Static in vitro digestion model adapted to the general older adult population: an INFOGEST international consensus.

Understanding the mechanisms of food digestion is of paramount importance to determine the effect foods have on human health. Significant knowledge on the fate of food during digestion has been generated in healthy adults due to the development of physiologically-relevant in vitro digestion models. However, it appears that the performance of the oro-gastrointestinal tract is affected by ageing and that a model simulating the digestive conditions found in a younger adult (<65 years) is not relevant for an older adult (>65 years). The objectives of the present paper were: (1) to conduct an exhaustive literature search to find data on the physiological parameters of the older adult oro-gastrointestinal tract, (2) to define the parameters of an in vitro digestion model adapted to the older adult. International experts have discussed all the parameters during a dedicated workshop organized within the INFOGEST network. Data on food bolus properties collected in the older adult were gathered, including food particle size found in older adult boluses. In the stomach and small intestine, data suggest that significant physiological changes are observed between younger and older adults. In the latter, the rate of gastric emptying is slowed down, the pH of the stomach content is higher, the amount of secretions and thus the hydrolytic activities of gastric and intestinal digestive enzymes are reduced and the concentration of bile salts lower. The consensus in vitro digestion model of the older adult proposed here will allow significant progress to be made in understanding the fate of food in this specific population, facilitating the development of foods adapted to their nutritional needs. Nevertheless, better foundational data when available and further refinement of the parameters will be needed to implement the proposed model in the future.

Determination of blood pressure percentiles in normal-weight children: some methodological issues.

Blood pressure in children has consistently been related to adult blood pressure, with implications for long-term prevention of cardiovascular disease. The epidemic of obesity in children has resulted in corresponding increases in childhood blood pressure. In this paper, the authors develop norms for childhood blood pressure among normal-weight children (body mass index <85th percentile based on Centers for Disease Control and Prevention guidelines) as a function of age, sex, and height, using data from 49,967 children included in the database of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents (the Pediatric Task Force). The authors considered three types of models for pediatric blood pressure data, including polynomial regression, restricted cubic splines, and quantile regression, with the latter providing the best fit. The sex-specific norms presented here are a nonlinear function of both age and height and are generally slightly lower than previously developed norms based on Pediatric Task Force data including both normal-weight and overweight children.

Urinary beta 2-microglobulin in full-term newborns: evidence for proximal tubular dysfunction in infants with meconium-stained amniotic fluid.

Urinary concentrations of beta 2-microglobulin (beta 2M) and creatinine were measured in normal term infants and in those born with meconium-stained amniotic fluid. None of the infants or their mothers had conditions known to modify beta 2M excretion. Measurements of beta 2M were made on urines collected by bagging; urines obtained from diapers were not satisfactory. Urinary beta 2M concentrations increased significantly (P less than .02) in the normal infants from the first day (0.36 +/- 0.29 mg/L: n = 29) to the third day (0.60 +/- 0.43 mg/L: n = 21) postpartum. Compared with the normal infants, values for the infants with meconium-stained amniotic fluid were increased significantly on days 1 (1.64 +/- 2.16 mg/L: n = 25: P less than .005) and 3 (2.12 +/- 2.04 mg/L: n = 23: P less than .005). Levels exceeded two standard deviations above the normal mean in 12 of the 26 infants with meconium-stained amniotic fluid on postpartum day 1, and 12 of the 23 infants with meconium-stained amniotic fluid on day 3. Urinary creatinine levels were similar in both the normal infants and those with meconium-stained amniotic fluid. All infants with meconium-stained amniotic fluid with a one-minute Apgar score of 6 or less had an elevated urinary beta 2M concentration. The elevated levels of urinary beta 2M in infants with meconium-stained amniotic fluid indicate the existence of tubular dysfunction, probably mild acute tubular necrosis secondary to hypoxia.

Abnormal 24-hour blood pressure patterns in children after renal transplantation.

