tbuckley/cabot-search huggingface dataset:
First case series on the use of imiquimod for morphoea
Authors: M. Dytoc, P.T. Ting, J. Man, D. Sawyer, L. Fiorillo
Journal: British Journal of Dermatology (2005)

Morphoea is characterized by fibrosis, which is mediated by cytokines including transforming growth factor (TGF)-beta.Our objective was to use imiquimod 5% cream (Aldara), an inducer of interferon-gamma, known to inhibit TGF-beta, to treat morphoea.Patients with morphoea were treated with imiquimod and evaluated during their follow-up visits to 6 months.The dyspigmentation, induration and erythema of 12 patients with morphoea lesions improved. The histology of the skin also showed a decrease in dermal thickness.This is the first case series describing the successful application of imiquimod in the management of morphoea.
Direct assessment of liver glycogen storage by 13C nuclear magnetic resonance spectroscopy and regulation of glucose homeostasis after a mixed meal in normal subjects.
Authors: R Taylor, I Magnusson, D L Rothman, G W Cline, A Caumo, C Cobelli, G I Shulman
Journal: Journal of Clinical Investigation (1996)

Despite extensive recent studies, understanding of the normal postprandial processes underlying immediate storage of substrate and maintenance of glucose homeostasis in humans after a mixed meal has been incomplete. The present study applied 13C nuclear magnetic resonance spectroscopy to measure sequential changes in hepatic glycogen concentration, a novel tracer approach to measure postprandial suppression of hepatic glucose output, and acetaminophen to trace the pathways of hepatic glycogen synthesis to elucidate the homeostatic adaptation to the fed state in healthy human subjects. After the liquid mixed meal, liver glycogen concentration rose from 207 +/- 22 to 316 +/- 19 mmol/liter at an average rate of 0.34 mmol/liter per min and peaked at 318 +/- 31 min, falling rapidly thereafter (0.26 mmol/liter per min). The mean increment at peak represented net glycogen synthesis of 28.3 +/- 3.7 g (approximately 19% of meal carbohydrate content). The contribution of the direct pathway to overall glycogen synthesis was 46 +/- 5 and 68 +/- 8% between 2 and 4 and 4 and 6 h, respectively. Hepatic glucose output was completely suppressed within 30 min of the meal. It increased steadily from 60 to 255 min from 0.31 +/- 32 to 0.49 +/- 18 mg/kg per min then rapidly returned towards basal levels (1.90 +/- 0.04 mg/kg per min). This pattern of change mirrored precisely the plasma glucagon/insulin ratio. These data provide for the first time a comprehensive picture of normal carbohydrate metabolism in humans after ingestion of a mixed meal.
Anorectal Squamous-Cell Carcinoma: Conservative or Radical Treatment?
Authors: Wilbert H. Hohm, Raymond J. Jackman
Journal: JAMA (1964)

Eighty-five patients with squamous-cell carcinoma of the anorectum were studied and classified into two groups: (1) those with lesions involving the pectinate line and (2) those with lesions distal to the pectinate line. The number of patients as a whole and the subgroups particularly was so small that no accurate statistical conclusions can be drawn from them. The data should rather be thought of as indicating trends. However, the following recommendations seem reasonable: (1) Lesions involving the pectinate line should be treated by radical surgery. (2) Lesions distal to the pectinate line should be treated by conservative methods.
Abstract P6-10-05: SU2C Phase 1b Trial of Dual PI3K/ mTOR Inhibitor BEZ235 with Letrozole in ER+/HER2− Metastatic Breast Cancer (MBC)
Authors: IA Mayer, VG Abramson, JM Balko, SJ Isakoff, A Forero, MG Kuba, ME Sanders, Y Li, E Winer, CL Arteaga
Journal: Cancer Research (2012)

