tbuckley/cabot-search huggingface dataset:
Abstract 1266: Do Gender Differences Exist in the Relation of Physical Activity with Changes in Body Mass Index and Waist Circumference over 20 years: the CARDIA Study
Authors: Arlene L Hankinson, Martha L Daviglus, Cora E Lewis, Pamela J Schreiner, Stephen Sidney, Kaiser Permanente, Kiang Liu
Journal: Circulation (2008)

Public health guidelines recommend physical activity to minimize weight gain. Yet, the data are ambiguous; some studies show weaker associations between activity and adiposity/weight changes in women perhaps due to inability to control for gender differences in energy intake and fat distribution. We hypothesized that after accounting for energy intake and fat distribution, associations between high activity levels and changes in weight, body mass index (BMI) or waist circumference over 20 years would not differ by gender. Black and white adults ages 18 –30 from the CARDIA Study, an NHLBI sponsored multi-center longitudinal study, had anthropometric measures taken and activity habits assessed using an interviewer-based questionnaire at 7 exams over 20 years (n=3555). Generalized estimating equations were used to calculate average annual changes in weight (pounds), BMI (kg/m 2 ), and waist circumference (cm) by long-term activity level over 20 years, stratified by sex and baseline overweight status. High activity was associated with smaller gains in weight, BMI and waist circumference in men and women over 20 years (Table , weight data not shown). Formal interaction tests by sex and baseline overweight status were significant (p&lt;0.05). When comparing high versus low activity, women showed larger differences in weight change than men. Compared with low activity, normal weight women with high activity gained 16.8 fewer pounds over 20 years while normal weight men gained 5.6 fewer pounds. Consistently high activity during young adulthood is associated with smaller gains in weight, BMI and waist circumference. The difference in weight gain between high and low activity is greater in women and persists after adjustment for energy intake. These results suggest that weight gain in young adults, particularly women, may be slowed by incorporating high activity into daily life in a manner that can be maintained over many years. Table: Average annual changes in BMI and waist circumference by long-term activity categories, stratified by gender and baseline overweight status
Endomorphins: potential roles and therapeutic indications in the development of opioid peptide analgesic drugs
Authors: Wei X. Liu, Rui Wang
Journal: Medicinal Research Reviews (2011)

Abstract The application of endomorphins as clinical available analgesic drugs has been impeded by their relatively poor receptor selectivity compared with alkaloid analgesics, rapid degradation in vivo, inefficient to penetrate the blood–brain barrier (BBB), and undesirable or toxic effects, such as acute tolerance and physical dependence, respiratory depression, and inhibition of gastrointestinal motility. Extensive studies have been performed so far striving to conquer these problems. In this article we review and discuss conformational and topographical modifications of the peptide amide bond and amino acid side groups to attain the most appropriate receptor binding affinity and high receptor selectivity; diverse strategies such as insertion of unnatural amino acids, covalent or noncovalent constraints as well as cyclization of linear peptides to enhance the enzymatic stability; designing of peptidomimetic ligands, glycopeptides, and N ‐terminal amidinationed analogues (such as incorporating guanidine into endomorphins) to penetrate the BBB. Also, several pertinent examples of bivalent and/or multivalent (such as mixed µ‐agonist/δ‐antagonist profile) compounds are discussed based on the existing literature and current data intending to give an insight into the development of opioid peptides expressing low tendency to produce acute tolerance and physical dependence. © 2011 Wiley Periodicals, Inc. Med Res Rev, 32, No. 3, 536–580, 2012
Eligibility for Hematopoietic Stem-Cell Transplantation for Primary Systemic Amyloidosis Is a Favorable Prognostic Factor for Survival
Authors: Angela Dispenzieri, Martha Q. Lacy, Robert A. Kyle, Terry M. Therneau, Dirk R. Larson, S. Vincent Rajkumar, Rafael Fonseca, Philip R. Greipp, Thomas E. Witzig, John A. Lust, Morie A. Gertz
Journal: Journal of Clinical Oncology (2001)

