tbuckley/cabot-search huggingface dataset:
Cardiorespiratory Fitness as a Predictor of Cancer Mortality Among Men With Pre-Diabetes and Diabetes
Authors: Angela M. Thompson, Timothy S. Church, Ian Janssen, Peter T. Katzmarzyk, Conrad P. Earnest, Steven N. Blair
Journal: Diabetes Care (2008)

The purpose of this article was to examine the risk of cancer mortality across levels of fitness and to examine the fitness-mortality relation for site-specific cancers in men with pre-diabetes and diabetes.We examined the fitness-mortality relation for all-cause and site-specific cancer mortality among 18,858 men with pre-diabetes and 2,805 men with diabetes (aged 46.3 +/- 9.7 years [mean +/- SD]) from the Aerobics Center Longitudinal Study. We identified 719 cancer deaths during 354,558 person-years of risk. The duration of follow-up was 16.4 +/- 7.8 years (range <1-30.0 years).In men with pre-diabetes, moderate (hazard ratio 0.71 [95% CI 0.57-0.88]) and high fitness (0.76 [0.60-0.96]) were associated with lower risks of cancer mortality compared with the low-fit group in a model adjusted for age, examination year, smoking, alcohol use, fasting glucose concentration, previous cancer, and BMI. Similarly, for individuals with diabetes, moderate (0.53 [0.35-0.82]) and high fitness (0.44 [0.26-0.73]) were associated with lower risks of cancer mortality compared with the low-fit group. Among all men, being fit was associated with a lower risk of mortality from gastrointestinal (0.55 [0.39-0.77]), colorectal (0.53 [0.30-0.96]), liver (0.22 [0.07-0.71]), and lung cancer (0.43 [0.30-0.60]).In men with pre-diabetes and diabetes, higher levels of cardiorespiratory fitness were associated with lower risk of cancer mortality, particularly as a result of cancers of the gastrointestinal tract, compared with those who had low levels of fitness.
Erythroleukemia: In vitro studies of erythropoiesis
Authors: M. M. Newcomb, L. Balducci, M. B. Coleman, M. H. Steinberg
Journal: American Journal of Hematology (1978)

We studied the growth of erythroid burst-forming units (BFU-E) and erythroid colony forming units (CFU-E) from bone marrow and blood in six patients with erythroleukemia. Five patients grew CFU-E, while BFU-E were found in the marrow of two and in the peripheral blood of only one patient. In all cases with colony growth, the numbers of colonies were markedly decreased with respect to normal controls. Patient BFU-E were composed of fewer clusters than those of controls. BFU-E and CFU-E growth was dependent on the addition of erythropoietin to the medium, and no growth was observed in absence of erythropoietin. At present it is not known if the growth obtained is derived from residual normal erythropoietic stem cells or from abnormal erythroid precursors of the leukemic cells.
The Model Muddle: In Search of Tumor Growth Laws
Authors: Philip Gerlee
Journal: Cancer Research (2013)

Abstract In this article, we will trace the historical development of tumor growth laws, which in a quantitative fashion describe the increase in tumor mass/volume over time. These models are usually formulated in terms of differential equations that relate the growth rate of the tumor to its current state and range from the simple one-parameter exponential growth model to more advanced models that contain a large number of parameters. Understanding the assumptions and consequences of such models is important, as they often underpin more complex models of tumor growth. The conclusion of this brief survey is that although much improvement has occurred over the last century, more effort and new models are required if we are to understand the intricacies of tumor growth. Cancer Res; 73(8); 2407–11. ©2013 AACR.
Adverse Effects of Preoperative Radiation Therapy for Rectal Cancer: Long-Term Follow-Up of the Swedish Rectal Cancer Trial
Authors: Helgi Birgisson, Lars Påhlman, Ulf Gunnarsson, Bengt Glimelius
Journal: Journal of Clinical Oncology (2005)

