by additive combination effects of xenoestrogens deserve serious consideration.
Transformation of Follicular Lymphoma to Epstein-Barr Virus-Related Hodgkin-Like Lymphoma
Authors: Madhu P. Menon, Lloyd Hutchinson, Joanne Garver, Elaine S. Jaffe, Bruce A. Woda
Journal: Journal of Clinical Oncology (2013)

Case ReportA 53-year-old white woman with generalized lymphadenopathy was diagnosed with follicular lymphoma, grades 1 to 2, stage III.Three months later, she was started on six cycles of rituximab, cyclophosphamide, vincristine, and prednisone therapy with minimal response.A repeat lymph node biopsy approximately 1 year later revealed persistent follicular lymphoma (grades 1 to 2) after which the patient received six cycles of bendamustine therapy.Epstein-Barr virus (EBV)-encoded RNA in situ hybridization (EBER-ISH) on the lymph node biopsy failed to demonstrate EBV infection.
Testosterone Gel Supplementation for Men With Refractory Depression: A Randomized, Placebo-Controlled Trial
Authors: Harrison G. Pope, Geoffrey H. Cohane, Gen Kanayama, Arthur J. Siegel, James I. Hudson
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: Testosterone supplementation may produce antidepressant effects in men, but until recently it has required cumbersome parenteral administration. In an 8-week randomized, placebo-controlled trial, the authors administered a testosterone transdermal gel to men aged 30–65 who had refractory depression and low or borderline testosterone levels. METHOD: Of 56 men screened, 24 (42.9%) displayed morning serum total testosterone levels of 350 ng/dl or less (normal range=270–1070). Of these men, 23 entered the study. One responded to an initial 1-week single-blind placebo period, and 22 were subsequently randomly assigned: 12 to 1% testosterone gel, 10 g/day, and 10 to identical-appearing placebo. Each subject continued his existing antidepressant regimen. Ten subjects receiving testosterone and nine receiving placebo completed the 8-week trial. RESULTS: The groups were closely matched on baseline demographic and psychiatric measures. Subjects receiving testosterone gel had significantly greater improvement in scores on the Hamilton Depression Rating Scale than subjects receiving placebo. These changes were noted on both the vegetative and affective subscales of the Hamilton Depression Rating Scale. A significant difference was also found on the Clinical Global Impression severity scale but not the Beck Depression Inventory. One subject assigned to testosterone reported increased difficulty with urination, suggesting an exacerbation of benign prostatic hyperplasia; no other subject reported adverse events apparently attributable to testosterone. CONCLUSIONS: These preliminary findings suggest that testosterone gel may produce antidepressant effects in the large and probably underrecognized population of depressed men with low testosterone levels.
SARCOMA ON LUPUS SCAR
Authors: LOUIS SAVATARD
Journal: British Journal of Dermatology (1932)

Journal Article SARCOMA ON LUPUS SCAR Get access LOUIS SAVATARD LOUIS SAVATARD Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 44, Issue 11, 1 November 1932, Pages 542–543, https://doi.org/10.1111/j.1365-2133.1932.tb09555.x Published: 01 November 1932
Pseudarthrosis of the first rib in the overhead athlete: Figure 1
Authors: K Mithöfer, E Giza
Journal: British Journal of Sports Medicine (2004)

Fractures of the first rib are uncommon in athletes and present a different clinical entity from traumatic first rib fracture associated with high energy thoracic trauma. These fractures are stress induced and precipitated by chronic muscular forces acting on the first rib. Typically they heal with conservative treatment. This report describes a fracture of the first rib in a tennis player that developed into a symptomatic pseudarthrosis as a result of persistent overhead activities. Symptoms mimicked ipsilateral shoulder injury. Pseudarthrosis of the first rib should be included in the differential diagnosis of chronic persistent shoulder pain in the overhead athlete.
Lipoxin A4 and B4 are potent stimuli for human monocyte migration and adhesion: selective inactivation by dehydrogenation and reduction.
Authors: J F Maddox, C N Serhan
Journal: The Journal of Experimental Medicine (1996)

