Biomedical subjects

R C Hermida

Publications and source records attributed to R C Hermida.

At least 37 records · Page 2Linked to original sources

PubMed1999

Circadian variation of plasma cortisol in prepubertal children with normal stature, short stature and growth hormone deficiency.

OBJECTIVES: When studying the relationship between spontaneous secretion of growth hormone (GH) and cortisol in children, most studies show no correlation in mean levels of these two hormones, while others found positive or even strongly negative correlations. These contradictory results could be partly due to the inability to properly compare hormones that are characterized by circadian and ultradian variations in their secretory profiles. We aim here to study possible differences in rhythm characteristics of plasma cortisol with stature and to compare the circadian secretory patients of cortisol and GH. PATIENTS: We analysed data from 135 prepubertal children: (1) 14 GH-deficient children; (2) 36 children with short stature (2-3 SD below their peer group mean); (3) 57 children with very short stature (3-4 SD below their peer group mean); and (4) a reference group of 28 children with normal stature (+/- 2 SD). Subjects were living in a hospital setting on a diurnal waking (07.30-22.30 h), nocturnal resting routine during sampling, consuming the usual hospital diet at fixed times. MEASUREMENTS: Cortisol and GH concentrations were determined by radioimmunoassay in plasma obtained at about 2-3 h intervals during most of the day and at half-hour intervals between 22.00 and 02.00 h. Circadian rhythm characteristics obtained by least-squares estimation were compared between groups divided according to gender and stature with a parameter test. RESULTS: Show a statistically significant circadian rhythm in cortisol secretion for all groups studied (P < 0.001 in all cases). A comparison of circadian parameters indicated similar characteristics between subjects of short, very short and normal stature. Despite a borderline statistically significant difference in rhythm-adjusted mean and amplitude of GH between nondeficient and GH-deficient children, there was no difference in the circadian pattern of cortisol secretion between these two groups. No correlation was found in circadian mean, amplitude, average, standard deviation, standard error, minimum or maximum between GH and cortisol for any of the groups of children. CONCLUSIONS: Any possible relation between GH and cortisol remains unclear. Moreover, GH-deficient children are not necessarily characterized by either hyper- or hypocortisolaemia.

Child↗

PubMed1999

Short-term leptin infusion does not affect circulating levels of LH, testosterone or cortisol in food-restricted pubertal male rhesus macaques.

OBJECTIVES: Although the adipocyte protein leptin has been implicated in the control of reproductive function in rodents, its role in primate reproductive physiology is poorly understood. Because primates in puberty show nighttime LH secretion and there is considerable evidence that the fertile state requires adequate nutrition, we reasoned that animals on the verge of reproductive competence would respond to leptin infusions by secreting LH. Food restriction reduces circulating leptin levels and slows or stops the GnRH pulse generator. Therefore, we examined the endocrine effects of leptin infusions in food-restricted male pubertal primates during the night when they normally secrete LH. In addition, we investigated the effect of leptin on in vitro testosterone production by Leydig cells. SUBJECTS: Four pubertal male rhesus macaques (Macaca mulatta), 4-5.5 kg in weight (2.5-4-year-old) were examined in this study. Leydig cells from adult male rats were to investigate in vitro effects of leptin. DESIGN: To document that animals had entered puberty, blood samples were collected from each of the four animals at 15-minute intervals for 15 h both during the day and at night. Since at this age animals secrete LH mainly at night, blood samples were collected at 15-minute intervals from each of the four animals on two separate occasions for 15 h between 1500 and 0600h. During the experiment, animals were feeding from 0800 to 0830h, cages were completely cleaned of food at 0900h and the afternoon meal was not given to individual animals on the day they were studied. One of the studies served as the control (food restricted group) and during the other, 2 mg (n = 4) or 0.3 mg (n = 3) of recombinant human leptin was administered intravenously during 2000-0100h (food restricted plus leptin group). Blood samples (1 ml) were collected through the indwelling catheter and immediately transferred from the plastic syringe into chilled glass tubes containing 10 microl 14% EDTA. The samples were centrifuged at 5-h intervals and the plasma withdrawn and stored frozen at - 20 degrees C in polypropylene vials until assays were performed. MEASUREMENTS: Bioactive LH was determined and testosterone, cortisol and leptin were measured by radioimmunoassay. RESULTS: During daytime experiments in these animals, LH pulses were sometimes observed late in the day and generally continued for 12-15 h. Food-restricted pubertal males showed delayed or absent LH pulses. Short-term leptin administration to food-restricted male rhesus macaques had no effect on LH, testosterone, or cortisol levels either during or after the infusion. Leptin also had no direct effect on basal or LH-stimulated testosterone production in Leydig cells. CONCLUSIONS: Our data support the notion that leptin is not the missing signal for the acute suppression of reproductive hormones secretion in food-restricted primates.

