Resting metabolic rate and protein turnover in apparently healthy elderly Gambian men.

Body composition, resting energy expenditure (REE), and whole body protein metabolism were studied in 26 young and 28 elderly Gambian men matched for body mass index during the dry season in a rural village in The Gambia. REE was measured by indirect calorimetry (hood system) in the fasting state and after five successive meals. Rates of whole body nitrogen flux, protein synthesis, and protein breakdown were determined in the fed state from the level of isotopic enrichment of urinary ammonia over a period of 12 h after a single oral dose of [15N]glycine. Expressed in absolute value, REE was significantly lower in the elderly compared with the young group (3.21 +/- 0.07 vs. 4.04 +/- 0.07 kJ/min, P < 0.001) and when adjusted to body weight (3.29 +/- 0.05 vs. 3.96 +/- 0.05 kJ/min, P < 0.0001) and fat-free mass (FFM; 3.38 +/- 0.01 vs. 3.87 +/- 0.01 kJ/min, P < 0.0001). The rate of protein synthesis averaged 207 +/- 13 g protein/day in the elderly and 230 +/- 13 g protein/day in the young group, whereas protein breakdown averaged 184 +/- 13 g protein/day in the elderly and 203 +/- 13 g protein/day in the young group (nonsignificant). When values were adjusted for body weight or FFM, they did not reveal any difference between the two groups. It is concluded that the reduced REE adjusted for body composition observed in elderly Gambian men is not explained by a decrease in protein turnover.

Reduction of small infrarenal abdominal aortic aneurysm expansion rate by statins.

BACKGROUND: To evaluate the effect of statins on the annual expansion rate (ER) of small infrarenal abdominal aortic aneurysms (AAA). PATIENTS AND METHODS: All patients under regular surveillance for small AAA between January 2000 and September 2007, in the Department of Angiology, Lausanne University Hospital, were included. Inclusion criteria were baseline abdominal aortic diameter between 25 and 55 mm, at least two measurements of AAA diameter and a minimum follow up of 6 months. Patients with Marfan disease, infectious or inflammatory AAA, and patients with prior AAA repair were excluded. The influence of statin use and other factors on ER were examined by bivariate and multivariate analysis. RESULTS: Among 589 patients who underwent an abdominal aorta evaluation, 94 patients (89 % men, mean age 69.1 years) were finally included in the analysis. Baseline AAA size was 39.9 ± 7.7 mm (mean±SE) and 48.7 ± 8.4 mm at end of follow-up. Patients had a regular aneurysm size assessment during 38.5 ± 27.7 months. Mean ER was 3.59 mm/y (± 2.81). The 50 patients who were treated with statin during the study period had a lower ER compared to the 44 controls (2.91 vs 4.37 mm/year, p = 0.01). CONCLUSIONS: This study confirms the considerable individual variations in the AAA expansion rate, and emphasizes the need for regular aortic diameter assessments. In this study, patients treated with statin demonstrate a significant decrease in the ER compared to controls. This finding need to be evaluated in prospective interventional studies powered to demonstrate the potential benefit of statin treatment.

Stochastic demography and the neutral substitution rate in class-structured populations.

The neutral rate of allelic substitution is analyzed for a class-structured population subject to a stationary stochastic demographic process. The substitution rate is shown to be generally equal to the effective mutation rate, and under overlapping generations it can be expressed as the effective mutation rate in newborns when measured in units of average generation time. With uniform mutation rate across classes the substitution rate reduces to the mutation rate.

Pregnancy-related changes in activity energy expenditure and resting metabolic rate in Switzerland.

BACKGROUND/OBJECTIVES: To measure resting metabolic rate (RMR), activity energy expenditure (AEE), total energy expenditure (TEE) and physical activity pattern, that is, duration and intensity (in metabolic equivalents, METs) of activities performed in late pregnancy compared with postpartum in healthy, well-nourished women living in Switzerland. SUBJECTS/METHODS: Weight, height, RMR, AEE, TEE and physical activity patterns were measured longitudinally in 27 healthy women aged 23-40 years at 38.2+/-1.5 weeks of gestation and 40.0+/-7.2 weeks postpartum. RESULTS: The RMR during late pregnancy was 7480 kJ per day, that is, 1320+/-760 kJ per day (21.4%) higher than the postpartum RMR (P<0.001). Absolute changes in RMR were positively correlated with the corresponding changes in body weight (r=0.61, P<0.001). RMR per kg body weight was similar in late pregnancy vs postpartum (P=0.28). AEE per kg during pregnancy and postpartum was 40+/-13 and 50+/-20 kJ/kg, respectively (P=0.001). There were significant differences in daily time spent at METs<1.5 (1067 vs 998 min, P=0.045), at 2.5< or =METs <3.0 (58 vs 82 min, P=0.002) and METs> or =6 (1 vs 6 min, P=0.014) during pregnancy and postpartum, respectively. CONCLUSIONS: Energy expenditure in healthy women living in Switzerland increases in pregnancy compared with the postpartum state. Additional energy expenditure is primarily attributed to an increase in RMR, which is partly compensated by a decrease in AEE. The decrease in physical activity-related energy costs is achieved by selecting less demanding activities and should be taken into account when defining extra energy requirements for late pregnancy in Switzerland.

