tbuckley/cabot-search huggingface dataset:
Sex Disparities in Control and Treatment of Modifiable Cardiovascular Disease Risk Factors Among Patients With Diabetes
Authors: Assiamira Ferrara, Carol M. Mangione, Catherine Kim, David G. Marrero, David Curb, Mark Stevens, Joseph V. Selby
Journal: Diabetes Care (2007)

Cardiovascular disease (CVD) mortality has decreased in men but not in women with diabetes. We investigated whether sex differences in control and treatment of CVD risk factors might underlie this disparity.We performed cross-sectional analyses from a cohort of patients with diabetes sampled from 10 U.S. managed care health plans. Study end points included not being in control for CVD risk factors (>or=140 mmHg for systolic blood pressure [SBP], >or=3.35 mmol/l for LDL cholesterol, and >or=8.0% for A1C) and the intensity of medication management (number of medication classes) for patients not in control. Logistic regression models with random intercepts were used to adjust probabilities of control and management for demographics, clinical characteristics, and clustering within health plans.There were 1,315 women and 1,575 men with a history of CVD and 3,415 women and 2,516 men without a history of CVD. Among patients with CVD, adjusted estimated probabilities for not being in control and risk differences varied significantly between men and women for SBP (men 41.2%, women 46.6%; risk difference -5.4% [95% CI -9.5 to -1.3]) and LDL cholesterol (men 22.4%, women 28.3%; risk difference -5.9% [-9.9 to -1.8]). There were no significant sex differences in intensity of medication management for patients not in control. In patients without CVD there were no significant differences in control or intensity of medication management.In diabetic patients with CVD, poorer control of SBP and LDL cholesterol for women may contribute to the sex disparity in CVD mortality trends.
AutoSet nasal CPAP titration: constancy of pressure, compliance and effectiveness at 8 month follow-up
Authors: H Teschler, AA Farhat, V Exner, N Konietzko, M Berthon-Jones
Journal: European Respiratory Journal (1997)

We have previously shown that AutoSet satisfactorily improves sleep-disordered breathing and sleep architecture in subjects with obstructive sleep apnoea (OSA) syndrome. The aim of this study was to determine, in subjects treated with long-term conventional fixed pressure continuous positive airway pressure (CPAP) at the AutoSet recommended pressure, whether: the long-term compliance is satisfactory; the improvement persists once initial rebound is over; the titration pressure is stable with time; and the titration pressure is comparable with manual titration pressure using a similar end-point. Twenty males with OSA, previously studied with full polysomnography on their diagnostic night, at manual and AutoSet titration, and at the AutoSet recommended fixed pressure, were re-studied after a mean of 3 and 8 months of treatment at the recommended fixed pressure. Re-study included home respiratory monitoring (Nellcor EdenTrace), and repeated manual and AutoSet titration with polysomnography. Compliance was assessed with hour-meter readings. Mean (+/-SEM) usage was 5.7 +/- 0.1 h.night-1 at 3 and 8 months. The arousal index remained normalized. Diagnostic respiratory disturbance index (RDI) was 60.3 +/- 5.7 events.h-1. On AutoSet at fixed CPAP, RDI was initially 2.6 +/- 0.7 events.h-1, then rose slightly (p &lt; 0.001) to 4.3 +/- 0.6 events.h-1 at 3 months, and was 3.6 +/- 0.5 events.h-1 at 8 months. AutoSet titration pressure was: 9.9 +/- 0.4 cmH2O initially, 10.6 +/- 0.4 cmH2O at 3 months, and 9.7 +/- 0.5 cmH2O at 8 months (NS). Manual titration pressure at 8 months was 10.4 +/- 0.4 cmH2O. The standard deviation of the discrepancy with AutoSet was 0.84 cmH2O. In conclusion, the AutoSet recommended pressure varies little with time, and closely predicts the final manual titration pressure; the improvement in respiratory disturbance index was largely maintained, and compliance was good, although probably enhanced by close supervision.
Pathophysiology of Neuropathic Pain in Type 2 Diabetes
Authors: Chi-Chao Chao, Ming-Tsung Tseng, Ya-Ju Lin, Wei-Shiung Yang, Song-Chou Hsieh, Yea-Huey Lin, Ming-Jang Chiu, Yang-Chyuan Chang, Sung-Tsang Hsieh
Journal: Diabetes Care (2010)