Animals↗

PubMed1999

Administration time-dependent effects of aspirin in women at differing risk for preeclampsia.

This study extends previous results on the effects of low-dose aspirin on blood pressure in pregnant women at differing risk of developing hypertension in pregnancy and who received aspirin at different times according to their rest-activity cycle. A double-blind, randomized, placebo-controlled trial was conducted in 240 pregnant women randomly assigned to 1 of 6 groups according to treatment (placebo or aspirin, 100 mg/d, starting at 12 to 16 weeks of gestation) and the time of treatment: on awakening (time 1), 8 hours after awakening (time 2), or before bedtime (time 3). Blood pressure and heart rate for each subject were automatically monitored for 2 days every 4 weeks from the day of recruitment until delivery, as well as at puerperium (6 to 8 weeks after delivery). Subjects were further divided for comparative purposes according to the results of the tolerance-hyperbaric test for early identification of those with a higher risk for developing hypertensive complications in pregnancy. Results indicated that there was no effect of aspirin on blood pressure at time 1 (compared with placebo). A blood pressure reduction was, however, highly statistically significant at time 2 and, to a greater extent, at time 3 (mean reductions of 14.2 and 9.6 mm Hg in 24-hour means for systolic and diastolic blood pressure, respectively, at the time of delivery compared with placebo given at the same time). Effects of aspirin on blood pressure were significantly larger for women with a positive test at the time of recruitment (P<0.001). Differences in blood pressure among pregnant women receiving aspirin at different times in the circadian cycle disappeared at puerperium (P>0.212). There was no effect of aspirin or placebo on heart rate. This study corroborates the statistically significant, time-dependent effect of low-dose aspirin on blood pressure in pregnant women with differing risk of developing hypertensive complications in pregnancy. Although the mechanism involved in the administration-time-dependent responsiveness of blood pressure to aspirin still remains uncertain, the use of doses of aspirin <80 mg/d that do not affect placental thromboxane, initiation of the use of aspirin after 16 weeks' gestation, and the lack of circadian timing for aspirin administration could all explain the lack of positive results in previous clinical trials.

Administration, Oral↗

PubMed1999

Circadian interleukin-6 secretion and quantity and depth of sleep.

Patients with pathologically increased daytime sleepiness and fatigue have elevated levels of circulating interleukin-6 (IL-6). The latter is an inflammatory cytokine, which causes sickness manifestations, including somnolence and fatigue, and activation of the hypothalamic-pituitary-adrenal axis. In this study, we examined: 1) the relation between serial measurements of plasma IL-6 and quantity and depth of sleep, evaluated by polysomnography; and 2) the effects of sleep deprivation on the nyctohemeral pattern of IL-6 secretion. Eight healthy young male volunteers were sampled for 24 h twice, at the baseline state, after a normal night's sleep and after total overnight sleep deprivation. At the baseline state, IL-6 was secreted in a biphasic circadian pattern with two nadirs at 0800 and 2100 and two zeniths at 1900 and 0500 (P < 0.01). The baseline amount of sleep correlated negatively with the overall daytime secretion of the cytokine (P < 0.05). Also, depth of sleep at baseline correlated negatively with the postdeprivation increase of daytime secretion of IL-6 (P < 0.05). Sleep deprivation changed the temporal pattern of circadian IL-6 secretion but not the overall amount. Indeed, during the post-deprivation period, the mean daytime (0800-2200 h) levels of IL-6 were significantly higher (P < 0.05), whereas the nighttime (2200-0600 h) levels were lower than the predeprivation values. Thus, sleep-deprived subjects had daytime oversecretion and nighttime under-secretion of IL-6; the former might be responsible for their daylong somnolence and fatigue, the latter for the better quality (depth) of their sleep. These data suggest that a good night's sleep is associated with decreased daytime secretion of IL-6 and a good sense of well-being and that good sleep is associated with decreased exposure of tissues to the proinflammatory and potentially detrimental actions of IL-6. Sleep deprivation increases daytime IL-6 and causes somnolence and fatigue during the next day, whereas postdeprivation decreases nighttime IL-6 and is associated with deeper sleep.

