tbuckley/cabot-search huggingface dataset:
Hydroxyurea therapy for sickle cell disease in Britain
Authors: A Olujohungbe, K. I Cinkotai, A Yardumian
Journal: BMJ (1998)

Sickle cell disease is the commonest inherited haemoglobinopathy in Britain and affects over 9000 people.1 Clinical severity varies considerably, but patients with the most severe disease have a life expectancy of just over 40 years. Conventional management of the disease is largely supportive, highlighting a pressing need for approaches that can alter the course of the disease. Trials in America have suggested that hydroxyurea can have a significant impact on the course of the disease, but in Britain it is proving virtually impossible to recruit patients into trials to confirm these results in a British population.

The fact that the clinical severity of the sickle cell disease varies even within groups of patients with the same β globin genotype2 has led to the concept that the disease is a multigene disorder, with inheritance of α thalassemia and genes controlling the concentration of fetal haemoglobin, among others, modulating disease expression. …
Abstract #LB-298: Short-term starvation based strategy for differential protection against multiple chemotherapy agents
Authors: Fernando Safdie, Changhan Lee, Lizzia Raffaghello, Min Wei, Edoardo Parrella, Giovanna Bianchi, Valter Longo
Journal: Cancer Research (2009)

The side effects of chemotherapy are a major limiting factor in cancer treatment. Although progress has been made in the development of chemoprotectants, they are not widely used due to their drug- and tissue-specificity. Our previous research revealed the role of starvation and starvation-regulated genetic pathways in the protection of cells and organisms against a variety of toxins. Recently, we reported that a short-term starvation (STS) selectively protected normal cells and mice against etoposide but provided no, or minor, protection to neuroblastoma cells in vitro and in vivo, respectively (differential stress resistance, DSR). Our DSR hypothesis is based on the fact that stress resistance is inhibited by oncogenic pathways and thus cannot be activated in cancer cells. We have investigated whether STS protects mice against other drugs and studied its effect on the resistance of different malignant cells to chemotherapy. The reported STS regimen consisted in 48-60 hours fast prior to chemotherapy administration. Here we show that protection to cisplatin requires a 48 hour pre-chemo and 24 hour post-chemotherapy fast. Using luciferase expressing melanoma and neuroblastoma cells, we monitored the effect of chemotherapy in vivo. Our results confirmed that STS protects the host from chemotoxicity, and suggest that it does not protect neuroblastoma cells and may sensitize melanoma cells to multiple cycles of doxorubicin treatment. These results indicate that short-term starvation has the potential to be effective in the differential protection of normal and cancer cells against a wide range of chemo drugs and may enhance chemotherapy efficacy and health outcomes.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr LB-298.
Abstract 13742: The Role of PDGF on F-actin Reorganizatio and Proplatelet Formation via PDGF beta-receptors and Erk/akt Pathways
Authors: Mo Yang, Yuanshan Cheng, Jieyu Ye, Enyu Liang, Lixia Zhou, Qizhou Lian
Journal: Circulation (2014)

Introduction:  Our previous study demonstrated that Platelet-derived growth factor (PDGF) has a promoting effect on thrombopoiesis in an irradiated-mice model (Ye et al,  Haematologica , 2010).   Hypothesis:  PDGF may enhance platelet function and number via PDGFR and Erk/Akt pathways.   Methods:  PDGF receptors were identified on platelets and megakaryocytic cells (MKs) by ELISA, flow cytometry and immunocytochemical staining.   Results:  Both PDGFR subtype were identified on platelets and MKs; levels of PDGF beta-receptors exceeded that of alpha-receptors. PDGF-BB significantly stimulated MKs proliferation; this mitogenic effect was partially neutralized by antibodies directed against the PDGF beta-receptors. Western blot also determine that these receptors mediate PDGF-BB-inducible expression of c-fos. In MKs apoptotic model, PDGF had a similar anti-apoptotic effect as TPO. We demonstrated that PDGF activated the Akt pathway, while addition of imatinib mesylate reduced p-Akt expression, suggesting that the PDGF-initiated protective effect is likely to be mediated via PDGF receptors with subsequent activation of the Akt pathway. PDGF also promoted proplatelet formation in MKs and this effect was reduced by PDGFR antibodies. In PDGF-BB and TPO groups had more proplatelet bearing MKs; Proplatelet bearing MKs in PDGF-BB treatment group was (15 % ± 3.2), and in TPO group was (18 % ± 2.5) in 200 MKs, which were significantly more than the control group (7 % ± 2.6) (n=5). Whether PDGF has an effect on cytoskeleton reorganization of MKs, and whether the effect can be reduced by Erk1/2 inhibitor PD98059, MKs were stained with F-actin specific binder rhodamine-phalloidin. We observed that polymerized actin level is lower in control group refer to PDGF-BB group and distributed throughout the cytoplasm with occasionally few aggregation. In contrast, polymerization actin level was higher in PDGF-BB group. Adding PD98059, the fluorescence intensity was reduced (n=5).   Conclusions:  Our data demonstrated that treated with PDGF-BB for 30 minutes Erk1/2 was activated in MKs. This study suggests that PDGF has a potent effect on F-actin reorganization and proplatelet formation via PDGF beta-receptors, p-ERK1/2 or p-Akt pathway.
Ethical debate: Truth, the first casualty Deadly charades Communication is a vital part of care Doctors and patients should be fellow travellers
Authors: M. Blennerhassett, M. Tattersall, P. Ellis, D Metcalfe
Journal: BMJ (1998)

