tbuckley/cabot-search huggingface dataset:
Compliance with pulmonary medication in general practice
Authors: FW Dekker, FE Dieleman, AA Kaptein, JD Mulder
Journal: European Respiratory Journal (1993)

We wanted to assess compliance with regular pulmonary medication, in 156 patients in a general practice setting. Patients completed a questionnaire on their reported daily intake, the perceived prescription, and their self-assessed perceived compliance with pulmonary medication. Compliance was defined as a reported daily intake > or = 50% of the prescribed amount. Using this definition, 30% of patients were considered to be compliant. Compliant patients had daily symptoms more often, were more often prescribed two or more different medications, and a greater proportion of them had at some time consulted a chest physician. When patients correctly perceived the prescription to refer to medication which had to be taken on a regular basis, they were more likely to be compliant. We conclude that, since less than one third of patients was compliant with medication, more efforts are needed to improve compliance in general practice. Non-compliance with medication may well provide an alternative explanation for the discrepancy between prescribed medication and medical outcome, which has been labelled in the literature as "undertreatment".
Vascular endothelial ageing, heartbeat after heartbeat
Authors: E. Thorin, N. Thorin-Trescases
Journal: Cardiovascular Research (2009)

The vascular endothelium starts to age at the first heartbeat. There is no longer a need to demonstrate that an increased resting heart rate--above 70 b.p.m.--is associated with the onset of cardiovascular events and reduces lifespan in humans. Each cardiac cycle imposes a mechanical constraint on the arteries, and we would like to propose that this mechanical stress damages the vascular endothelium, its dysfunction being the prerequisite for atherogenesis. Consequently, reducing heart rate could protect the endothelium and slow the onset of atherosclerosis. The potential mechanisms by which reducing heart rate could be beneficial to the endothelium are likely a combination of a reduction in mechanical stress and tissue fatigue and a prolongation of the period of steady laminar flow, and thus sustained shear stress, between each systole. With age, irreparable damage accumulates in endothelial cells and leads to senescence, which is characterized by a pro-atherogenic phenotype. In the body, the highest mechanical stress occurs in the coronary vessels, where blood only flows during diastole and even reverses during systole; thus, coronary arteries are the prime site of atherosclerosis. All classical risk factors for cardiovascular diseases add up, to accelerate atherogenesis, but hypertension, which further raises mechanical stress, is likely the most damaging. By inducing flow through the arteries, the heart rate determines shear stress and its stability: mechanical stress and the associated damage induced by each systole are efficiently counteracted by the repair capacities of a healthy endothelium. The maintenance of a physiological, low heart rate may be key to prolonging the endothelial healthy lifespan and thus, vascular health.
NERVE FIBRILS IN THE SINO-AURICULAR NODE
Authors: B. S. Oppenheimer, Adele Oppenheimer
Journal: The Journal of Experimental Medicine (1912)

Aside from the nerve fibers which enter the pace-making node from the subepicardium, there were observed within the limits of the node a few ganglionic cells and a plexus of moniliform nerve fibrils in very close relation to its muscle fibers, hence the sino-auricular node, like the auriculo-ventricular, may be considered from a histological standpoint a neuromuscular organ.
HETEROGENEITY IN RIGHT VENTRICULAR REGIONAL MECHANICS IN PATIENTS WITH PULMONARY HYPERTENSION BY THREE-DIMENSIONAL ECHOCARDIOGRAPHIC SPECKLE TRACKING STRAIN
Authors: Keiko Ryo, Tetsuari Onishi, Josef Marek, Mohamed Ahmed, Kristina Haugaa, Hunter Champion, John Gorcsan
Journal: Journal of the American College of Cardiology (2013)
Host genotype-specific therapies for tuberculosis
Authors: Joanna Devlin
Journal: Thorax (2012)