Adult↗

PubMed1998

Blood pressure excess for the early identification of gestational hypertension and preeclampsia.

We have examined prospectively whether the combined approach of establishing tolerance intervals for the circadian variability of blood pressure (BP) as a function of gestational age, and then determining the so-called hyperbaric index (area of BP excess above the upper limit of the tolerance interval) by comparison of any patient's BP profile (obtained by ambulatory monitoring) with those intervals provides a high sensitivity test for the early detection of pregnant women who subsequently will develop gestational hypertension or preeclampsia. We analyzed 657 BP series from 92 women with uncomplicated pregnancies and 378 series from 60 women who developed gestational hypertension or preeclampsia. BP was sampled for about 48 hours once every 4 weeks after the first obstetric consultation. Circadian 90% tolerance limits were determined as a function of trimester of gestation from 497 series previously sampled from a reference group of 189 normotensive pregnant women. The hyperbaric index was then determined for each individual BP series in the validation sample. Sensitivity of this test for diagnosing gestational hypertension was 93% for women sampled during the first trimester of gestation and increased up to 99% in the third trimester. The positive and negative predictive values were above 96% in all trimesters. Despite the limitations of ambulatory monitoring, the approach presented here, now validated prospectively, represents a reproducible, noninvasive, and high sensitivity test for the very early identification of subsequent gestational hypertension and preeclampsia, on the average, 23 weeks before the clinical confirmation of the disease.

Blood Pressure↗

PubMed1998

Reanalysis of filter-feeding behavior of caddis fly (Brachycentrus) larvae reveals masking and circadian rhythmicity.

Data published on the subjectively determined presence or absence of circadian periodicity in feeding of Brachycentrus occidentalis Banks, an aquatic insect belonging to the order Trichoptera, were reanalyzed by statistical methods based on the cosine model. The 4h data for 5 days of synchronized environmental conditions followed by 5 days of constant conditions (using original values and purified values after removal of an 8h component attributed to the feeding schedule) were quantified for rhythm characteristics by the least-squares fit of cosines. A circadian rhythm was highly significant during synchronized conditions (light-dark and cycling water temperature) and in continuous light when water temperature continued to cycle. A circadian rhythm in the percentage of larvae feeding during continuous light and constant water temperature, which had not been observed by visual inspection in the original data, was detected in the unmasked data with a "free-running" period not overlapping 24.0h (95% confidence limits from 18.95h to 21.66h). Effects of masking brought about by manually feeding the larvae every 8h were statistically significant under both synchronized and constant environmental conditions.

Animals↗

PubMed1998

Inferential statistical method for analysis of nonsinusoidal hybrid time series with unequidistant observations.

Most variables of interest in laboratory medicine show predictable changes with several frequencies in the span of time investigated. The waveform of such nonsinusoidal rhythms can be well described by the use of multiple components rhythmometry, a method that allows fitting a linear model with several cosine functions. The method, originally described for analysis of longitudinal time series, is here extended to allow analysis of hybrid data (time series sampled from a group of subjects, each represented by an individual series). Given k individual series, we can fit the same linear model with m different frequencies (harmonics or not from one fundamental period) to each series. This fit will provide estimations for 2m + 1 parameters, namely, the amplitude and acrophase of each component, as well as the rhythm-adjusted mean. Assuming that the set of parameters obtained for each individual is a random sample from a multivariate normal population, the corresponding population parameter estimates can be based on the means of estimates obtained from individuals in the sample. Their confidence intervals depend on the variability among individual parameter estimates. The variance-covariance matrix can then be estimated on the basis of the sample covariances. Confidence intervals for the rhythm-adjusted mean, as well as for the amplitude-acrophase pair, of each component can then be computed using the estimated covariance matrix. The p-values for testing the zero-amplitude assumption for each component, as well as for the global model, can finally be derived using those confidence intervals and the t and F distributions. The method, validated by a simulation study and illustrated by an example of modeling the circadian variation of heart rate, represents a new step in the development of statistical procedures in chronobiology.

Biometry↗

PubMed1997

Time-dependent effects of low-dose aspirin administration on blood pressure in pregnant women.

