tbuckley/cabot-search huggingface dataset:
Prevalence of Diabetes, Impaired Fasting Glucose, and Impaired Glucose Tolerance in U.S. Adults: The Third National Health and Nutrition Examination Survey, 1988–1994
Authors: Maureen I Harris, Katherine M Flegal, Catherine C Cowie, Mark S Eberhardt, David E Goldstein, Randie R Little, Hsiao-Mei Wiedmeyer, Danita D Byrd-Holt
Journal: Diabetes Care (1998)

OBJECTIVE To evaluate the prevalence and time trends for diagnosed and undiagnosed diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults by age, sex, and race or ethnic group, based on data from the Third National Health and Nutrition Examination Survey, 1988–1994 (NHANES 111) and prior Health and Nutrition Examination Surveys (HANESs). RESEARCH DESIGN AND METHODS NHANES III contained a probability sample of 18,825 U.S. adults ≥20 years of age who were interviewed to ascertain a medical history of diagnosed diabetes, a subsample of 6,587 adults for whom fasting plasma glucose values were obtained, and a subsample of 2,844 adults between 40 and 74 years of age who received an oral glucose tolerance test. The Second National Health and Nutrition Examination Survey, 1976–1980, and Hispanic HANES used similar procedures to ascertain diabetes. Prevalence was calculated using the 1997 American Diabetes Association fasting plasma glucose criteria and the 1980–1985 World Health Organization (WHO) oral glucose tolerance test criteria. RESULTS Prevalence of diagnosed diabetes in 1988–1994 was estimated to be 5.1% for U.S. adults ≥20 years of age (10.2 million people when extrapolated to the 1997 U.S. population). Using American Diabetes Association criteria, the prevalence of undiagnosed diabetes (fasting plasma glucose ≥126 mg/dl) was 2.7% (5.4 million), and the prevalence of impaired fasting glucose (110 to &amp;lt;126 mg/dl) was 6.9% (13.4 million). There were similar rates of diabetes for men and women, but the rates for non-Hispanic blacks and Mexican-Americans were 1.6 and 1.9 times the rate for non-Hispanic whites. Based on American Diabetes Association criteria, prevalence of diabetes (diagnosed plus undiagnosed) in the total population of people who were 40–74 years of age increased from 8.9% in the period 1976–1980 to 12.3% by 1988–1994. A similar increase was found when WHO criteria were applied (11.4 and 14.3%). CONCLUSIONS The high rates of abnormal fasting and postchallenge glucose found in NHANES III, together with the increasing frequency of obesity and sedentary lifestyles in the population, make it likely that diabetes will continue to be a major health problem in the U.S
A National Cancer Institute Workshop on Hereditary Nonpolyposis Colorectal Cancer Syndrome: Meeting Highlights and Bethesda Guidelines
Authors: M. A. Rodriguez-Bigas, C. R. Boland, S. R. Hamilton, D. E. Henson, S. Srivastava, J. R. Jass, P. M. Khan, H. Lynch, T. Smyrk, M. Perucho, L. Sobin
Journal: JNCI Journal of the National Cancer Institute (1997)
Fasting Insulin Levels and Metabolic Risk Factors in Type 2 Diabetic Patients at the First Visit in Japan
Authors: Ikuro Matsuba, Kazumi Saito, Masahiko Takai, Koichi Hirao, Hirohito Sone
Journal: Diabetes Care (2012)

OBJECTIVE To investigate the relationship between fasting insulin levels and metabolic risk factors (MRFs) in type 2 diabetic patients at the first clinic/hospital visit in Japan over the years 2000 to 2009. RESEARCH DESIGN AND METHODS In total, 4,798 drug-naive Japanese patients with type 2 diabetes were registered on their first clinic/hospital visits. Conventional clinical factors and fasting insulin levels were observed at baseline within the Japan Diabetes Clinical Data Management (JDDM) study between consecutive 2-year groups. Multiple linear regression analysis was performed using a model in which the dependent variable was fasting insulin values using various clinical explanatory variables. RESULTS Fasting insulin levels were found to be decreasing from 2000 to 2009. Multiple linear regression analysis with the fasting insulin levels as the dependent variable showed that waist circumference (WC), BMI, mean blood pressure, triglycerides, and HDL cholesterol were significant, with WC and BMI as the main factors. ANCOVA after adjustment for age and fasting plasma glucose clearly shows the decreasing trend in fasting insulin levels and the increasing trend in BMI. CONCLUSIONS During the 10-year observation period, the decreasing trend in fasting insulin was related to the slight increase in WC/BMI in type 2 diabetes. Low pancreatic β-cell reserve on top of a lifestyle background might be dependent on an increase in MRFs.
Effect of exercise training on the ability of the rat heart to tolerate hydrogen peroxide
Authors: R Taylor
Journal: Cardiovascular Research (2003)