Journal clubHost genotype-specific therapies for tuberculosis This paper suggests that therapies for tuberculosis (TB) will, in the future, be tuned specifically to the patient's genotype.Using zebra fish and human models, Tobin et al demonstrated that susceptibility to TB can be caused by both reduced and increased inflammatory activity, which in turn is governed by the patient's genotype.The increased inflammatory pathway begins with increased leukotriene A4 hydrolase (LTA4H) activity, which leads to increased production of a proinflammatory eicosanoid (LBT4) and tumour necrosis factor.The decreased inflammatory pathway begins with reduced LTA4H activity resulting in increased anti-inflammatory activity and increased production of lipoxins.Both mechanisms cause lysis of macrophages.These findings suggests that by identifying whether a patient infected with TB is in a high or reduced inflammatory state, as dictated by their LTA4H genotype and the detrimental effects of each extreme countered, patient morbidity and mortality would be improved.Blindly used 'scatter-gun' therapies may be either beneficial or detrimental, depending on the inflammatory state of the patient.In the increased inflammatory state produced by increased LTA4H activity, targeted therapies, such as aspirin, may be useful as this inexpensive drug inhibits tumour necrosis factor activity.Similarly, in those with a reduced inflammatory state (the low-activity LTA4H genotype) limiting the increased anti-inflammatory activity may be beneficial.The development of genotype-directed treatment strategies for TB and other serious infections will be an interesting area of future research.
Nutrient regulation of human intestinal sugar transporter (SGLT1) expression.
Authors: J Dyer, K B Hosie, S P Shirazi-Beechey
Journal: Gut (1997)

BACKGROUND: The activity of most intestinal nutrient transporters is adaptively regulated by the type and amounts of nutrients entering the intestinal lumen. The concentration and activity of the intestinal Na+/glucose cotransporter (SGLT1) are regulated by dietary sugars in most animal species. The activity and abundance of SGLT1 in biopsy specimens removed from human jejunal regions exposed to, and having limited access to, luminal nutrients have been measured and compared. AIMS: To study the effects of luminal nutrients on the expression of SGLT1 in the human intestine. PATIENT AND METHODS: Brush border membrane vesicles (BBMV) were prepared from biopsy specimens removed from the intestine of a 50 year old man who had developed a high output jejunal fistula, and adjacent mucosal fistula, a condition present for 12 months after surgery for a strangulated hernia. BBMV prepared from intestine exposed to luminal nutrients, and from dysfunctional intestine with a limited exposure to nutrients, were used to measure Na+ dependent glucose transport and abundance of SGLT1 protein. RESULTS: The levels of SGLT1 activity and abundance in the BBMV prepared from control biopsy specimens were similar to those found in BBMV prepared from the intestine of healthy individuals. BBMV from the dysfunctional intestine, exposed to limited levels of luminal nutrients, had reduced levels of SGLT1 activity. This reduction in SGLT1 activity and abundance was above that associated with any villus atrophy, as assessed by the abundance/activity of lactase and villin concentrations. CONCLUSIONS: These data indicate that the activity and expression of SGLT1 in human intestine is maintained by the presence of luminal nutrients.
Improved Outcomes From Adding Sequential Paclitaxel but Not From Escalating Doxorubicin Dose in an Adjuvant Chemotherapy Regimen for Patients With Node-Positive Primary Breast Cancer
Authors: I. Craig Henderson, Donald A. Berry, George D. Demetri, Constance T. Cirrincione, Lori J. Goldstein, Silvana Martino, James N. Ingle, M. Robert Cooper, Daniel F. Hayes, Katherine H. Tkaczuk, Gini Fleming, James F. Holland, David B. Duggan, John T. Carpenter, Emil Frei, Richard L. Schilsky, William C. Wood, Hyman B. Muss, Larry Norton
Journal: Journal of Clinical Oncology (2003)

This study was designed to determine whether increasing the dose of doxorubicin in or adding paclitaxel to a standard adjuvant chemotherapy regimen for breast cancer patients would prolong time to recurrence and survival.After surgical treatment, 3,121 women with operable breast cancer and involved lymph nodes were randomly assigned to receive a combination of cyclophosphamide (C), 600 mg/m(2), with one of three doses of doxorubicin (A), 60, 75, or 90 mg/m(2), for four cycles followed by either no further therapy or four cycles of paclitaxel at 175 mg/m(2). Tamoxifen was given to 94% of patients with hormone receptor-positive tumors.There was no evidence of a doxorubicin dose effect. At 5 years, disease-free survival was 69%, 66%, and 67% for patients randomly assigned to 60, 75, and 90 mg/m(2), respectively. The hazard reductions from adding paclitaxel to CA were 17% for recurrence (adjusted Wald chi(2) P =.0023; unadjusted Wilcoxon P =.0011) and 18% for death (adjusted P =.0064; unadjusted P =.0098). At 5 years, the disease-free survival (+/- SE) was 65% (+/- 1) and 70% (+/- 1), and overall survival was 77% (+/- 1) and 80% (+/- 1) after CA alone or CA plus paclitaxel, respectively. The effects of adding paclitaxel were not significantly different in subsets defined by the protocol, but in an unplanned subset analysis, the hazard ratio of CA plus paclitaxel versus CA alone was 0.72 (95% confidence interval, 0.59 to 0.86) for those with estrogen receptor-negative tumors and only 0.91 (95% confidence interval, 0.78 to 1.07) for patients with estrogen receptor-positive tumors, almost all of whom received adjuvant tamoxifen. The additional toxicity from adding four cycles of paclitaxel was generally modest.The addition of four cycles of paclitaxel after the completion of a standard course of CA improves the disease-free and overall survival of patients with early breast cancer.
<i>KRAS</i> and <i>BRAF</i> Mutations in Advanced Colorectal Cancer Are Associated With Poor Prognosis but Do Not Preclude Benefit From Oxaliplatin or Irinotecan: Results From the MRC FOCUS Trial
Authors: Susan D. Richman, Matthew T. Seymour, Philip Chambers, Faye Elliott, Catherine L. Daly, Angela M. Meade, Graham Taylor, Jennifer H. Barrett, Philip Quirke
Journal: Journal of Clinical Oncology (2009)