Hypertension after renal transplantation occurs commonly and is associated with decreased allograft survival. Hypertension is usually diagnosed by casual blood pressure (BP) measurements in the outpatient clinic that may not reflect the overall 24-hour BP pattern. To better describe the pattern of BP in children after renal transplantation, 24-hour ambulatory BP monitoring (APBM) was performed in 42 patients with stable renal function. BP was measured every 20 minutes during the daytime and every 30 minutes at night. Mean patient age was 12.8 +/- 5.2 years, and mean time after transplantation was 34 +/- 36 months. Seventy-six percent of the patients were administered antihypertensive medications. Twenty-four-hour mean systolic BP (SBP) was 127 +/- 11 mm Hg, and diastolic BP (DBP) was 80 +/- 11 mm Hg. Mean 24-hour BP load values (percentage of BP readings > 95th percentile based on Task Force criteria) were 59% for SBP and 50% for DBP, which were significantly elevated compared with healthy children (P < 0.001). An attenuated decline in sleep BP (nondipping) was found in 78% of the patients for SBP and 50% for DBP. Sleep BP exceeded awake BP in 24% of the patients for SBP and 17% for DBP. Boys had a greater SBP load (66% versus 45%; P = 0.03) and DBP load (57% versus 38%; P = 0.04) than girls. These results confirm in children the high prevalence of hypertension by ABPM criteria after renal transplantation and show attenuation of normal sleep BP decreases. These BP disturbances may shorten renal allograft survival and predispose children to long-term hypertensive end-organ damage.

Ambulatory blood pressure monitoring and interdialytic weight gain in children receiving chronic hemodialysis.

Volume overload appears to induce hypertension in hemodialysis patients, yet studies of the effect of hydration status on interdialytic blood pressure (BP) have yielded contradictory results. We measured interdialytic BP by ambulatory BP monitoring (ABPM) during inpatient fluid restriction in 12 children receiving chronic hemodialysis to describe the overall BP pattern and to determine the effect of weight gain on BP change. Weight was measured on admission and four times each day. For each weight, casual BP was measured and compared with the mean of 3 hours of ABPM surrounding the weight measurement. Sleep BP decreased from daytime BP by 6% for systolic BP (SBP) and 11% for diastolic BP (DBP). Sleep loads were greater than daytime loads (P < 0.01) for SBP (53% v 28%) and DBP (57% v 27%). Overall, 58% (7 of 12) of the patients had sleep SBP load greater than 50%, and 67% (8 of 12) of the patients had sleep DBP load greater than 50%. Casual and ABPM measurements of BP showed moderate correlations for SBP (r = 0.51) and DBP (r = 0.46) and mean differences between methods of 6.3 +/- 13.2 mm Hg and -1.4 +/- 12.6 mm Hg, respectively. Increases in interdialytic weight were positively associated with increases in SBP (r = 0.41; P < 0.001), and interdialytic BP changes varied closely with corresponding weight changes. We conclude that in children receiving chronic hemodialysis: (1) sleep BP decreases are attenuated and sleep BP loads are elevated, (2) casual BP correlates poorly with ABPM, and (3) interdialytic weight and BP are related.

Evaluation of white coat hypertension in children: importance of the definitions of normal ambulatory blood pressure and the severity of casual hypertension.

To better describe the phenomenon of white coat hypertension (WCH) in children, we reviewed our single-center experience using ambulatory blood pressure monitoring to determine: 1) how the choice of threshold limits for defining ambulatory hypertension affects the determination of WCH, and 2) whether the severity of casual hypertension predicts the occurrence of WCH. Using the same daytime ambulatory blood pressure (ABP) data from 71 children (age 11.9 3.4 years) with persistently elevated casual blood pressure (BP), the prevalence of WCH was compared using 95th percentile BP limits from the Task Force on High Blood Pressure in Children (TF) and from normative pediatric daytime ambulatory BP (ABP) data. To quantify casual hypertension severity, average clinic BP was divided by the patient-specific TF 95th percentile BP to generate a BP index (ie, BP index of 1.1=10% above 95th percentile). The WCH prevalence was lower by normative ABP criteria than by TF criteria (31% v 59%, P < .001), but did not vary significantly by age, gender, race, or body mass index. Logistic regression showed that higher systolic BP index (P < .001) or diastolic BP index (P < .01) was associated with a lower probability of WCH. Specifically, as systolic BP index increased from 1.0 to 1.2, the estimated probability of WCH decreased from 87% to 15%, respectively. These data suggest that the use of the lower TF limits, derived solely from resting BP measurements, may overestimate WCH prevalence in ambulatory children. In addition, these data confirm in children the finding in adults that WCH is highly prevalent when casual hypertension is borderline or mild, but uncommon when moderate or severe.