Abstract Background: Mutations in PIK3CA, the gene encoding the p110alpha subunit of PI3K, have been associated with antiestrogen resistance in ER+ BC. In general, antiestrogen-resistant cancers retain ER and responsiveness to estradiol, suggesting that treatment of ER+/PI3K mutant BC should include PI3K inhibitors plus endocrine therapy. Methods: We are conducting a phase Ib open-label trial of letrozole (2.5 mg/d) with the dual PI3K/ mTOR inhibitor BEZ235 (400 mg BID, sachet formulation) in post-menopausal patients with ER+/HER2 negative MBC. Upon toxicity, BEZ235 was reduced to 400 mg in AM/ 200 mg in PM (dose level 1), and 200 mg BID (dose level 2), in a standard 3+3 de-escalation design. Treatment continues until unacceptable toxicity or disease progression. Tumor assessments are performed every 2 months. All tumor biopsies are being analyzed for PI3K pathway alterations. Results: To date, 9 patients have been accrued; 6 on dose level 1 (400 mg BID) and 3 on dose level 1 (400 mg in AM/ 200 mg in PM). Of note, the latter 3 patients have been on treatment for less than 2 weeks at the time of abstract submission. Median age was 55 years (range 40–65); all patients had disease progression on previous endocrine therapy, and 100% had bone metastases and 30% had visceral metastases. Preliminary toxicities for dose level 1 cohort (400 mg BID) are summarized in the table below. The DLT was grade 3 mucositis, which happened less than 3 weeks of study initiation, in a total of 3 out of 6 patients. All grade 3 mucositis cases improved after BEZ235 interruption for 7 days and subsequent dose reduction. These 3 events triggered activation of the dose level 1 cohort (400 mg AM/ 200 mg PM). The first 3 patients on dose level 1 cohort (2 of which have PIK3CA mutated tumors) had their tumor assessment scans at 8 weeks post treatment initiation; all patients were found to have stable disease. Discussion: The combination of letrozole/BEZ235 is still being evaluated in patients with ER+/HER2MBC. Safety, tolerability and preliminary antitumor activity data will be updated at the meeting. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-10-05.
Staphylococcus aureus complex from animals and humans in three remote African regions
Authors: Frieder Schaumburg, Maude Pauly, Etile Anoh, Arsene Mossoun, Lidewij Wiersma, Grit Schubert, Arnaud Flammen, Abraham S. Alabi, Jean-Jacques Muyembe-Tamfum, Martin P. Grobusch, Stomy Karhemere, Chantal Akoua-Koffi, Emmanuel Couacy-Hymann, Peter G. Kremsner, Alexander Mellmann, Karsten Becker, Fabian H. Leendertz, Georg Peters
Journal: Clinical Microbiology and Infection (2014)
International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) &amp; European Competence Network on Mastocytosis (ECNM) consensus response criteria in advanced systemic mastocytosis
Authors: Jason Gotlib, Animesh Pardanani, Cem Akin, Andreas Reiter, Tracy George, Olivier Hermine, Hanneke Kluin-Nelemans, Karin Hartmann, Wolfgang R. Sperr, Knut Brockow, Lawrence B. Schwartz, Alberto Orfao, Daniel J. DeAngelo, Michel Arock, Karl Sotlar, Hans-Peter Horny, Dean D. Metcalfe, Luis Escribano, Srdan Verstovsek, Ayalew Tefferi, Peter Valent
Journal: Blood (2013)
What works? Interventions for maternal and child undernutrition and survival
Authors: Zulfiqar A Bhutta, Tahmeed Ahmed, Robert E Black, Simon Cousens, Kathryn Dewey, Elsa Giugliani, Batool A Haider, Betty Kirkwood, Saul S Morris, HPS Sachdev, Meera Shekar
Journal: The Lancet (2008)
Prostaglandins mediate the vasodilatory effect of mannitol in the hypoperfused rat kidney.
Authors: P A Johnston, D B Bernard, N S Perrin, N G Levinsky
Journal: Journal of Clinical Investigation (1981)