Activating mutation of the KRAS oncogene is an established predictive biomarker for resistance to anti-epidermal growth factor receptor (anti-EGFR) therapies in advanced colorectal cancer (aCRC). We wanted to determine whether KRAS and/or BRAF mutation is also a predictive biomarker for other aCRC therapies.The Medical Research Council Fluorouracil, Oxaliplatin and Irinotecan: Use and Sequencing (MRC FOCUS) trial compared treatment sequences including first-line fluorouracil (FU), FU/irinotecan or FU/oxaliplatin in aCRC. Tumor blocks were obtained from 711 consenting patients. DNA was extracted and KRAS codons 12, 13, and 61 and BRAF codon 600 were assessed by pyrosequencing. Mutation (mut) status was assessed first as a prognostic factor and then as a predictive biomarker for the benefit of adding irinotecan or oxaliplatin to FU. The association of BRAF-mut with loss of MLH1 was assessed by immunohistochemistry.Three hundred eight (43.3%) of 711 patients had KRAS-mut and 56 (7.9%) of 711 had BRAF-mut. Mutation of KRAS, BRAF, or both was present in 360 (50.6%) of 711 patients. Mutation in either KRAS or BRAF was a poor prognostic factor for overall survival (OS; hazard ratio [HR], 1.40; 95% CI, 1.20 to 1.65; P < .0001) but had minimal impact on progression-free survival (PFS; HR, 1.16; 95% CI, 1.00 to 1.36; P = .05). Mutation status did not affect the impact of irinotecan or oxaliplatin on PFS or OS. BRAF-mut was weakly associated with loss of MLH1 staining (P = .012).KRAS/BRAF mutation is associated with poor prognosis but is not a predictive biomarker for irinotecan or oxaliplatin. There is no evidence that patients with KRAS/BRAF mutated tumors are less likely to benefit from these standard chemotherapy agents.
Eating Disorders in White and Black Women
Authors: Ruth H. Striegel-Moore, Faith A. Dohm, Helena C. Kraemer, C. Barr Taylor, Stephen Daniels, Patricia B. Crawford, George B. Schreiber
Journal: American Journal of Psychiatry (2003)

Epidemiological studies of eating disorders in the United States have focused on white women and girls, and the prevalence of eating disorders in ethnic minority groups is unknown. This study examined the prevalence of anorexia nervosa, bulimia nervosa, and binge eating disorder in a geographically and economically diverse community sample of young white and black women who previously participated in the 10-year National Heart, Lung, and Blood Institute (NHLBI) Growth and Health Study.All NHLBI Growth and Health Study participants were recruited for this study. A two-stage case finding method was used, consisting of a telephone screening (sensitivity=0.90, specificity=0.98) and an in-person confirmatory diagnostic interview.A total of 86.0% of the original NHLBI Growth and Health Study cohort participated, including 985 white women (mean age=21.3) and 1,061 black women (mean age=21.5). Fifteen white (1.5%) and no black women met lifetime criteria for anorexia nervosa; more white women (N=23, 2.3%) than black women (N=4, 0.4%) met criteria for bulimia nervosa; binge eating disorder also was more common among white women (N=27, 2.7%) than black women (N=15, 1.4%). Few women (white: N=16, 28.1%; black: N=1, 5.3%) ever had received treatment for an eating disorder.Results suggest that eating disorders, especially anorexia nervosa and bulimia nervosa, are more common among white women than among black women. The low treatment rates in both groups suggest that health professionals need to be more alert to the possibility of eating disorders in women.
Risk Adjustment in Health Insurance Exchanges for Individuals With Mental Illness
Authors: Colleen L. Barry, Jonathan P. Weiner, Klaus Lemke, Susan H. Busch
Journal: American Journal of Psychiatry (2012)