Monocyte recruitment and adherence are important events in inflammatory and vascular diseases. Here, we evaluated the actions of lipoxin A4 (LXA4) and LXB4, a series of lipoxygenase products from arachidonic acid generated by cell-cell interactions, on human monocytes. LXA4 and LXB4 (10(-7) M) each increased monocyte migration in chamber chemotaxis assays and, in migration under agarose, exhibited chemotactic indices similar to those of the chemotactic peptide formyl-methionyl-leucyl-phenylalanine at 10(-10)-10(-8) M and to the chemokine macrophage inflammatory protein-1 alpha (MIP-1 alpha) at 10(-8)-10(-7) M with a rank order of potency: Monocyte chemotactic protein-1 alpha &amp;gt; LXA4 approximately LXB4 approximately MIP-1 alpha. Lipoxins also stimulated monocyte adherence to laminin. In addition, human monocytes rapidly transformed LXA4 and LXB4 to several metabolites. LXB4 (&amp;gt; 80%) was converted within 30 s to new products, in a trend similar to that of LXA4. The novel monocyte-derived LXB4 products were identified as 5-oxo-6,7-dihydro-LXB4 and 6,7-dihydro-LXB4, indicating a role for site-selective dehydrogenation and reduction. Unlike monocytes, intact polymorphonuclear leukocytes (PMN) did not metabolize LXA4 in significant quantities, and only approximately 12% of exogenous LXB4 was omega-oxidized to 20-OH-LXB4 and 20-COOH-LXB4 by PMN. To determine if lipoxin conversion altered bioactivity, we evaluated the actions of these metabolites on monocytes. Each of the novel products of LXA4 and LXB4 from monocytes, namely oxo- and dihydrolipoxins, were essentially inactive in stimulating monocyte adherence. In contrast, the omega-oxidation products of LXB4 isolated from PMN were equipotent with LXB4 for monocyte adherence. Dehydrogenation of LXA4 in monocytes appears to be carried out by a 15-hydroxyprostaglandin dehydrogenase, which is present in human monocytes as determined by reverse transcription PCR and Western blots. Together, these results provide the first evidence that LXA4 and LXB4 are both potent stimulants for migration and adherence of human monocytes. Moreover, they underscore the importance of the major route of lipoxin metabolism in leukocytes, namely, the rapid dehydrogenation and inactivation carried out by monocytes.
Recognizing, treating and understanding pernicious anaemia
Authors: Leonard Sinclair
Journal: Journal of the Royal Society of Medicine (2008)

In 1824, James Combe of Edinburgh reported a case of severe pallor in a man who also had diarrhoea, thirst, and passed a great deal of urine. 1 Although Combe is sometimes credited with having been the first to describe what became called pernicious anaemia, it was not until Thomas Addison provided a clinico-pathological description that this anaemia began to be recognized as a distinct entity, 2 which the French physician Trousseau dubbed 'Addisonian anaemia'.Addison described a condition with an insidious clinical course and a curious type of dingy pigmentation found at postmortem examination.This was not the classical lemon colour of the skin that is now recognized clinically, but a darker, sometimes mottled discolouration that pervaded most tissues, including the gums.It is difficult to recognize pernicious anaemia as we know it today from this description, and although the paper was entitled 'Anaemia: disease of the supra-renal capsules', it did not actually contain a description of the patient's blood, and reported minimal involvement of the suprarenal glands.The earliest description of the disease in mainland Europe was by Michael Anton Biermer, a German physician who also noted the condition's insidious course and, because it was untreatable at the time, first referred to it as 'pernicious' anaemia. 3ntil the liver was recognized to be important in haematopoiesis, the treatment of pernicious anaemia was unsuccessful and arbitrary.Sir William Osler's textbook suggested that some patients had benefited from diet and others from sunlight, but he even suggested trying Fowler's Solution -an arsenical preparation developed by Sir James Kingston Fowler, a fashionable physician of the Middlesex Hospital -which may well have dispatched patients more quickly than their disease.Research into blood substitutes and ways of improving haematopoiesis was stimulated by the massive loss of life from blood loss during the First World War, when transfusion services had proved inadequate.This may have stimulated George
Therapeutic Potential of Genetically Modified Mesenchymal Stem Cells After Neonatal Hypoxic-Ischemic Brain Damage
Authors: Cindy TJ van Velthoven, Luca Braccioli, Hanneke LDM Willemen, Annemieke Kavelaars, Cobi J Heijnen
Journal: Molecular Therapy (2013)