We have previously reported that mannitol strikingly increases blood flow to rat kidneys hypoperfused at 35-40mm Hg. This vasodilator effect is not due to volume expansion or alterations in plasma osmolality. We have tested the hypothesis that the vasodilatory effect of mannitol in the ischemic rat kidney is mediated by one of the vasoactive renal hormone systems: renin-angiotension, kallikrein-kinin, or prostaglandins. Rats were infused with 5% mannitol in 0.9% saline to 3-5% of body weight. In agreement with our previous studies, RBF increased 1.3 +/- 0.1 ml/min despite maintenance of perfusion pressure at 35-40 mm Hg. The cyclooxygenase inhibitors, meclofenamate and indomethacin had no effect on renal blood flow (RBF) in hypoperfused kidneys. However, in rats pretreated with these inhibitors, expansion with mannitol increased RBF by only 0.37 +/- 0.02 ml/min, 28% of the response in the untreated group (p less than 0.001). Infusion of prostacyclin (PGI2) into the renal artery during reduced perfusion resulted in an increase in RBF of 1.0 +/- 0.1 ml/min. Subsequent expansion with mannitol increased RBF by only 0.5 +/- 0.1 ml/min more, less than one-half of the effect of mannitol in a concurrent group of rats not treated with PGI2. Unlike PGI2 prostaglandin E2 had only a minimal vasodilator effect during hyperperfusion. Imidazole, an inhibitor of thromboxane synthesis, did not alter RBF or renal vascular resistance during hypoperfusion. Treatment of rats during hypoperfusion. with the angiotensin-converting enzyme (kininase II) inhibitor teprotide increased RBF by 1.1 +/- 0.3 ml/min. However, teprotide did not alter the vascular response to mannitol: RBF increased 1.2 +/- 0.1 ml/min more when mannitol was infused into teprotide-treated rats. The renal vascular response to mannitol was not altered by treatment with aprotinin, an inhibitor of the kallikrein-kinin system. Aprotinin was ineffective whether given before or after the vascular response to mannitol was established. We conclude that the vasodilator response to mannitol in the ischemic rat kidney is mediated in large part by increased prostaglandin (PGI2) activity. The failure of converting enzyme inhibition and aprotinin to block the vasodilator response to mannitol is evidence against a role for the renin-angiotension or kallikreinkinin systems in mediating the vasodilator response.
Royal College of Physicians votes to ballot members on whether to demand health bill's withdrawal
Authors: Z. Kmietowicz
Journal: BMJ (2012)

Fellows of the Royal College of Physicians voted five to one (80% versus 16%) to survey the college’s 25 500 members on whether it should call for further changes to the Health and Social Care Bill or demand its withdrawal.

In other motions, which are not binding to the college but will be sent to its council for consideration, 89% of 186 fellows who attended the meeting on 27 February agreed that the bill will damage the NHS and the health of patients and 79% said that the college should call for it to be withdrawn.

Furthermore 81% endorsed a call for the college to join forces with other health bodies that want the proposed NHS changes to be scrapped, such as the BMA and the royal colleges representing GPs, paediatricians, psychiatrists, nurses, and midwives and societies representing radiographers, geriatricians, and others.

With the Royal College of Surgeons due …
Effects of Cabozantinib on Pain and Narcotic Use in Patients with Castration-resistant Prostate Cancer: Results from a Phase 2 Nonrandomized Expansion Cohort
Authors: Ethan Basch, Karen A. Autio, Matthew R. Smith, Antonia V. Bennett, Aaron L. Weitzman, Christian Scheffold, Christopher Sweeney, Dana E. Rathkopf, David C. Smith, Daniel J. George, Celestia S. Higano, Andrea L. Harzstark, A. Oliver Sartor, Michael S. Gordon, Nicholas J. Vogelzang, Johann S. de Bono, Naomi B. Haas, Paul G. Corn, Frauke Schimmoller, Howard I. Scher
Journal: European Urology (2014)
Comparison of Tc-99m Methylene Diphosphonate, Tc-99m Human Immune Globulin, and Tc-99m–Labeled White Blood Cell Scintigraphy in the Diabetic Foot
Authors: Seher N. Ünal, Hulya Birinci, Selçuk Baktiroğlu, Sema Cantez
Journal: Clinical Nuclear Medicine (2001)