Temporal blood pressure patterns in children.

Circadian rhythms of BP are established early in life. The ABPM coupled with an objective measure of activity is a powerful tool for the management of hypertension and is a sensitive tool for the dissection of the determinants of hypertension. The challenge for pediatricians in the future includes such important goals as establishing normal values for the circadian assessment of BP for a growing child, coupling of BP determinations with activity, using the ABPM to better understand BP tracking, studying the rhythms of families using the ABPM, educating the medical and lay communities of the importance of rhythmic phenomena, studying longitudinally patients with varying forms of hypertension, using the ABPM to test and optimize antihypertensive medications, and determining the proper diagnosis of hypertension in children based on end-organ damage rather than surrogate measures.

Comparison of arbitrary definitions of circadian time periods with those determined by wrist actigraphy in analysis of ABPM data.

Determining blood pressure (BP) values at different daily time periods is a well recognised measure to assess the risk of end-organ damage. However, the use of various definitions of these periods, eg, day vs night, sleep vs wake or arbitrary definitions, makes clinical decisions based on available data difficult. In the present study, we compared BP loads in actual sleep-wake periods to default day-night definition provided by the ambulatory BP monitoring (ABPM) software (day 06.00-22.00; night 22.00-06.00) as well as to an arbitrary definition of sleep-wake periods in children published in Journal of Pediatrics (Soergel et al, 1997) (awake 08.00-20:00 and sleep 00.00-06.00). We used an actigraph, an accelerometer, to define the actual sleep-wake periods in 46 patients with essential hypertension who are on various treatment regimens. BP data were obtained by using Spacelabs 90207 monitors for a full 24 hours. There were significant differences between actual sleep-wake and default definition for BP load. No similar findings were noted when arbitrary definition was used. The proportion of hypertensives was not significantly different when default and arbitrary definitions were used. Classification of dippers and non-dippers is greatly affected by the definition of sleep interval using the default method. Although some of the misclassifications were not statistically significant, their clinical importance must be considered. Determination of sleep and wake periods for analysis of ABPM data should be based on careful determination of actual periods. Using other definitions may not provide complete information or accommodate for individual variation.

Comparison of arbitrary definitions of circadian time periods with those determined by wrist actigraphy in analysis of ABPM data.

Determining blood pressure (BP) values at different daily time periods is a well recognised measure to assess the risk of end-organ damage. However, the use of various definitions of these periods, eg, day vs night, sleep vs wake or arbitrary definitions, makes clinical decisions based on available data difficult. In the present study, we compared BP loads in actual sleep-wake periods to default day-night definition provided by the ambulatory BP monitoring (ABPM) software (day 06.00 to 22.00; night 22.00 to 06.00) as well as to an arbitrary definition of sleep-wake periods in children published in Soergel et al (J Pediatr 1997; 130: 178-184)1 (awake 08.00 to 20.00 and sleep 00.00 to 06.00. We used an actigraphy, an accelerometer, to define the actual sleep-wake periods in 46 patients with essential hypertension who are on various treatment regimens. BP data was obtained by using Spacelabs 90207 monitors for a full 24 h. There were significant differences between actual sleep-wake and default definition for BP load. No similar finding was noted when arbitrary definition was used. The proportion of hypertensives was not significantly different when default and arbitrary definitions were used. Classification of dippers and non-dippers is greatly affected by the definition of sleep interval using the default method. Although some of the misclassifications were not statistically significant, their clinical importance must be considered. Determination of sleep and wake periods for analysis of ABPM data should be based on careful determination of actual periods. Using other definitions may not provide complete information or accommodate for individual variation.

