tbuckley/cabot-search huggingface dataset:
Effects of acidosis on force-sarcomere length and force-velocity relations of rat cardiac muscle
Authors: L. RICCIARDI, J. J J BUCX, H. E D J T. KEURS
Journal: Cardiovascular Research (1986)

The effect of hypercapnic acidosis was compared with that of lowering extracellular calcium concentration ([Ca++]o) in rat cardiac trabeculae. The relations between force and sarcomere length and between force and velocity were studied. Sarcomere length was measured by means of laser diffraction techniques and sarcomere shortening velocity by means of isovelocity releases. The curve representing the relation between force and sarcomere length shifted from convex towards the ordinate (pH 7.35) to convex towards the abscissa (pH 6.68) as after [Ca++]o had been reduced from 1.5 to 0.3 mmol X litre-1. Increasing [Ca++]o at low pH from 1.5 to 4.0 mmol X litre-1 allowed the shape of the relation to be restored, but force values failed to return to control values. The relation between force and pH over the range 6.22-7.94 was also tested. During steady low pH maximum unloaded sarcomere shortening velocity was not significantly different from control values whereas it was decreased at low [Ca++]o. Under both conditions maximum isometric tension (Po) was reduced. The results are consistent with the hypothesis that H+ ions cause a shift of the force-p Ca curve to the right at all sarcomere lengths, as a result of competition between Ca++ and H+ ions for binding to the myofilaments.
Monitoring Platelet GP IIb/IIIa Antagonist Therapy
Authors: Barry S. Coller
Journal: Circulation (1998)

2][3][4] A number of low-molecular-weight GP IIb/IIIa antagonists patterned on the arginine-glycine-aspartic acid (RGD) cell recognition sequence have also shown benefit in the prevention and treatment of ischemic thrombotic coronary artery disease and currently are in advanced stages of development and approval.
Aspirin to Prevent Cardiovascular Disease: The Association of Aspirin Dose and Clopidogrel With Thrombosis and Bleeding
Authors: Steven R. Steinhubl
Journal: Annals of Internal Medicine (2009)

Background: The optimal aspirin dose for the prevention of cardiovascular events remains controversial. Objective: To assess the incidence of and risk factors for adverse clinical outcomes by investigator-determined aspirin dose in a primary prevention trial. Design: Post hoc observational analyses of data from a double-blind, placebo-controlled, randomized trial. Setting: Outpatient. Patients: 15 595 patients with cardiovascular disease or multiple risk factors. Intervention: Clopidogrel, 75 mg/d, or placebo, with aspirin, 75 to 162 mg/d, as selected by the investigators. Measurements: Incidence of the composite outcome of myocardial infarction, stroke, or cardiovascular death (efficacy end point), and incidence of severe or life-threatening bleeding (safety end point), at a median of 28 months (interquartile range, 23 to 31 months) of follow-up. Results: Daily aspirin doses were categorized as less than 100 mg (75 or 81 mg) (n = 7180), 100 mg (n = 4961), and greater than 100 mg (150 or 162 mg) (n = 3454). The hazard of the primary efficacy end point was the same regardless of dose (adjusted hazard ratio, 0.95 [95% CI, 0.80 to 1.13] for 100 mg vs. less than 100 mg, and 1.0 [CI, 0.85 to 1.18] for greater than 100 mg vs. less than 100 mg). The hazard of the primary safety end point also did not depend on dose (adjusted hazard ratio, 0.85 [CI, 0.57 to 1.26] for 100 mg vs. less than 100 mg and 1.05 [CI, 0.74 to 1.48] for greater than 100 mg vs. less than 100 mg). In patients also receiving clopidogrel, daily aspirin doses greater than 100 mg seemed to be non–statistically significantly associated with reduced efficacy (adjusted hazard ratio, 1.16 [CI, 0.93 to 1.44]) and increased harm (adjusted hazard ratio, 1.30 [CI, 0.83 to 2.04]). Limitation: The analysis was post hoc, and aspirin use was not randomized or blinded. Conclusion: Daily aspirin doses of 100 mg or greater were associated with no clear benefit in patients taking aspirin only and possibly with harm in patients taking clopidogrel. Daily doses of 75 to 81 mg may optimize efficacy and safety for patients requiring aspirin for long-term prevention, especially for those receiving dual antiplatelet therapy. Primary Funding Source: None.
Abdominal distention in a 36-year-old with a gastric ulcer
Authors: K. Singh Sodhi, A. Kumar R, B D Radotra, L Kaman, N Khandelwal
Journal: Gut (2007)

