tbuckley/cabot-search huggingface dataset:
Hypoglycemia Unawareness Is Associated With Reduced Adherence to Therapeutic Decisions in Patients With Type 1 Diabetes
Authors: Charlotte B. Smith, Pratik Choudhary, Andrew Pernet, David Hopkins, Stephanie A. Amiel
Journal: Diabetes Care (2009)

Hypoglycemia unawareness increases severe hypoglycemia risk. Hypoglycemia avoidance restores awareness, but it is difficult to sustain. We compared adherence to treatment changes by awareness status.Case notes of 90 type 1 diabetic patients were analyzed retrospectively, identifying awareness status and insulin regimens over four visits. The proportion of patients adhering to advice and percent advice taken were calculated.A total of 31 patients with hypoglycemia awareness and 19 patients with hypoglycemia unawareness were identified, with insulin regimens available in 23 and 13, respectively. Patients with hypoglycemia unawareness were older (P = 0.001) and had longer diabetes duration (P = 0.002) and lower A1C (P = 0.007). More patients with hypoglycemia unawareness reported severe hypoglycemia (P = 0.002) and fewer were adherent (53.8 vs. 87.0%, P = 0.046), with lower adherence scores (42.5 +/- 24.7 vs. 75.3 +/- 27.5%, P = 0.001).Reduced adherence to changes in insulin regimen in hypoglycemia unawareness is compatible with habituation to hypoglycemic stress. Therapies aimed at reversing repetitive harmful behaviors may be useful to restore hypoglycemia awareness and protection from severe hypoglycemia.
Impact of Computer-Generated Personalized Goals on HbA1c
Authors: Claresa S. Levetan, Karen R. Dawn, David C. Robbins, Robert E. Ratner
Journal: Diabetes Care (2002)

OBJECTIVE—The public is increasingly aware of the importance of HbA1c testing, yet the vast majority of patients with diabetes do not know their HbA1c status or goal. We set forth to evaluate the impact of a system that provides uniquely formatted and personalized reports of diabetes status and goals on changes in HbA1c levels. RESEARCH DESIGN AND METHODS—A total of 150 patients with diabetes were randomized to receive either standard care or intervention inclusive of a computer-generated 11” × 17” color poster depicting an individual’s HbA1c status and goals along with personalized steps to aid in goal achievement. All patients enrolled received diabetes education during the 3 months before enrollment. HbA1c was performed at baseline and 6 months. RESULTS—At baseline, there were no significant differences between patient groups in terms of age, sex, education level, race, and HbA1c or lipid levels. Among patients with baseline HbA1c ≥7.0%, there was an 8.6% (0.77% absolute) reduction in HbA1c among control subjects compared with a 17.0% (1.69% absolute) decline in the intervention group (P = 0.032). There were no differences between the control and intervention groups with respect to the frequency of patients experiencing any decline in HbA1c (63 vs. 69%, P = 0.87); among these patients experiencing a decline, the most substantial reductions were seen with the control group, which had a 13.3% (1.15% absolute) decline compared with the intervention patients, who reduced their HbA1c by 24.2% (2.26% absolute reduction; P = 0.0048). At study close, 77% of the patients had their poster displayed on their refrigerator. CONCLUSIONS—This unique and personalized computer-generated intervention resulted in HbA1c lowering comparable to that of hypoglycemic agents.
Phylogeny of Shiga Toxin-Producing Escherichia coli O157 Isolated from Cattle and Clinically Ill Humans
Authors: J. L. Bono, T. P. L. Smith, J. E. Keen, G. P. Harhay, T. G. McDaneld, R. E. Mandrell, W. K. Jung, T. E. Besser, P. Gerner-Smidt, M. Bielaszewska, H. Karch, M. L. Clawson
Journal: Molecular Biology and Evolution (2012)

