Bruce A. Barton

Stress in Fishes: A Diversity of Responses with Particular Reference to Changes in Circulating Corticosteroids

Abstract Physical, chemical and perceived stressors can all evoke non-specific responses in fish, which are considered adaptive to enable the fish to cope with the disturbance and maintain its homeostatic state. If the stressor is overly severe or long-lasting to the point that the fish is not capable of regaining homeostasis, then the responses themselves may become maladaptive and threaten the fishs health and well-being. Physiological responses to stress are grouped as primary, which include endocrine changes such as in measurable levels of circulating catecholamines and corticosteroids, and secondary, which include changes in features related to metabolism, hydromineral balance, and cardiovascular, respiratory and immune functions. In some instances, the endocrine responses are directly responsible for these secondary responses resulting in changes in concentration of blood constituents, including metabolites and major ions, and, at the cellular level, the expression of heat-shock or stress proteins. Tertiary or whole-animal changes in performance, such as in growth, disease resistance and behavior, can result from the primary and secondary responses and possibly affect survivorship. Fishes display a wide variation in their physiological responses to stress, which is clearly evident in the plasma corticosteroid changes, chiefly cortisol in actinopterygian fishes, that occur following a stressful event. The characteristic elevation in circulating cortisol during the first hour after an acute disturbance can vary by more than two orders of magnitude among species and genetic history appears to account for much of this interspecific variation. An appreciation of the factors that affect the magnitude, duration and recovery of cortisol and other physiological changes caused by stress in fishes is important for proper interpretation of experimental data and design of effective biological monitoring programs.

Effects of morphine analgesia in ventilated preterm neonates: primary outcomes from the NEOPAIN randomised trial

BACKGROUND Opioid analgesia is commonly used during neonatal intensive care. We undertook the Neurologic Outcomes and Pre-emptive Analgesia in Neonates (NEOPAIN) trial to investigate whether pre-emptive morphine analgesia decreases the rate of a composite primary outcome of neonatal death, severe intraventricular haemorrhage (IVH), and periventricular leucomalacia (PVL) in preterm neonates. METHODS Ventilated preterm neonates (n=898) from 16 centres were randomly assigned masked placebo (n=449) or morphine (n=449) infusions. After a loading dose (100 microg/kg), morphine infusions (23-26 weeks of gestation 10 microg kg(-1) h(-1); 27-29 weeks 20 microg kg(-1) h(-1); 30-32 weeks 30 microg kg(-1) h(-1)) were continued as long as clinically justified (maximum 14 days). Open-label morphine could be given on clinical judgment (placebo group 242/443 [54.6%], morphine group 202/446 [45.3%]). Analyses were by intention to treat. FINDINGS Baseline variables were similar in the randomised groups. The placebo and morphine groups had similar rates of the composite outcome (105/408 [26%] vs 115/419 [27%]), neonatal death (47/449 [11%] vs 58/449 [13%]), severe IVH (46/429 [11%] vs 55/411 [13%]), and PVL (34/367 [9%] vs 27/367 [7%]). For neonates who were not given open-label morphine, rates of the composite outcome (53/225 [24%] vs 27/179 [15%], p=0.0338) and severe IVH (19/219 [9%] vs 6/189 [3%], p=0.0209) were higher in the morphine group than the placebo group. Placebo-group neonates receiving open-label morphine had worse rates of the composite outcome than those not receiving open-label morphine (78/228 [34%] vs 27/179 [15%], p<0.0001). Morphine-group neonates receiving open-label morphine were more likely to develop severe IVH (36/190 [19%] vs 19/219 [9%], p=0.0024). INTERPRETATION Pre-emptive morphine infusions did not reduce the frequency of severe IVH, PVL, or death in ventilated preterm neonates, but intermittent boluses of open-label morphine were associated with an increased rate of the composite outcome. The morphine doses used in this study decrease clinical signs of pain but can cause significant adverse effects in ventilated preterm neonates.