To analyze the occurrence of subacute and late adverse effects in patients treated with preoperative irradiation for rectal cancer.The study population included 1,147 patients randomly assigned to preoperative radiation therapy or surgery alone in the Swedish Rectal Cancer Trial conducted 1987 through 1990. Patient data were matched against the Swedish Hospital Discharge Register to identify patients admitted to hospital after the primary treatment of the rectal cancer. Patients with known residual disease were excluded, and patients with a recurrence were censored 3 months before the date of recurrence. Relative risks (RR) with 95% CIs were calculated.Irradiated patients were at increased risk of admissions during the first 6 months from the primary treatment (RR = 1.64; 95% CI, 1.21 to 2.22); these were mainly for gastrointestinal diagnoses. Overall, the two groups showed no difference in the risk of admissions more than 6 months from the primary treatment (RR = 0.95; 95% CI, 0.80 to 1.12). Regarding specific diagnoses, however, RRs were increased for admissions later than 6 months from the primary treatment in irradiated patients for unspecified infections, bowel obstruction, abdominal pain, and nausea.Gastrointestinal disorders, resulting in hospital admissions, seem to be the most common adverse effect of short-course preoperative radiation therapy in patients with rectal cancer. Bowel obstruction was the diagnosis of potentially greatest importance, which was more frequent in irradiated than in nonirradiated patients.
Private sector may take elective patients in event of crisis in hospital emergency units, says NHS chief
Authors: A. Cole
Journal: BMJ (2014)

The NHS in England is better placed to cope with winter pressures on emergency services this year than it has been for many years, Bruce Keogh, NHS England’s medical director, told MPs this week.

Keogh, who published the first part of his review into urgent and emergency care services in November,1 was speaking at an evidence session of the parliamentary health select committee’s inquiry into the performance of emergency units in England.

He told MPs that planning had begun much earlier than in previous years and that extra funding had been allocated earlier. In addition, much of that funding was going “to the communities where we think patients are most at risk of problems in winter.” Of the £400m allocated to deal with winter …
There is no clear association between low serum ferritin and chronic diffuse telogen hair loss
Authors: R Sinclair
Journal: British Journal of Dermatology (2002)

Low iron stores are considered a possible cause of chronic diffuse telogen hair loss in women. Estimation of serum ferritin is recommended as part of the initial assessment when women present with chronic diffuse telogen hair loss, and iron supplementation therapy is commonly recommended for those found to have low iron stores.To evaluate the relationship between low serum ferritin (</=20 micro g L-1) and chronic diffuse telogen hair loss in women.Between 1997 and 1999, 194 consecutive women who presented to a specialist hair clinic were assessed for diffuse telogen hair loss of greater than 6 months duration. All underwent biochemical investigations that included serum ferritin and had two 4-mm punch biopsies taken from the vertex of the scalp. One biopsy was sectioned horizontally and the other vertically.Twelve women were found to have a serum ferritin of 20 micro g L-1 or less (6.2%). Androgenetic alopecia was found on scalp biopsy in seven of these 12 women, while the other five women had normal histology. The five women with low iron stores and normal histology were treated with iron supplementation alone. This was continued until the serum ferritin was > 20 micro g L-1. Cessation or reversal of hair loss was not seen in any of these women.No direct relationship between low serum ferritin and hair loss can be established. The usefulness of serum ferritin in the routine investigation of women with chronic diffuse telogen hair loss is unclear, as is the role of iron supplementation therapy in the management of hair loss.
Carbapenem antibiotics for serious infections
Authors: P. M. Hawkey, D. M. Livermore
Journal: BMJ (2012)

An 81 year old woman with a long term, indwelling urinary catheter is admitted with fever and hypotension thought to be due to septicaemia secondary to urinary tract infection. She is treated empirically with intravenous cefotaxime and gentamicin, but her condition deteriorates over 24 hours, with increasing hypotension and continuing fever. For broader spectrum coverage, her empirical antibiotic treatment is changed to intravenous meropenem. The next day, urine and blood cultures grow an Escherichia coli producing an extended spectrum β lactamase (ESBL), conferring resistance to cefotaxime and gentamicin but not to meropenem. The meropenem is continued for seven days, with clinical and bacteriological resolution of the patient’s infection.

Carbapenems are β lactam antibiotics, as are penicillins and cephalosporins, but differ from these other classes in their exact chemical structure. Carbapenem use has increased as a result of the rising resistance to cephalosporin antibiotics in Enterobacteriaceae ( Escherichia coli , Klebsiella , Enterobacter , and related genera). This cephalosporin resistance is largely due to the spread of extended spectrum β lactamases (ESBLs), which hydrolyse cephalosporins.1 ESBL producers are associated with poor clinical outcomes in severe infections: a meta-analysis found that bacteraemias caused by bacteria with these enzymes had 1.85-fold increased mortality (95% confidence interval 1.39 to 2.47, P<0.001), reflecting extended delays before effective therapy was initiated.2 ESBLs now occur in 10–12% of E coli from bacteraemias in the UK3 and in 50–80% of those in India and China, with many ESBL producing strains also resistant to quinolones and aminoglycosides.4