Cattle are a major reservoir for Shiga toxin-producing Escherichia coli O157 (STEC O157) and harbor multiple genetic subtypes that do not all associate with human disease. STEC O157 evolved from an E. coli O55:H7 progenitor; however, a lack of genome sequence has hindered investigations on the divergence of human- and/or cattle-associated subtypes. Our goals were to 1) identify nucleotide polymorphisms for STEC O157 genetic subtype detection, 2) determine the phylogeny of STEC O157 genetic subtypes using polymorphism-derived genotypes and a phage insertion typing system, and 3) compare polymorphism-derived genotypes identified in this study with pulsed field gel electrophoresis (PFGE), the current gold standard for evaluating STEC O157 diversity. Using 762 nucleotide polymorphisms that were originally identified through whole-genome sequencing of 189 STEC O157 human- and cattle-isolated strains, we genotyped a collection of 426 STEC O157 strains. Concatenated polymorphism alleles defined 175 genotypes that were tagged by a minimal set of 138 polymorphisms. Eight major lineages of STEC O157 were identified, of which cattle are a reservoir for seven. Two lineages regularly harbored by cattle accounted for the majority of human disease in this study, whereas another was rarely represented in humans and may have evolved toward reduced human virulence. Notably, cattle are not a known reservoir for E. coli O55:H7 or STEC O157:H− (the first lineage to diverge within the STEC O157 serogroup), which both cause human disease. This result calls into question how cattle may have originally acquired STEC O157. The polymorphism-derived genotypes identified in this study did not surpass PFGE diversity assessed by BlnI and XbaI digestions in a subset of 93 strains. However, our results show that they are highly effective in assessing the evolutionary relatedness of epidemiologically unrelated STEC O157 genetic subtypes, including those associated with the cattle reservoir and human disease.
Improving access to GPs will help reduce pressure on emergency departments, says NHS
Authors: A. O'Dowd
Journal: BMJ (2013)

Fresh efforts to improve access to general practices will help relieve some of the growing pressure on hospital emergency departments in England in the short and long term, officials have told MPs.

Problems in primary care such as poor services and access had an effect, said government officials during an evidence session on 18 December of the public accounts committee for its inquiry into managing demand in emergency admissions to hospitals.

MPs said various reports had concluded that poor access to a GP was linked to higher rates of emergency admissions and asked whether “abandoning” the 48 hour guarantee of getting a GP appointment had led to more admissions.

Barbara Hakin, chief operating officer for NHS England, giving …
Microsomal epoxide hydrolase, glutathione S-transferase P1, traffic and childhood asthma
Authors: M. T Salam, P.-C. Lin, E. L Avol, W J. Gauderman, F. D Gilliland
Journal: Thorax (2007)

Background: Microsomal epoxide hydrolase (EPHX1) metabolises xenobiotics including polyaromatic hydrocarbons (PAHs). Functional variants at this locus have been associated with respiratory diseases. The effects of EPHX1 variants may depend upon exposures from tobacco smoke and traffic emissions that contain PAHs as well as variants in other enzymes in the PAH metabolic pathway such as glutathione S-transferase (GST) genes. A study was undertaken to investigate associations of variants in EPHX1, GSTM1, GSTP1 and GSTT1 with asthma and the relationships between asthma, EPHX1 metabolic phenotypes and exposure to sources of PAHs. Methods: Odds ratios (ORs) and 95% confidence intervals (CIs) were computed to estimate the associations of genetic variants and exposures with asthma phenotypes using data from 3124 children from the Children's Health Study. Results: High EPHX1 activity was associated with an increased risk for lifetime asthma (OR 1.51, 95% CI 1.14 to 1.98) which varied by GSTP1 Ile105Val genotype and by residential proximity to major roads (p for interaction = 0.006 and 0.03, respectively). Among children with GSTP1 105Val/Val genotype, those who had high EPHX1 phenotype had a fourfold (95% CI 1.97 to 8.16) increased risk of lifetime asthma than children with low/intermediate EPHX1 phenotype. Among children living within 75 metres of a major road, those with high EPHX1 activity had a 3.2-fold (95% CI 1.75 to 6.00) higher lifetime asthma risk than those with low/intermediate activity. The results were similar for current, early persistent and late onset asthma. Children with high EPHX1 phenotype, GSTP1 Val/Val genotype who lived <75 metres from a major road were at the highest asthma risk. Conclusion: EPHX1 and GSTP1 variants contribute to the occurrence of childhood asthma and increase asthma susceptibility to exposures from major roads.
Diaphragm electromyograms recorded from multiple surface electrodes following magnetic stimulation
Authors: J. C. Glerant, N. Mustfa, W. D. Man, Y. M. Luo, G. Rafferty, M. I. Polkey, J. Moxham
Journal: European Respiratory Journal (2006)