Longitudinal changes in physical activity in a biracial cohort during adolescence

PURPOSE This report describes the development and use of two self-report methods and an objective measure to assess longitudinal changes in physical activity in a large biethnic cohort of young girls from childhood through adolescence. METHODS The NHLBI Growth and Health Study (NGHS) is a multicenter study of obesity development in 2379 black and white girls followed from ages 9-10 yr to 18-19 yr (NGHS years 1-10). A Caltrac activity monitor was used to objectively quantify activity levels in years 3-5. A 3-d diary (AD) and a habitual patterns questionnaire (HAQ) were administered annually and biannually, respectively, to subjectively quantify physical activity levels. The changing pattern of activities as the girls matured during the 10-yr study period necessitated periodic form changes. Empirical analytic approaches were developed to help distinguish between true longitudinal changes in activity levels from potential numerical artifacts resulting from modifications in forms. RESULTS The longitudinal activity data indicate a steep decline in the level of reported activity from baseline to year 10 as indicated by AD scores (446.8 to 292.1 MET-min x d(-1), 35%) as well as by HAQ scores (29.3 to 4.9 MET-times x wk(-1), 83%). This parallel trend in the pattern of the decline in activity among the two self-report methods was mirrored by a similar decline using the Caltrac method of physical activity assessment. From years 3 to 5, the AD decreased by 22%, whereas both the HAQ and Caltrac declined by 21%. CONCLUSION The longitudinal data on physical activity collected in the NGHS cohort further confirm a dramatic decrease in the overall level of physical activity during the transition from childhood to adolescence. The consistency among the three methods indicate that both the AD and HAQ are useful tools for the assessment of activity levels in adolescent girls.

Morphine Does Not Provide Adequate Analgesia for Acute Procedural Pain Among Preterm Neonates

Background. Morphine alleviates prolonged pain, reduces behavioral and hormonal stress responses induced by surgery among term neonates, and improves ventilator synchrony and sedation among ventilated preterm neonates, but its analgesic effects on the acute pain caused by invasive procedures remain unclear. Objective. To investigate the analgesic efficacy of intravenously administered morphine on heel stick-induced acute pain among preterm neonates. Design. This study was nested within a prospective, randomized, double-blind, multicenter, placebo-controlled trial (the NEOPAIN Trial). Setting. A tertiary-care NICU in a teaching hospital. Participants. Forty-two preterm neonates undergoing ventilation. Interventions. Neonates were randomized to either the morphine (loading dose of 100 μg/kg, followed by infusions of 10–30 μg/kg per hour according to gestation, N = 21) or placebo (5% dextrose infusions, N = 21) group. Pain responses to 3 heel sticks were evaluated, ie, before the loading dose (T1), 2 to 3 hours after the loading dose (T2), and 20 to 28 hours after the loading dose (T3). Main Outcomes Measures. Pain was assessed with the Douleur Aiguë Nouveau-né (DAN) scale (behavioral pain scale) and the Premature Infant Pain Profile (PIPP) (multidimensional pain scale); plasma morphine levels were measured at T3. Results. Infants in the placebo and morphine groups had similar gestational ages (mean ± SD: 27.2 ± 1.7 vs 27.3 ± 1.8 weeks) and birth weights (972 ± 270 vs 947 ± 269 g). Mean ± SD DAN pain scores at T1, T2, and T3 were 4.8 ± 4.0, 4.6 ± 2.9, and 4.7 ± 3.6, respectively, for the placebo group and 4.5 ± 3.8, 4.4 ± 3.7, and 3.1 ± 3.4 for the morphine group. The within-group factor (pain at T1, T2, and T3) was not statistically different over time. The between-group analysis (infants receiving placebo versus those receiving morphine) showed no significant differences. Mean ± SD PIPP pain scores at T1, T2, and T3 were 11.5 ± 4.8, 11.1 ± 3.7, and 9.1 ± 4.0, respectively, for the placebo group and 10.0 ± 3.6, 8.8 ± 4.9, and 7.8 ± 3.6 for the morphine group. The within-group factor was statistically different over time. The between-group analysis showed no significant differences. Mean ± SD plasma morphine levels at T3 were 0.44 ± 1.79 ng/mL and 63.36 ± 33.35 ng/mL for the placebo and morphine groups, respectively. There was no correlation between plasma morphine levels and pain scores at T3 (DAN, R = −0.05; PIPP, R = −0.02). Conclusions. Despite its routine use in the NICU, morphine given as a loading dose followed by continuous intravenous infusions does not appear to provide adequate analgesia for the acute pain caused by invasive procedures among ventilated preterm neonates.