Carbapenems are the sole β lactam antibiotics with proven efficacy in severe infections due to ESBL producing bacteria: most Enterobacteriaceae strains with ESBLs in the UK are resistant to the β lactamase inhibitor combinations of amoxicillin-clavulanate and piperacillin-tazobactam—not because the ESBLs evade inhibition but because ESBL producers often also …
Antibody and Complement in Transplant Vasculopathy
Authors: Jennifer Wehner, Craig N. Morrell, Taylor Reynolds, E. Rene Rodriguez, William M. Baldwin
Journal: Circulation Research (2007)

Advances in immunosuppression have decreased the incidence of acute rejection, but the development of vasculopathy in the coronary arteries of transplants continues to limit the survival of cardiac allografts. Transplant vasculopathy has also been referred to as accelerated graft arteriosclerosis because it has features of arteriosclerosis, but it is limited to the graft and develops over a period of months to years. Although the pathological features of transplant vasculopathy are well defined, the causative mechanisms are not completely understood. This review focuses on the mechanisms by which antibody and complement can cause or contribute to coronary vasculopathy in cardiac transplants. Antibodies and complement can have independent effects, but the combination of antibodies and complement with inflammatory cells has greater pathogenic potential for the endothelial and smooth muscle cells of the coronary arteries. For example, stimulation through receptors for IgG or complement split products can activate macrophages, but stimulation through combinations of these receptors generates synergistic results. Together, antibodies and complement efficiently integrate the activation of endothelial cells, platelets, and macrophages, which are 3 of the primary components in the pathogenesis of transplant vasculopathy. Recent findings indicate that antibodies and complement produced within the transplant may contribute to vascular pathology in some transplants. Acute rejection caused by antibodies and complement has been treated by combinations of plasmapheresis, intravenous γ -globulin and monoclonal antibodies to CD20 on B lymphocytes. The effect of these treatment modalities on the development of coronary vasculopathy is unknown.
Measurement theory is a poor model of the relation of kinematic geometry and perception of motion
Authors: Dejan Todorovič
Journal: Behavioral and Brain Sciences (2001)

The Kubovy-Epstein proposal for the formalization of the relation between kinematic geometry and perception of motion has formal problems in itself. Motion phenomena are inadequately captured by the relational structures and the notion of isomorphism taken over from measurement theory. [Kubovy &amp; Epstein]
Mutation of N-myristoylation site converts endothelial cell nitric oxide synthase from a membrane to a cytosolic protein.
Authors: W C Sessa, C M Barber, K R Lynch
Journal: Circulation Research (1993)

Endothelial cell nitric oxide synthase (ECNOS) is a membrane-associated enzyme that generates endothelium-derived relaxing factor/nitric oxide (EDRF/NO) from L-arginine. We have suggested, from the cloning of the bovine ECNOS cDNA, that the presence of an N-myristoylation consensus sequence may impart its membrane localization since cytosolic forms of NOS do not contain such domains. To test the hypothesis that N-myristoylation is necessary for particulate ECNOS, we performed site-directed mutagenesis of the myristic acid acceptor site, Gly-2, and changed the glycine codon to alanine by a single nucleotide substitution. Expression of wild-type ECNOS in COS cells resulted in greater than 95% of the enzymatic activity in crude membrane fractions (as measured by the conversion of [3H]L-arginine to [3H]L-citrulline). In contrast, expression of the Gly-2 to Ala-2 mutant (G2A) demonstrated 8% ECNOS activity in membranes and 92% in the cytosol. The back mutation (from Ala-2 to Gly-2, A2G) restored ECNOS activity to the particulate fraction as seen with the wild type. Both wild-type membrane ECNOS and cytosolic G2A ECNOS activities were dependent on NADPH and calcium and were inhibited to the same extent by NG-monomethyl L-arginine (L-NMMA) and NG-nitro-L-arginine methyl ester (L-NAME). Moreover, kinetic analysis of these enzymes revealed similar Kms for L-arginine (2-4 microM, n = 3), demonstrating that the mutation did not affect ECNOS function. Thus, N-myristoylation is necessary for the membrane localization of ECNOS and may be of special significance for the basal or flow-induced production of NO by the endothelium.
Abstract P4-06-13: Discovering serum biomarkers for predicting accumulation of nanotherapeutics to different tumor and organ microenvironments
Authors: K Yokoi, T Tanei, B Godin, AL van de Ven, J Alexander, Y Saito, M Ferrari
Journal: Cancer Research (2013)