Objective:The purpose of this study was to determine whether exercise training could precondition the myocardium against hydrogen peroxide (H O )-induced damage.Methods: Male Fischer 344 rats ran on a treadmill for 9 weeks (60 min / day, 22 m / min, 68 grade, 5 2 2 days / week).Isolated perfused working hearts from exercise trained (ET, n58) and sedentary (SED, n510) animals were perfused with 150 mM H O .Results: Pre-H O baseline values for cardiac external work (COxSP), coronary flow (CF), and lactate dehydrogenase 2 2 2 2 (LDH) release were similar between groups.At 5 min of H O , COxSP was unchanged from baseline but CF was increased 30% in SED 2 2 and 46% in ET (P,0.05 vs. SED).COxSP began to decline similarly thereafter in both groups, dropping to 20% of baseline at 20 min.CF in ET remained higher than SED throughout (P,0.05).LDH leakage remained near baseline during the first 15 min of H O 2 2exposure, but was elevated (P,0.05)72% in SED and 40% in ET after 20 min, and was 2.2-fold greater in SED than ET (P,0.05) after 25 min.Heat shock protein 70 was 2.1-fold greater in ET than SED (P,0.05), but ET did not change catalase and glutathione peroxidase. Conclusions:The results of this study indicate that chronic moderate exercise will enhance coronary flow and attenuate the development of myocardial injury when exposed to H O , but will not affect H O -induced decrease in pump function.
Helicobacter pylori infection prevents erosive reflux oesophagitis by decreasing gastric acid secretion
Authors: T Koike
Journal: Gut (2001)

Helicobacter pylori infection is less prevalent and atrophic gastritis is less extensive in patients with reflux oesophagitis than those without it, but few studies have examined this relationship directly.We investigated the relationship between H pylori infection, acid secretion, and reflux oesophagitis in Japanese subjects.A total of 105 patients with erosive reflux oesophagitis were compared with 105 sex and age matched patients without reflux oesophagitis.The diagnosis of H pylori infection was made by histological examination of gastric mucosal biopsy specimens, rapid urease test, and detection of serum IgG antibodies. Acid secretion was assessed by the endoscopic gastrin test.H pylori infection was present in 36 patients with erosive reflux oesophagitis (34.3%) and in 80 control subjects (76.2%) (odds ratio 0.163, 95% confidence interval 0.09-0.29). Overall acid secretion was significantly greater in patients with reflux oesophagitis. Among H pylori positive patients, acid secretion was greater in patients with reflux oesophagitis than those without oesophagitis.In Japan, erosive reflux oesophagitis occurs most often in the absence of H pylori infection and gastric hyposecretion. Even in the presence of H pylori infection, reflux oesophagitis is more likely to develop in patients without gastric hyposecretion. H pylori infection may inhibit reflux oesophagitis by inducing hypoacidity.
TB, or not TB: that is the question – does TLR signaling hold the answer?
Authors: Terence M. Doherty, Moshe Arditi
Journal: Journal of Clinical Investigation (2004)

Innate immunity critically depends on signaling by Toll-like receptors (TLRs) that rely heavily on an intracellular adapter protein called myeloid differentiation factor 88 (MyD88). Adaptive immune defenses are generally thought to be orchestrated by innate immune responses and so should require intact TLR-MyD88 signaling pathways. But a surprising new study in MyD88-null mice infected with Mycobacterium tuberculosis challenges this view and instead suggests that MyD88 may not be absolutely required for a normal adaptive immune response.
Nasal ventilation to facilitate weaning in patients with chronic respiratory insufficiency.
Authors: Z F Udwadia, G K Santis, M H Steven, A K Simonds
Journal: Thorax (1992)