Overweight, fat patterning, and cardiovascular disease risk factors in black and white boys.

PURPOSE To evaluate the relationships of overweight and fat patterning with cardiovascular disease (CVD) risk factors in black and white boys. DESIGN Cross-sectional analysis of CVD risk factors by weight and central adiposity groups in black and white boys, aged 10 to 15 years. Mean adiposity, lipid, and blood pressure variables were compared between weight and central adiposity groups within race by using linear regression models. Observed clustering of risk factors within weight and adiposity groups was compared with the expected clustering under an assumption of no association. RESULTS Within each racial group, overweight boys had greater skinfolds, lower high-density lipoprotein cholesterol levels, higher low-density lipoprotein cholesterol and triglyceride levels, and higher systolic and diastolic blood pressure than non-overweight boys. Among overweight boys, greater central adiposity was associated with higher risk factor levels and increased clustering of risk factors. CONCLUSION Overweight and central adiposity together profoundly affect CVD risk factor levels and risk factor clustering in black and white boys.

Salmonid Fishes Differ in Their Cortisol and Glucose Responses to Handling and Transport Stress

Abstract Uniformly acclimated juvenile salmonid fishes subjected to 30-s handling or 2-h transport stressors showed differences in the magnitude of poststress plasma cortisol and glucose increases. Lake trout Salvelinus namaycush had the highest maximum plasma cortisol after handling (143 ng/mL), rainbow trout Oncorhynchus mykiss had the lowest levels (43 ng/mL), and brown trout Salmo trutta and brook trout Salvelinus fontinalis had intermediate levels (111 and 89 ng/mL, respectively). Lake trout had the highest peak posttransport plasma cortisol (124 ng/mL) compared with brook trout (69 ng/mL) and rainbow trout (57 ng/mL). Peak posthandling plasma glucose levels were highest in brown trout (257 mg/dL) followed by brook, rainbow, and lake trout (177, 153, and 150 mg/dL, respectively). Rainbow trout, however, had the highest peak plasma glucose concentration (223 mg/dL) after transport, and lake trout the lowest (143 mg/dL). Species considered as most stressed based on plasma cortisol elevations were not n...

Stress coping style predicts aggression and social dominance in rainbow trout

Social stress is frequently used as a model for studying the neuroendocrine mechanisms underlying stress-induced behavioral inhibition, depression, and fear conditioning. It has previously been shown that social subordination may result in increased glucocorticoid release and changes in brain signaling systems. However, it is still an open question which neuroendocrine and behavioral differences are causes, and which are consequences of social status. Using juvenile rainbow trout of similar size and with no apparent differences in social history, we demonstrate that the ability to win fights for social dominance can be predicted from the duration of a behavioral response to stress, in this case appetite inhibition after transfer to a new environment. Moreover, stress responsiveness in terms of confinement-induced changes in plasma cortisol was negatively correlated to aggressive behavior. Fish that exhibited lower cortisol responses to a standardized confinement test were markedly more aggressive when being placed in a dominant social position later in the study. These findings support the view that distinct behavioral-physiological stress coping styles are present in teleost fish, and these coping characteristics influence both social rank and levels of aggression.

Overweight, fat patterning, and cardiovascular disease risk factors in black and white girls: The National Heart, Lung, and Blood Institute Growth and Health Study

OBJECTIVE To determine the association of overweight and central adiposity with cardiovascular disease risk factors in black and white 9- and 10-year-old girls. DESIGN Cross-sectional analysis of baseline data collected from participants in the National Heart, Lung, and Blood Institute Growth and Health Study. Girls were classified as overweight or not with the use of the age- and sex-specific 85th percentiles of the body mass index (kilograms per square meter) distributions from the combined NHANES (I and II) data set. Mean indexes of central adiposity, blood pressure levels, and lipid concentrations and the clustering of risk factors based on published cut points were compared between weight groups by race and by central adiposity group within weight and race groups. RESULTS Overweight was associated with increased risk factor levels and with increased clustering in both black and white girls. Among overweight girls greater central adiposity was associated with higher risk factor levels and increased clustering. CONCLUSIONS Given the associations between cardiovascular disease risk factors and both overweight and central adiposity, the secular trends toward increased obesity in American youth portend a worsening of cardiovascular disease risk profiles.