A 36 year old man presented with 3 month history of pain in the abdomen and abdominal distension. He had no previous history of surgery, abdominal trauma or tuberculosis. On physical examination, the abdomen was distended and non-tender. On palpation, a firm to …
Peer Support in Health Care and Prevention: Cultural, Organizational, and Dissemination Issues
Authors: Edwin B. Fisher, Muchieh Maggy Coufal, Humberto Parada, Jennifer B. Robinette, Patrick Y. Tang, Diana M. Urlaub, Claudia Castillo, Laura M. Guzman-Corrales, Sayaka Hino, Jaimie Hunter, Ariana W. Katz, Yael R. Symes, Heidi P. Worley, Cuirong Xu
Journal: Annual Review of Public Health (2014)

As reviewed in the article by Perry and colleagues (2014) in this volume, ample evidence has documented the contributions of peer support (PS) to health, health care, and prevention. Building on that foundation, this article discusses characteristics, contexts, and dissemination of PS, including (a) fundamental aspects of the social support that is often central to it; (b) cultural influences and ways PS can be tailored to specific groups; (c) key features of PS and the importance of ongoing support and backup of peer supporters and other factors related to its success; (d) directions in which PS can be expanded beyond prevention and chronic disease management, such as in mental health or interventions to prevent rehospitalization; (e) other opportunities through the US Affordable Care Act, such as through patient-centered medical homes and chronic health homes; and (f) organizational and policy issues that will govern its dissemination. All these demonstrate the extent to which PS needs to reflect its contexts--intended audience, health problems, organizational and cultural settings--and, thus, the importance of dissemination policies that lead to flexible response to contexts rather than constraint by overly prescriptive guidelines.
Research ethics policies and practices in health research institutions in sub-Saharan African countries: results of a questionnaire-based survey
Authors: Chris Zielinski, Derege Kebede, Peter Ebongue Mbondji, Issa Sanou, Wenceslas Kouvividila, Paul-Samson Lusamba-Dikassa
Journal: Journal of the Royal Society of Medicine (2014)

Objective To describe the state of research ethics policies and practices in health research institutions in sub-Saharan African countries. Design A structured questionnaire was used to solicit information on research ethics from health research institutions. Setting Forty-two sub-Saharan African countries. Participants Key informants from the health research institutions. Main outcome measures Existence of institutional ethics review policies and mechanisms. Results About half (51%) of respondent institutions reported having policies on research ethics and 58% had written policies requiring that researchers obtain informed consent of research participants. About one-third of respondent institutions (34%) had established ethics review committees, 42% required that studies went through ethics review committees and 46% had linkages with national or regional ethics organisations. Regarding operating procedures for ethics review committees, 53% had adopted standard operating procedures. Less than one-quarter of respondent institutions reported having policies in place to monitor ongoing research. Of the institutions that monitored ongoing research, 34% did an annual ethical review and 74% required a periodic written report. Only 36% provided any type of ethics training for staff, including those conducting health research and those who were not members of the ethics review committee. Conclusions There are substantial gaps in the capacity of health research institutions in the WHO African Region to undertake ethical review of studies before, during and after studies conducted. There is a need to strengthen such capacity in order to ensure the wellbeing of individuals enrolled in studies and that of communities that host these studies.
Skin tumours in the West of Scotland renal transplant population
Authors: L.J. Mackintosh, C.C. Geddes, R.M. Herd
Journal: British Journal of Dermatology (2012)

Organ transplant recipients have an increased risk of skin cancers. A specialist dermatology clinic for renal transplant recipients (RTRs) was established in 2005.To analyse the type and incidence of skin cancers in prevalent patients in the West of Scotland after renal transplant, and to analyse the impact of the time since transplant and the immunosuppression regimen.Skin cancer data for RTRs attending the transplant dermatology clinic over a 38-month period were collected and recorded in the West of Scotland electronic renal patient record. Skin cancer data were intrinsically linked to each individual's transplant and immunosuppression data.Overall, 610 patients attended. The median follow-up time from the date of first transplant was 10 years. Ninety-three patients (15.2%) had experienced a total of 368 skin cancers since transplant, and the prevalence increased with time since transplant. Basal cell carcinomas (BCCs) occurred in 74 patients (12.1%) and squamous cell carcinomas (SCCs) in 42 patients (6.9%). Three patients (0.5%) had experienced a melanoma. The SCC:BCC ratio was 0.7. Survival analysis showed significant reduction in the time to develop skin cancer in patients transplanted from 1995 onwards (P < 0.0001) and in patients who had been on triple immunosuppressant therapy at 1 year after transplant, compared with dual therapy (P < 0.0001).This is the first study of skin cancer in prevalent Scottish RTRs. The incidence of skin cancer is high and appears to have a direct relationship to the overall burden of immunosuppression. The SCC:BCC ratio, which is lower than reports from other centres, deserves further scrutiny.
The Vulnerability of the Heart As a Pluricellular Paracrine Organ
Authors: Gilles W. De Keulenaer, Kris Doggen, Katrien Lemmens
Journal: Circulation Research (2010)