The diaphragm compound-muscle action potential (CMAPdi), elicited by unilateral magnetic stimulation (UMS) of the phrenic nerve can be recorded using surface electrodes. However, there is no consensus on the best positioning of surface electrodes and there are no data on the reproducibility of the signal. Using 36 surface electrode pairs, in five healthy subjects, the CMAPdi elicited by UMS and electrical stimulation (ES) were compared and 12 pairs were identified as providing acceptable signals. The latency and amplitude were measured for each CMAPdi, following UMS at 60-100% of maximal stimulator output, in 12 healthy subjects, on two occasions. Latencies obtained using UMS and ES ranged between 6.1-7.33 and 6.25-7.17 ms, respectively. Optimum CMAPdi were not recorded from the same electrode pair in all subjects, or for both hemidiaphragms in each subject. However, the optimal recording site for a particular individual remained unchanged on subsequent testing. When recorded from the optimal site, latencies and amplitudes of CMAPdi elicited on the two occasions were not significantly different. The current study suggests that the use of multiple chest wall electrodes can identify an optimal electrode pair, from which it is possible to obtain reproducible compound-muscle action potential signals.
Cutaneous cryptococcosis: treatment with oral fluconazole
Authors: D. SHUTTLEWORTH, C.M. PHILPOT, A. G. KNIGHT
Journal: British Journal of Dermatology (1989)

A case of cutaneous cryptococcosis is described in an immunocompromised patient. The initial lesion developed on the dorsum of the hand following trauma and was initially thought to be neoplastic. Satellite subcutaneous lesions developed in a ‘sporotrichoid’ pattern along the forearm. Treatment with oral fluconazole resulted in the complete resolution of the lesions. This is the first published report of the use of fluconazole in the treatment of cutaneous cryptococcosis.
Abstract 4568: Estrogen receptor and progesterone receptor immunocytochemistry staining in circulating tumor cells as compared to primary tumor or metastatic biopsy
Authors: Julie Ann Mayer, Tony J. Pircher, Tam Pham, Karina Wong, Eligie Villarin, Farideh Z. Bischoff
Journal: Cancer Research (2012)

Abstract Introduction: Hormone receptor (estrogen receptor (ER) and progesterone receptor (PR)) status in all breast cancer patients is recommended by immunohistochemistry (IHC) and is considered standard practice for selection of treatment options. However, the analytical sensitivity of IHC in detecting low levels of ER/PR is often poor and likely due to methodological variation. Because biopsy is not often feasible in all patients presenting with recurrent and/or metastatic breast disease, circulating tumor cells (CTCs) offer an attractive alternative source of tumor tissue for determining ER/PR status and can be monitored more readily to enable a more effective course of treatment. Experimental Design: Twenty ml of peripheral blood was collected prospectively from 14 patients diagnosed with late stage metastatic/recurrent breast cancer. CTCs were isolated using the microfluidic OncoCEETM platform. A cocktail of antibodies was utilized for CTC capture and detection with an expanded anti-cytokeratin (CK) cocktail mixture and anti-CD45. ER/PR protein expression was assessed by immunocytochemistry (ICC) on the cells captured within the microchannels and compared to IHC performed on the primary tumor or metastatic biopsy. Results: CK+/CD45-/DAPI+ cells were located and assessed for ER/PR immunocytochemistry. Among the 14 cases a high concordance (12/14; 86%) in ER/PR status between primary tumor/metastatic biopsy and CTCs was observed. Two cases were found to be discordant where one was positive by IHC and negative on the CTCs and the other was negative on by IHC on the primary tumor/metastatic biopsy and positive on the CTCs. However, both cases that were discordant had low numbers of CTCs detected. Conclusions: There is significant heterogeneity between ER/PR protein expression in CTCs and primary tumor/metastatic biopsy and this status may change over time due to therapy. ER/PR ICC on CTCs from peripheral blood using the OncoCEETM platform is shown to be feasible with high concordance (86%) in ER/PR status between primary tumor/metastatic biopsy (by IHC) and CTCs (by ICC). The significance of heterogeneity at the ER/PR protein level in CTCs ascertaining to the prognosis and predictive response to anti-estrogen therapy needs further evaluation in larger prospective clinical trials. 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 4568. doi:1538-7445.AM2012-4568
Genomic Profiling Reveals an Alternate Mechanism for Hepatic Tumor Promotion by Perfluorooctanoic Acid in Rainbow Trout
Authors: Susan C. Tilton, Gayle A. Orner, Abby D. Benninghoff, Hillary M. Carpenter, Jerry D. Hendricks, Cliff B. Pereira, David E. Williams
Journal: Environmental Health Perspectives (2008)