BACKGROUND: The non-invasive technique of nasal intermittent positive pressure ventilation (NIPPV) has an established role in providing domiciliary nocturnal ventilatory support in patients with chest wall disorders, neuromuscular disease, and chronic obstructive lung disease. NIPPV was used to simplify ventilatory management and assist the return of spontaneous breathing in patients with chronic respiratory insufficiency who had failed to wean from conventional intermittent positive pressure ventilation (IPPV). METHODS: A trial of NIPPV was carried out in 22 patients with weaning difficulties. Nine patients had chest wall disorders or primary lung disease, six had neuromuscular conditions, and seven had cardiac disorders with additional pulmonary disease. Conventional IPPV via an endotracheal tube or tracheostomy had been continued postoperatively in nine patients and 13 had been ventilated after acute cardiorespiratory decompensation. RESULTS: Conventional IPPV had been continued for a median of 31 days (range 2-219). Eighteen patients were successfully transferred to NIPPV and discharged home a median of 11 days (range 8-13) after starting this type of ventilation. Sixteen patients remain well 1-50 months after hospital discharge and 10 of these continue on domiciliary nocturnal NIPPV. Seven patients have returned to work. CONCLUSION: NIPPV can be used to facilitate the return of spontaneous breathing and to reduce the need for intensive care accommodation in patients with an acute exacerbation of chronic respiratory insufficiency that requires intubation and IPPV.
Imaging-Guided Gene Therapy of Experimental Gliomas
Authors: Andreas H. Jacobs, Maria Adele Rueger, Alexandra Winkeler, Hongfeng Li, Stefan Vollmar, Yannic Waerzeggers, Benedikt Rueckriem, Christiane Kummer, Claus Dittmar, Markus Klein, Michael T. Heneka, Ulrich Herrlinger, Cornel Fraefel, Rudolf Graf, Klaus Wienhard, Wolf-Dieter Heiss
Journal: Cancer Research (2007)

To further develop gene therapy for patients with glioblastomas, an experimental gene therapy protocol was established comprising a series of imaging parameters for (i) noninvasive assessment of viable target tissue followed by (ii) targeted application of herpes simplex virus type 1 (HSV-1) amplicon vectors and (iii) quantification of treatment effects by imaging. We show that viable target tissue amenable for application of gene therapy vectors can be identified by multitracer positron emission tomography (PET) using 2-(18)F-fluoro-2-deoxy-D-glucose, methyl-(11)C-L-methionine, or 3'-deoxy-3'-(18)F-fluoro-L-thymidine ([(18)F]FLT). Targeted application of HSV-1 amplicon vectors containing two therapeutic genes with synergistic antitumor activity (Escherichia coli cytosine deaminase, cd, and mutated HSV-1 thymidine kinase, tk39, fused to green fluorescent protein gene, gfp) leads to an overall response rate of 68%, with 18% complete responses and 50% partial responses. Most importantly, we show that the "tissue dose" of HSV-1 amplicon vector-mediated gene expression can be noninvasively assessed by 9-[4-(18)F-fluoro-3-(hydroxymethyl)butyl]guanine ([(18)F]FHBG) PET. Therapeutic effects could be monitored by PET with significant differences in [(18)F]FLT accumulation in all positive control tumors and 72% in vivo transduced tumors (P = 0.01) as early as 4 days after prodrug therapy. For all stably and in vivo transduced tumors, cdIREStk39gfp gene expression as measured by [(18)F]FHBG-PET correlated with therapeutic efficiency as measured by [(18)F]FLT-PET. These data indicate that imaging-guided vector application with determination of tissue dose of vector-mediated gene expression and correlation to induced therapeutic effect using multimodal imaging is feasible. This strategy will help in the development of safe and efficient gene therapy protocols for clinical application.
Functional antagonism: tolerance produced by inhaled beta 2 agonists.
Authors: D. W. Cockcroft, V. A. Swystun
Journal: Thorax (1996)

The development of tolerance to the beneficial effects ofinhaled P2 agonists has been suggested as one possible explanation for the deleterious effects of frequent use of these agents in asthma.'The two main beneficial phar- macological effects of inhaled 12 agonists in asthma are bronchodilation and functional ant- agonism.2Although it has been difficult to show appreciable tolerance to the bronchodilator efficacy of these agents,3 regular use of inhaled 12 agonists predictably causes tolerance to the functional antagonist (bronchoprotective effect) of these drugs.'In this review we will discuss the topic of tolerance to the broncho- protective effect of inhaled 12 agonist and its potential clinical relevance.
MITOTIC BEHAVIOUR OF THE BUCCAL MUCOSAL EPITHELIUM IN PSORIASIS
Authors: K. H. KAIDBEY, A. K. KURBAN
Journal: British Journal of Dermatology (1971)

