tbuckley/cabot-search huggingface dataset:
New Zealand's independent practitioner associations: a working model of clinical governance in primary care?
Authors: L. Malcolm, N. Mays
Journal: BMJ (1999)

2][3] Yet there remains considerable confusion and uncertainty about its scope and purpose.Since 1991-2, the NHS has invested in the development of clinical audit, but this has rarely been related to the parallel development of various forms of devolved budget holding, both within hospitals and in primary care.However, we believe the integration of clinical and financial accountability is essential for the development of effective clinical governance.Over the past five years, New Zealand's independent practitioner associations have been developing a working model of such clinical governance in primary care. 4 5 We think this is relevant to clinical governance in budget holding primary care groups in England and local health groups in Wales.Although Scotland's local health care cooperatives do not hold budgets or commission services, they too will need to make arrangements for clinical governance.
Abstract 289: Hydrogen bond surrogate (HBS) helices as orthosteric regulator of hypoxia inducible transcription
Authors: Swati Kushal, Brooke Bullock, Laura Henchey, Paramjit Arora, Bogdan Olenyuk
Journal: Cancer Research (2012)

Abstract Hypoxia-Inducible Factor (HIF-1) is a heterodimeric transcriptional activator which plays a critical role in tumorigenesis and therefore is an important therapeutic target. Transcriptional activation of HIF-1 is known to involve the interaction between cysteine-histidine rich region1 (CH1) of a coactivator protein p300 or Creb Binding Protein (CBP) and C-terminal activation domain (C-TAD) of its α-subunit (HIF-1α C-TAD). Based on the hydrogen bond surrogate (HBS) approach, we have rationally designed stabilized alpha helix that can disrupt the binding interface between C-TAD domain of HIF-1α and CH1 domain of p300/CBP. We have shown by fluorescence polarization that such stabilized alpha helix mimetics can directly bind to the CH1 domain of p300 and also can disrupt the HIF-1α/p300 complex. HBS helix mimetics are also shown to selectively downregulate the hypoxia inducible genes in cell culture. Thus, orthosteric inhibition of the HIF-1 transcriptional complex by rationally designed helix mimetics offers a novel approach to downregulate the expression of key hypoxia inducible genes responsible for tumor progression. 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 289. doi:1538-7445.AM2012-289
European MPs offer extension of patents to companies developing drugs for children
Authors: Rory Watson
Journal: BMJ (2005)

European Union legislation designed to encourage pharmaceutical companies to develop drugs specifically tailored to children's needs has moved closer to the statute book after members of the European parliament (MEPs) voted to endorse it.

Francoise Grossetete, the French Christian Democrat member who steered the bill through the parliament, said after the vote: “What concerns me are the 100 million Europeans who are under 18 years of age. Thanks to the European Union, our children will soon benefit from appropriate and safe medicines and will no longer have to depend on the good will of …
Normal Growth and Development during Adolescence
Authors: Harold C. Stuart
Journal: New England Journal of Medicine (1946)

ADOLESCENCE, according to Webster's first definition, is "the state or process of growing up from childhood to manhood or womanhood," and this is the meaning that will be given to the term in this review. Some confusion is apparent in the literature because a second definition by Webster limits adolescence to a much shorter terminal phase of the developmental period — that is, "the period of life between puberty and manhood."As examples of the confusion caused by this difference of interpretation, one author refers to the "pubescent period" in girls as that preceding the menarche and the "adolescent period" . . .
Effect of positive ionisation of inspired air on the response of asthmatic children to exercise.
Authors: I Lipin, I Gur, Y Amitai, I Amirav, S Godfrey
Journal: Thorax (1984)

To evaluate the effect of positive ionisation of inspired air on bronchial reactivity, 12 asthmatic children were twice challenged by exercise in random order. During one test positively ionised air (5-10 X 10(5) ions/cm) was breathed. All challenges were matched in terms of basal lung function and exercise tests were matched in terms of ventilation and respiratory heat loss. Exercise induced asthma was significantly aggravated by exposure to positively ionised air, the postexercise fall in FEV1 (delta FEV1) being 24.7% (SEM and 5.3%) and 35.3% (5%) after the control and ionised air tests respectively (p less than 0.04). It is concluded that positive ionisation aggravates the bronchial response to exercise.
Pulsatile uptake of CO in the human lung
Authors: Harold A. Menkes, Kazuaki Sera, Robert M. Rogers, Richard W. Hyde, Robert E. Forster, Arthur B. DuBois
Journal: Journal of Clinical Investigation (1970)