PURPOSE: Based on the success of hematopoietic stem-cell transplantation (HSCT) for multiple myeloma, HSCT is being used to treat patients with primary systemic amyloidosis (AL). This article addresses the extent to which eligibility to undergo HSCT is a favorable prognostic feature and explores prognostic factors within the subset of eligible patients. PATIENTS AND METHODS: The Mayo Clinic amyloid database was queried for all patients with AL seen at the Mayo Clinic from 1983 through 1997 who would have been eligible for peripheral-blood stem-cell transplantation. Inclusion criteria included biopsy-proven amyloid, symptomatic disease, absence of a clinical diagnosis of multiple myeloma, age ≤ 70 years, cardiac interventricular septal thickness ≤ 15 mm, cardiac ejection fraction more than 55%, serum creatinine ≤ 2 mg/dL, and direct bilirubin ≤ 2.0 mg/dL. RESULTS: Median age was 56 years (range, 25 to 70) with 79 (34%) older than 60 years. One hundred patients had early cardiac involvement; 41, hepatic involvement; 167, renal involvement; and 39, nerve involvement. The 229 patients have had a median follow-up of 52 months, and 151 have died. The median survival was 42 months with 5- and 10-year survival rates of 36% and 15%, respectively. Important predictors of survival were size of M-component in 24-hour urine, number of involved organs, alkaline phosphatase, performance score, and weight loss. CONCLUSION: The same patients who are eligible for HSCT are a good-risk population who do relatively well with chemotherapy (median survival, 42 months), substantially better than the expected median survival of 18 months for all patients with AL. A randomized trial is needed to assess the true effect of HSCT.
Abstract 292: Surviving 60% Blood Loss Using 7.5% NaCl With Adenosine, Lidocaine and Magnesium (ALM) in the Rat Model of Battlefield Hemorrhagic Shock
Authors: Hayley L. Letson, Geoffrey P. Dobson
Journal: Circulation (2010)

Soldiers with catastrophic blood loss often die on the battlefield before they can be evacuated. In an effort to translate the protective effects of AdenocaineTM (adenosine, lidocaine and Mg2+) (ALM) from cardiac surgery to resuscitation science, we examined the early hypotensive resuscitative effects of 7.5% NaCl with ALM following near lethal blood loss of 60% in the rat model.  

Methods: Male Sprague-Dawley rats (250–350g, n=32) were anesthetized and randomly assigned to one of four groups: 1) Untreated, 2) 7.5% NaCl, 3) 7.5% NaCl/6% Dextran-70 (RescueFlow®), 4) 7.5% NaCl/ALM. Shock was induced by removing  60% blood (volume controlled) over 50 min and maintaining the MAP between 30 to 40 mmHg. Animals were left in shock at 34°C for an additional 30 min. Total shock time was  80 min. 0.3 ml bolus was injected into the femoral vein and hemodynamics monitored for 60 min (Phase 1). Shed blood was replaced and function monitored for another 60 min (Phase 2). Lead II ECG, arterial pressures, MAP, heart rate (HR) and rate-pressure product (RPP) were monitored.  

Results: Mortality (%) for Untreated, 7.5% NaCl, 7.5% NaCl/6% Dextran-70, and 7.5% NaCl ALM groups were 100%, 75%, 87.5% and 0% respectively. Times to death after bolus injection were 9±3, 19±4 and 45±12 min respectively. The MAP of survivors at the end of Phase 1 was 24±3 (n=2), 26±0.1 (n=3) and 40±2 mmHg (P<0.05) (n=8) respectively. After blood was returned, the MAP at 60 min for the three treatment groups was 67±5 (n=2), 47 (n=1) and 69±5 mmHg (n=8) respectively. All rats, except the 7.5% NaCl ALM group, were profoundly proarrhythmic; Dextran doubled the arrhythmias compared with 7.5% NaCl alone. No severe arrhythmias occurred in ALM group in Phase 1 or 2, and 60 min after return of shed blood HR, MAP and RPP were 96%, 75% and 83% of their pre-shock values.  

Conclusions: Ultra-small (<1 ml/kg) IV bolus of 7.5% NaCl with ALM led to 100% survival with no arrhythmias in Phase 1 following 60% blood loss. Compared to untreated animals, 7.5% NaCl and the Dextran group delayed time to death by a factor of 2 and 5 respectively. Only one rat receiving 7.5% NaCl/6% Dextran-70 survived and it was profoundly proarrhythmic. Further work is required to test if 7.5% NaCl ALM, with its low cube/high resuscitation capability, has field applications.
Reasons for referral for pulmonary function testing: An audit of four Australian adult lung function laboratories
Authors: Jeffrey Pretto, Paul Guy, Danny Brazzale, Jane Williams, Michael Hensley
Journal: European Respiratory Journal (2011)