Mechanisms to compensate insurance plans covering disproportionate numbers of chronically mentally ill patients in the planned health insurance exchanges are generally adequate, according to an analysis of past claims data. After implementation of the Affordable Care Act (ACA) in 2014, financial solvency will be largely ensured through "risk adjustment" by a pool of contributions from all plans in the state. The ACA also designates two temporary measures: commercial reinsurance purchased by each plan for costs above a certain threshold and "risk corridors" of payments flowing from the federal government to plans with higher than expected costs, in conjunction with payments coming in from plans with lower costs.
Oral Clofarabine in the Treatment of Patients With Higher-Risk Myelodysplastic Syndrome
Authors: Stefan Faderl, Guillermo Garcia-Manero, Zeev Estrov, Farhad Ravandi, Gautam Borthakur, Jorge E. Cortes, Susan O'Brien, Varsha Gandhi, William Plunkett, Anna Byrd, Monica Kwari, Hagop M. Kantarjian
Journal: Journal of Clinical Oncology (2010)

Purpose Efficacy and toxicity profile of orally administered clofarabine were evaluated in patients with higher-risk myelodysplastic syndrome (MDS). Patients and Methods Thirty-two patients were treated, of whom 22 had intermediate-2 or high-risk disease (International Prognostic Scoring System). Median age was 70 years (range, 53 to 86), nine patients had secondary MDS, and 20 patients experienced prior therapy failure with hypomethylating agents. Three doses of clofarabine were evaluated: 40 mg/m 2 , 30 mg/m 2 , and 20 mg/m 2 daily for 5 days. Courses were repeated every 4 to 8 weeks. Results Eight patients (25%) achieved complete remission (CR), three had (9%) hematologic improvement (HI), and three had (9%) clinical benefit (CB; overall response rate, 43%). Responses in patients who experience treatment failure with hypomethylating agents included CR in two (10%), HI in two (10%), and CB in two patients (10%). No patients died within 6 weeks of induction. Renal failure occurred in four patients in the context of myelosuppresssion-associated infectious complications. Common adverse events were gastrointestinal and hepatic. Myelosuppression was common, but prolonged myelosuppression (&gt; 42 days) was rare. The toxicity profile was better with lower doses of clofarabine, whereas response rates did not differ significantly. Conclusion Oral clofarabine has achieved a response rate of 43% in patients with higher-risk MDS. The optimal dose and schedule and the appropriate patient population for such therapy remain to be further defined.
ATRIOVENTRICULAR CONDUCTION DELAY PREDICTS VENTRICULAR TACHYCARDIA IN LAMIN A/C MUTATION CARRIERS
Authors: Nina E. Hasselberg, Thor Edvardsen, Helle Petri, Knut Erik Berge, Trond Leren, Henning Bundgaard, Kristina H. Haugaa
Journal: Journal of the American College of Cardiology (2012)
Combined EST and Proteomic Analysis Identifies Rapidly Evolving Seminal Fluid Proteins in Heliconius Butterflies
Authors: J. R. Walters, R. G. Harrison
Journal: Molecular Biology and Evolution (2010)

Seminal fluid proteins (SFPs) directly influence a wide range of reproductive processes, including fertilization, sperm storage, egg production, and immune response. Like many other reproductive proteins, the molecular evolution of SFPs is generally characterized by rapid and frequently adaptive evolution. However, the evolutionary processes underlying this often-documented pattern have not yet been confidently determined. A robust understanding of the processes governing SFP evolution will ultimately require identifying SFPs and characterizing their evolution in many different taxa, often where only limited genomic resources are available. Here, we report the first comprehensive molecular genetic and evolutionary analysis of SFPs conducted in Lepidoptera (moths and butterflies). We have identified 51 novel SFPs from two species of Heliconius butterflies (Heliconius erato and Heliconius melpomene) by combining "indirect" bioinformatic and expression analyses of expressed sequence tags from male accessory gland and wing tissues with "direct" proteomic analyses of spermatophores. Proteomic analyses identified fewer SFPs than the indirect criteria but gave consistent results. Of 51 SFPs, 40 were identified in both species but fewer than half could be functionally annotated via similarity searches (Blast, IPRscan, etc.). The majority of annotated Heliconius SFPs were predicted to be chymotrypsins. Comparisons of Heliconius SFPs with those from fruit fly, mosquito, honeybee, and cricket suggest that gene turnover is high among these proteins and that SFPs are rarely conserved across insect orders. Pairwise estimates of evolutionary rates between SFPs and nonreproductive proteins show that, on average, Heliconius SFPs are evolving rapidly. At least one of these SFPs is evolving adaptively (dN/dS > 1), implicating a role for positive selection in this rapid evolution. This work establishes a strong precedent for future research on the causes and consequences of reproductive protein evolution in the Lepidoptera. Butterflies and moths have an extremely rich history of organismal research, which will provide an informative ecological context for further molecular evolutionary investigations.
Detection of Silent Myocardial Ischemia in Asymptomatic Diabetic Subjects
Authors: Narendra C. Bhalodkar, Steve Blum
Journal: Diabetes Care (2005)