The instantaneous uptake of CO in the lungs was measured with a water-filled body plethysmograph in normal man. First, control measurements of plethysmograph pressure were made while the subject held his breath for 7 sec after breathing gas mixtures prepared to bring his alveolar P(O2) and P(CO2) close to mixed venous levels. Then, CO uptake measurements were made while he held his breath after inhaling the same gas mixtures with added CO (2.0%). The change in lung volume on CO minus the change in lung volume during the control measurement was a measure of the CO uptake in the lungs. Cardiopneumatic changes in lung gas volume were subtracted electrically. All of five subjects showed pulsatile CO uptake. The mean CO uptake was 103 ml/min. A peak uptake of 2.0 (range 1.6-2.3) times the mean uptake occurred 0.3-0.4 sec after the R wave of the EKG and a minimum uptake of 0.4 (range 0.2-0.5) times the mean uptake occurred during the tenth of a second before the R wave of the EKG. These results suggest that pulmonary capillary blood volume is pulsatile during the cardiac cycle.
Into the Valley: Death and the Socialization of Medical Students
Authors: Samuel W. Bloom
Journal: JAMA (1992)

For those who look at medical education as more than technical training, the experience of medical students in the anatomy laboratory has always had special significance as a rite de passage. Yet, beyond the obvious observation that this is where death is first encountered and that the dissection is an introduction to the professional privilege of intervention in the human body, the analysis of this experience has eluded detailed understanding to all but a few. Renee Fox's classic papers on detached concern and training for uncertainty are the outstanding exceptions,<sup>1,2</sup>and, in a different way, LeBaron's autobiographical account<sup>3</sup>is another. Now, Hafferty offers a lucid, perceptive, detailed report of his study of how the dissection of the human body, and death in general, is part of the socialization for the physician's role. This is by no means a book that is easy to read, although the writing is
Transcription factor HNF-6/OC-1 inhibits the stimulation of theHNF-3?/Foxa1 gene by TGF-? in mouse liver
Authors: Nicolas Plumb–Rudewiez, Frédéric Clotman, Hélène Strick–Marchand, Christophe E. Pierreux, Mary C. Weiss, Guy G. Rousseau, Frédéric P. Lemaigre
Journal: Hepatology (2004)

A network of liver–enriched transcription factors controls differentiation and morphogenesis of the liver. These factors interact via direct, feedback, and autoregulatory loops. Previous work has suggested that hepatocyte nuclear factor (HNF)–6/OC–1 and HNF–3α/FoxA1 participate coordinately in this hepatic network. We investigated how HNF–6 controls the expression of Foxa1 . We observed that Foxa1 expression was upregulated in the liver of Hnf6 -/- mouse embryos and in bipotential mouse embryonic liver (BMEL) cell lines derived from embryonic Hnf6 -/- liver, suggesting that HNF–6 inhibits the expression of Foxa1 . Because no evidence for a direct repression of Foxa1 by HNF–6 was found, we postulated the existence of an indirect mechanism. We found that the expression of a mediator and targets of the transforming growth factor beta (TGF–β) signaling was increased both in Hnf6 -/- liver and in Hnf6 -/- BMEL cell lines. Using these cell lines, we demonstrated that TGF–β signaling was increased in the absence of HNF–6, and that this resulted from upregulation of TGF–β receptor II expression. We also found that TGF–β can stimulate the expression of Foxa1 in Hnf6 +/+ cells and that inhibition of TGF–β signaling in Hnf6 -/- cells down–regulates the expression of Foxa1 . In conclusion , we propose that Foxa1 upregulation in the absence of HNF–6 results from increased TGF–β signaling via increased expression of the TGF–β receptor II. We further conclude that HNF–6 inhibits Foxa1 by inhibiting the activity of the TGF–β signaling pathway. This identifies a new mechanism of interaction between liver–enriched transcription factors whereby one factor indirectly controls another by modulating the activity of a signaling pathway. (Hepatology 2004;40:1266-1274.)
MITRAL VALVE LEAFLET ABNORMALITIES CORRELATE WITH LEFT VENTRICULAR REMODELLING AND OBSTRUCTION IN HYPERTROPHIC CARDIOMYOPATHY: A QUANTITATIVE 3D TRANSTHORACIC ECHOCARDIOGRAPHIC STUDY
Authors: Denisa Muraru, Chiara Calore, Paola Melacini, Umberto Cucchini, Sorina Mihaila, Diletta Peluso, Laura Ucci, Marcelo Miglioranza, Sabino Iliceto, Luigi Badano
Journal: Journal of the American College of Cardiology (2014)
Plasma levels of 8-methoxypsoralen in psoriatic patients receiving topical 8-methoxypsoralen
Authors: V.S. NEILD, L.V. SCOTT
Journal: British Journal of Dermatology (1982)