This study investigated the effects of low-dose acetylsalicylic acid (aspirin) on blood pressure in pregnant women who were at risk of developing gestational hypertension or preeclampsia and who received aspirin at different times of the day according to their rest-activity cycle. A double-blind, randomized, controlled trial was conducted in 100 pregnant women. Blood pressure for each subject was automatically monitored for 2 days every 4 weeks from the day of recruitment until delivery. Women were randomly assigned to one of six groups according to treatment (placebo, 50 subjects or aspirin, 100 mg/d, starting at 12 to 16 weeks of gestation) and the time of treatment: on awakening (time 1), 8 hours after awakening (time 2), or before bedtime (time 3). Results indicated that there was (1) no effect on blood pressure from placebo at any time (P>.212) and (2) a highly statistically significant (P<.001) time-dependent effect on blood pressure from aspirin. There was no effect of aspirin on blood pressure at time 1 (compared with placebo), but the blood pressure reduction was highly statistically significant after time 2 and, to a greater extent, after time 3 (mean reduction of 12 and 8 mm Hg in 24 hours for systolic and diastolic blood pressure, respectively, at the time of delivery compared with placebo given at the same time). These time-dependent effects of aspirin on blood pressure should be taken into account for the optimization of long-term aspirin administration at low doses for prevention of preeclampsia. In any meta-analysis of aspirin effects, inquiries about the time when the subjects took the drug are indicated and may account for discrepancies in the literature.

Adolescent↗

PubMed1997

Circadian blood pressure variability in healthy and complicated pregnancies.

With the aim to describe the circadian pattern of noninvasive ambulatorily monitored blood pressure during the trimesters of pregnancy in clinically healthy women as well as in pregnant women who developed gestational hypertension or preeclampsia, we analyzed 759 blood pressure series sampled by ambulatory monitoring for about 48 hours every 4 weeks after the first obstetric visit in 71 women with uncomplicated pregnancies, 28 with gestational hypertension, and 14 with preeclampsia. The circadian pattern of blood pressure variation for each group (complicated versus uncomplicated pregnancies) and trimester of gestation was established by linear least-squares methods. A highly statistically circadian pattern is demonstrated for systolic and diastolic blood pressure for both groups of pregnant women in all trimesters (P<.001 in all cases). Blood pressure decreases from the first trimester to the second and rises again in the third for healthy pregnant women. For women who developed gestational hypertension or preeclampsia, blood pressure is stable during the first half of pregnancy and then continuously increases until delivery. The differences in circadian rhythm-adjusted mean between complicated and uncomplicated pregnancies are highly statistically significant in all trimesters (always P<.001). This study confirms and extends to ambulatory everyday life conditions the predictable circadian variability in blood pressure during gestation. The differences in blood pressure between healthy and complicated pregnancies can be observed as early as the first trimester of pregnancy. Those differences are found when both systolic and diastolic blood pressures for women with a later diagnosis of gestational hypertension or preeclampsia are well within the accepted normal physiological range of blood pressure variability.

Adolescent↗

PubMed1997

Blood pressure variability during gestation in healthy and complicated pregnancies.

The evaluation of predictable variability in blood pressure by the use of ambulatory devices, and the proper processing of the time series thus obtained, can be useful for the early assessment of hypertensive complications in pregnancy. We have used this approach to quantify a predictable pattern of blood pressure and heart rate throughout pregnancy in clinically healthy women as well as in pregnant women who developed gestational hypertension or preeclampsia. We analyzed 503 blood pressure series from 71 healthy pregnant women and 256 series from 42 women who developed gestational hypertension or preeclampsia. Blood pressure monitoring (48-hour) was done once every 4 weeks after the first obstetric consultation. The pattern of variation along gestation of the 24-hour mean of blood pressure for groups of normotensive and hypertensive pregnant women was established by polynomial regression analysis. This method revealed predictable patterns of variation of 24-hour means with gestational age: for normotensive pregnant women, results indicate a steady decrease in blood pressure up to the 21st week of pregnancy, followed by an increase in blood pressure up to the day of delivery. This pattern of variation is not found in pregnancies complicated with gestational hypertension or even preeclampsia: the 24-hour mean of blood pressure is stable until the 22nd week of pregnancy and then correlated with gestational age, indicating a significant linear increase of blood pressure in the second half of pregnancy. For both healthy and complicated pregnancies, heart rate slightly increases until the end of the second trimester, and it is stable thereafter. This study confirms and extends to ambulatory everyday life conditions the predictable pregnancy-associated variability in blood pressure. The differences between uncomplicated and complicated pregnancies offer new end points for an early identification of gestational hypertension and preeclampsia.

