Late cardiac effects of chemotherapy in breast cancer survivors treated with adjuvant doxorubicin: 10-year follow-up

Doxorubicin (Dox), a mainstay of adjuvant breast cancer treatment, is associated with cardiac toxicity in the form of left ventricular dysfunction (LVD), LV diastolic dysfunction, or LV systolic dysfunction. Study objectives were to evaluate the prevalence of LVD in long-term breast cancer survivors treated with Dox and determine if brain-type natriuretic peptide (BNP) may help identify patients at risk for LVD. Patients who participated in prospective clinical trials of adjuvant Dox-based chemotherapy for breast cancer with a baseline left ventricular (LV) ejection fraction evaluation from 1999 to 2006 were retrospectively identified from the St Vincent's University Hospital database. Patients were invited to undergo transthoracic echocardiography, BNP analysis, and cardiovascular (CV) risk factor assessment. LVDD was defined as left atrial volume index >34 mL/m(2) and/or lateral wall E prime <10 m/s, and LVSD as LVEF <50 %. Of 212 patients identified, 154 participated, 19 patients had died (no cardiac deaths), and 39 declined. Mean age was 60.7 [55:67] years. A majority of the patients (128, 83 %) had low CV risk (0/1 risk factors), 21 (13.6 %) had 2 RFs, and 5 (3.2 %) ≥3 RFs. BMI was 27.2 ± 4.9 kg/m(2). Median Dox dose was 240 mg/m(2) [225-298]; 92 patients (59.7 %) received ≤240 mg/m(2) and 62 (40.3 %) > 240 mg/m(2). Baseline LVEF was 68.2 ± 8 %. At follow-up of 10.8 ± 2.2 years, LVEF was 64.4 ± 6 %. Three (1.9 %) subjects had LVEF <50 % and one (0.7 %) had LVDD. Dox >240 mg/m2 was associated with any LVEF drop. BNP levels at follow-up were 20.3 pg/ml [9.9-36.5] and 21.1 pg/ml [9.8-37.7] in those without LVD and 61.5 pg/ml [50-68.4] in those with LVD (p = 0.04). Long-term prospective data describing the impact of Dox on cardiotoxicity are sparse. At over 10 years of follow-up, decreases in LVEF are common, and dose related, but LVD as defined is infrequent (2.6 %). Monitoring with BNP for subclinical LVD needs further evaluation.

Importance of risk factor management in diabetic patients and reduction in Stage B heart failure

BACKGROUND: A number of studies have demonstrated the presence of a diabetic cardiomyopathy, increasing the risk of heart failure development in this population. Improvements in present-day risk factor control may have modified the risk of diabetes-associated cardiomyopathy.

AIM: We sought to determine the contemporary impact of diabetes mellitus (DM) on the prevalence of cardiomyopathy in at-risk patients with and without adjustment for risk factor control.

DESIGN: A cross-sectional study in a population at risk for heart failure.

METHODS: Those with diabetes were compared to those with other cardiovascular risk factors, unmatched, matched for age and gender and then matched for age, gender, body mass index, systolic blood pressure and low density lipoprotein cholesterol.

RESULTS: In total, 1399 patients enrolled in the St Vincent's Screening to Prevent Heart Failure (STOP-HF) cohort were included. About 543 participants had an established history of DM. In the whole sample, Stage B heart failure (asymptomatic cardiomyopathy) was not found more frequently among the diabetic cohort compared to those without diabetes [113 (20.8%) vs. 154 (18.0%), P = 0.22], even when matched for age and gender. When controlling for these risk factors and risk factor control Stage B was found to be more prevalent in those with diabetes [88 (22.2%)] compared to those without diabetes [65 (16.4%), P = 0.048].

CONCLUSION: In this cohort of patients with established risk factors for Stage B heart failure superior risk factor management among the diabetic population appears to dilute the independent diabetic insult to left ventricular structure and function, underlining the importance and benefit of effective risk factor control in this population on cardiovascular outcomes.

Un-Editing Alfred: Rethinking Modern Editions of Pre-modern Texts from a Post-modern Sensibility

Thesis (Ph.D.)--University of Washington, 2016-06

The “social” aspect of social-ecological systems: a critique of analytical frameworks and findings from a multisite study of coastal sustainability