Using a high‐pressure liquid chromatographic technique, plasma psoralen levels have been measured in patients receiving total‐body topical photochcmothcrapy (PUVA). Levels comparable with those found during oral 8‐methoxypsoralen (8‐MOP) treatment were observed, suggesting that topical therapy has no advantage over the oral route as far as the hazards of systemic therapy are concerned.
Frequent loss of heterozygosity on chromosome 22 in hepatocellular carcinoma
Authors: Kazuhiro Takahashi, Jiro Kudo, Hiromi Ishibashi, Yasuhiko Hirata, Yoshiyuki Niho
Journal: Hepatology (1993)

We investigated 24 hepatocellular carcinomas in Japan to find loss of heterozygosity with 15 polymorphic DNA markers that detect allelic losses at specific chromosome loci. Loss of heterozygosity on chromosomes 10q, 17p and 22q was detected in 3 of 12 (25%), 9 of 21 (43%) and 5 of 15 (33%) informative cases of hepatocellular carcinoma, respectively. This is the first report of loss of heterozygosity on chromosome 22q in hepatocellular carcinoma; the newly recognized common chromosome loss was considered to exist between D22S9 and D22S10 on 22q11. On the basis of this and other studies, we believe it is likely that such a chromosome loss in hepatocellular carcinoma is a signal for malignant transformation and that loss of unknown genes on chromosomes 10q, 17p and 22q may contribute to tumor progression in hepatocellular carcinoma.
The Effect of Weight Reduction on Blood Pressure, Plasma Renin Activity, and Plasma Aldosterone Levels in Obese Patients
Authors: Michael L. Tuck, James Sowers, Leslie Dornfeld, Gary Kledzik, Morton Maxwell
Journal: New England Journal of Medicine (1981)

We investigated the relation between changes in the renin-aldosterone axis and reduction in blood pressure in 25 obese patients placed on a 12-week reducing diet; sodium intake was either medium (120 mmol) or low (40 mmol). Plasma renin activity (PRA) declined with weight loss, so that by 12 weeks there was a significant decrease in PRA (P<0.01) as well as plasma aldosterone (P<0.05), regardless of sodium intake. Weight loss with low sodium intake was equal to that with medium intake. The reduction in PRA but not in aldosterone correlated with weight loss in both sodium-intake groups (r = 0.58). Mean arterial pressure fell significantly and equally in both groups, correlating with weight loss throughout the study (r = 0.56) and with PRA from the fourth through 12th weeks (r = 0.48). These results demonstrate that weight loss is accompanied by reductions in PRA and aldosterone; PRA reductions, irrespective of sodium intake, may contribute to the decline in blood pressure. (N Engl J Med. 1981; 304:930–3.)
Physicians taking adolescent medicine from benches to trenches
Authors: Kimberly Glasbrenner
Journal: JAMA (1986)

Today, there's a "seamless whole" of medical problems that affect adolescents. And the issues that comprise this whole are often the result of complex interactions among biology, culture, and society, says Robert Haggerty, MD, president of the William T. Grant Foundation, New York City, and immediate past-president of the American Academy of Pediatrics. "The biggest of these problems, the things that kill kids—accidents, homicides, and suicides—are the things we ought to be able to prevent," says Marianne Felice, MD, director of adolescent medicine at University of California Hospital, San Diego, and immediate past-president of the Society for Adolescent Medicine. At the Society for Adolescent Medicine's meeting, "Controversies in Adolescent Health Care: From the Benches to the Trenches," physicians, nurses, and other health professionals discussed how physicians can detect and treat, better understand, and prevent these and other problems including school failure and delinquency, eating disorders, alcohol and other drug abuse,
Androgen receptor and 5α-reductase immunohistochemical profiles in extramammary Paget disease
Authors: S. Kasashima, S. Ozaki, A. Kawashima, Y. Zen, T. Moriya, M. Inoue
Journal: British Journal of Dermatology (2009)