We read the results of the DIAD study (1) with great interest and congratulate all of the investigators. However, the study leaves some questions unanswered and raises others.

1 ) Since there is no nondiabetic control group with similar baseline characteristics, we don’t know whether the reported prevalence of silent ischemia (22%) is higher than in nondiabetic patients. Such a comparison is necessary to determine how many scans are needed to diagnose one addional silent ischemia in asymptomatic diabetic patients. Therefore, the clinician is not assisted in determining whether performing …
Mechanical Stretch Enhances mRNA Expression and Proenzyme Release of Matrix Metalloproteinase-2 (MMP-2) via NAD(P)H Oxidase–Derived Reactive Oxygen Species
Authors: Karsten Grote, Inna Flach, Maren Luchtefeld, Elvan Akin, Steven M. Holland, Helmut Drexler, Bernhard Schieffer
Journal: Circulation Research (2003)

Mechanical stretch is a hallmark of arterial hypertension and leads to vessel wall remodeling, which involves matrix metalloproteinases (MMPs). Because mechanical stretch is further capable of inducing reactive oxygen species (ROS) formation via the NAD(P)H oxidase, we assessed whether mechanical stretch enhances MMP expression and activity in a NAD(P)H oxidase-dependent manner. Therefore, vascular smooth muscle cells (VSMCs) isolated from C57BL/6 mice were exposed to cyclic mechanical stretch. The impact of ROS was assessed using VSMCs isolated from p47phox-/- mice, deficient for a NAD(P)H oxidase subunit responsible for ROS formation. Transcript levels were investigated by cDNA array and confirmed by RT-PCR. ROS formation was determined by DCF fluoroscopy and MMP-2 activity by zymography. Mechanical stretch of wild-type VSMCs resulted in a rapid ROS formation and p47phox membrane translocation that is followed by an increase in Nox-1 transcripts. ROS formation was completely abrogated in p47phox-/- VSMCs. cDNA array further revealed an increase of MMP-2 mRNA in response to mechanical stretch, which was validated by RT-PCR. Using p47phox-/- VSMCs, this increase in MMP-2 mRNA was completely blunted. mRNA expression of tissue inhibitor of MMP-2 TIMP-1 and TIMP-2 and membrane-type 1 MMP was unaffected by mechanical stretch. Gelatinolytic activity of pro-MMP-2 has been increased rapidly in wild-type VSMCs and was completely abolished in p47phox-/- VSMCs. These results indicate that mechanical stretch induces ROS formation via the NAD(P)H oxidase and thereby enhances MMP-2 mRNA expression and pro-MMP-2 release. These results are consistent with the notion that in arterial hypertension, reactive oxygen species are involved in vascular remodeling via MMP activation. The full text of this article is available online at http://www.circresaha.org.
Cigarette smoking and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (Panc4)
Authors: C. Bosetti, E. Lucenteforte, D.T. Silverman, G. Petersen, P.M. Bracci, B.T. Ji, E. Negri, D. Li, H.A. Risch, S.H. Olson, S. Gallinger, A.B. Miller, H.B. Bueno-de-Mesquita, R. Talamini, J. Polesel, P. Ghadirian, P.A. Baghurst, W. Zatonski, E. Fontham, W.R. Bamlet, E.A. Holly, P. Bertuccio, Y.T. Gao, M. Hassan, H. Yu, R.C. Kurtz, M. Cotterchio, J. Su, P. Maisonneuve, E.J. Duell, P. Boffetta, C. La Vecchia
Journal: Annals of Oncology (2011)