# Truth, the first casualty {#article-title-2}

In the past, patients with cancer were often not told the truth about their condition. This would be considered unacceptable nowadays. Yet Mitzi Blennerhassett's account of her treatment for anal cancer shows that truth can still be one of the firstcasualties of a system of medical education and training that may dehumanise patients … and doctors. Here a cancer specialistand a former professor of general practice comment on Ms Blennerhassett's experience.

# Deadly charades {#article-title-3}

   ![][1] 

Being fed “tailored” truth and outright lies was psychological torment I felt continually humiliated, manipulated, out of control. The need for truth became an obsession. The necessity to prove competence in order to obtain information became a barrier to communication. They withheld my rights: I confiscated theirs. With integrity eroded, status erased, I felt as though I was living through One Flew Over the Cuckoo's Nest.1 Smiles deceived, reassurances deluded, suspicions were not shared. But misplaced kindness became brutality as the bad news broke. And the deceit hurt.

The diagnosis was squamous carcinoma of the anal canal.“Basaloid” was written in my notes. Passing from surgeon to oncologist, treatment options reduced from three to two and my“hernia” changed category. I was not informed they were about to take a biopsy specimen. Silence intensified as they prepared a needle for the lump in my groin. Suspicions confirmed, I gave my“informed” consent over the phone.

Side effects, I was told, were“nausea, tiredness, diarrhoea and wind.” Nobody mentioned pain. Nobody said this was pioneering treatment (fluorouracil, mitomycin, and radiotherapy (85 Gy)).2Nobody mentioned risks or long term effects yet only I could have assessed the full implications of these. Recently, with great persistence (impossible when debilitated), I learned that high dose radiotherapy causes progressive damage in anal cancer, giving a 70-75% probability of late failure. (The remaining 25% of patients presumably …

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Abstract 13469: Drp1 Accumulates in Mitochondria and Plays a Protective Role in the Heart in Response to Pressure Overload
Authors: Akihiro Shirakabe, Yoshiyuki Ikeda, Peiyong Zai, Junichi Sadoshima
Journal: Circulation (2014)