Journal Article Androgen receptor and 5α‐reductase immunohistochemical profiles in extramammary Paget disease Get access S. Kasashima, S. Kasashima Department of Pathology, National Hospital Organization, Kanazawa Medical Center, 1‐1 Shimoishibikimachi, Kanazawa 920‐8650, Japan Satomi Kasashima. E‐mail: sato‐kasa@kinbyou.hosp.go.jp Search for other works by this author on: Oxford Academic Google Scholar S. Ozaki, S. Ozaki Divisions of Pathology Search for other works by this author on: Oxford Academic Google Scholar A. Kawashima, A. Kawashima Department of Pathology, National Hospital Organization, Kanazawa Medical Center, 1‐1 Shimoishibikimachi, Kanazawa 920‐8650, Japan Search for other works by this author on: Oxford Academic Google Scholar Y. Zen, Y. Zen Institute of Liver Studies, King’s College Hospital, London, U.K. Search for other works by this author on: Oxford Academic Google Scholar T. Moriya, T. Moriya Division of Pathology, Kawasaki Medical University, Kurashiki, Japan Search for other works by this author on: Oxford Academic Google Scholar M. Inoue M. Inoue Gynecology, Kanazawa University Hospital, Kanazawa, Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 162, Issue 5, 1 May 2010, Pages 1098–1102, https://doi.org/10.1111/j.1365-2133.2009.09603.x Published: 01 May 2010
Frequency of citation and outcome of cholesterol lowering trials.
Authors: U. Ravnskov
Journal: BMJ (1992)

intervention can be recommended.In addition, use of a daytime average of 160/95mmHg must deny treatment to many patients who would receive it on the basis of the World Health Organisation criteria,8 and may deny some of them the benefits in terms of preventing stroke.Furthermore, as a separate issue, we are concerned that the common assumption that patients with "white coat" hypertension are not at risk may be flawed.9We believe that there is a need for prospectively collected data on the clinical outcome of patients managed on the basis of ambulatory rather than clinic pressures and suggest that this is an urgent concern.Such data might be collected by the joint action of academic centres working in this research area.Until such data have been collected, wholesale introduction of this technique in clinical practice may be premature.
T Cells Kill Bacteria Captured by Transinfection from Dendritic Cells and Confer Protection in Mice
Authors: Aránzazu Cruz-Adalia, Guillermo Ramirez-Santiago, Carmen Calabia-Linares, Mónica Torres-Torresano, Lidia Feo, Marta Galán-Díez, Elena Fernández-Ruiz, Eva Pereiro, Peter Guttmann, Michele Chiappi, Gerd Schneider, José López Carrascosa, Francisco Javier Chichón, Gloria Martínez del Hoyo, Francisco Sánchez-Madrid, Esteban Veiga
Journal: Cell Host & Microbe (2014)
Standardized Uptake Value of 2-[18F] Fluoro-2-Deoxy-D-Glucose in Predicting Outcome in Head and Neck Carcinomas Treated by Radiotherapy With or Without Chemotherapy
Authors: A. S. Allal
Journal: Journal of Clinical Oncology (2002)