SUMMARY.— The mitotic activity of the uninvolved skin and buccal mucosa of patients with active psoriasis was investigated, using in vitro labelling with tritiated thymidine. The number of synthesizing DNA cells in these patients was significantly higher than in normal controls. The estimated turnover time of the normal buccal mucosa was found to be 5–8 days.
Gemcitabine plus CI-994 offers no advantage over gemcitabine alone in the treatment of patients with advanced pancreatic cancer: results of a phase II randomized, double-blind, placebo-controlled, multicenter study
Authors: D.A. Richards, K.A. Boehm, D.M. Waterhouse, D.J. Wagener, S.S. Krishnamurthi, A. Rosemurgy, W. Grove, K. Macdonald, S. Gulyas, M. Clark, K.D. Dasse
Journal: Annals of Oncology (2006)
Tissue and cellular basis for impaired bone formation in aluminum-related osteomalacia in the pig.
Authors: A B Sedman, A C Alfrey, N L Miller, W G Goodman
Journal: Journal of Clinical Investigation (1987)

Bone formation is impaired in aluminum-associated bone disease. Reductions in the number of osteoblasts or in the function of individual osteoblasts could account for this finding. Thus, quantitative bone histology and measurements of bone formation were done at three skeletal sites in piglets given aluminum (Al) parenterally, 1.5 mg/kg per d, for 8 wk (Al, n = 4) and in control animals (C, n = 4). Bone Al was 241 +/- 40 mg/kg per dry weight in Al and 1.6 +/- 0.9 in C, P less than 0.001. All Al-treated animals developed osteomalacia with increases in osteoid seam width, osteoid volume, and mineralization lag time at each skeletal site, P less than 0.05 vs. C for all values. Mineralized bone formation at the tissue level was lower in Al than in C, P less than 0.05 for each skeletal site, due to reductions in active bone forming surface. Bone formation at the cellular level was similar in each group, however, and total osteoid production by osteoblasts did not differ in C and Al. Aluminum impairs the formation of mineralized bone in vivo by decreasing the number of active osteoblasts, and this change can be distinguished from the effect of aluminum to inhibit, either directly or indirectly, the calcification of osteoid.
Home vs. outpatient narrowband ultraviolet B therapy for the treatment of nonsegmental vitiligo: a retrospective questionnaire study
Authors: B.S. Wind, M.W. Kroon, J.F. Beek, J.P.W. Van Der Veen, L. Nieuweboer-Krobotová, A.A. Meesters, J.D. Bos, A. Wolkerstorfer
Journal: British Journal of Dermatology (2010)

Conflicts of interest: none declared. Madam, Narrowband ultraviolet B (NB‐UVB) therapy is considered the first‐line therapy for nonsegmental vitiligo.1, 2 A major drawback, though, is the fact that this treatment requires months to years of frequent visits to a clinic‐based phototherapy unit.3 For that reason home UVB therapy was introduced in 1979, mainly for psoriasis,4 and in the early 1990s for vitiligo as well. However, the safety, effectiveness and compliance associated with home treatment have been debated.5–8 This study is the first to provide data on the pros and cons of home vs. outpatient UVB therapy in patients with nonsegmental vitiligo. From March 2008 until January 2009, all consecutive patients with generalized nonsegmental vitiligo who completed total‐body NB‐UVB therapy, either at the Netherlands Institute for Pigment Disorders or at home, were included. All patients were mailed a package containing a questionnaire. Nonresponders were reminded by telephone with a maximum of five follow‐up calls.
The General Medical Council and the future of revalidation: Regulation, regulation, regulation
Authors: Michael O'Donnell
Journal: BMJ (2005)

The General Medical Council and the future of revalidation GMC member respondsEditor-Esmail and Kmietowicz give an inaccurate account of the General Medical Council's policy development on revalidation, ignoring an iterative process with interested parties since 1998 in an attempt to introduce the most fundamental change to medical regulation since its foundation in 1858. 1 2 The GMC clearly has had regard to the legitimate interests of three principal groups-government and the NHS, patients and the public, and the various tribes that make up the UK medical profession.Despite suggestions to the contrary, an initial exploratory meeting on revalidation convened by Sir Donald Irvine in June 1998 was held in the context of a high profile professional conduct case, but well before the Bristol inquiry report and absolutely nothing to do with Rodney Ledward or, indeed, Harold Shipman.It was recognised then that some doctors were not keeping fully up to date nor were they indulging in reflective practice.Irvine correctly proposed that there was a need to make registration with the GMC more meaningful to the public than a mere recognition that doctors had reached a certain standard of professional knowledge in their early 20s.Both articles promote the idea that the doctors' regulator should be filling the vacuum within the NHS created by its failing to fulfil its public responsibility to monitor doctors' clinical standards.Clinical governance is now, slowly, being developed and eventually will extend from systems and teams to individuals-but is it reasonable, as both authors postulate, that such monitoring should become the financial and moral responsibility of the GMC sitting in London and Manchester rather than local managers at the coalface?Although revalidation is a continuing process, it becomes summative only every five years.The NHS and its local systems must not be allowed to abrogate their responsibility for the safety of patients on a day to day basis.Nor should they demand that the GMC and its prime function of assuring fitness to practise and the meaning of the medical register be inappropriately promoted as the first line of defence for the maintenance of clinical quality and safety.
OCT1 is a determinant of synbindin-related ERK signalling with independent prognostic significance in gastric cancer
Authors: Jin Qian, Xuan Kong, Niantao Deng, Patrick Tan, Haoyan Chen, Jilin Wang, Zhaoli Li, Ye Hu, Weiping Zou, Jie Xu, Jing-Yuan Fang
Journal: Gut (2014)