Changes in circadian rhythm of blood pressure in on-call pediatric residents.

To provide an objective measure of the effects of on-call stress on the blood pressure (BP) of a group of pediatric residents, we used a SpaceLabs Ambulatory Blood Pressure Monitor (ABPM) to compare 37 pediatric residents' on- and off-call BPs. Residents wore the ABPM for 24 h (once on call and again off call) to assess systolic and diastolic BPs every 30 min during the day and hourly overnight. We found significantly higher MESOR (an acronym for midline estimating statistic of rhythm, which yields a mean value more representative of the true mean than an average of a series of measurements) BPs and BP loads (%BP readings > 135 mm Hg for systolic and/or 85 mm Hg diastolic) during the on-call period. Some residents became hypertensive on call, and the normal 24-h pattern of lower nighttime blood pressures was altered during this period. ABPM monitoring may prove useful in evaluating the effectiveness of interventions to reduce the stress of residency training.

Chronobiologic evaluation of blood pressure in school children.

Blood pressure (BP) and heart rate (HR) data were collected over 24 h with an ambulatory BP monitor to (a) determine the existence of 12-, 24-, and combined 12- and 24-h BP patterns in children as previously noted for adults; (b) provide MESOR (an acronym for midline estimating statistics of rhythm), amplitude, and acrophase data for subgroups of students by race and gender; and (c) determine the influence of HR (as an estimate of activity) on BP and BP patterns for 100 normal, healthy students 9-12 years of age. We found no statistically significant differences between various racial groups or between gender for MESOR, amplitude, acrophase, or degree of sinusoidality of circadian rhythmicity (R2 values) for BP; clinically interesting differences were observed, including lower MESOR BPs in Hispanic males when compared with their female counterparts and slightly higher MESOR BPs in blacks of both genders when compared with whites. In addition, we demonstrated subgroups of students who exhibited specific 24-h and combined 12- and 24-h patterns. Also, 67% of subjects showed stable or nonrhythmic BP patterns, perhaps related to BP sampling intervals. Differences in HR, as a surrogate measure of activity, accounted for 56% of the variation in systolic BP but only 26% in diastolic BP over the 24 h.

Technical aspects of blood pressure measurement in pediatric patients.

BACKGROUND: Prolonged hypertension in adults has been associated with end-organ damage, in addition to increased morbidity and mortality. Accurate measurement of blood pressure in pediatric and adult patients is imperative for the appropriate diagnosis of hypertension, so that measures may be instituted to prevent these adverse sequelae. Although intermittent office measurement of blood pressure is practiced in most parts of the world, the technique is fraught with problems. Errors during the actual measurement and difficulties in interpretation of the data are well-studied challenges associated with intermittent blood pressure measurements that have been well studied. Ambulatory blood pressure monitoring offers several advantages over intermittent measurement: blood pressure measurements are available over a prolonged period of time (including the sleep period), measurements are not as dependent on observer biases as are intermittent measurements, and in adults the data appear to correlate well to measures of end-organ damage. In children, the ambulatory blood pressure monitor is well tolerated and accurate. This new technology may offer pediatric specialists the opportunity to identify more accurately the child with increased blood pressure, so that preventive measures can be instituted to reduce the well-known morbidity and mortality associated with hypertension. OBJECTIVE: To review the technical aspects of blood pressure measurement in children, with special attention to the emerging field of ambulatory blood pressure monitoring and its potential use in children.

Comparison of the actigraph versus patients' diary information in defining circadian time periods for analyzing ambulatory blood pressure monitoring data.