Parental heart rate variability during pediatric consultation

OBJECTIVE: Research regarding communication between pediatricians and parents in pediatric consultation has mainly focused on parental satisfaction, on its influence on compliance and on communication techniques used by pediatricians. However, there is paucity in research regarding parental stress levels during pediatric consultation. Therefore, the aim of our study was to measure parental heart rate variability related as a measure of stress levels during pediatric consultation. METHODS: Video recordings with simultaneous monitoring and recording of parental heart rate were obtained from 38 pediatric consultations in the ambulatory or hospital setting of the department of pediatrics (HFR, Fribourg, Switzerland). Pulse variation was measured every 5 seconds and heart rate variability (increase or decrease were analyzed) in relation to various sections of the consultation. RESULTS: Heart rate significantly decreased at the end of the consultation compared to the beginning of the consultation (p= 0.0567). In addition, heart rate significantly decreased at the beginning of clinical examination (p= 0.0476) compared to psychosocial history taking. During the discussion of laboratory findings and diagnosis, heart rate was significantly elevated compared to the discussion of the prognosis (p=0.0505). CONCLUSION: We conclude that pediatric consultation has a significant impact on parental stress levels shown by parental heart variability. In general, it can be shown that stress levels significantly decrease at the end of the consultation compared to the beginning of the consultation. In addition, stress levels decrease at the beginning of clinical examination and increase during psychosocial history taking and discussion of laboratory findings and diagnosis. Therefore, our findings highlight the importance of a thorough consultation which include a comprehensive clinical examination with special care taken regarding psychosocial issues and information given regarding the diagnosis.

Change in individual growth rate and its link to gill-net fishing in two sympatric whitefish species

Size-selective fishing is expected to affect traits such as individual growth rate, but the relationship between the fishery-linked selection differentials and the corresponding phenotypic changes is not well understood. We analysed a 25-year monitoring survey of sympatric populations of the two Alpine whitefish Coregonus albellus and C. fatioi. We determined the fishing-induced selection differentials on growth rates, the actual change of growth rates over time, and potential indicators of reproductive strategies that may change over time. We found marked declines in adult growth rate and significant selection differentials that may partly explain the observed declines. However, when comparing the two sympatric species, the selection differentials on adult growth were stronger in C. albellus while the decline in adult growth rate seemed more pronounced in C. fatioi. Moreover, the selection differential on juvenile growth was significant in C. albellus but not in C. fatioi, while a significant reduction in juvenile growth over the last 25 years was only found in C. fatioi. Our results suggest that size-selective fishing affects the genetics for individual growth in these whitefish, and that the link between selection differentials and phenotypic changes is influenced by species-specific factors.

Confounding effects of heart rate on pulse wave velocity in paced patients with a low degree of atherosclerosis.

BACKGROUND: Pulse wave velocity (PWV), an index of arterial wall stiffness, is modulated by blood pressure (BP). Whether heart rate (HR) is also a modulator of PWV is controversial. Recent research involving mainly patients with high aortic PWV have found either no change or a positive correlation between the two. Given that PWV is increasingly being measured in cardiovascular studies, the relationship between HR and PWV should be known in patients with preserved arterial wall elasticity. OBJECTIVE: The aim of this study was to evaluate the importance of HR as a determinant of the variability in PWV in patients with a low degree of atherosclerosis. DESIGN AND METHODS: Fourteen patients (five female, nine male; aged 68 +/- 8 years) were evaluated post pacemaker implantation due to sick sinus or carotid hypersensitivity syndromes. Carotid-femoral PWV was measured at rest and during atrial pacing at 80, 90 and 100 bpm (paced HR). Arterial femoral blood flow (AFBF) was measured by echodoppler. RESULTS: PWV increased from 6.2 +/- 1.5 m/s (mean +/- SD) during resting sinus rhythm (HR 62 +/- 8 bpm; mean +/- SD) to 6.8 +/- 1.0, 7.0 +/- 0.9, and 7.6 +/- 1.1 m/s at pacing rates of 80, 90 and 100 bpm, respectively (P < 0.0001). Systolic (SBP) and mean blood pressure (MBP) remained constant at all HR levels, whereas AFBF increased in a linear fashion. CONCLUSIONS: These results demonstrate that even in patients with a low degree of atherosclerosis, HR is a potential modulator of carotid-femoral PWV.