We evaluate whether society can adequately be conceptualized as a component of social-ecological systems, given social theory and the current outputs of systems-based research. A mounting critique from the social sciences posits that resilience theory has undertheorized social entities with the concept of social-ecological systems. We trace the way that use of the term has evolved, relating to social science theory. Scientometic and network analysis provide a wide range of empirical data about the origin, growth, and use of this term in academic literature. A content analysis of papers in Ecology and Society demonstrates a marked emphasis in research on institutions, economic incentives, land use, population, social networks, and social learning. These findings are supported by a review of systems science in 18 coastal assessments. This reveals that a systems-based conceptualization tends to limit the kinds of social science research favoring quantitative couplings of social and ecological components and downplaying interpretive traditions of social research. However, the concept of social-ecological systems remains relevant because of the central insights concerning the dynamic coupling between humans and the environment, and its salient critique about the need for multidisciplinary approaches to solve real world problems, drawing on heuristic devices. The findings of this study should lead to more circumspection about whether a systems approach warrants such claims to comprehensiveness. Further methodological advances are required for interdisciplinarity. Yet there is evidence that systems approaches remain highly productive and useful for considering certain social components such as land use and hybrid ecological networks. We clarify advantages and restrictions of utilizing such a concept, and propose a reformulation that supports engagement with wider traditions of research in the social sciences.

Treadmill exercise testing of asymptomatic men and women without evidence of heart disease

The aim of this study was to test the hypothesis of differences in performance including differences in ST-T wave changes between healthy men and women submitted to an exercise stress test. Two hundred (45.4%) men and 241 (54.6%) women (mean age: 38.7 ± 11.0 years) were submitted to an exercise stress test. Physiologic and electrocardiographic variables were compared by the Student t-test and the chi-square test. To test the hypothesis of differences in ST-segment changes, data were ranked with functional models based on weighted least squares. To evaluate the influence of gender and age on the diagnosis of ST-segment abnormality, a logistic model was adjusted; P < 0.05 was considered to be significant. Rate-pressure product, duration of exercise and estimated functional capacity were higher in men (P < 0.05). Sixteen (6.7%) women and 9 (4.5%) men demonstrated ST-segment upslope ≥0.15 mV or downslope ≥0.10 mV; the difference was not statistically significant. Age increase of one year added 4% to the chance of upsloping of segment ST ≥0.15 mV or downsloping of segment ST ≥0.1 mV (P = 0.03; risk ratio = 1.040, 95% confidence interval (CI) = 1.002-1.080). Heart rate recovery was higher in women (P < 0.05). The chance of women showing an increase of systolic blood pressure ≤30 mmHg was 85% higher (P = 0.01; risk ratio = 1.85, 95%CI = 1.1-3.05). No significant difference in the frequency of ST-T wave changes was observed between men and women. Other differences may be related to different physical conditioning.

Effect of eight weeks of strength training on fatigue resistance in men and women

The purpose of the present study was to compare the effects of eight weeks of strength training on fatigue resistance in men and women. Thirty-three men and twenty-three women performed eight weeks of strength training in three weekly sessions. Subjects performed four sets using 80% of 1-RM tests on bench press, squat and arm curl. Fatigue index (FI) was used for analysis of decline in motor performance along the sets. The sum of the number of repetitions accomplished in the four sets in each exercise was used to indicate the fatigue resistance. Anova or Ancova two-way ( time x gender) was employed for statistical analysis ( P < 0.05). Eight weeks of strength training increased significantly 1-RM strength, fatigue resistance and total number of repetitions in both genders. FI decreased significantly in both genders after training ( men = 50% vs. women = Time x gender interaction was observed in the total number of repetitions in squat ( P = 0.04) and arm curl exercises, regarding gains to women ( P = 0.01). In conclusion, eight weeks of ST improved strength, FR, FI and total number of repetitions performed. However, women obtained greater adaptations than men.

Influence of total solids contents of milk whey on the acidifying profile and viability of various lactic acid bacteria

The main objectives of the present study were (a) to study the effects of the different combinations of Lactobacillus delbrueckii subsp. bulgaricus (Lb), Lactobacillus acidophilus (La), Lactobacillus rhamnosus (Lr), and Bifidobacterium animalis subsp. lactis (BI) in co-culture with Streptococcus thermophilus (St) on the rate of acid development in milk and milk-whey mixture, and (b) the effect of the level of the total solids of the different bases on the acidification profile and viability of potential health-promoting microorganisms. The co-culture of St-Lr showed the lowest values V(max) in all bases; while the co-culture St-Bl had high t(Vmax) in milk and whey bases (12 and 10 g/100 g, respectively). Co-cultures St-La and St-Lb reached V(max) at pH 5.5, while St-Lr and St-Bl at pH 5.91. Fermentation time to reach pH 4.5 was longer when St-Lr co-culture was used, while St-Lb had the lowest value. All the products had slight development of acid during the storage period, and lowest values were observed when the St-Bl co-culture was employed. Lb, BI and St cultures had high counts at pH 4.5 in the three bases. The total solids affected the viability of Lb and La. The technological interest of these combinations is discussed in this article. (C) 2008 Swiss Society of Food Science and Technology. Published by Elsevier Ltd. AM rights reserved.