Abstract Surrogate biomarkers in the circulation for the enhanced permeation and retention (EPR) effect in different tumor and organ microenvironment shall aid in selecting patients who are likely to accumulate higher amount of nanotherapeutics to tumors and thus show better response to the therapeutics. In this study, 4T1 and 3LL murine cancer cell lines, known to have similar sensitivity to pegylated liposomal doxorubicin (PLD) in vitro, were shown to accumulate significantly different quantities of PLD in vivo. PLD accumulation correlated with tumor-specific differences in therapeutic efficacy and vascular permeability, which was modulated by the extent of coverage of tumor-associated endothelial cells by basement membrane. Matrix metalloproteinase (MMP)-9 and its endogenous inhibitor, tissue inhibitor of metalloproteinase (TIMP)-1, played a pivotal role in these phenomena. Differences in vascular permeability and PLD accumulation were also organ-specific and significantly correlated with the relative ratio of MMP-9 and TIMP-1 in the systemic circulation of the tumor-bearing mice. Our findings support the further development of MMP-9 and TIMP-1 as paired serum biomarkers for predicting accumulation of PLD to tumor and the application of these biomarkers could be expanded to other types of nanotherapeutics utilizing the EPR effect for the personalization of cancer therapy. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-06-13.
Cost-Effectiveness of Sublingual Specific Immuno-Therapy Versus Current Symptomatic Treatments in Adults with Allergic Rhinitis and Asthma, in the Societal Perspective
Authors: P. Berto, G.W. Canonica, N. Crimi, F. Frati, C. Ortolani, G. Passalacqua, G. Senna
Journal: Journal of Allergy and Clinical Immunology (2006)
Type 1 Diabetic Drivers With and Without a History of Recurrent Hypoglycemia–Related Driving Mishaps
Authors: Daniel J. Cox, Boris P. Kovatchev, Stacey M. Anderson, William L. Clarke, Linda A. Gonder-Frederick
Journal: Diabetes Care (2010)

Collisions are more common among drivers with type 1 diabetes than among their nondiabetic spouses. This increased risk appears to be attributable to a subgroup of drivers with type 1 diabetes. The hypothesis tested is that this vulnerable subgroup is more at risk for hypoglycemia and its disruptive effects on driving.Thirty-eight drivers with type 1 diabetes, 16 with (+history) and 22 without (-history) a recent history of recurrent hypoglycemia-related driving mishaps, drove a virtual reality driving simulator and watched a videotape of someone driving a simulator for 30-min periods. Driving and video testing occurred in a double-blind, randomized, crossover manner during euglycemia (5.5 mmol/l) and progressive hypoglycemia (3.9-2.5 mmol/l). Examiners were blind to which subjects were +/-history, whereas subjects were blind to their blood glucose levels and targets.During euglycemia, +history participants reported more autonomic and neuroglycopenic symptoms (P≤0.01) and tended to require more dextrose infusion to maintain euglycemia with the same insulin infusion (P<0.09). During progressive hypoglycemia, these subjects demonstrated less epinephrine release (P=0.02) and greater driving impairments (P=0.03).Findings support the speculation that there is a subgroup of type 1 diabetic drivers more vulnerable to experiencing hypoglycemia-related driving mishaps. This increased vulnerability may be due to more symptom "noise" (more symptoms during euglycemia), making it harder to detect hypoglycemia while driving; possibly greater carbohydrate utilization, rendering them more vulnerable to experiencing hypoglycemia; less hormonal counterregulation, leading to more profound hypoglycemia; and more neuroglycopenia, rendering them more vulnerable to impaired driving.
Is there a "point of no return" in progressive renal disease?
Authors: G Maschio, L Oldrizzi, C Rugiu
Journal: Journal of the American Society of Nephrology (1991)