Neuropathic pain due to small-fiber sensory neuropathy in type 2 diabetes can be diagnosed by skin biopsy with quantification of intra-epidermal nerve fiber (IENF) density. There is, however, a lack of noninvasive physiological assessment. Contact heat-evoked potential (CHEP) is a newly developed approach to record cerebral responses of Aδ fiber-mediated thermonociceptive stimuli. We investigated the diagnostic role of CHEP.From 2006 to 2009, there were 32 type 2 diabetic patients (20 males and 12 females, aged 51.63 ± 10.93 years) with skin denervation and neuropathic pain. CHEPs were recorded with heat stimulations at the distal leg, where skin biopsy was performed.CHEP amplitude was reduced in patients compared with age- and sex-matched control subjects (14.8 ± 15.6 vs. 33.7 ± 10.1 μV, P < 0.001). Abnormal CHEP patterns (reduced amplitude or prolonged latency) were noted in 81.3% of these patients. The CHEP amplitude was the most significant parameter correlated with IENF density (P = 0.003) and pain perception to contact heat stimuli (P = 0.019) on multiple linear regression models. An excitability index was derived by calculating the ratio of the CHEP amplitude over the IENF density. This excitability index was higher in diabetic patients than in control subjects (P = 0.023), indicating enhanced brain activities in neuropathic pain. Among different neuropathic pain symptoms, the subgroup with evoked pain had higher CHEP amplitudes than the subgroup without evoked pain (P = 0.011).CHEP offers a noninvasive approach to evaluate the degeneration of thermonociceptive nerves in diabetic neuropathy by providing physiological correlates of skin denervation and neuropathic pain.
Effectiveness of policy to provide breastfeeding groups (BIG) for pregnant and breastfeeding mothers in primary care: cluster randomised controlled trial
Authors: P. Hoddinott, J. Britten, G. J Prescott, D. Tappin, A. Ludbrook, D. J Godden
Journal: BMJ (2009)

<b>Objective</b> To assess the clinical effectiveness and cost effectiveness of a policy to provide breastfeeding groups for pregnant and breastfeeding women. <b>Design</b> Cluster randomised controlled trial with prospective mixed method embedded case studies to evaluate implementation processes. <b>Setting</b> Primary care in Scotland. <b>Participants</b> Pregnant women, breastfeeding mothers, and babies registered with 14 of 66 eligible clusters of general practices (localities) in Scotland that routinely collect breastfeeding outcome data. <b>Intervention</b> Localities set up new breastfeeding groups to provide population coverage; control localities did not change group activity. <b>Main outcome measures</b> Primary outcome: any breast feeding at 6-8 weeks from routinely collected data for two pre-trial years and two trial years. Secondary outcomes: any breast feeding at birth, 5-7 days, and 8-9 months; maternal satisfaction. <b>Results</b> Between 1 February 2005 and 31 January 2007, 9747 birth records existed for intervention localities and 9111 for control localities. The number of breastfeeding groups increased from 10 to 27 in intervention localities, where 1310 women attended, and remained at 10 groups in control localities. No significant differences in breastfeeding outcomes were found. Any breast feeding at 6-8 weeks declined from 27% to 26% in intervention localities and increased from 29% to 30% in control localities (P=0.08, adjusted for pre-trial rate). Any breast feeding at 6-8 weeks increased from 38% to 39% in localities not participating in the trial. Women who attended breastfeeding groups were older (P&lt;0.001) than women initiating breast feeding who did not attend and had higher income (P=0.02) than women in the control localities who attended postnatal groups. The locality cost was £13 400 (€14 410; $20 144) a year. <b>Conclusion</b> A policy for providing breastfeeding groups in relatively deprived areas of Scotland did not improve breastfeeding rates at 6-8 weeks. The costs of running groups would be similar to the costs of visiting women at home. <b>Trial registration</b> Current Controlled Trials ISRCTN44857041.
Hand and Foot Surgery Rates in Rheumatoid Arthritis Have Declined From 1986 to 2011, but Large‐Joint Replacement Rates Remain Unchanged: Results From Two UK Inception Cohorts
Authors: Elena Nikiphorou, Lewis Carpenter, Stephen Morris, Alex J. MacGregor, Josh Dixey, Patrick Kiely, David W. James, David A. Walsh, Sam Norton, Adam Young
Journal: Arthritis & Rheumatology (2014)