Purpose The aims of this prospective study were to evaluate the contribution of Tc-99m methylene diphosphonate (MDP), Tc-99m human immune globulin (HIG), and Tc-99m white blood cell (WBC) to the diagnosis of osteomyelitis in the diabetic foot and to evaluate the surgical or medical therapy with Tc-99m HIG and Tc-99m WBC scans. Methods Twenty patients (15 men, 5 women) with suspected pedal osteomyelitis were included in the study. All patients had type II diabetics. Three- and four-phase bone scintigraphy (3P-MDP, 4P-MDP), early (e) and late (l) HIG, and WBC scans were completed within 1 week in all patients. The lesion-to-background ratios were calculated for early and late images of the feet for all scans and named as the indices. Eight weeks after the end of medical or surgical therapy, Tc-99m HIG and Tc-99m WBC scans were repeated in 10 patients. The difference in indices between 3P-MDP and 4P-MDP for osteomyelitis and indices for osteomyelitis, cellulitis, and inflammation in Tc-99m HIG and Tc-99m WBC in early and late scans were tested for significance. Results In 20 patients, 53 lesions were investigated. Among these 53 lesions were 25 sites of proved osteomyelitis, 6 sites of cellulitis, and 22 sites of inflammation confirmed by radiography, microbiologic culture, and clinical evaluation. 4P-MDP was more specific than 3P-MDP for detecting osteomyelitis (50% and 67%, respectively). There was also a significant difference between the mean indices of 3P-MDP and 4P-MDP (P < 0.000). The index values were increased in 4P-MDP scans. There was no significant difference between the indices of early and late Tc-99m HIG scans for inflammation, cellulitis, and osteomyelitis. Early and late Tc-99m WBC scans did not show a significant difference in differentiating osteomyelitis. However, Tc-99m WBC scans could differentiate aseptic inflammation from infection (P < 0.031) in early and late scans. There was a significant difference of index values between pre- and post-treatment Tc-99m HIG and Tc-99m WBC scans. The best combination of scans for detecting osteomyelitis was 4P-MDP with WBC scans, with an accuracy rate of 92%. Conclusions These results show that four-phase bone scintigraphy with early Tc-99m WBC scanning is preferred for detecting osteomyelitis of the diabetic foot. To evaluate the response to therapy, Tc-99m WBC scans are the preferred method, but if this is not available, Tc-99m HIG scanning can be used.
Optic Atrophy in Children After Diiodohydroxyquin Therapy
Authors: Myles M. Behrens
Journal: JAMA (1974)

<h3>To the Editor.—</h3> The neurotoxicity of the halogenated hydroxyquinolines was recently reviewed (225:395, 1973) following numerous reports linking subacute myelo-optic neuropathy (SMON) to iodochlorhydroxyquin. Optic atrophy without other neurologic involvement in two children followed treatment with diiodohydroxyquin (Diodoquin), a drug differing structurally by only one halogen atom.<sup>1,2</sup>A 3 1/2-year-old1 who had received 3,200 mg daily for two years for acrodermatitis enteropathica developed visual loss in the 20/200 range one month after increase of the dosage to 3,600 mg daily. Optic atrophy was noted; vision improved with lowering of the dose but worsened when it was raised. A 3 1/2-year-old<sup>2</sup>developed severe visual loss after eight weeks of 1,950 mg daily for "nonspecific" diarrhea, with evident optic atrophy on examination four weeks later and without improvement three years later. I have seen two similar cases of primary optic atrophy, otherwise unexplained, in children following treatment with diiodohydroxyquin. <h3>Case</h3>
US lowers lead limits
Authors: D A Gidlow
Journal: BMJ (1991)