Dynamin-related protein 1 (Drp1) plays an essential role in maintaining the quality control of mitochondria through mitochondrial (Mt) fission and mitophagy. We investigated how Mt function, autophagy and Drp1 are regulated in the heart during pressure overload (PO) and whether endogenous Drp1 plays an important role in regulating cardiac function. Mice were subjected to transverse aortic constriction (TAC) at multiple time points between 6 hours and 30 days. Left ventricular (LV) weight/tibial length (LVW/TL) was significantly elevated at Day 7 (TAC vs sham; 5.92 ± 0.27 vs 4.22 ± 0.12, p&lt;0.05). Ejection fraction (EF) was maintained at Day 7, but gradually decreased thereafter (at 30 days; 65±9 vs 83±9 %, p&lt;0.05). LC3-II was decreased (-45.7%, p&lt;0.05) while p62 accumulated (1.17 fold, p&lt;0.05) significantly at Day 7. Both Mt ATP content (-65.6%, p&lt;0.05) and production (-90.3%, p&lt;0.05) were reduced significantly at Days 7 and 14, respectively, and thereafter. Mt mass, evaluated by electron microscopy, was also reduced (-19.9%, p&lt;0.05) at Day 7. Drp1 accumulated in mitochondria at Day 7, and S616 phosphorylation of Drp1, associated with increased activity, was increased at Day 7. Thus, PO suppresses autophagy and induces Mt dysfunction by Day 7, at which time Drp1 accumulates in mitochondria and Mt mass is decreased. To examine the functional significance of endogenous Drp1 during PO, cardiac-specific heterozygous Drp1 knock out (Drp-hetCKO) mice were subjected to TAC. At Day 7, decreases in EF (61± 2 vs 84 ± 7%, p&lt;0.05) and increases in LVW/TL (7.22 ± 0.26 vs 5.86 ± 0.65, p&lt;0.05) and lung weight/TL (12.01 ± 1.10 vs 6.31 ± 1.19, p&lt;0.05) were exacerbated in Drp-hetCKO compared to in control mice. LV end diastolic pressure was significantly higher (22.0 ± 2.8 vs 5.7 ± 2.9 mmHg, p&lt;0.05) and myocardial fibrosis (14.1 ± 2.5 vs 6.2 ± 4.3 %, p&lt;0.05) was greater in Drp-hetCKO than in control mice. Mt mass was also significantly greater in Drp-hetCKO than in control mice (relative Mt mass, 1.21 ± 0.46 vs 1.00 ± 0.02, p&lt;0.05). These results suggest that PO inhibits autophagy and induces mitochondrial dysfunction by Day7, which coincides with Mt accumulation of Drp1. Drp1 plays an adaptive role in this condition, mediating decreases in Mt mass and protecting the heart from dysfunction.
Molecular Remission in PML/RARα-Positive Acute Promyelocytic Leukemia by Combined All-trans Retinoic Acid and Idarubicin (AIDA) Therapy
Authors: Franco Mandelli, Daniela Diverio, Giuseppe Avvisati, Anna Luciano, Tiziano Barbui, Carlo Bernasconi, Giorgio Broccia, Raffaella Cerri, Michele Falda, Giuseppe Fioritoni, Franco Leoni, Vincenzo Liso, Maria Concetta Petti, Francesco Rodeghiero, Giuseppe Saglio, Maria Luce Vegna, Giuseppe Visani, Ulrich Jehn, Roel Willemze, Petra Muus, Pier Giuseppe Pelicci, Andrea Biondi, Francesco Lo Coco
Journal: Blood (1997)
Abstract MP15: Innovative Self-Regulation Strategies Reduce Weight Gain in Young Adults
Authors: Rena R Wing, Deborah Tate, Mark Espeland, Cora E Lewis, Amy Gorin, Jessica LaRose, Judy Bahnson, Letitia Perdue, Karen Erickson, Erica Ferguson, Wei Lang
Journal: Circulation (2015)

Introduction: Young adults gain an average of 2 pounds per year, increasing their risk for obesity and co-morbidities. To date, no approaches have successfully reduced this weight gain. The Study of Novel Approaches to Prevention of Weight Gain (SNAP) is a randomized clinical trial testing two innovative self-regulation interventions. Hypothesis: We hypothesized that both interventions would reduce weight change over an average follow-up of 3 years relative to a control. Methods: Participants age 18-35 with a BMI of 21-30 were recruited in Raleigh-Durham, NC and Providence, RI. The 599 participants included 27% from minority groups and 22% males, mean age 28.4 (SD 4.4) yrs and BMI 25.4 (2.6). The interventions were based on a self-regulation model, involving frequent self-weighing and changes in eating and activity if weight gain occurred. The SMALL changes approach focused on making small (100 calorie) changes in daily eating and exercise; LARGE changes emphasized larger initial changes in eating and exercise, to create a 5 to 10-pound buffer against anticipated weight gain. Interventions were delivered via 8 face-to-face group sessions in the first 4 months, followed by ongoing weight reporting and feedback and optional Internet refreshers. CONTROL received one face-to-face session. Assessments were at baseline, 4 months, and then annually. Results: Data collection ends 12/31/14; final results will be presented. Retention at year 3 is 87%. Currently, mean (SE) weight changes across 3 years differ significantly between the groups (see Fig 1); for LARGE, mean weight loss is -2.48 (0.22) kg, which differs significantly from -0.75 (0.22) kg loss in SMALL, and both differ from the +0.10 (0.22) kg gain in Control. For secondary outcomes of weight gain from baseline to 2 years and % gaining &gt;1 lb at 2 years, both interventions significantly differed from Control, but not from each other. Conclusion: Self-regulation approaches using LARGE or SMALL change strategies reduce weight gain in young adults.
Update on the pathogenesis of post-transplant skin cancer in renal transplant recipients
Authors: W.L. Ho, G.M. Murphy
Journal: British Journal of Dermatology (2007)