Strength Training Preserves the Bone Mineral Density of Postmenopausal Women Without Hormone Replacement Therapy

Objective: The study was designed to evaluate the effects of strength training (ST) on the bone mineral density (BMD) of postmenopausal women without hormone replacement therapy. Method: Subjects were randomized into untrained (UN) or trained (TR) groups. The TR group exercised three ST sessions per week for 24 weeks, and body composition, muscular strength, and BMD of the lumbar spine and femur neck were evaluated. Results: Body weight, mass index, and fat percentage were lower after 24 weeks only in the TR group (p < .05). SR also improved the one repetition maximum test in 46% and 39% of upper and lower limbs, respectively. The percentage of demineralization was higher in the UN group than in the TR group at the lumbar spine and femoral neck (p < .05). Discussion: Results indicated that 24 weeks of ST improved body composition parameters, increased muscular strength, and preserved BMD in postmenopausal women.

Comparison of differentiated dendritic cell infiltration of autoimmune and osteoarthritis synovial tissue

Objective. Infiltration of rheumatoid arthritis (RA) synovial tissue (ST) by differentiated dendritic cells (DC) is a consistent feature in patients with active disease. However, mononuclear cells (MNC), including DC, may be nonspecifically chemoattracted to inflammatory sites regardless of etiology, Therefore, to evaluate the specificity of ST infiltration by differentiated DC, synovial biopsies from patients with RA, spondylarthropathy (SpA), osteoarthritis (OA), and gout were examined. Methods. Formalin-fixed ST sections were analyzed by double immunohistochemical staining for vascularity and infiltration by differentiated DC, lymphocytes, and macrophages. Results, DC containing nuclear RelB were found in perivascular MNC aggregates from patients with all arthritides studied. Infiltration by differentiated DC was similar in RA and SpA ST, but reduced in OA ST. Differentiated DC were always observed in close association with lymphocytes, and the correlation between these variables suggested that the infiltration of inflammatory sites by DC and lymphocytes was associated. Conclusion, Perivascular infiltration by DC, lymphocytes, and macrophages is nonspecifically related to inflammation, but signals present in RA and SpA ST lead to more intense cellular infiltration and accumulation.

Association of clinical, radiological and synovial immunopathological responses to anti-rheumatic treatment in rheumatoid arthritis

Objectives. To compare immunohistochemical scoring with clinical scoring and radiology for the assessment of rheumatoid arthritis (RA) disease activity, synovial tissue (ST) biopsied arthroscopically was assessed from 18 patients before and after commencement of disease-modifying anti-rheumatic drug (DMARD) therapy. Methods. Lymphocytes, macrophages, differentiated dendritic cells (DC), vascularity, tumour necrosis factor (TNF)alpha and interleukin-1 beta levels were scored. Clinical status was scored using the American College of Rheumatology (ACR) core set and serial radiographs were scored using the Larsen and Sharp methods. Histopathological evidence of activity included infiltration by lymphocytes, DC, macrophages. tissue vascularity, and expression of lining and sublining TNF alpha. These indices co-varied across the set of ST biopsies and were combined as a synovial activity score for each biopsy. Results. The change in synovial activity with treatment correlated with the ACR clinical response and with decreased radiological progression by the Larsen score, The ACR response to DMARD therapy. the change in synovial activity score and the slowing of radiological progression were each greatest in patients with high initial synovial vascularity. Conclusions. The data demonstrate an association between clinical, radiological and synovial immunopathological responses to anti-rheumatic treatment in RA. High ST vascularity may predict favourable clinical and radiological responses to treatment.

Militares Medici in Nummis Repraesentati: The heritage of military

Coins and commemorative medals constitute one special repository of the history of military medicine. The numismatic record has proven to be the most enduring, albeit one of the most selective, records of the progress of history. Matters of health, and especially of military medicine, have been central to the endeavors and indeed the survival of many cultures and societies. Many such themes in the national and international history of military medicine are preserved in the medallic record. Coins and medallions thus constitute one record of the chronology of this profession, one parallel to that of the more traditional history to be found in oral and written records. This account presents a four-part classification of medical coins and medals of military interest. These examples include (1) medals that portray military surgeons and physicians; (2) medals that commemorate special events of military medicine; (3) coins that portray the themes of the discipline of military medicine and health; and (4) a miscellaneous group that includes such examples as disease touch pieces and the militarily worn medals of such bodies as the International Red Cross and the Order of St. John, the latter of which are awarded inter alia for contributions to prehospital care in the field. A representative photo archive of such exemplars is included in this account.

Adulticidal activity against Stegomyia aegypti (Diptera: Culicidae) of three Piper spp.