Pulmonary function (PF) testing provides a cornerstone for diagnosis and management of most respiratory conditions and accurate interpretation of test results is an important component of the final report. As part of developing a structured approach to interpretation of PF results we wished to characterise primary reasons for referral for testing in a range of PF laboratories.   Methods:  Three public, university-affiliated PF labs and one private lab using similar PF databases participated. Reasons for performance of PF tests were extracted from the databases and collated for analysis. Over 5,000 consecutive tests were evaluated from each lab.   Results:  Identifiable reason for referral was found in 83% of 24,602 test results and categorised. The major categories were follow-up of known respiratory disease (53% of 20,308 tests), investigation of specific symptoms (18%), possible specific lung disease (13%), possible induced lung disease (5%), investigation of lung function in known other diseases (5%) and pre-operative evaluation (5%). Testing in known disease and/or assessing for PF change was the primary reason for testing in 60% of tests performed.   Discussion:  These data highlight the predominance of ongoing assessment of PF and the importance of access to previous test results to provide clinically useful test reports. They also emphasize the need for having valid criteria describing what constitutes a real change in the various PF parameters.   Conclusion:  Since the majority of PF tests are performed to follow disease progress or response to treatment, there is a great need for defining clinically important change in pulmonary function.
IgG4‐Related Disease: Clinical and Laboratory Features in One Hundred Twenty‐Five Patients
Authors: Zachary S. Wallace, Vikram Deshpande, Hamid Mattoo, Vinay S. Mahajan, Maria Kulikova, Shiv Pillai, John H. Stone
Journal: Arthritis & Rheumatology (2015)

IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition that can affect nearly any organ. Prior studies have focused on individual cases of IgG4-RD or small case series. This study was undertaken to report detailed clinical and laboratory findings in a larger group of patients with IgG4-RD whose diagnosis was established by strict clinicopathologic correlation.The baseline features of 125 patients with biopsy-proven IgG4-RD were reviewed. The diagnosis was confirmed by pathologists' review, based on consensus diagnostic criteria and correlation with clinicopathologic features. Disease activity and damage were assessed using the IgG4-RD Responder Index (RI). Flow cytometry was used to assess levels of circulating plasmablasts.Of the 125 patients, 107 had active disease and 86 were not receiving treatment for IgG4-RD. Only 51% of the patients with active disease had elevated serum IgG4 concentrations. However, patients with active disease and elevated serum IgG4 concentrations were older, had a higher IgG4-RD RI score, a greater number of organs involved, lower complement levels, higher absolute eosinophil counts, and higher IgE levels compared to those with active disease but normal serum IgG4 concentrations (P < 0.01 for all comparisons). The correlation between IgG4+ plasmablast levels and the IgG4-RD RI of disease activity (Spearman's ρ = 0.45, P = 0.003) was stronger than the correlation between total plasmablast levels and the IgG4-RD RI. Seventy-six (61%) of the patients were male, but no significant differences according to sex were observed with regard to disease severity, organ involvement, or serum IgG4 concentrations. Treatment with glucocorticoids failed to produce sustained remission in 77% of patients.Nearly 50% of this patient cohort with biopsy-proven, clinically active IgG4-RD had normal serum IgG4 concentrations. Elevations in the serum IgG4 concentration appeared to identify a subset of patients with a more severe disease phenotype. In addition, the levels of IgG4+ plasmablasts correlated well with the extent of disease activity.
Multicenter comparative evaluation of two rapid immunoassay methods for the detection of Chlamydia trachomatis antigen in endocervical specimens
Authors: Ólafur Steingrímsson, Catherine Pawlak, Barbara Van Der Pol, Buffy P. Turner, Jó Hjaltalín Ólafsson, Lauren Dolphin, James E. Williams, Cynthia E. Peyton, Robert E. Klepper, Robert B. Jones, Garland D. Anderson, Neda Rashti, Alice S. Weissfeld, Allan Pronovost
Journal: Clinical Microbiology and Infection (1997)
Review focus series: sarcomeric proteins as key elements in integrated control of cardiac function
Authors: R. J. Solaro, P. P. de Tombe
Journal: Cardiovascular Research (2007)