Blood Pressure↗

PubMed1997

Diagnosing gestational hypertension and preeclampsia with the 24-hour mean of blood pressure.

The use of ambulatory blood pressure monitoring has provided a method of blood pressure assessment that may compensate for some of the limitations of isolated measurements. Here we aim to examine prospectively the effectiveness of the commonly used 24-hour mean as a potential screening test for the identification of gestational hypertension and preeclampsia. We analyzed 503 blood pressure series from 71 healthy pregnant women and 256 series from 42 women who developed gestational hypertension or preeclampsia. Forty-eight-hour blood pressure monitoring was done once every 4 weeks after the first obstetric consultation. Sensitivity and specificity of the 24-hour mean of blood pressure were computed for each trimester of pregnancy by comparing distributions of values obtained for healthy and complicated pregnancies, without assuming an a priori threshold for diagnosing gestational hypertension on the basis of mean blood pressure. Sensitivity ranges from 31.8% for diastolic blood pressure in the second trimester to 84.1% for systolic blood pressure in the third trimester. However, specificity is as low as 6.9% for diastolic blood pressure in the first trimester. The positive predictive value does not reach 55% for any variable in any trimester. The higher relative risk was consistently obtained for systolic blood pressure (4.9 in the third trimester). Despite the highly statistically significant differences in blood pressure found between healthy and complicated pregnancies in all trimesters, the daily mean of blood pressure does not provide a proper and stable individualized test for diagnosing hypertensive complications in pregnancy. Other indexes obtained from the blood pressure series have been shown, however, to identify early in pregnancy those women who subsequently will develop gestational hypertension or preeclampsia, rendering ambulatory blood pressure monitoring a useful, but still costly, technique in pregnancy.

Blood Pressure↗

PubMed1997

Nocturnal rise of leptin in normal prepubertal and pubertal children and in patients with perinatal stalk-transection syndrome.

We studied 24-h profiles of circulating leptin levels using a sensitive and specific radioimmunoassay in healthy pre- (Tanner 1) and pubertal boys and girls (Tanner 3-4) as well as in a group of patients with perinatal stalk-transection syndrome. Similar nyctohemeral rhythm in serum leptin levels were found in prepubertal (MESOR: 2.34 +/- 0.2 ng/ml; amplitude 0.32 +/- 0.1 ng/ml) and pubertal boys (MESOR 2.2 +/- 0.2 ng/ml; amplitude 0.38 +/- 0.07 ng/ml). Likewise, no differences were found between prepubertal (MESOR 6.6 +/- 1.07 ng/ml; amplitude 1.67 +/- 0.4 ng/ml) and pubertal girls (MESOR 4.05 +/- 0.5 ng/ml; amplitude 0.95 +/- 0.2 ng/ml). In contrast, higher MESOR (p < 0.002) and amplitude values (p < 0.005) were found in prepubertal and pubertal girls than in prepubertal and pubertal boys. Finally a significant nyctohemeral rhythm in serum leptin levels was found in patients with perinatal stalk-transection syndrome (MESOR: 9.3 +/- 2.3 ng/ml; amplitude 1.46 +/- 0.4 ng/ml). This data shows the existence of sexual dimorphism in the nyctohemeral rhythm in serum leptin levels that are not influenced by the pubertal stage or by pulsatile anterior pituitary hormone secretion.

Adolescent↗

PubMed1997

High sensitivity test for the early diagnosis of gestational hypertension and preeclampsia. I. Predictable variability of cardiovascular characteristics during gestation in healthy and hypertensive pregnant women.

The evaluation of predictable variability in blood pressure and heart rate by (a) the use of fully ambulatory devices, and (b) the proper processing of the time series thus obtained, can be useful in assessing early cardiovascular disease risk in pregnancy. We have used this approach to quantify a predictable time structure of blood pressure throughout pregnancy in clinically healthy women as well as in pregnant women who developed gestational hypertension of preeclampsia. We analyzed a total of 745 blood pressure series sampled by ambulatory monitoring for about 48 hours in each of several occasions in 189 women with uncomplicated pregnancies, 71 with gestational hypertension, and 29 with preeclampsia. The pattern of variation along gestation of the 24-hour mean of blood pressure for groups of normotensive and hypertensive pregnant women was established by polynomial regression analysis. Regression analysis revealed predictable patterns of variation of 24-hour means with gestational age: for normotensive pregnant women, results indicate a steady decrease in blood pressure up to the 20th week of pregnancy, followed by an increase in blood pressure up to the day of delivery. Women with gestational hypertension or preeclampsia are characterized, however, by a continuous linear increase of blood pressure with gestational age, starting from the beginning of pregnancy. This study confirms and extends to ambulatory everyday life conditions the predictable pregnancy-associated variability in blood pressure. The differences between uncomplicated and complicated pregnancies offer new endpoints for an early identification of gestational hypertension and preeclampsia.