Perfluorooctanoic acid (PFOA) is a potent hepatocarcinogen and peroxisome proliferator (PP) in rodents. Humans are not susceptible to peroxisome proliferation and are considered refractory to carcinogenesis by PPs. Previous studies with rainbow trout indicate they are also insensitive to peroxisome proliferation by the PP dehydroepiandrosterone (DHEA), but are still susceptible to enhanced hepatocarcinogenesis after chronic exposure.In this study, we used trout as a unique in vivo tumor model to study the potential for PFOA carcinogenesis in the absence of peroxisome proliferation compared with the structurally diverse PPs clofibrate (CLOF) and DHEA. Mechanisms of carcinogenesis were identified from hepatic gene expression profiles phenotypically anchored to tumor outcome.We fed aflatoxin B(1) or sham-initiated animals 200-1,800 ppm PFOA in the diet for 30 weeks for tumor analysis. We subsequently examined gene expression by cDNA array in animals fed PFOA, DHEA, CLOF, or 5 ppm 17beta-estradiol (E(2), a known tumor promoter) in the diet for 14 days.PFOA (1,800 ppm or 50 mg/kg/day) and DHEA treatments resulted in enhanced liver tumor incidence and multiplicity (p < 0.0001), whereas CLOF showed no effect. Carcinogenesis was independent of peroxisome proliferation, measured by lack of peroxisomal beta-oxidation and catalase activity. Alternately, both tumor promoters, PFOA and DHEA, resulted in estrogenic gene signatures with strong correlation to E(2) by Pearson correlation (R = 0.81 and 0.78, respectively), whereas CLOF regulated no genes in common with E(2).These data suggest that the tumor-promoting activities of PFOA in trout are due to novel mechanisms involving estrogenic signaling and are independent of peroxisome proliferation.
Moderate-to-Severe Diabetic Retinopathy Is More Prevalent in Mexico City Than in San Antonio, Texas
Authors: Maria Elena González Villalpando, Clicerio González Villalpando, Beatriz Arredondo Pérez, Sandra Virginia Martínez Díaz, Braxton Mitchell, David Rivera Martínez, Ronald Klein, Steven M Haffner, Michael P Stern
Journal: Diabetes Care (1997)

OBJECTIVE To compare the prevalence of diabetic retinopathy (DR) between low-income Mexicans from Mexico City and Mexican-Americans from San Antonio, Texas. RESEARCH DESIGN AND METHODS We designed a cross-sectional population-based study in low-income neighborhoods of Mexico City and San Antonio. The men and non-pregnant women included in the study had NIDDM and were between 35 and 64 years of age. Ophthalmologic evaluation was performed in 414 patients, 204 in San Antonio and 210 in Mexico City. Seven field standard stereophotographs of each eye were obtained, adapting the Early Treatment Diabetic Retinopathy Study protocol, and graded at the Fundus Photograph Reading Center of the University of Wisconsin. RESULTS Early nonproliferative DR occurred in 37 (17.6%) and 39 (19.1%) patients in Mexico City and San Antonio, respectively. Moderate-to-severe nonproliferative DR occurred in 55 (26.2%) and 37 (18.1%) patients in Mexico City and San Antonio, respectively, and proliferative DR occurred in 12 (5.7%) and 7 (3.4%) patients in Mexico City and San Antonio, respectively. Using univariate and multivariate logistic regression analysis with DR as the dependent variable, age, duration of disease, and fasting glucose concentration were positively and significantly associated with retinopathy, whereas city, systolic blood pressure, and other selected metabolic variables were not. We defined moderate-to-severe DR to include the categories of moderate-to-severe nonproliferative and proliferative DR. For this combined category, Mexico City patients with diabetes had a significantly higher prevalence (P &amp;lt; 0.01) than those from San Antonio when analyzed by multiple logistic regression analysis (odds ratio for Mexico City/San Antonio, 1.72; 95% CI 1.10–2.70). CONCLUSIONS Overall prevalence of DR is similar in both cities. However, moderate-to-severe DR is significantly higher in Mexico City.
Early tumor shrinkage and depth of response predict long-term outcome in metastatic colorectal cancer patients treated with first-line chemotherapy plus bevacizumab: results from phase III TRIBE trial by the Gruppo Oncologico del Nord Ovest
Authors: C. Cremolini, F. Loupakis, C. Antoniotti, S. Lonardi, G. Masi, L. Salvatore, E. Cortesi, G. Tomasello, R. Spadi, A. Zaniboni, G. Tonini, C. Barone, S. Vitello, R. Longarini, A. Bonetti, M. D'Amico, S. Di Donato, C. Granetto, L. Boni, A. Falcone
Journal: Annals of Oncology (2015)
Cetuximab, docetaxel, and cisplatin as first-line treatment in patients with recurrent or metastatic head and neck squamous cell carcinoma: a multicenter, phase II GORTEC study
Authors: J. Guigay, J. Fayette, A.F. Dillies, C. Sire, J.N. Kerger, I. Tennevet, J.P. Machiels, S. Zanetta, Y. Pointreau, L. Bozec Le Moal, S. Henry, A. Schilf, J. Bourhis
Journal: Annals of Oncology (2015)
Macrophage Delivery of an Oncolytic Virus Abolishes Tumor Regrowth and Metastasis after Chemotherapy or Irradiation
Authors: Munitta Muthana, Samuel Rodrigues, Yung-Yi Chen, Abigail Welford, Russell Hughes, Simon Tazzyman, Magnus Essand, Fiona Morrow, Claire E. Lewis
Journal: Cancer Research (2012)