Three Piper species, Piper longum, P. ribesoides and P. sarmentosum, were selected for investigation of adulticidal potential against Stegomyia aegypti, a main vector of dengue and dengue haemorrhagic fever. Successive extraction by maceration with 95% ethanol showed percentage yields of ethanolic extracts, which derived from P. longum, P. ribesoides and P. sarmentosum, of 8.89, 3.21 and 5.30% (w/w), respectively. All Piper extracts illustrated an impressive adulticidal activity when tested against female mosquitoes by topical application. The susceptibility of St. aegypti females to ethanol-extracted Piper was dose dependent and varied among the plant species. The highest adulticidal effect was established from P. sarmentosum, followed by P. ribesoides and P. longum, with LD50 values of 0.14, 0.15 and 0.26 µg/female, respectively. The potential of these Piper species, as possible mosquitocides, established convincing activity for further researches to develop natural substances for combat against adult mosquitoes.

Chest pain in the emergency room. Importance of a systematic approach

OBJECTIVE: To evaluate the efficiency of a systematic diagnostic approach in patients with chest pain in the emergency room in relation to the diagnosis of acute coronary syndrome (ACS) and the rate of hospitalization in high-cost units. METHODS: One thousand and three consecutive patients with chest pain were screened according to a pre-established process of diagnostic investigation based on the pre-test probability of ACS determinate by chest pain type and ECG changes. RESULTS: Of the 1003 patients, 224 were immediately discharged home because of no suspicion of ACS (route 5) and 119 were immediately transferred to the coronary care united because of ST elevation or left bundle-branch block (LBBB) (route 1) (74% of these had a final diagnosis of acute myocardial infarction [AMI]). Of the 660 patients that remained in the emergency room under observation, 77 (12%) had AMI without ST segment elevation and 202 (31%) had unstable angina (UA). In route 2 (high probability of ACS) 17% of patients had AMI and 43% had UA, whereas in route 3 (low probability) 2% had AMI and 7 % had UA. The admission ECG has been confirmed as a poor sensitivity test for the diagnosis of AMI ( 49%), with a positive predictive value considered only satisfactory (79%). CONCLUSION: A systematic diagnostic strategy, as used in this study, is essential in managing patients with chest pain in the emergency room in order to obtain high diagnostic accuracy, lower cost, and optimization of the use of coronary care unit beds.

Diabetes Mellitus and Glucose as Predictors of Mortality in Primary Coronary Percutaneous Intervention

Background: Diabetes mellitus and admission blood glucose are important risk factors for mortality in ST segment elevation myocardial infarction patients, but their relative and individual role remains on debate. Objective: To analyze the influence of diabetes mellitus and admission blood glucose on the mortality of ST segment elevation myocardial infarction patients submitted to primary coronary percutaneous intervention. Methods: Prospective cohort study including every ST segment elevation myocardial infarction patient submitted to primary coronary percutaneous intervention in a tertiary cardiology center from December 2010 to May 2012. We collected clinical, angiographic and laboratory data during hospital stay, and performed a clinical follow-up 30 days after the ST segment elevation myocardial infarction. We adjusted the multivariate analysis of the studied risk factors using the variables from the GRACE score. Results: Among the 740 patients included, reported diabetes mellitus prevalence was 18%. On the univariate analysis, both diabetes mellitus and admission blood glucose were predictors of death in 30 days. However, after adjusting for potential confounders in the multivariate analysis, the diabetes mellitus relative risk was no longer significant (relative risk: 2.41, 95% confidence interval: 0.76 - 7.59; p-value: 0.13), whereas admission blood glucose remained and independent predictor of death in 30 days (relative risk: 1.05, 95% confidence interval: 1.02 - 1.09; p-value ≤ 0.01). Conclusion: In ST segment elevation myocardial infarction patients submitted to primary coronary percutaneous intervention, the admission blood glucose was a more accurate and robust independent predictor of death than the previous diagnosis of diabetes. This reinforces the important role of inflammation on the outcomes of this group of patients.

Expectations, Learning and Monetary Policy: An Overview of Recent Research

Expectations about the future are central for determination of current macroeconomic outcomes and the formulation of monetary policy. Recent literature has explored ways for supplementing the benchmark of rational expectations with explicit models of expectations formation that rely on econometric learning. Some apparently natural policy rules turn out to imply expectational instability of private agents’ learning. We use the standard New Keynesian model to illustrate this problem and survey the key results about interest-rate rules that deliver both uniqueness and stability of equilibrium under econometric learning. We then consider some practical concerns such as measurement errors in private expectations, observability of variables and learning of structural parameters required for policy. We also discuss some recent applications including policy design under perpetual learning, estimated models with learning, recurrent hyperinflations, and macroeconomic policy to combat liquidity traps and deflation.