Blood Pressure↗

PubMed1997

High sensitivity test for the early diagnosis of gestational hypertension and preeclampsia. II. Circadian blood pressure variability in health and hypertensive pregnant women.

The aim of this study was to describe the circadian pattern of non-invasive ambulatorily monitored blood pressure during the trimesters of pregnancy in clinically healthy women as well as in pregnant women who developed gestational hypertension or preeclampsia, and to compare sensitivity and specificity of diagnosis based on the average of the blood pressure series with the values obtained on the basis of casual measurements. We analyzed a total of 745 blood pressure series sampled by ambulatory monitoring for about 48 hours in each of several occasions in 189 women with uncomplicated pregnancies, 71 with gestational hypertension, and 29 with preeclampsia. The circadian pattern of BP variation for each group (complicated vs. uncomplicated pregnancies) and trimester of gestation was established by linear least-squares methods. Highly statistically different circadian patterns are demonstrated for systolic, mean arterial and diastolic blood pressure for both groups of pregnant women in all trimesters (P < 0.001 in all cases). Blood pressure decreases from the first trimester to the second and raises again in the third for healthy pregnant women, but continuously increases during gestation in women who developed gestational hypertension or preeclampsia. The differences in circadian rhythm-adjusted mean between complicated and uncomplicated pregnancies are highly statistically significant in all trimesters (P < .001). Sensitivity and specificity of diagnosing gestational hypertension based on the circadian mean are 73% and 48%, respectively, too low for a proper individualized diagnosis of gestational hypertension or preeclampsia. This study confirms the predictable circadian variability in blood pressure during gestation. The differences between healthy and complicated pregnancies can be observed as early as in the first trimester of pregnancy, but the use of the 24-hour mean BP does not provide a good approach for early diagnosis of gestational hypertension or preeclampsia.

Blood Pressure↗

PubMed1997

Influence of aspirin usage on blood pressure: dose and administration-time dependencies.

This study investigates the possible effects of acetylsalicylic acid (ASA; aspirin) on systolic (S) and diastolic (D) blood pressure (BP) in healthy and mildly hypertensive subjects receiving ASA at different times according to their rest-activity cycle. A double-blind, randomized, controlled trial was conducted in 73 healthy young adult volunteers and 18 previously untreated subjects with mild hypertension. The BP of each subject was automatically monitored every 30 minutes for 48h before the trial and at the end of a one-week course of placebo and a one-week course of ASA. Healthy volunteers were randomly assigned to one of six groups, defined according to the dose of ASA (either 500 mg/day, the usual commercial dose; or 100 mg/day) and timing of ASA and placebo (within 2h after awakening, Time 1; 7h to 9h after awakening, Time 2; or within 2h of bedtime, Time 3). Subjects with mild hypertension received the low dose of 100 mg/day ASA, as well as one week of placebo, and were randomly assigned to one of the same three groups defined above according to the time of treatment. A small (approximately 2 mmHg in the 24h mean of SBP), but statistically significant, BP reduction was found when 500 mg/day ASA was given to healthy volunteers at Time 2. With 100 mg/day, the effect of ASA in healthy subjects was comparable to the BP reduction found with the higher dose for Time 2; there was again no effect on BP at Time 1, but we found a statistically significant effect at Time 3 (2.3 mmHg reduction in the 24h mean of SBP), larger than for Time 2. For hypertensive patients, the BP reduction was again statistically significant for Time 2 and, to a greater extent, for Time 3 (approximately 4.5 mmHg for both SBP and DBP); all patients in these two groups showed a BP reduction after one week of ASA. The effect was about three times as large as the BP reduction obtained in healthy subjects treated with 100 mg/day ASA. Results indicate a statistically significant time- and dose-dependent effect of ASA on BP. In any meta-analysis of ASA effects, inquiries about the time when subjects took the drug are indicated and may account for discrepancies in the literature. Moreover, the influence of ASA on BP demonstrated here indicates the need to identify and control for ASA effects in patients using ASA before and during their participation in antihypertension medication trials.