PURPOSE: In patients with head and neck cancer enrolled onto a prospective study of positron emission tomography (PET), pretreatment 2-[18F] fluoro-2- deoxy-d-glucose (FDG) uptake was evaluated as a predictor of local control and disease-free survival (DFS) after treatment by radiotherapy (RT) with or without chemotherapy. PATIENTS AND METHODS: We studied 63 patients with carcinomas of the head and neck who had an FDG-PET scan before radical RT. Tumor FDG uptake was measured with the semiquantitative standardized uptake value (SUV). All patients but one were treated with accelerated or hyperfractionated RT schedules. Thirteen patients received concomitant cisplatin-based chemotherapy. RESULTS: In 25 patients who presented with any component of treatment failure, the SUV was significantly higher than in the remaining patients without any such failure. Patients having tumors with high FDG uptake had a significantly lower 3-year local control (55% v 86%, P = .01) and DFS (42% v 79%, P = .005) compared with patients having low uptake tumors. In the multivariate analysis, the only factor that retained its significance for DFS was SUV category, whereas T category was of borderline significance. For local control, T category remained a significant factor, whereas a lower local control was observed for tumors with a high SUV compared with those with low SUV. CONCLUSION: FDG uptake, as measured by the SUV, has potential value in predicting local control and DFS in head and neck carcinomas treated by RT. High FDG uptake may be a useful parameter for identifying patients requiring more aggressive treatment approaches.
MYC Synergizes with Activated BRAFV600E in Mouse Lung Tumor Development by Suppressing Senescence
Authors: Vedrana Tabor, Matteo Bocci, Nyosha Alikhani, Raoul Kuiper, Lars-Gunnar Larsson
Journal: Cancer Research (2014)

The activated RAS/RAF cascade plays a crucial role in lung cancer, but is also known to induce cellular senescence, a major barrier imposed on tumor cells early in tumorigenesis. MYC is a key factor in suppression of RAS/BRAF(V600E)-induced senescence in vitro. However, it is still unclear whether MYC has the same role during tumor development in vivo. Using a conditional, compound knock-in model of Cre-activated BRAF(V600E) and tamoxifen-regulatable MycER, we show that tamoxifen-induced activation of MYC accelerated the onset and increased the number and size of BRAF(V600E)-driven adenomas in a dose-dependent manner, resulting in reduced survival. Furthermore, MYC activation leads to reduced expression of the senescence markers p16(INK4A), p21(CIP1), and H3K9me3-containing heterochromatin foci, and an increased percentage of Ki67(+) tumor cells. This suggests that MYC already early during tumor formation suppresses a BRAF(V600E)-induced senescence-like state. Initial activation of MYC followed by tamoxifen withdrawal still resulted in an increased number of tumors and reduced survival. However, these tumors were of smaller size, showed increased expression of p16(INK4A) and p21(CIP1), and reduced number of Ki67(+) cells, indicating that MYC inactivation restores BRAF(V600E)-induced senescence. Surprisingly, MYC activation did not promote adenoma to carcinoma progression. This suggests that senescence suppression by MYC is a discrete step in tumor development important for sustained tumor growth but preceding malignant transformation and that additional oncogenic events are required for carcinoma development and metastasis. These findings contribute to our understanding of the neoplastic transformation process, with implications for future treatment strategies.
Melanoma Complicating Treatment with Natalizumab for Multiple Sclerosis
Authors: John T. Mullen, Timothy K. Vartanian, Michael B. Atkins
Journal: New England Journal of Medicine (2008)

To the Editor: We report on two cases of melanoma in women with multiple sclerosis who were treated with natalizumab (Tysabri, Biogen Idec and Elan Pharmaceuticals), a humanized monoclonal antibody against α4 integrins. Patient 1 was a 46-year-old woman who, shortly after receiving her first dose of natalizumab, noticed a rapidly changing mole on her shoulder; on evaluation, it proved to be a thick, nonulcerated melanoma with metastatic disease in the regional lymph nodes. Patient 2 was a 45-year-old woman who had a long-standing ocular nevus that developed into an ocular melanoma after the administration of several doses of . . .
The Effect of Aureomycin and Chloramphenicol on the Fungal and Bacterial Flora of Children
Authors: Joseph J. McGovern, Robert H. Parrott, Chester W. Emmons, Sidney Ross, Frederic G. Burke, E. Clarence Rice
Journal: New England Journal of Medicine (1953)

SEVERAL reports in the literature have suggested that chloramphenicol and aureomycin commonly have undesirable side effects, especially involving the mucous membranes.1 2 3 These include glossitis, stomatitis, sore throat, proctitis, pruritus vulvae and and, nausea, vomiting, diarrhea, bronchomoniliasis, mycotic endocarditis and meningitis, and the sprue syndrome.4 5 6 7 8 Oral manifestations alone have been recorded in 6 to 20 per cent of patients who received aureomycin or chloramphenicol.1 Nearly all the patients in whom these complications occurred have been adults who had received relatively long-term therapy.The explanations for these phenomena vary. One hypothesis advanced suggests that they are a direct result of increased growth . . .