Treated History of Noninvasive Grade 1 Transitional Cell Carcinoma

A total of 178 patients with grade 1 noninvasive (stage Ta) bladder tumors followed from 1 to 10 years (median 58 months) was prospectively evaluated by cystoscopy, transurethral resection, mucosal biopsies, cytology, size and number of tumors at diagnosis, recurrences, progression in grade and stage, number of negative or positive cystoscopies and death from all causes. Histopathological and cytological studies were confirmed by a Central Pathology Laboratory using the criteria for grade 1 as described previously. Of the patients 122 (68.5%) had a single tumor. Three-quarters of the patients had tumors of less than 2 cm., 95% had mild or no urothelial dysplasia and 1 had positive cytology results. There were 419 recurrent tumors in 109 patients (61%). Patients with multiple tumors were at a significantly greater risk for recurrences (p < 0.001). Size of tumor significantly affected the rate of recurrence in the first 2 years after initial diagnosis in single tumor patients only. Of the multiple tumor patients 90% experienced a recurrence compared to 46% of the single tumor patients. Of the 1,112 cystoscopies performed in 122 single tumor patients 18% were positive, compared to 33% of the 686 cystoscopies performed in 56 multiple tumor patients. A total of 29 patients had a change in grade, 5 having grade 3 and 24 having grade 2 tumors. Progression to stage T1 occurred in 5 patients and to stage T2 or greater in 3. Of the 36 patients who died, 1 died of obstruction due to bladder cancer. Experimental evidence supports the opinion that the cells of stage Ta, grade 1 tumors are different in several ways from normal urothelium. There are little data to support the use of the term papilloma to describe stage Ta, grade 1 tumors without reservation. The data demonstrate that the tumor diathesis being expressed ceases with time and for unknown reasons. Multiple tumor patients with stage Ta, grade 1 disease might be included in chemotherapy trials only with stratification and a control arm of transurethral resection/fulguration alone.

Culturally appropriate storytelling to improve blood pressure: a randomized trial

BACKGROUND Storytelling is emerging as a powerful tool for health promotion in vulnerable populations. However, these interventions remain largely untested in rigorous studies. OBJECTIVE To test an interactive storytelling intervention involving DVDs. DESIGN Randomized, controlled trial in which comparison patients received an attention control DVD. Separate random assignments were performed for patients with controlled or uncontrolled hypertension. (ClinicalTrials.gov registration number: NCT00875225) SETTING An inner-city safety-net clinic in the southern United States. PATIENTS 230 African Americans with hypertension. INTERVENTION 3 DVDs that contained patient stories. Storytellers were drawn from the patient population. MEASUREMENTS The outcomes were differential change in blood pressure for patients in the intervention versus the comparison group at baseline, 3 months, and 6 to 9 months. RESULTS 299 African American patients were randomly assigned between December 2007 and May 2008 and 76.9% were retained throughout the study. Most patients (71.4%) were women, and the mean age was 53.7 years. Baseline mean systolic and diastolic pressures were similar in both groups. Among patients with baseline uncontrolled hypertension, reduction favored the intervention group at 3 months for both systolic (11.21 mm Hg [95% CI, 2.51 to 19.9 mm Hg]; P = 0.012) and diastolic (6.43 mm Hg [CI, 1.49 to 11.45 mm Hg]; P = 0.012) blood pressures. Patients with baseline controlled hypertension did not significantly differ over time between study groups. Blood pressure subsequently increased for both groups, but between-group differences remained relatively constant. LIMITATION This was a single-site study with 23% loss to follow-up and only 6 months of follow-up. CONCLUSION The storytelling intervention produced substantial and significant improvements in blood pressure for patients with baseline uncontrolled hypertension. PRIMARY FUNDING SOURCE Finding Answers: Disparities Research for Change, a national program of the Robert Wood Johnson Foundation.