Journal Article Update on the pathogenesis of post‐transplant skin cancer in renal transplant recipients Get access W.L. Ho, W.L. Ho Department of Dermatology, Beaumont Hospital, Dublin 9, Ireland Correspondence: Wen Lyn Ho. E‐mail: drwlho@yahoo.com Search for other works by this author on: Oxford Academic Google Scholar G.M. Murphy G.M. Murphy Department of Dermatology, Beaumont Hospital, Dublin 9, Ireland Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 158, Issue 2, 1 February 2008, Pages 217–224, https://doi.org/10.1111/j.1365-2133.2007.08363.x Published: 01 February 2008
Diagnosis of Sulfonamide Hypersensitivity Reactions by In-Vitro "Rechallenge" with Hydroxylamine Metabolites
Authors: M J Rieder, J Uetrecht, N H Shear, M Cannon, M Miller, S P Spielberg
Journal: Annals of Internal Medicine (1989)

To determine whether differences in in-vitro detoxification of sulfonamide-reactive metabolites can be detected among the lymphocytes from controls, patients with sulfonamide hypersensitivity reactions, and patients with nonhypersensitivity reactions to the sulfonamide agents.In-vitro toxicity assay on lymphocytes.Clinics for adverse drug reactions in an adult and pediatric tertiary care center.Peripheral blood lymphocytes were obtained from 46 normal volunteers and 76 patients referred to the clinic for assessment of adverse drug reactions to sulfonamide agents. Thirty-one patients had clinical histories consistent with a diagnosis of hypersensitivity reaction, whereas 45 patients had clinical histories felt to be inconsistent with a diagnosis of hypersensitivity reaction.Lymphocytes were assayed with tetrazolium to determine toxicity from the hydroxylamine of sulfamethoxazole.The lymphocytes from patients with a history of hypersensitivity reactions showed markedly increased toxicity across a tenfold-concentration toxicity-concentration curve compared with those from controls and patients with a history of nonhypersensitivity reactions. These differences were highly significant (P less than 0.01). No difference was found between the toxicity shown by the lymphocytes from controls and that shown by the lymphocytes from patients with a history of nonhypersensitivity reactions.Metabolic differences in the production and detoxification of reactive metabolites of sulfonamide agents are important determinants of hypersensitivity reactions to these agents. These results suggest that the hydroxylamine derivative of sulfamethoxazole may be a reactive metabolite mediating these reactions. Sulfonamide hydroxylamines are useful in the diagnosis and study of the pathogenesis of hypersensitivity reactions to sulfonamide agents.
The New Evolution: Zoogenesis.
Authors: Austin Hobart Clark
Journal: JAMA (1930)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 07: Longitudinal Patterns of Change in Systolic Blood Pressure (SBP) and Incidence of Cardiovascular Disease. The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Natalia Petruski-Ivleva, Anthony Viera, David Couper, Daichi Schimbo, Paul Muntner, Christy Avery, Andrea Schneider, Anna Kucharska-Newton
Journal: Circulation (2015)