Abstract : In this review, we address clinical aspects and mechanisms of ventricular dysfunction induced by anticancer drugs targeted to the ErbB2 receptor. ErbB2 antagonists prolong survival in cancer, but also interfere with homeostatic processes in the heart. ErbB2 is a coreceptor for ErbB4, which is activated by neuregulin-1. This epidermal growth factor–like growth factor is released from endothelial cells in the endocardium and in the myocardial microcirculation, hence contributing to intercellular crosstalk in the ventricle. We look at the physiological aspects of neuregulin-1/ErbB signaling in the ventricle, and review its (mal)adaptive responses in chronic heart failure. We also compare structural aspects of ErbB receptor activation in cancer and cardiac cells, and analyze the mode of action of current ErbB2 antagonists. This allows us to predict how these drugs interfere with paracrine processes in the ventricle. Differences in the mode of action of individual ErbB2 antagonists affect their impact on the function of the ventricle, considered to be “on-target” or “off-target.” Establishing the relation between the cardiac side effects of ErbB2 antagonists and their impact on paracrine ventricular control mechanisms may direct the design of a next generation of ErbB2 inhibitors. For cardiologists, there are lessons to be learned from the unexpected side effects of ErbB2-targeted cancer therapy. The vulnerability of the heart as a pluricellular paracrine system appears greater than anticipated and intercellular crosstalk an essential component of its functional and structural integrity.
Systematic Review: Blood Pressure Target in Chronic Kidney Disease and Proteinuria as an Effect Modifier
Authors: Ashish Upadhyay, Amy Earley, Shana M. Haynes, Katrin Uhlig
Journal: Annals of Internal Medicine (2011)

Background: The optimal blood pressure target in patients with chronic kidney disease (CKD) is unclear. Purpose: To summarize trials comparing lower versus higher blood pressure targets in adult patients with CKD and focus on proteinuria as an effect modifier. Data Sources: MEDLINE and the Cochrane Central Register of Controlled Trials (July 2001 through January 2011) were searched for reports from randomized, controlled trials with no language restriction. Study Selection: Authors screened abstracts to identify reports from trials comparing blood pressure targets in adults with CKD that had more than 50 participants per group; at least 1-year follow-up; and outcomes of death, kidney failure, cardiovascular events, change in kidney function, number of antihypertensive agents, and adverse events. Data Extraction: Reviewers extracted data on study design, methods, sample characteristics, interventions, comparators, outcomes, number of medications, and adverse events and rated study quality and quality of analyses for proteinuria subgroups. Data Synthesis: Three trials with a total of 2272 participants were included. Overall, trials did not show that a blood pressure target of less than 125/75 to 130/80 mm Hg is more beneficial than a target of less than 140/90 mm Hg. Lower-quality evidence suggests that a low target may be beneficial in subgroups with proteinuria greater than 300 to 1000 mg/d. Participants in the low target groups needed more antihypertensive medications and had a slightly higher rate of adverse events. Limitations: No study included patients with diabetes. Trial duration may have been too short to detect differences in clinically important outcomes, such as death and kidney failure. Ascertainment and reporting of adverse events was not uniform. Conclusion: Available evidence is inconclusive but does not prove that a blood pressure target of less than 130/80 mm Hg improves clinical outcomes more than a target of less than 140/90 mm Hg in adults with CKD. Whether a lower target benefits patients with proteinuria greater than 300 to 1000 mg/d requires further study. Primary Funding Source: Kidney Disease: Improving Global Outcomes (KDIGO).
Gut microbiota composition and development of atopic manifestations in infancy: the KOALA Birth Cohort Study
Authors: J. Penders, C. Thijs, P. A van den Brandt, I. Kummeling, B. Snijders, F. Stelma, H. Adams, R. van Ree, E. E Stobberingh
Journal: Gut (2006)