BACKGROUND: Assessment of 24-h changes in blood pressure is one of the unique features that ambulatory blood pressure monitoring (ABPM) can provide. Most studies agree that sleep/wake periods should be based on patients' actual sleep and wake times. Actual wake and sleep time determinations are often based on patients' diary information. Several publications indicate that actigraphy is, at least, as accurate as activity diary in determining sleep/wake periods. OBJECTIVES: To compare subjects' compliance with actigraphy and diary keeping and to compare actigraphy and diary data in determination of sleep and wake times, mean blood pressures, classification of hypertension, and assessment of nocturnal dipping status. METHODS: We evaluated ABPM studies of 62 subjects. Blood pressure data were obtained using Spacelabs monitors for 24h. Sleep and wake times were determined by both the actigraph and patients' activity diary. RESULTS: In the 62 studies, 56 subjects had successful actigraphy (90%), 44 had activity diary completion (71%), and 38 subjects had both (61%). There was no statistically significant difference between the mean wake and sleep onset using the two methods, but up to 3 hours' difference in wake or sleep onset was noted in some studies. Although the two methods did not significantly affect the calculated systolic blood pressure (SBP) or diastolic blood pressure (DBP) loads in either awake or sleep periods, approximately 55% of the subjects' dipping status was changed when diary information on sleep time was used compared to actigraph. CONCLUSIONS: Our data indicate that in children and young adults, compliance with the actigraph was superior to diary completion and use of the actigraphy method rather than diary information changed the interpretation of some ABPM data. Our study suggested that actigraphy is superior to diary keeping in providing the information needed for appropriate interpretation of some ABPM data.

Stress-induced alterations of blood pressure and 24 h ambulatory blood pressure in adolescents.

OBJECTIVE: To examine the extent to which ambulatory blood pressure was predicted by blood pressure levels exhibited during talking segments of a laboratory protocol and by resting blood pressures in male and female adolescents from three ethnic groups: African, European and Hispanic Americans. DESIGN: This was a laboratory-field study incorporating an experimental study of reactivity of blood pressure during a laboratory protocol and an observational study of 24h ambulatory blood pressure (ABP) monitoring. METHODS: Resting blood pressure, reactivity of blood pressure, 24h ABP, and activity, height, and maturation of a multi-ethnic sample of 373 male and female adolescents aged 11-16 years were measured. A mixed-effects model for repeated measures was the statistical approach, with systolic and diastolic blood pressures as separate, dependent variables. RESULTS: Percentiles of ABP by sex, ethnic group, and height are presented. High and mixed blood pressure reactors in the laboratory had higher levels of 24h ABP and higher levels of blood pressure load during the daytime. African Americans had higher ABP than did European and Hispanic Americans. CONCLUSIONS: Blood pressure measured during laboratory tasks that require talking might be useful as a screening device to identify adolescents with high blood pressures. Further study will be necessary in order to quantify the sensitivity of the laboratory protocol as an indicator of high blood pressure compared with casual measurement of blood pressures. If laboratory patterns of blood pressure could be used to predict which individuals have high levels of blood pressure during the course of daily activities, the laboratory protocol would be a useful screening tool, identifying high-risk individuals.

Population studies of ambulatory blood pressure monitoring in Brazilian children.

BACKGROUND: The determination of hypertension in a given population depends on the knowledge of population norms for blood pressure. This is true for both casual blood pressure (CBP) measurements and the newest and most promising technology of ambulatory blood pressure monitoring (ABPM). OBJECTIVE: To design an ambitious multinational co-operative study to determine normal blood pressure data in Brazilian children. METHODS: The study was designed to determine normative data for CBP, using the Task Force technical recommendations for age-, sex- and height-percentile-specific blood pressure values. The proposed procedure is as follows. ABPM will be studied in a random subgroup of individuals, to develop similar normative data. These data will be correlated to CBP measurements and to echocardiographic findings as a measure of end-organ damage. All patients who are diagnosed by CBP measurement to be hypertensive will also be studied by ABPM, and studies of target-organ damage will be performed. Family and medical histories will be evaluated by questionnaire and first-degree relatives will be evaluated for CBP measurement. Hypertensive patients will form a cohort for long-term follow-up. These data will be the foundation for studies of hypertension in Brazilian children.

Hypertension in children.

Early identification of children at risk for hypertension, proper evaluation, and appropriate management is important to prevent the serious long-term complications associated with the condition. This article defines primary and secondary hypertension in children, describes accurate blood pressure measurement techniques in children, presents the evaluation of a child with hypertension, and discusses therapy and prevention.