To assess whether there have been any secular changes in orthopedic interventions in patients with rheumatoid arthritis (RA) since 1986, as examined in 2 early rheumatoid arthritis (RA) inception cohorts with up to 25 years of followup.The study examined orthopedic data from the UK Early RA Study (1986-1999, 9 centers; n = 1,465) and the UK Early RA Network (2002-2012, 23 centers; n = 1,236) with linkage to national data sets (Hospital Episode Statistics, National Joint Registry, and Office of National Statistics). Clinical and laboratory measures and hand and foot radiographs were standardized and obtained yearly in both cohorts. The use of disease-modifying antirheumatic drugs (DMARDs), corticosteroids, and biologic therapies reflected the contemporary conventional practices and guidelines of the time frames examined. Recruitment years were grouped into 6 periods, and interventions were classified into major, intermediate, and minor categories.A total of 1,602 orthopedic surgical procedures were performed in 770 patients (29%) over a maximum of 25 years of followup. The 25-year cumulative incidence rate of major interventions was 21.7% (range 19.4-24.0%), and that of intermediate interventions was 21.5% (range 17.8-25.5%). There was a decline in the 10-year cumulative incidence of intermediate surgeries over time (P < 0.001), but not of major/minor surgery. This decline coincided with a gradual shift from sequential monotherapy to combination DMARD therapies and biologic agents in recent recruitment periods.Orthopedic surgery is an important and common outcome in RA. Only the rates of hand/foot surgery showed a consistent decline from 1986 to 2011. Possible explanations include differences in the pathophysiologic processes affecting the joints, variations in the responses to therapy between large-joint and small-joint destructive processes, and changes in service provision and thresholds for surgery over time.
Pulmonary vasodilator activity of prostacyclin (PGI2) in the cat.
Authors: A L Hyman, P J Kadowitz
Journal: Circulation Research (1979)

We studied the pulmonary vascular effects of prostacylin, PGI2, in the cat with intact chest under conditions of controlled blood flow. Intralobar injections of PGI2, 0.03--1 microgram, decreased arterial pressure in the perfused lobe in a dose-dependent manner. Inasmuch as lobar blood flow was held constant and left artrial pressure was unchanged, the fall in lobar arterial pressure reflects a decrease in lobar vascular resistance. Prostaglandin E1 (PGE1) and nitroglycerin also decreased lobar arterial pressure; however, PGI2 had greater vasodilator activity than did these substances. Vasodilator responses to PGI2, PGE1, and nitroglycerin in absolute terms were dependent on the baseline level of tone in the pulmonary vascular bed. Prostacyclin reversed the hypertensive and platelet aggregating effects of ADP in the lobar vascular bed. These data indicate that PGI2 has significant vasodilator activity in the feline pulmonary lobar vascular bed.
Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production
Authors: Aurora Merovci, Carolina Solis-Herrera, Giuseppe Daniele, Roy Eldor, Teresa Vanessa Fiorentino, Devjit Tripathy, Juan Xiong, Zandra Perez, Luke Norton, Muhammad A. Abdul-Ghani, Ralph A. DeFronzo
Journal: Journal of Clinical Investigation (2014)

Chronic hyperglycemia impairs insulin action, resulting in glucotoxicity, which can be ameliorated in animal models by inducing glucosuria with renal glucose transport inhibitors. Here, we examined whether reduction of plasma glucose with a sodium-glucose cotransporter 2 (SGLT2) inhibitor could improve insulin-mediated tissue glucose disposal in patients with type 2 diabetes. Eighteen diabetic men were randomized to receive either dapagliflozin (n = 12) or placebo (n = 6) for 2 weeks. We measured insulin-mediated whole body glucose uptake and endogenous glucose production (EGP) at baseline and 2 weeks after treatment using the euglycemic hyperinsulinemic clamp technique. Dapagliflozin treatment induced glucosuria and markedly lowered fasting plasma glucose. Insulin-mediated tissue glucose disposal increased by approximately 18% after 2 weeks of dapagliflozin treatment, while placebo-treated subjects had no change in insulin sensitivity. Surprisingly, following dapagliflozin treatment, EGP increased substantially and was accompanied by an increase in fasting plasma glucagon concentration. Together, our data indicate that reduction of plasma glucose with an agent that works specifically on the kidney to induce glucosuria improves muscle insulin sensitivity. However, glucosuria induction following SGLT2 inhibition is associated with a paradoxical increase in EGP. These results provide support for the glucotoxicity hypothesis, which suggests that chronic hyperglycemia impairs insulin action in individuals with type 2 diabetes.
Inflammatory bowel disease stimulates formation of carcinogenic N-nitroso compounds
Authors: T M C M de Kok
Journal: Gut (2005)