<b>Background and aims:</b> Perturbations in intestinal microbiota composition due to lifestyle changes may be involved in the development of atopic diseases. We examined gut microbiota composition in early infancy and the subsequent development of atopic manifestations and sensitisation. <b>Methods:</b> The faeces of 957 infants aged 1 month and participating in the KOALA Birth Cohort Study were analysed using quantitative real-time PCR. Information on atopic symptoms (eczema, wheeze) and potential confounders was acquired through repeated questionnaires. Total and specific IgE were measured in venous blood samples collected during home visits when the infant was 2 years old. During these home visits a clinical diagnosis of atopic dermatitis was made according to the UK-Working Party criteria. <b>Results:</b> The presence of <i>Escherichia coli</i> was associated with a higher risk of developing eczema (OR<sub>adj</sub> = 1.87; 95% CI 1.15 to 3.04), this risk being increased with increasing numbers of <i>E coli</i> (p<sub>for trend</sub> = 0.016). Infants colonised with <i>Clostridium difficile</i> were at higher risk of developing eczema (OR<sub>adj</sub> = 1.40; 95% CI 1.02 to 1.91), recurrent wheeze (OR<sub>adj</sub> = 1.75; 95% CI 1.09 to 2.80) and allergic sensitisation (OR<sub>adj</sub> = 1.54; 95% CI 1.02 to 2.31). Furthermore, the presence of <i>C difficile</i> was also associated with a higher risk of a diagnosis of atopic dermatitis during the home visit (OR<sub>adj</sub> = 1.73; 95% CI 1.08 to 2.78). <b>Conclusion:</b> This study demonstrates that differences in gut microbiota composition precede the development of atopy. Since <i>E coli</i> was only associated with eczema and <i>C difficile</i> was associated with all atopic outcomes, the underlying mechanisms explaining these association may be different.
Tumor-Specific Urinary Matrix Metalloproteinase Fingerprinting: Identification of High Molecular Weight Urinary Matrix Metalloproteinase Species
Authors: Roopali Roy, Gwendolyn Louis, Kevin R. Loughlin, Dmitri Wiederschain, Susan M. Kilroy, Carolyn C. Lamb, David Zurakowski, Marsha A. Moses
Journal: Clinical Cancer Research (2008)

Abstract Purpose: We have previously reported that matrix metalloproteinases MMP-2, MMP-9, and the complex MMP-9/NGAL can be detected in urine of patients with a variety of cancers including prostate and bladder carcinoma. In addition, we also detected several unidentified urinary gelatinase activities with molecular weights &amp;gt;125 kDa. The objective of the current study was to identify these high molecular weight (HMW) species, determine their potential as predictors of disease status, and ask whether a tumor-specific pattern existed based on urinary MMP analysis. Experimental Design: Chromatography, zymography, and mass spectrometry was used to identify HMW gelatinase species of ∼140, 190, and &amp;gt;220 kDa in urine of cancer patients. To determine whether a tumor-specific pattern of appearance existed among the MMPs detected, we analyzed the urine of 189 patients with prostate or bladder cancer and controls. Results: The ∼140, &amp;gt;220 kDa, and ∼190 HMW gelatinase species were identified as MMP-9/tissue inhibitor of metalloproteinase 1 complex, MMP-9 dimer, and ADAMTS-7, respectively. The frequency of detection of any MMP species was significantly higher in urine from prostate and bladder cancer groups than controls. MMP-9 dimer and MMP-9 were independent predictors for distinguishing between patients with prostate and bladder cancer (P &amp;lt; 0.001 for each) by multivariable analysis. Conclusions: This study is the first to identify a tumor-specific urinary MMP fingerprint that may noninvasively facilitate identification of cancer presence and type. This information may be of diagnostic and prognostic value in the detection and/or clinical monitoring of disease progression and therapeutic efficacy in patients with bladder or prostate cancer.
Myocardial Relaxation, Restoring Forces, and Early-Diastolic Load Are Independent Determinants of Left Ventricular Untwisting Rate
Authors: Anders Opdahl, Espen W. Remme, Thomas Helle-Valle, Thor Edvardsen, Otto A. Smiseth
Journal: Circulation (2012)