<h3>Background</h3> Between-country differences have been described in antibiotic prescribing for respiratory tract infection (RTI) in primary care, but not yet for diagnostic testing procedures and prescribing confidence. <h3>Aim</h3> To describe between-country differences in RTI management, particularly diagnostic testing and antibiotic prescribing, and investigate which factors relate to antibiotic prescribing and GPs’ prescribing confidence. <h3>Design &amp; setting</h3> Prospective audit in 18 European countries. <h3>Method</h3> An audit of GP-registered patient, clinical, and management characteristics for patients presenting with sore throat and/or lower RTI (<i>n</i> = 4982), and GPs9 confidence in their antibiotic prescribing decision. Factors related to antibiotic prescribing and confidence were analysed using multi-level logistic regression. <h3>Results</h3> Antibiotic prescribing proportions varied considerably: &lt;20% in four countries, and &gt;40% in six countries. There was also considerable variation in point-of-care (POC) testing (0% in Croatia, Moldova, and Romania, and &gt;65% in Denmark and Norway, mainly for C-reactive protein [CRP] and group A streptococcal [strep A] infection), and in laboratory or hospital-based testing (&lt;3% in Hungary, the Netherlands, and Spain, and &gt;30% in Croatia, Georgia, Greece, and Moldova, mainly chest X-ray and white blood cell counting). Antibiotic prescribing was related to illness severity, comorbidity, age, fever, and country, but not to having performed a POC test. In nearly 90% of consultations, GPs were confident in their antibiotic prescribing decision. <h3>Conclusion</h3> Despite high confidence in decisions about antibiotic prescribing, there is considerable variation in the primary care of RTI in European countries, with GPs prescribing antibiotics overall more often than is considered appropriate. POC testing may enhance the quality of antibiotic prescribing decisions if it can safely reverse decisions confidently made on clinical grounds alone to prescribe antibiotics.
Inactivation and adaptation of number neurons
Authors: J. Patrick Mayo
Journal: Behavioral and Brain Sciences (2009)

Single-neuron recordings may help resolve the issue of abstract number representation in the parietal lobes. Two manipulations in particular - reversible inactivation and adaptation of apparent numerosity - could provide important insights into the causal influence of "numeron" activity. Taken together, these tests can significantly advance our understanding of number processing in the brain.
Analysis of <i>VHL</i> Gene Alterations and their Relationship to Clinical Parameters in Sporadic Conventional Renal Cell Carcinoma
Authors: Alison C. Young, Rachel A. Craven, Dena Cohen, Claire Taylor, Christopher Booth, Patricia Harnden, David A. Cairns, Dewi Astuti, Walter Gregory, Eamonn R. Maher, Margaret A. Knowles, Adrian Joyce, Peter J. Selby, Rosamonde E. Banks
Journal: Clinical Cancer Research (2009)