The difference between the basal metabolic rate and the sleeping metabolic rate in Japanese.

Previous studies have demonstrated the difference between the basal metabolic rate (BMR) and the sleeping metabolic rate (SMR): however, the difference in the Japanese population has not yet been explored. This study examined the relationship between the BMR and SMR in ninety-four healthy Japanese subjects (37 males and 57 females, 39 +/- 12 y of age and 22.0 +/- 7.4% body fat) in a respiratory chamber. The SMR was significantly lower than the BMR (1416 +/- 245 vs. 1492 +/- 256 kcal/d): however, there was a highly significant correlation between the two (r = 0.867; p < 0.001). The ratio of SMR/BMR largely varied among individuals (0.95 +/-0.08, 8.4% of the coefficient of variation). The ratio was significantly lower in males than in females (0.93 +/- 0.10 vs. 0.97 +/- 0.06, p < 0.05). None of the anthropometric measures (age, weight, body mass index, body surface area or percent body fat) correlated with the ratio. These results showed that SMR was 95%, of BMR on average in a healthy Japanese group. However, when applied over a longer time period (24 h or more), the difference tends to become negligible for most analyses in a group. Although the difference between SMR and BMR will induce a 5% gap of physical activity level defined as the total energy expenditure divided by the BMR or SMR, this factor seems to have little practical importance in epidemiological research.

Estimation of glomerular filtration rate in hospitalised patients: are we overestimating renal function?

QUESTIONS UNDER STUDY AND PRINCIPLES: Estimating glomerular filtration rate (GFR) in hospitalised patients with chronic kidney disease (CKD) is important for drug prescription but it remains a difficult task. The purpose of this study was to investigate the reliability of selected algorithms based on serum creatinine, cystatin C and beta-trace protein to estimate GFR and the potential added advantage of measuring muscle mass by bioimpedance. In a prospective unselected group of patients hospitalised in a general internal medicine ward with CKD, GFR was evaluated using inulin clearance as the gold standard and the algorithms of Cockcroft, MDRD, Larsson (cystatin C), White (beta-trace) and MacDonald (creatinine and muscle mass by bioimpedance). 69 patients were included in the study. Median age (interquartile range) was 80 years (73-83); weight 74.7 kg (67.0-85.6), appendicular lean mass 19.1 kg (14.9-22.3), serum creatinine 126 μmol/l (100-149), cystatin C 1.45 mg/l (1.19-1.90), beta-trace protein 1.17 mg/l (0.99-1.53) and GFR measured by inulin 30.9 ml/min (22.0-43.3). The errors in the estimation of GFR and the area under the ROC curves (95% confidence interval) relative to inulin were respectively: Cockcroft 14.3 ml/min (5.55-23.2) and 0.68 (0.55-0.81), MDRD 16.3 ml/min (6.4-27.5) and 0.76 (0.64-0.87), Larsson 12.8 ml/min (4.50-25.3) and 0.82 (0.72-0.92), White 17.6 ml/min (11.5-31.5) and 0.75 (0.63-0.87), MacDonald 32.2 ml/min (13.9-45.4) and 0.65 (0.52-0.78). Currently used algorithms overestimate GFR in hospitalised patients with CKD. As a consequence eGFR targeted prescriptions of renal-cleared drugs, might expose patients to overdosing. The best results were obtained with the Larsson algorithm. The determination of muscle mass by bioimpedance did not provide significant contributions.

Assessment of adult formulas for glomerular filtration rate estimation in children.

BACKGROUND: Estimated glomerular filtration rate (eGFR) is an important diagnostic instrument in clinical practice. The National Kidney Foundation-Kidney Disease Quality Initiative (NKF-KDOQI) guidelines do not recommend using formulas developed for adults to estimate GFR in children; however, studies confirming these recommendations are scarce. The aim of our study was to evaluate the accuracy of the new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula, the Modification of Diet in Renal Disease (MDRD) formula, and the Cockcroft-Gault formula in children with various stages of chronic kidney disease (CKD). METHODS: A total of 550 inulin clearance (iGFR) measurements for 391 children were analyzed. The cohort was divided into three groups: group 1, with iGFR >90 ml/min/1.73 m(2); group 2, with iGFR between 60 and 90 ml/min/1.73 m(2); group 3, with iGFR of <60 ml/min/1.73 m(2). RESULTS: All formulas overestimate iGFR with a significant bias (p < 0.001), present poor accuracies, and have poor Spearman correlations. For an accuracy of 10 %, only 11, 6, and 27 % of the eGFRs are accurate when using the MDRD, CKD-EPI, and Cockcroft-Gault formulas, respectively. For an accuracy of 30 %, these formulas do not reach the NKF-KDOQI guidelines for validation, with only 25, 20, and 70 % of the eGFRs, respectively, being accurate. CONCLUSIONS: Based on our results, the performances of all of these formulas are unreliable for eGFR in children across all CKD stages and cannot therefore be applied in the pediatric population group.