In patients with inflammatory bowel disease (IBD), an increased incidence of colorectal cancer is observed.1 Although severe inflammatory conditions per se represent a risk factor for neoplasia, we would like to draw attention to the possible role of increased activity of inducible nitric oxide synthase (iNOS), as found in IBD patients,2 in the endogenous formation of carcinogenic N -nitroso compounds (NOC). In healthy individuals, relatively small amounts of NOC are formed by the interaction between NOC precursors (NOCP), present in dietary items such as meat and fish, and nitrosating agents derived from dietary nitrate. It has been proposed that endogenous formation of NOC may explain the link between meat consumption and colon cancer risk found in epidemiological studies.3 We hypothesised that as a result …
Potassium permeability in β-thalassemia minor red blood cells
Authors: Robert B. Gunn, David N. Silvers, Wendell F. Rosse
Journal: Journal of Clinical Investigation (1972)

The intracellular content of K+ in thalassemia minor red blood cells is markedly reduced after incubation in autologous serum for 24 hr at 37°C. There is no compensatory increase in intracellular Na+ concentration of the cell thus reduced. This change is due to an acquired increase in selective permeability of the membrane to K+. This phenomenon follows the depletion of energy sources in the thalassemia minor cells but does not follow comparable depletion in normal cells. The loss of osmotically active intracellular contents probably accounts for the increased resistance of incubated thalassemia minor red blood cells to osmotic lysis.
Effects of pentachlorophenol and tetrachlorohydroquinone on mitogen-activated protein kinase pathways in Jurkat T cells.
Authors: Bambang Wispriyono, Masato Matsuoka, Hideki Igisu
Journal: Environmental Health Perspectives (2002)

When Jurkat human T cells were incubated with 20 microM of pentachlorophenol (PCP) or its metabolite, tetrachlorohydroquinone (TCHQ), for 10 hr, flow cytometric analyses revealed marked increase in the number of apoptotic cells. DNA fragmentation was also observed in these cells. TCHQ was more potent than PCP in causing apoptosis. After incubation with 20 microM TCHQ for 1 hr, all mitogen-activated protein kinases (MAPKs) examined [i.e., extracellular signal-regulated protein kinase (ERK), p38, and c-Jun NH(2)-terminal kinase (JNK)] were phosphorylated, whereas no clear phosphorylation was induced by PCP. TCHQ-induced apoptosis was markedly suppressed by treatment with a p38 inhibitor (SB203580) and mildly (but significantly) suppressed by treatment with a MAPK/ERK kinase inhibitor (U0126). When cells were treated with both inhibitors at the same time, TCHQ-induced apoptosis disappeared almost completely. PCP-induced apoptosis was also suppressed by SB203580 and/or U0126. Nevertheless, treatment with LL-Z1640-2, which inhibits JNK phosphorylation, did not suppress the apoptosis caused by either TCHQ or PCP. Thus, p38 and ERK appear to be important signal transduction pathways leading to apoptosis in a human T-cell line exposed to a ubiquitous pollutant or its metabolite in the general and occupational environment.
Expression of Interleukin-4 Receptor Alpha in Human Pleural Mesothelioma Is Associated with Poor Survival and Promotion of Tumor Inflammation
Authors: Bryan M. Burt, Andrew Bader, Daniel Winter, Scott J. Rodig, Raphael Bueno, David J. Sugarbaker
Journal: Clinical Cancer Research (2012)

The origin and pathogenesis of malignant pleural mesothelioma (MPM) are closely aligned with inflammation. MPM tumors express interleukin-4 receptor α (IL-4Rα), the principal subunit of the IL-4 receptor. We set out to determine the biologic function and clinical relevance of IL-4Rα in human MPM.Expression of IL-4Rα by human MPM tumors was determined by quantitative real-time PCR (n = 37) and immunohistochemistry (n = 52). Intracellular cytokine analysis of T-cell-derived IL-4 was carried out on matched tumor and blood samples from eight patients with MPM. Four human MPM cell lines were used to determine the direct effects of IL-4 on MPM tumor cells.High tumor mRNA expression of IL-4Rα was an independent predictor of poor survival in patients with epithelial MPM [HR, 3.13, 95% confidence interval (CI), 1.68-7.15; P = <0.0001]. Ninety-seven percent of epithelial MPM tumors and 95% of nonepithelial MPM tumors expressed IL-4Rα protein by immunohistochemistry, and strong IL-4Rα staining correlated with worse survival in patients with epithelial histology (P = 0.04). A greater percentage of tumor-infiltrating T cells produced IL-4 compared with matched blood T cells (21% ± 7% vs. 4% ± 2%, P = 0.0002). In response to IL-4, human MPM cells showed increased STAT-6 phosphorylation and increased production of IL-6, IL-8, and VEGF, without effect on proliferation or apoptosis.Tumor expression of IL-4Rα is inversely correlated with survival in patients undergoing surgical resection for epithelial MPM. Tumor-infiltrating T cells in MPMs are polarized to produce IL-4 and may provide endogenous activation signals to MPM tumor cells in situ. The IL-4/IL-4 receptor axis is a potential therapeutic target in human MPM.
Easy Navigating Through the Forest of Survivorship Care
Authors: Hink Boer, Janine Nuver, Joop D. Lefrandt, Arjan W. Duijzer, Sophie Bunskoek, Annette J. Berendsen, Sabine Siesling, Jourik A. Gietema
Journal: Journal of Clinical Oncology (2013)