Mesenchymal stem cells (MSCs) have been shown to improve outcomes after neonatal hypoxic-ischemic (HI) brain injury possibly by secretion of growth factors stimulating repair processes. We investigated whether MSCs, modified to secrete specific growth factors, can further enhance recovery. Using an in vitro assay, we show that MSC-secreting brain derived neurotrophic factor (BDNF), epidermal growth factor-like 7 (EGFL7), persephin (PSP), or sonic hedgehog (SHH) regulate proliferation and differentiation of neural stem cells. Moreover, mice that received an intranasal application of 100,000 MSC-BDNF showed significantly improved outcomes as demonstrated by improved motor function and decreased lesion volume compared with mice treated with empty vector (EV) MSCs. Treatment with MSC-EGFL7 improved motor function but had no effect on lesion size. Treatment with MSC-PSP or MSC-SHH neither improved outcome nor reduced lesion size in comparison with MSC-EV–treated mice. Moreover, mice treated with MSC-SHH showed even decreased functional outcomes when compared with those treated with MSC-EV. Treatment with MSC-BDNF induced cell proliferation in the ischemic hemisphere lasting at least 18 days after MSC administration, whereas treatment with MSC-EV did not. These data suggest that gene-modified cell therapy might be a useful approach to consider for treatment of neonatal HI brain damage. However, care must be taken when selecting the agent to overexpress. Mesenchymal stem cells (MSCs) have been shown to improve outcomes after neonatal hypoxic-ischemic (HI) brain injury possibly by secretion of growth factors stimulating repair processes. We investigated whether MSCs, modified to secrete specific growth factors, can further enhance recovery. Using an in vitro assay, we show that MSC-secreting brain derived neurotrophic factor (BDNF), epidermal growth factor-like 7 (EGFL7), persephin (PSP), or sonic hedgehog (SHH) regulate proliferation and differentiation of neural stem cells. Moreover, mice that received an intranasal application of 100,000 MSC-BDNF showed significantly improved outcomes as demonstrated by improved motor function and decreased lesion volume compared with mice treated with empty vector (EV) MSCs. Treatment with MSC-EGFL7 improved motor function but had no effect on lesion size. Treatment with MSC-PSP or MSC-SHH neither improved outcome nor reduced lesion size in comparison with MSC-EV–treated mice. Moreover, mice treated with MSC-SHH showed even decreased functional outcomes when compared with those treated with MSC-EV. Treatment with MSC-BDNF induced cell proliferation in the ischemic hemisphere lasting at least 18 days after MSC administration, whereas treatment with MSC-EV did not. These data suggest that gene-modified cell therapy might be a useful approach to consider for treatment of neonatal HI brain damage. However, care must be taken when selecting the agent to overexpress.
Enhanced amyloid deposition in Bowen's disease treated with radiotherapy
Authors: A.M. Layton, W.J. Cunliffe, W. Jones
Journal: British Journal of Dermatology (1991)

Journal Article Enhanced amyloid deposition in Bowen's disease treated with radiotherapy Get access A.M. Layton, A.M. Layton Department of Dermatology, The General Infirmary at Leeds, Leeds LSI 3EX. U.K. Search for other works by this author on: Oxford Academic Google Scholar W.J. Cunliffe, W.J. Cunliffe Department of Dermatology, The General Infirmary at Leeds, Leeds LSI 3EX. U.K. Search for other works by this author on: Oxford Academic Google Scholar W. Jones W. Jones Department of Radiotheraphy, Cookridge Hospital, Leeds LS16 6QB, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 125, Issue 6, 1 December 1991, Page 606, https://doi.org/10.1111/j.1365-2133.1991.tb14811.x Published: 01 December 1991
Temporary hemodialysis catheters: recent advances
Authors: Edward G. Clark, Jeffrey H. Barsuk
Journal: Kidney International (2014)