Octamer transcription factor 1 (OCT1) was found to be expressed in intestinal metaplasia and gastric cancer (GC), but the exact roles of OCT1 in GC remain unclear. The objective of this study was to determine the functional and prognostic implications of OCT1 in GC.Expression of OCT1 was examined in paired normal and cancerous gastric tissues and the prognostic significance of OCT1 was analysed by univariate and multivariate survival analyses. The functions of OCT1 on synbindin expression and extracellular signal-regulated kinase (ERK) phosphorylation were studied in vitro and in xenograft mouse models.The OCT1 gene is recurrently amplified and upregulated in GC. OCT1 overexpression and amplification are associated with poor survival in patients with GC and the prognostic significance was confirmed by independent patient cohorts. Combining OCT1 overexpression with American Joint Committee on Cancer staging improved the prediction of survival in patients with GC. High expression of OCT1 associates with activation of the ERK mitogen-activated protein kinase signalling pathway in GC tissues. OCT1 functions by transactivating synbindin, which binds to ERK DEF domain and facilitates ERK phosphorylation by MEK. OCT1-synbindin signalling results in the activation of ERK substrates ELK1 and RSK, leading to increased cell proliferation and invasion. Immunofluorescent study of human GC tissue samples revealed strong association between OCT1 protein level and synbindin expression/ERK phosphorylation. Upregulation of OCT1 in mouse xenograft models induced synbindin expression and ERK activation, leading to accelerated tumour growth in vivo.OCT1 is a driver of synbindin-mediated ERK signalling and a promising marker for the prognosis and molecular subtyping of GC.
Phase II Study of Extended-Dose Temozolomide in Patients With Melanoma
Authors: Petra Rietschel, Jedd D. Wolchok, Susan Krown, Scott Gerst, Achim A. Jungbluth, Klaus Busam, Katherine Smith, Irene Orlow, Katherine Panageas, Paul B. Chapman
Journal: Journal of Clinical Oncology (2008)

We conducted a phase II trial of extended-dose temozolomide (TMZ) in patients with melanoma to test the hypothesis that the approximately 30% response rate observed in patients treated with extended-dose TMZ with antiangiogenic agents was caused by TMZ alone. We hypothesized that expression of methylguanine methyltransferase (MGMT) in the tumor would correlate with drug resistance to TMZ.Patients with stage IV or unresectable stage III melanoma were treated with TMZ 75 mg/m(2)/d for 6 weeks followed by a 2-week rest period. Cycles were repeated until progression. Patients were stratified by M1c disease or not. The primary end point was objective response proportion. MGMT expression was assessed by methylation-specific pyrosequencing of the promoter and by immunohistochemistry.Forty-nine patients (25 with M1c disease) were assessable. Three patients (12.5%) in each cohort experienced partial responses; there were no complete responses. Ten patients (21%) had stable disease lasting more than 24 weeks. Median time to progression was 3.3 months. Median survival was 10.1 months; survival was similar in the two cohorts. The estimated 18-month survival was 27%. There was no correlation between response and either immunohistochemistry staining for MGMT or for MGMT promoter methylation. Seventy-five percent of patients developed CD4(+) lymphopenia after three cycles.Extended-dose TMZ therapy did not result in a 30% responses rate, which has been observed using extended-dose TMZ with antiangiogenic agents. Response did not correlate with MGMT expression or promoter methylation as a continuous variable, suggesting that other resistance mechanisms are important.
Anaplastic lymphoma kinase activity is essential for the proliferation and survival of anaplastic large-cell lymphoma cells
Authors: Weihua Wan, Mark S. Albom, Lihui Lu, Matthew R. Quail, Nadine C. Becknell, Linda R. Weinberg, Dandu R. Reddy, Beverly P. Holskin, Thelma S. Angeles, Ted L. Underiner, Sheryl L. Meyer, Robert L. Hudkins, Bruce D. Dorsey, Mark A. Ator, Bruce A. Ruggeri, Mangeng Cheng
Journal: Blood (2005)