PURPOSE: This study aimed to carry out a comprehensive analysis of genetic and epigenetic changes of the von Hippel Lindau (VHL) gene in patients with conventional (clear cell) renal cell carcinoma and to determine their significance relative to clinicopathologic characteristics and outcome. EXPERIMENTAL DESIGN: The VHL status in 86 conventional renal cell carcinomas was determined by mutation detection, loss of heterozygosity (LOH), and promoter methylation analysis, extending our original cohort to a total of 177 patients. Data were analyzed to investigate potential relationships between VHL changes, clinical parameters, and outcome. RESULTS: LOH was found in 89.2%, mutation in 74.6%, and methylation in 31.3% of evaluable tumors; evidence of biallelic inactivation (LOH and mutation or methylation alone) was found in 86.0% whereas no involvement of VHL was found in only 3.4% of samples. Several associations were suggested, including those between LOH and grade, nodal status and necrosis, mutation and sex, and methylation and grade. Biallelic inactivation may be associated with better overall survival compared with patients with no VHL involvement, although small sample numbers in the latter group severely limit this analysis, which requires independent confirmation. CONCLUSIONS: This study reports one of the highest proportions of conventional renal cell carcinoma with VHL changes, and suggests possible relationships between VHL status and clinical variables. The data suggest that VHL defects may define conventional renal cell carcinomas but the clinical significance of specific VHL alterations will only be clarified by the determination of their biological effect at the protein level rather than through genetic or epigenetic analysis alone. (Clin Cancer Res 2009;15(24):7582-92).
Immunotherapy of Cytotoxic T Cell–resistant Tumors by T Helper 2 Cells
Authors: Joerg Mattes, Mark Hulett, Wei Xie, Simon Hogan, Marc E. Rothenberg, Paul Foster, Christopher Parish
Journal: The Journal of Experimental Medicine (2003)

Currently most attempts at cancer immunotherapy involve the generation of CD8+ cytotoxic T lymphocytes (CTLs) against tumor-associated antigens. Many tumors, however, have been immunoselected to evade recognition by CTLs and thus alternative approaches to cancer immunotherapy are urgently needed. Here we demonstrate that CD4+ T cells that recognize a secreted tumor-specific antigen and exhibit a cytokine secretion profile characteristic of Th2 cells, are capable of clearing established lung and visceral metastases of a CTL-resistant melanoma. Clearance of lung metastases by the Th2 cells was found to be totally dependent on the eosinophil chemokine, eotaxin, and partially dependent on the transcription activator signal transducer and activator of transcription 6 (STAT6), with degranulating eosinophils within the tumors inducing tumor regression. In contrast, tumor-specific CD4+ Th1 cells, that recruited macrophages into the tumors, had no effect on tumor growth. This work provides the basis for a new approach to adoptive T cell immunotherapy of cancer.
Peroxiredoxin 1 Interacts with Androgen Receptor and Enhances Its Transactivation
Authors: Soo-Yeon Park, Xiaofei Yu, Clement Ip, James L. Mohler, Paul N. Bogner, Young-Mee Park
Journal: Cancer Research (2007)

Abstract Although hypoxia is accepted as an important microenvironmental factor influencing tumor progression and treatment response, it is usually regarded as a static global phenomenon. Consequently, less attention is given to the impact of dynamic changes in tumor oxygenation in regulating the behavior of cancer cells. Androgen receptor (AR) signaling plays a critical role in prostate cancer. We previously reported that hypoxia/reoxygenation, an in vitro condition used to mimic an unstable oxygenation climate in a tumor, stimulates AR activation. In the present study, we showed that peroxiredoxin 1 (Prx1), a member of the peroxiredoxin protein family, acts as a key mediator in this process. We found that the aggressive LN3, C4-2, and C4-2B prostate cancer cell lines derived from LNCaP possess constitutively elevated Prx1 compared with parental cells, and display greater AR activation in response to hypoxia/reoxygenation. Although the cell survival–enhancing property of Prx1 has traditionally been attributed to its antioxidant activity, the reactive oxygen species–scavenging activity of Prx1 was not essential for AR stimulation because Prx1 itself was oxidized and inactivated by hypoxia/reoxygenation. Increased AR transactivation was observed when wild-type Prx1 or mutant Prx1 (C52S) lacking antioxidant activity was introduced into LNCaP cells. Reciprocal immunoprecipitation, chromatin immunoprecipitation, and in vitro pull-down assays corroborated that Prx1 interacts with AR and enhances its transactivation. We also show that Prx1 is capable of sensitizing a ligand-stimulated AR. Based on the above information, we suggest that disrupting the interaction between Prx1 and AR may serve as a fruitful new target in the management of prostate cancer. [Cancer Res 2007;67(19):9294–303]