The insertion of non-tunneled temporary hemodialysis catheters (NTHCs) is a core procedure of nephrology practice. While urgent dialysis may be life-saving, mechanical and infectious complications related to the insertion of NTHCs can be fatal. In recent years, various techniques that reduce mechanical and infectious complications related to NTHCs have been described. Evidence now suggests that ultrasound guidance should be used for internal jugular and femoral vein NTHC insertions. The implementation of evidence-based infection-control 'bundles' for central venous catheter insertions has significantly reduced the incidence of bloodstream infections in the intensive care unit setting with important implications for how nephrologists should insert NTHCs. In addition, the Cathedia Study has provided the first high-level evidence about the optimal site of NTHC insertion, as it relates to the risk of infection and catheter dysfunction. Incorporating these evidence-based techniques into a simulation-based program for training nephrologists in NTHC insertion has been shown to be an effective way to improve the procedural skills of nephrology trainees. Nonetheless, there are some data suggesting nephrologists have been slow to adopt evidence-based practices surrounding NTHC insertion. This mini review focuses on techniques that reduce the complications of NTHCs and are relevant to the practice and training of nephrologists.
Increased H1N1 Infection Rate in Asthmatic Children
Authors: K.M. Kloepfer, J.P. Olenec, W. Lee, T.E. Pappas, G. Liu, R.F. Vrtis, M.D. Evans, R.E. Gangnon, J.E. Gern
Journal: Journal of Allergy and Clinical Immunology (2011)
A hyperplastic cause of hyperemesis
Authors: Preethi Dasilva, Neil Rajoriya, Tom Morgan, Peter Johnson, David A Gorard
Journal: Gut (2013)

A 46-year-old lady presented with a 3-month history of severe, worsening epigastric discomfort. This pain was associated with increasingly frequent episodes of vomiting. Her repeated vomiting led to weight loss of 6.5 kg. A trial of metoclopramide produced some initial symptomatic relief but its beneficial effects subsequently wore off.

Clinical examination revealed some tenderness in the upper abdomen. Blood tests showed unremarkable haematological and biochemical profiles, with normal inflammatory markers. At upper gastrointestinal endoscopy there …
Potential role of oxidative and nitrosative stress in breast carcinogenesis in women with high body mass index
Authors: Maria Moroni, Courtney Proctor, Craig D. Shriver, Laura Pedraza, Allen Lyngdoh, Jeffrey Hooke, Amir D. Meram, Aizen J. Marrogi
Journal: Cancer Research (2004)

764   The by-products of oxidative, nitrosative stress and lipid peroxidation pathways are reported to play major roles in the carcinogenesis of chronic inflammation associated malignancies. Our previous work has shown that reactive oxygen species ( ROS ) and products of lipid peroxidation have high tendencies to bind to cellular DNA forming adducts that induce structural mutations in  p53  in colitis- and heavy metals associated-liver cancers. Breast cancer has been linked to high dietary fat intake and obesity, although the proposed pathogenesis of these risk factors in breast carcinogenesis is yet to be fully elucidated. We propose that obesity is a form of chronic inflammation and that specific by-products of lipid peroxidation and oxidative stress may be responsible for the high risk of sporadic non-familial type of breast cancer ( SN-FBC ) in women with high dietary fat intake and obesity. Expression of two enzymes involved in the biogenesis of oxidative stress, nitric oxide synthase-2 ( NOS 2  ) and cyclooxygenase –2 (COX 2 ), and two major scavenger of peroxides and superoxides, superoxide dismutase ( SOD ) and glutathione peroxidase ( GPX ), were studied by immunohistochemistry on formalin fixed paraffin embedded tissue samples from 20 postmenopausal women with body mass index (BMI) ranging from 18 to 42. A pathologist evaluated the intensity of the stain and a score of 0 to 4 (0 is lowest and 4 is highest) was assigned to each tissue component for each slide. GPX expression was found to be dramatically lower in the tumor lesion of women with high BMI. In non-obese women (BMI  2 ), GPX was expressed in hyperplasia as well as in the tumor (DCIS, LCIS and invasive cancer), while obese women (BMI >30kg/m 2 ) showed very little expression in the malignant component but comparable levels in the hyperplastic region. No difference in the expression of NOS 2 , and COX 2  was seen. SOD showed highest expression in hyperplasia for both populations. Of the four enzymes tested, COX 2 , NOS 2 , SOD and GPX, only GPX was found differently expressed in women with high and low BMI. GPX, a major peroxide-scavenging enzyme, was found expressed at very low levels only in tumors of women with high BMI. Although the study population is limited, confirmation of this observation on a larger population may suggest a role for oxidative stress in breast carcinogenesis of obese women. A relationship between sustained oxidative stress, as in the case of obesity, and breast cancer may be helpful in identifying patients at risk and enroll them in early detection and prevention programs.
Hydroxyurea and Etoposide: In Vitro Synergy and Phase I Clinical Trial
Authors: M. J. Ratain, R. L. Schilsky, B. R. Wojack, T. Simon, E. K. Senekjian, N. J. Vogelzang
Journal: JNCI Journal of the National Cancer Institute (1988)