Abstract Frontline anticancer therapies such as chemotherapy and irradiation often slow tumor growth, but tumor regrowth and spread to distant sites usually occurs after the conclusion of treatment. We recently showed that macrophages could be used to deliver large quantities of a hypoxia-regulated, prostate-specific oncolytic virus (OV) to prostate tumors. In the current study, we show that administration of such OV-armed macrophages 48 hours after chemotherapy (docetaxel) or tumor irradiation abolished the posttreatment regrowth of primary prostate tumors in mice and their spread to the lungs for up to 27 or 40 days, respectively. It also significantly increased the lifespan of tumor-bearing mice compared with those given docetaxel or irradiation alone. These new findings suggest that such a novel, macrophage-based virotherapy could be used to markedly increase the efficacy of chemotherapy and irradiation in patients with prostate cancer. Cancer Res; 73(2); 490–5. ©2012 AACR.
Optimal Therapy for Unresectable Stage III Non–Small-Cell Lung Cancer
Authors: Everett E. Vokes
Journal: Journal of Clinical Oncology (2005)

The treatment of patients with unresectable regionally advanced non–small-cell lung cancer (NSCLC) has continued to evolve over the last two decades. In the 1980s, radiotherapy alone led to a median survival of less than 10 months and 3-year survival rates below 10%. The identification of drugs with single-agent activity in stage IV NSCLC allowed for subsequent investigations in the curative intent treatment setting. Combined-modality therapy initially focused on a sequential approach, using induction chemotherapy. Randomized phase III studies demonstrated an increase in median survival from 10 months to approximately 13 months with the addition of two cycles of cisplatin-based chemotherapy administered before radiotherapy. 1-3 Since locoregional control is infrequently achieved with radiotherapy alone, and most agents with single-agent systemic activity are also radiation sensitizers, the concomitant administration of both modalities has also been explored. Most studies evaluating single-agent cisplatin had negative results, but concomitant chemoradiotherapy using two drugs was shown to be superior to radiotherapy alone. 4-6 Thus, sequential and concomitant combined-modality strategies were each established to be superior to radiotherapy alone, although their effects might be mediated by different mechanism because concomitant chemoradiotherapy appears to prolong survival mainly by increasing locoregional control, whereas induction chemotherapy improves systemic control. The next generation of randomized trials directly compared induction chemotherapy with concomitant chemoradiotherapy in an effort to determine the most effective approach. Several randomized phase II and III studies have been presented that suggest that the concomitant approach results in a higher median survival of approximately 16 to 17 months, although in-field toxicity, in particular esophagitis, is also increased (grade 3 or 4 in approximately 25%). 7-9