Review and original articles in this focused issue of the Journal highlight the increased understanding of the role of sarcomeric proteins in control of cardiac function downstream of Ca2+ signalling. Figure 1 provides a context for integrating these articles in a minimal model of sarcomeric function in long- and short-term responses of the heart to stressors. In the model, state changes in the form of a physiological extrinsic stress, such as exercise or a pathophysiological stress such as hypertension promote a stream of mechanical and chemical signals, indicated as cytoskeletal, neurohormonal, and redox strains. Cytoskeletal strain induced by sarcomere length changes engage the Frank–Starling mechanism and also induce neurohormonal strains, as do feedback mechanisms. Readout of these neurohormonal signals is altered protein phosphorylation of cellular proteins including membrane proteins, transcription factors, and the sarcomeric proteins. Altered redox environment also induces post-translational modifications in sarcomeric proteins likely to trigger altered function independently of Ca2+ fluxes. Responses that compensate for the extrinsic stress maintain efficient cardiac function. For example, in exercise with increased venous return, rate and force of contraction and rate of relaxation are enhanced to match the increased heart rate and to permit cardiac output to increase with minimal increases in end-diastolic volume. A failure in the ability of the signalling cascade to engage compensatory pathways to maintain efficient function in response to an extrinsic stressor leads to decompensation and a viscous cycle ensues, exacerbating the stress.



 Figure 1  
Scheme summarizing signalling mechanisms controlling cardiac function. See text for further description.



Emerging evidence has substantially altered the understanding of the relative significance of mechanisms at the level of cardiac sarcomeric proteins in the processes summarized in Figure 1 . Sarcomeres are …
Sleep-related oxygen desaturation and daytime pulmonary haemodynamics in COPD patients
Authors: P Levi-Valensi, E Weitzenblum, Z Rida, P Aubry, A Braghiroli, C Donner, M Aprill, J Zielinski, G Wurtemberger
Journal: European Respiratory Journal (1992)

It has been hypothesized that in chronic obstructive pulmonary disease (COPD), sleep-related hypoxaemia could lead to pulmonary hypertension (PH) and cor pulmonale, even in patients with only mild daytime hypoxaemia. We investigated the relationships between sleep variables and daytime pulmonary haemodynamics in 40 COPD patients with daytime arterial oxygen tension (PaO2) between 60-70 mmHg (8-9.3 kPa). Patients were considered as desaturators if they spent at least 30% of the sleep recording time with a transcutaneous O2 saturation (StcO2) less than 90%. Daytime arterial blood gases and pulmonary volumes could not discriminate desaturators "D" (n = 18) from non-desaturators "ND" (n = 22), but awake baseline StcO2, measured just prior to the onset of sleep, was lower in group D. Pulmonary artery mean pressure was significantly higher in group D (19.1 +/- 4.7 vs 16.8 +/- 1.9 mmHg, p less than 0.05) and all patients with PH (6 out of 40) belonged to group D. PH was observed in 6 of the 15 patients whose mean nocturnal StcO2 was less than 90% but in none of the 25 with a mean nocturnal StcO2 greater than 90%. The PH patients (n = 6), all desaturators, differed from the desaturators with no PH (n = 12), and from ND (n = 22) in having higher numbers of desaturation dips, longer durations of dips, and lower mean nocturnal arterial oxygen saturation (SaO2). We conclude that a causal relation between nocturnal desaturation and permanent PH is very likely. Further studies are needed to see whether oxygen therapy can prevent PH in these patients.
Analysis of ventilation profile during six minutes walking test: Preliminary study
Authors: Giancarlo Piaggi, Manuela Piran, Veronica Rossi, Serena Cirio, Piero Ceriana
Journal: European Respiratory Journal (2013)