L1210 murine leukemia cells were treated with hydroxyurea (10–200 μM) for 24 hours and/or etoposide (0.17–3.4 μM) for 2 hours. Combination treatments used a fixed molar hydroxyurea: etoposide ratio of 58.9: 1, anddrug-drug interactions were quantitated according to the median effect principle. Hydroxyurea and etoposide were antagonistic at low doses at which the survival fraction was>0.5 and synergistic at higher doses at which the survival fraction was <0.25. In a phase I clinical trial, 19 patients were treated with the two drugs at one of three dose levels. The dose-limiting toxic effect was myelosuppression. Doses of 100 mg of etoposide/m2 per day by continuous infusion and 500 mg of hydroxyurea orally every 4 hours, both for 3 days, are recommended for phase II trials. [J Natl Cancer Inst 1988;80:1412–1416]
Time to benefit for colorectal cancer screening: survival meta-analysis of flexible sigmoidoscopy trials
Authors: V. Tang, W. J. Boscardin, I. Stijacic-Cenzer, S. J. Lee
Journal: BMJ (2015)

<b>Objective</b> To determine the time to benefit of using flexible sigmoidoscopy for colorectal cancer screening. <b>Design</b> Survival meta-analysis. <b>Data sources</b> A Cochrane Collaboration systematic review published in 2013, Medline, and Cochrane Library databases. <b>Eligibility criteria</b> Randomized controlled trials comparing screening flexible sigmoidoscopy with no screening. Trials with fewer than 100 flexible sigmoidoscopy screenings were excluded. <b>Results</b> Four studies were eligible (total n=459 814). They were similar for patients' age (50-74 years), length of follow-up (11.2-11.9 years), and relative risk for colorectal cancer related mortality (0.69-0.78 with flexible sigmoidoscopy screening). For every 1000 people screened at five and 10 years, 0.3 and 1.2 colorectal cancer related deaths, respectively, were prevented. It took 4.3 years (95% confidence interval 2.8 to 5.8) to observe an absolute risk reduction of 0.0002 (one colorectal cancer related death prevented for every 5000 flexible sigmoidoscopy screenings). It took 9.4 years (7.6 to 11.3) to observe an absolute risk reduction of 0.001 (one colorectal cancer related death prevented for every 1000 flexible sigmoidoscopy screenings). <b>Conclusion</b> Our findings suggest that screening flexible sigmoidoscopy is most appropriate for older adults with a life expectancy greater than approximately 10 years.
Book Review The Molecular Pathology of Autoimmune Diseases Edited by Constantin A. Bona, Katherine A. Siminovitch, Maurizio Zanetti, and Argyrios N. Theofilopoulos. 795 pp., illustrated. Langhorne, Pa., Harwood Academic, 1993. $175. 3-7186-0555-4 Autoimmunity: Physiology and Disease Edited by Antonio Coutinho and Michel D. Kazatchkine. 459 pp. New York, Wiley-Liss, 1994. $84.95. 0-471-59227-7
Authors: Robert S. Schwartz
Journal: New England Journal of Medicine (1994)
Whither <i>HER2</i>-Related Therapeutics?
Authors: Pradip De, Brian Leyland-Jones
Journal: Journal of Clinical Oncology (2010)

ethical concerns.To feel that such trials are not feasible or not ethical, investigators must believe that they already know the answers to these questions.As is often the case, however, we may know less than we think!We should take a step back and reflect on these issues.Having done so, we and our patients must have the courage to more clearly examine the role of these expensive but effective targeted therapies in a way that will allow them to be optimally applied to as broad a patient population as possible.