A gamma camera count rate saturation correction method for whole-body planar imaging.

Whole-body (WB) planar imaging has long been one of the staple methods of dosimetry, and its quantification has been formalized by the MIRD Committee in pamphlet no 16. One of the issues not specifically addressed in the formalism occurs when the count rates reaching the detector are sufficiently high to result in camera count saturation. Camera dead-time effects have been extensively studied, but all of the developed correction methods assume static acquisitions. However, during WB planar (sweep) imaging, a variable amount of imaged activity exists in the detector's field of view as a function of time and therefore the camera saturation is time dependent. A new time-dependent algorithm was developed to correct for dead-time effects during WB planar acquisitions that accounts for relative motion between detector heads and imaged object. Static camera dead-time parameters were acquired by imaging decaying activity in a phantom and obtaining a saturation curve. Using these parameters, an iterative algorithm akin to Newton's method was developed, which takes into account the variable count rate seen by the detector as a function of time. The algorithm was tested on simulated data as well as on a whole-body scan of high activity Samarium-153 in an ellipsoid phantom. A complete set of parameters from unsaturated phantom data necessary for count rate to activity conversion was also obtained, including build-up and attenuation coefficients, in order to convert corrected count rate values to activity. The algorithm proved successful in accounting for motion- and time-dependent saturation effects in both the simulated and measured data and converged to any desired degree of precision. The clearance half-life calculated from the ellipsoid phantom data was calculated to be 45.1 h after dead-time correction and 51.4 h with no correction; the physical decay half-life of Samarium-153 is 46.3 h. Accurate WB planar dosimetry of high activities relies on successfully compensating for camera saturation which takes into account the variable activity in the field of view, i.e. time-dependent dead-time effects. The algorithm presented here accomplishes this task.

Isochorismate synthase (PchA), the first and rate-limiting enzyme in salicylate biosynthesis of Pseudomonas aeruginosa.

In Pseudomonas aeruginosa the extracellular metabolite and siderophore pyochelin is synthesized from two major precursors, chorismate and l-cysteine via salicylate as an intermediate. The regulatory role of isochorismate synthase, the first enzyme in the pyochelin biosynthetic pathway, was studied. This enzyme is encoded by pchA, the last gene in the pchDCBA operon. The PchA protein was purified to apparent electrophoretic homogeneity from a PchA-overexpressing P. aeruginosa strain. The native enzyme was a 52-kDa monomer in solution, and its activity strictly depended on Mg(2+). At pH 7.0, the optimum, a K(m) = 4.5 microm and a k(cat) = 43.1 min(-1) were determined for chorismate. No feedback inhibitors or other allosteric effectors were found. The intracellular PchA concentration critically determined the rate of salicylate formation both in vitro and in vivo. In cultures grown in iron-limiting media to high cell densities, overexpression of the pchA gene resulted in overproduction of salicylate as well as in enhanced pyochelin formation. From this work and earlier studies, it is proposed that one important factor influencing the flux through the pyochelin biosynthetic pathway is the PchA concentration, which is determined at a transcriptional level, with pyochelin acting as a positive signal and iron as a negative signal.

Effects of caffeine on energy metabolism, heart rate, and methylxanthine metabolism in lean and obese women.

The magnitude of coffee-induced thermogenesis and the influence of coffee ingestion on substrate oxidation were investigated in 10 lean and 10 obese women, over two 24-h periods in a respiratory chamber. On one occasion the subjects consumed caffeinated coffee and on the other occasion, decaffeinated coffee. The magnitude of thermogenesis was smaller in obese (4.9 +/- 2.0%) than in lean subjects (7.6 +/- 1.3%). The thermogeneic response to caffeine was prolonged during the night in lean women only. The coffee-induced stimulation of energy expenditure was mediated by a concomitant increase in lipid and carbohydrate oxidation. During the next day, in postabsorptive basal conditions, the thermogenic effect of coffee had vanished, but a significant increase in lipid oxidation was observed in both groups. The magnitude of this effect was, however, blunted in obese women (lipid oxidation increased by 29 and 10% in lean and obese women, respectively). Caffeine increased urinary epinephrine excretion. Whereas urinary caffeine excretion was similar in both groups, obese women excreted more theobromine, theophylline, and paraxanthine than lean women. Despite the high levels of urinary methylxanthine excretion, thermogenesis and lipid oxidation were less stimulated in obese than in lean subjects.