Background: The evolution of the Respiratory Therapy has led us to cure the patients with comorbidities and/or chronically ill. Moreover, it has induced us to suspect that the six-minutes walking test (6-MWT) might be maximal for subgroup of patients.  Aim: Firstly, verify the percentage of patients of whom the 6-MWT has a maximal trend (6-MWT max) by analyzing their ventilation profile during the test. Secondly, identify the threshold characteristics and predictor parameters of patient’ 6-MWT max.  Methods: 97 COPD patients performed forced vital capacity (FVC), forced espiratory volume in 1 sec (FEV1), FEV1/FVC%, maximal voluntary ventilation, inspiratory capacity (CI), minute ventilation (VE) with portable spirometer Spiropalm®, before and immediately after 6-MWT. In the 6-MWT max we calculated the best thresholds using the resampling procedure called “bootstrapping”, in order to discriminate whether the test was a maximal performance or not. The discrimination capability of each threshold was evaluated in terms of accuracy of classification.  Results: About 70% of patients recruited achieved a 6-MWT max for symptoms, HR or VE max. About 57% of patients had a maximal performance exclusively from the ventilatory index. The most predictive parameters for a maximal test were: FEV1/FVC   Conclusion: Preliminary data suggest that FEV1/FVC%, FEV1% and MVV are predictor factors for a maximal performance. The 6MWT may underestimate the real potential of the patient. Instead, it would be more useful to assess, before starting the training, weather the 6-MWT was a maximal test or not.
Efficiency of the endo-bronchial volum reduction treatment for severe heterogeneous emphysema
Authors: Turhan Ece, Aysen Erer, Zuleyha Bingol, Tugce Hürkal, Alper Toker, Ferah Ece
Journal: European Respiratory Journal (2011)

Background:  Patients with advanced chronic obstructive pulmonary disease (COPD) have limited treatment options. Exercise capacity and health related quality of life (HRQL) of the patients are affected by the progress of respiratory failure. Volum reduction surgery is reported to be effective for selected patients with severe COPD. But there is a high risk for the surgery of these patients with hypoxemia hypercapnia. Endo-bronchial volum reduction treatment (EBVRT) by a valve application which is a minimally invasive method has been come up for these patients.   Method:  To study the safety and effectiveness of the EBVRT for heterogeneous emphysema.   Result:  EBVRT were applied to 21 patients. Most of the patients were male (66.6%). Valves were placed into upper lobe (n=15), lower lobes (n=5) and middle lobe (n=1). There were no procedure-related deaths. Only one patient with ischemic heart disease was died at the 3rd month. Device related complication was occurred in two patients; one patient was intubated and the other patient9s valve was occluded and worked inversely. Functional capacity was improved in 71% (n=15) of the patients but only 66% (n=10) of these patients were feeling and doing better. In these patients mean 10mmHG increase of PaO2 and mean 4.5mmHG decrease of PaCO2 were observed at 3rd month. HRQL were improved in 48% (n=10) of the patients. However, pulmonary functions, 6 minute walking distance were not significantly changed.   Conclusion:  Although FEV 1, 6 minute walking distance were not changed, PaO2, functional status and HRQL improvement were observed with EBVRT of advanced emphysema patients. EBVRT is a new method with acceptable safety for the patients with severe COPD.
Fetal Mammalian Heart Generates a Robust Compensatory Response to Cell Loss
Authors: Anthony C. Sturzu, Kuppusamy Rajarajan, Derek Passer, Karolina Plonowska, Alyssa Riley, Timothy C. Tan, Arun Sharma, Adele F. Xu, Marc C. Engels, Rebecca Feistritzer, Guang Li, Martin K. Selig, Richard Geissler, Keston D. Robertson, Marielle Scherrer-Crosbie, Ibrahim J. Domian, Sean M. Wu
Journal: Circulation (2015)

Background— Heart development is tightly regulated by signaling events acting on a defined number of progenitor and differentiated cardiac cells. Although loss of function of these signaling pathways leads to congenital malformation, the consequences of cardiac progenitor cell or embryonic cardiomyocyte loss are less clear. In this study, we tested the hypothesis that embryonic mouse hearts exhibit a robust mechanism for regeneration after extensive cell loss. Methods and Results— By combining a conditional cell ablation approach with a novel blastocyst complementation strategy, we generated murine embryos that exhibit a full spectrum of cardiac progenitor cell or cardiomyocyte ablation. Remarkably, ablation of up to 60% of cardiac progenitor cells at embryonic day 7.5 was well tolerated and permitted embryo survival. Ablation of embryonic cardiomyocytes to a similar degree (50% to 60%) at embryonic day 9.0 could be fully rescued by residual myocytes with no obvious adult cardiac functional deficit. In both ablation models, an increase in cardiomyocyte proliferation rate was detected and accounted for at least some of the rapid recovery of myocardial cellularity and heart size. Conclusion— Our study defines the threshold for cell loss in the embryonic mammalian heart and reveals a robust cardiomyocyte compensatory response that sustains normal fetal development.