Radivoyevitch and Saunthararajah 1 propose that female sex is associated with better survival in myelodysplastic syndromes.They also point out that our randomized study of lower-dose decitabine 2 had an imbalance in sex distribution between both arms.It should be noted that this trial followed an adaptive design that resulted in early termination of the study and fewer patients in arm B (this was because of an early determination of increased response rate in arm A).Therefore, it is not unexpected that imbalances in clinical characteristics could result from such a design.Despite this and with longer follow-up (reported in the article), both arms were associated with similar outcomes, and it is therefore obvious that sex imbalance did not have an effect on the results and the conclusion of the article.The data discussed by Radivoyevitch and Saunthararajah are of interest, but at this point, circumstantial and not based on significant prospective analysis, and do not seem to be supported by our study.
Non-fatal horse related injuries treated in emergency departments in the United States, 2001–2003
Authors: K E Thomas, J L Annest, J Gilchrist, D M Bixby-Hammett
Journal: British Journal of Sports Medicine (2006)

To characterise and provide nationally representative estimates of persons with non-fatal horse related injuries treated in American emergency departments.The National Electronic Injury Surveillance System All Injury Program (NEISS-AIP) is a stratified probability sample comprising 66 hospitals. Data on injuries treated in these emergency departments are collected and reported. NEISS-AIP data on all types (horseback riding and otherwise) of non-fatal horse related injuries from 2001 to 2003 were analysed.An estimated 102,904 persons with non-fatal horse related injuries (35.7 per 100,000 population) were treated in American emergency departments each year from 2001 to 2003 inclusive. Non-fatal injury rates were higher for females (41.5 per 100,000) than for males (29.8 per 100,000). Most patients were injured while mounted on a horse (66.1%), commonly from falling or being thrown by the horse; while not mounted, injuries most often resulted from being kicked by the horse. The body parts most often injured were the head/neck region (23.2%), lower extremity (22.2%), and upper extremity (21.5%). The most common principal diagnoses were contusions/abrasions (31.4%) and fractures (25.2%). For each year that was studied, an estimated 11 502 people sustained traumatic brain injuries from horse related incidents. Overall, more than 11% of those injured were admitted to hospital.Horse related injuries are a public health concern not just for riders but for anyone in close contact with horses. Prevention programmes should target horseback riders and horse caregivers to promote helmet use and educate participants about horse behaviour, proper handling of horses, and safe riding practices.
Combined Total Genome Loss of Heterozygosity Scan of Breast Cancer Stroma and Epithelium Reveals Multiplicity of Stromal Targets
Authors: Koichi Fukino, Lei Shen, Satoshi Matsumoto, Carl D. Morrison, George L. Mutter, Charis Eng
Journal: Cancer Research (2004)

Abstract Recent breast cancer studies have highlighted the importance of interactions between cancer epithelium and tumor stroma. Recently, the focus of solid tumor investigations has shifted from mutations in carcinomatous epithelium to disturbances of tissue organization in cancer. The genetic basis of this microenvironment, however, remains to be clarified. To begin to resolve this problem, a total genome loss of heterozygosity (LOH) scan was done on epithelial and stromal DNA from 134 sporadic invasive breast carcinomas. In addition to detecting more frequent LOH at three loci in stroma than in epithelium, we found strong evidence that LOH frequencies were significantly elevated in specific regions of each chromosome. We detected 57 markers, which were preferentially lost either in stroma (n = 38) or epithelium (n = 19), relative to the background LOH frequencies on their respective chromosomes. This multiplicity of stromal cell LOH, and hence loss of genetic material, provides a possible mechanism for interpatient variation in host-stromal response to invading adenocarcinoma cells. This is consistent with a model in which initial, random LOH occurs equally among epithelium and stroma, but subsequent clonal selection is driven by factors, which appear to be distinctly different between malignant epithelial and surrounding stromal cells. Genetic alterations in stroma did not mimic those in epithelium, but they could play a different and parallel role in carcinogenesis and tumor progression, probably by modifying some features specific to breast cancer.