Adult↗

PubMed1997

Computation of time-specified tolerance intervals for hybrid time series with nonequidistant sampling, illustrated for plasma growth hormone.

The ideal reference interval for a variable of clinical interest would be specific for all deterministic factors affecting that variable, including the time of sampling in relation to biological rhythms. In particular, growth hormone is characterized in children by circadian and ultradian variability, with high peaks of secretion occurring mainly during sleep. For clinical applications, the use of tolerance intervals has been recommended, and they should substitute, whenever possible, for prediction limits. In the case of hybrid data (time series of data collected from a group of subjects), such a tolerance interval could be very difficult to determine following a parametric approach similar to the procedure used for the computation of prediction intervals, especially when consideration of both within-subjects and among-subjects variances is wanted. Accordingly, we have developed a nonparametric method for the computation of such tolerance intervals. Because the method is based on bootstrap techniques, it does not require the assumption of normality or symmetry in the data and is also more appropriate when dealing with small samples. The method was used to establish time-qualified reference limits for a series of growth hormone sampled around the clock in groups of prepubertal children differentiated according to stature. The use of these tolerance intervals may eliminate many false-positive and false-negative diagnoses that might be obtained when relying on time-unspecified single samples. The provision of such tolerance limits introduces time-specification and time-structure evaluation into prevention, diagnosis, and treatment of growth disorders.

Activity Cycles↗

PubMed1997

High sensitivity test for the early diagnosis of gestational hypertension and preeclampsia. III. Computation of time-specified tolerance intervals as reference for blood pressure excess in the diagnosis of gestational hypertension.

According to classic embryological testbooks intervillous circulation is established early in the first trimester. This process starts with trophoblastic invasion of the decidua in which proteolytic enzymes facilitate the penetration and erosion of the adjacent maternal capillaries with formation of the lacunae. After the lacunar or previllous stage trophoblast invades deeper portions of endometrium with belonging spiral arteries. This gradual process finishes with direct opening of the spiral arteries in the intervillous space under the fully developed placenta. This classic concept of establishment of the intervillous circulation was challenged in 1987 and 1988 by the experiments of Hustin and Shaaps. The authors believed that blood flow in the intervillous space is absent in incompletely development before 12 weeks of gestation. After the introduction of the generation of far more sensitive color Doppler devices in the last few years, our group and several others reported a positive finding of intervillous circulation during the first trimester of pregnancy.

Blood Pressure↗

PubMed1997

High sensitivity test for the early diagnosis of gestational hypertension and preeclampsia. IV. Early detection of gestational hypertension and preeclampsia by the computation of a hyperbaric index.

UNLABELLED: The aims of this study were to examine whether the combined approach of 1) establishing tolerance intervals for the circadian variability of blood pressure as a function of gestational age, and 2) computing the hyperbaric index by comparison of any patient's blood pressure profile (obtained by ambulatory monitoring) with the tolerance limits, provides a new highly sensitive test for the early detection of gestational hypertension and preeclampsia. We analyzed a total of 745 blood pressure series sampled by ambulatory monitoring for about 48 hours in each of several occasions in 189 women with uncomplicated pregnancies, 71 with gestational hypertension, and 29 with preeclampsia. After synchronization of all data by expressing times of sampling in hours from bed-time, circadian tolerance limits were first computed from the normotensive subjects as a function of trimester of pregnancy. The hyperbaric index and the percentage time of excess were then computed for each individual blood pressure series. The maximum hyperbaric index was below 15 mmHg X hour for normotensive pregnant women in all trimesters of pregnancy, and mostly above that value for women who subsequently developed gestational hypertension or preeclampsia. Sensitivity of the test based on the maximum hyperbaric index was 97% for women sampled during the first trimester of gestation, and increased up to 100% in the third trimester. The positive predictive value was 100% in all trimesters. Moreover, the computation of the hyperbaric index provided, on the average, an early identification of gestational hypertension or preeclampsia 20 weeks prior to the clinical confirmation of the disease. CONCLUSIONS: Ambulatory monitoring of blood pressure during gestation provides sensitive endpoints for use in early risk assessment and as a guide for establishing preventive interventions. The approach presented here represents a simple, reproducible, non-invasive, and highly sensitive test for the very early identification of gestational hypertension and preeclampsia.

Blood Pressure↗