The pathogenesis of progressive renal damage is most probably multifactorial. Whatever the mechanisms involved in renal disease progression, the existence of a "point of no return" has been hypothesized, that is, a stage of structural and functional damage beyond which progression of renal disease occurs independently of dietary measures and/or pharmacological treatment. In experimental animals, dietary protein and phosphate restriction is not fully successful in ameliorating the progression of functional deterioration if administered when renal injury is severe and long standing. Similarly, late treatment with various pharmacological agents (mainly antihypertensive drugs) is less effective than early administration of the same substances. A serum creatinine of 176 mumol/L seems a critical point discriminating the results of either dietary protein and phosphate restriction or antihypertensive treatment in patients with chronic renal disease. The protective effects of both dietary and nondietary intervention seem to be most effective when at least 50% of the residual renal mass is still functioning. The extent to which glomerular sclerosis, vascular hyalinosis, and interstitial fibrosis have already developed can probably blunt or avert the expected results of treatment. Some clinical tests may identify those patients who would benefit from measures such as the reduction in glomerular hemodynamic stress, the long-term inhibition of the renin-angiotensin system, and the aggressive treatment of systemic hypertension. The continuous search for a rational preventive treatment before the disease process has reached the "point of no return" will undoubtedly constitute a formidable task for the modern nephrologist.
DREAMing about arthritic pain
Authors: H-Y M Cheng
Journal: Annals of the Rheumatic Diseases (2004)

The experience of acute pain serves a crucial biological purpose: it alerts a living organism to environmental dangers, inducing behavioural responses which protect the organism from further damage. In contrast, chronic pain arising from disease states and/or pathological functioning of the nervous system offers no advantage and may be debilitating to those afflicted. Despite recent advances in our understanding of pain mechanisms, the satisfactory management of pathological pain eludes current treatment strategies. We have demonstrated in a previous study on <i>dream</i> deficient mice the pivotal role of downstream regulatory element antagonistic modulator (DREAM) in modulating pain sensitivity in a number of behavioural models, including acute and chronic neuropathic pain. DREAM is a novel calcium binding transcriptional repressor for the prodynorphin gene in spinal cord neurones. The marked attenuation in pain behaviour exhibited by <i>dream<sup>−/−</sup></i> mice was shown, by pharmacological and biochemical analyses, to be due to increased activation of the endogenous κ-opioid system. Importantly, loss of DREAM also attenuated inflammatory pain. Thus, DREAM and the DREAM pathway constitute a novel therapeutic paradigm for the treatment of chronic pain in arthritis.
Identification and Validation of a Novel Gene Signature Associated with the Recurrence of Human Hepatocellular Carcinoma
Authors: Suk Mei Wang, London Lucien P.J. Ooi, Kam M. Hui
Journal: Clinical Cancer Research (2007)

Abstract Purpose: To improve the clinical management of human hepatocellular carcinoma (HCC) by accurate identification, at diagnosis, of patients at risk of recurrence after primary treatment for HCC. Experimental Design: Two clinicopathologic variables available at diagnosis, vascular invasion and cirrhosis, together with molecular profiling using Affymetrix human HG-U133A and HG-U133B oligonucleotide probe arrays, were used to identify recurrent HCC disease. Results: HCC patients presented clinically at diagnosis with vascular invasion and cirrhosis showed a high rate (78-83%) of developing recurrent disease within 6 to 35 months. In comparison, most of the HCC patients (80-100%) without vascular invasion and cirrhosis remained disease-free. However, the risk of recurrent disease for HCC patients with either vascular invasion or cirrhosis could not be accurately ascertained. Using a pool of 23 HCC patients with either vascular invasion or cirrhosis as training set, a 57-gene signature was derived and could predict recurrent disease at diagnosis, with 84% (sensitivity 86%, specificity 82%) accuracy, for a totally independent test set of 25 HCC patients with either vascular invasion or cirrhosis. On further analysis, the disease-free rate was significantly different between patients that were predicted to recur or not to recur in the test group (P = 0.002). Conclusion: We have presented data to show that by incorporating the status of vascular invasion and cirrhosis available at diagnosis for patients with HCC after partial curative hepatectomy and a novel 57-member gene signature, we could accurately stratify HCC patients with different risks of recurrence.
Safety and tolerability of SCH 530348 in patients undergoing non-urgent percutaneous coronary intervention: a randomised, double-blind, placebo-controlled phase II study
Authors: Richard C Becker, David J Moliterno, Lisa K Jennings, Karen S Pieper, Jinglan Pei, Alan Niederman, Khaled M Ziada, Gail Berman, John Strony, Diane Joseph, Kenneth W Mahaffey, Frans Van de Werf, Enrico Veltri, Robert A Harrington
Journal: The Lancet (2009)