Peak left ventricular (LV) untwisting rate (UTR) has been introduced as a clinical marker of diastolic function. This study investigates if early-diastolic load and restoring forces are determinants of UTR in addition to the rate of LV relaxation.In 10 anesthetized dogs we measured UTR by sonomicrometry and speckle tracking echocardiography at varying LV preloads, increased contractility, and myocardial ischemia. UTR was calculated as the time derivative of LV twist. Because preload modified end-diastolic twist, LV systolic twist was calculated in absolute terms with reference to the end-diastolic twist configuration at baseline. Relaxation rate was measured as the time constant (τ) of LV isovolumic pressure decay. Early-diastolic load was measured as LV pressure at the time of mitral valve opening. Circumferential-longitudinal shear strain was used as an index of restoring forces. In a multivariable mixed model analysis a strong association was observed between UTR and LV pressure at the time of mitral valve opening (parameter estimate [β]=6.9; P<0.0001), indicating an independent effect of early-diastolic load. Furthermore, the associations between UTR and circumferential-longitudinal shear strain (β=-11.3; P<0.0001) and τ (β=-1.6, P<0.003) were consistent with independent contributions from restoring forces and rate of relaxation. Maximal UTR before mitral valve opening, however, was determined only by relaxation rate and restoring forces.The present study indicates that early-diastolic load, restoring forces, and relaxation rate are independent determinants of peak UTR. However, only relaxation rate and restoring forces contributed to UTR during isovolumic relaxation.
Increasing Body Fat Mass in the First Year of Hemodialysis
Authors: EIJI ISHIMURA, SENJI OKUNO, MASAO KIM, TADASHI YAMAMOTO, TSUYOSHI IZUMOTANI, TATSUYUKI OTOSHI, TETSUO SHOJI, MASAAKI INABA, YOSHIKI NISHIZAWA
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Nutritional status affects well-being and survival in patients who are undergoing hemodialysis. It was examined how maintenance hemodialysis altered body fat mass. In 72 patients with chronic renal failure (age, 62 ± 12 yr; 42 men, 30 women), body fat was measured by dual x-ray absorptiometry 1 mo after initiation of maintenance hemodialysis and approximately 1 yr later (mean ± SD, 11 ± 2 mo). The second measurement showed significantly greater body fat mass than the first (11.38 ± 3.84 versus 10.09 ± 4.12 kg; P < 0.0001). After calculation of the change in body fat mass per month, no significant differences were evident in relation to gender or to presence of diabetes. Changes in body fat mass per month correlated negatively with baseline serum albumin concentration (r = -0.449, P < 0.0001) and baseline body fat mass (r = -0.423, P < 0.001). These factors independently influenced the change according to multiple regression analysis (R2 = 0.323, P < 0.0001). In conclusion, body fat mass increases significantly in the first year of maintenance hemodialysis, especially in patients with poor nutritional status. More general, dual x-ray absorptiometry assessment of body fat mass was found to be useful for evaluating the nutritional status of hemodialysis patients.
Medical Education and American Students at Guadalajara and Bologna
Authors: G. Halsey Hunt
Journal: JAMA (1971)

Before I discuss the American students at Guadalajara and Bologna, it may be well to present some background information, so that the question may be seen in perspective. First, as to numbers, according to a recent estimate,<sup>1</sup>the total number of American citizens studying medicine abroad is probably in the range of 3,500 to 4,000. The number of students finishing the medical course abroad and taking the Educational Council for Foreign Medical Graduates examination, however, is smaller than these figures would suggest. During the three calendar years 1968 through 1970, in six ECFMG examinations, a total of 2,103 examinations were administered to US citizens, an average of about 350 in each examination are repeaters. Of this whole group, a total of 737 American citizens passed the examination, an average of 123 for each examination, or 246 each year. During these three years a total of 72,096 examinations were administered
Cost-Effectiveness of Self-Monitoring of Blood Glucose in Type 2 Diabetic Patients Not Receiving Insulin
Authors: Mayer B. Davidson
Journal: Diabetes Care (2006)

Neeser et al. (1) challenge my argument that self-monitoring of blood glucose (SMBG) in type 2 diabetic patients not taking insulin is not beneficial for lowering glycemia and therefore is a waste of (a lot of) money (2).

In a meta-analysis of six randomized controlled trials, Welschen et al. (3) found a significant reduction of 0.39% in HbA1c (A1C) levels in type 2 diabetic patients not taking insulin who performed SMBG. Welschen et al. did point out that the reduction was only significant in two of the trials and that the conclusion that SMBG was …