Background:  Increasing SBP throughout the life course is associated with an increased risk of cardiovascular disease (CVD); however, patterns of SBP increase may differ among individuals. We sought to examine the association of longitudinal change in SBP with CVD outcomes among middle-aged adults.   Methods:  We used latent class growth models (STATA, traj) to identify patterns of longitudinal change in SBP among 11,565 ARIC cohort participants with non-missing SBP measurements at 4 clinical examinations (1987-1998) Model adequacy was assessed using BIC criteria, average posterior probabilities of group assignment, and odds of correct classification. The association of SBP pattern with incidence of CVD and mortality was examined in follow-up from the fourth clinical examination (1998) through Dec 31, 2011, using Poisson regression models adjusted for age and use of hypertension medication.   Results:  We identified six distinct patterns of SBP change, of which three showed a sustained increase within the normal range (   Conclusions:  Increase in SBP during midlife is associated with long-term risk of CVD, regardless of baseline SBP. Having an elevated SBP in mid-life increases the risk of CVD events and mortality. Our observations highlight the value of hypertension prevention efforts.
Features of<i>Staphylococcus aureus</i>colonization in patients with nummular eczema
Authors: W. J. Kim, H. C. Ko, M. B. Kim, D. W. Kim, J. M. Kim, B. S. Kim
Journal: British Journal of Dermatology (2012)

Funding sources: This research was supported by grant from Amore‐Pacific Grant in 2010. Conflicts of interest: none declared. MADAM, Nummular eczema (NE) is a common eczematous disorder sometimes complicated by bacterial infection.1 Although the positive culture rate of Staphylococcus aureus, a common transient of skin microflora, and atopic dermatitis severity are positively correlated, few data are available on the microbiological aspects of NE. Therefore, we conducted this study to assess the features of S. aureus colonization in patients with NE. The study protocol was approved by the local ethics committee and informed consent was obtained from all study subjects. Swabs for S. aureus were obtained from the skin, anterior nares and right second subungual space of 40 patients with NE and 40 of their healthy close contacts. Healthy close contacts consisted of individuals who lived with the patients with NE, including parents, grandparents, domestic helpers or siblings, and they were considered normal controls. Disease severity was evaluated using a dermatitis score.2 Toxin genes and the genotypic composition of all S. aureus isolates were determined by polymerase chain reaction (PCR) and pulsed‐field gel electrophoresis, respectively.
Wetlands of the world: Inventory, ecology and Management, vol. 1. Africa, Australia, Canada and Greenland, Mediterranean, Mexico, Papua New Guinea, South Asia, Tropical South America, United States edited by D.F. Whigharn, D. Dykyjová and S. Hejny Kluwer Academic Publishers, 1993. £162.00/$286.00 hbk (xx + 768 pages) ISBN 0 7923 1685 1
Authors: R Turner
Journal: Trends in Ecology & Evolution (1994)
Canadian medical president hid his conviction
Authors: David Spurgeon
Journal: BMJ (1998)

The new president of the Canadian Medical Association will remain in his post despite the fact that he concealed at his election last month a conviction of professional misconduct made just weeks before.

Allon Reddoch is appealing against a finding by a committee of the Yukon Medical Council in the death of a 16 year old girl from botulism. The committee found that he had failed to record a …
Imiquimod treatment of papilloma virus and DMBA /TPA-induced cutaneous skin cancer in Mastomys coucha: an unique animal model system useful for preclinical studies
Authors: J. Nafz, M. Ohnesorge, E. Stockfleth, F. Rösl, I. Nindl
Journal: British Journal of Dermatology (2007)

Immune response modifiers including imiquimod can be topically applied for the treatment of both genital warts and benign and malignant skin tumours (e.g. actinic keratosis). In an initial pilot study, we examined the response of spontaneously papillomavirus caused skin lesions (e.g. papillomas, keratoacanthomas) vs. chemically induced skin tumours of Mastomys coucha to imiquimod.Fourteen spontaneously and 16 chemically [initiation with 7,12-dimethylbenzanthracene (DMBA) followed by repeated 12-O-Tetradecanoylphorbol-13-acetate (TPA) applications] induced skin tumours were treated two to three times per week with 5% imiquimod or placebo.Notably, significant higher regression or growth arrest rates of imiquimod treated animals were observed in chemically vs. spontaneously induced skin tumours [9/14 (64%) vs. 2/11 (18%), P < 0.05]. Regression or growth arrest of both skin tumours from placebo treated animals were similar (1/2 vs. 1/3). Tumour growth of nonresponders was lowest in imiquimod treated animals compared to the placebo or untreated group.Imiquimod was able to reduce skin tumour growth particularly in chemically induced lesions of Mastomys coucha. The different clearance rates are most likely due to lower differentiation status of the DMBA/TPA-induced tumours, allowing a better uptake of imiquimod than spontaneously induced papillomas or keratoacanthomas, known to be highly keratinized.