This population study included 399 subjects, of whom 370 (93%) showed a significant diurnal blood pressure (BP) rhythm. The nocturnal BP fall was normally distributed and averaged 16 +/- 9 mm Hg systolic and 14 +/- 7 mm Hg diastolic (mean +/- SD). The amplitude of the diurnal BP curve followed a positively skewed distribution, with a mean of 16 +/- 5 mm Hg for systolic BP and 14 +/- 4 mm Hg for diastolic BP. The daily BP maximum occurred at 15:54 +/- 4:47 for systolic BP and at 15:11 +/- 4:20 for diastolic BP. Thirty-four subjects were reexamined after a median interval of 350 days. The test for the presence of a significant diurnal rhythm was discordant in only two subjects. Repeatability (twice the standard deviation of the differences between paired recordings expressed as a percentage of the mean) varied from 11 to 25% for the 24 h, daytime, and overnight BP, and from 76 to 138% for the parameters describing the diurnal BP rhythm. In nine subjects with an initial night/day ratio of mean BP less than 0.78, the nighttime BP was significantly increased at the repeat examination, whereas the opposite tendency was observed in nine subjects with an initial ratio greater than 0.87. In conclusion, the distribution of the nocturnal BP fall is unimodal. The reproducibility of the ambulatory BP is satisfactory for the level of BP and for the presence of a diurnal BP rhythm, but not for the parameters of the diurnal BP curve. Thus, one 24 h recording is insufficient to fully characterize an individual's diurnal BP profile.
The S100 proteins CAPL and CACY are expressed in a tissue- and cell-specific manner and have been reported to be associated with the metastatic phenotype of tumor cells. In order to study the biochemical, cation-binding, and conformational properties, we produced and purified large amounts of the recombinant human proteins in Escherichia coli. Several characteristics of native proteins are shown to correspond to those of the bacterially expressed proteins. Both are able to form homodimers in vitro, probably the biologically active species, but not heterodimers. The Ca(2+)-binding parameters were studied by flow offlysis at physiological ionic strength. Both isotherms show a maximum of two Ca2+ per protein and are insensitive to Mg2+, indicating that the sites are of the Ca(2+)-specific type. The isotherms show slight (CAPL, nH = 1.15) or pronounced (CACY, nH = 1.33) positive cooperativity with K0.5 values of 0.32 mM (CACY) and 0.15 mM (CAPL), indicating that the sites are of the low-affinity type. Conformational changes in the Tyr microenvironment of CACY indicate that Ca2+ binding induces a shift of Tyr to a less polar environment. Mg2+ does not affect the fluorescence properties nor does it induce a difference spectrum, thus suggesting that at physiological ionic conditions it does not interact with the protein. The Ca(2+)-induced difference spectra of CAPL are about 3 times smaller than those of CACY, suggesting that the additional Tyr84 in CACY is much more sensitive to Ca2+ than the two Tyr residues conserved in both proteins.
The plotting of cumulative sums (cusums), a technique of proven value in the detection of trends in data collected at intervals of time, may be modified to analyze circadian blood pressure patterns quantitatively. Mean 24-hour ambulatory blood pressure is taken as the reference value and is subtracted from each pressure value. The products of the remainders and the corresponding time intervals are summed in sequence and are plotted against time to form a modified cusum plot The slope of the plot over any given time period equals the difference between mean blood pressure during that period and mean 24-hour blood pressure. Crest and trough blood pressures (the mean blood pressures of the 6-hour periods of highest and lowest pressures) may be identified as the 6-hour periods where plot slopes are most steeply ascending and descending, respectively. The magnitude of the circadian blood pressure change, defined as the difference between crest and trough blood pressure, is calculated from the difference between crest and trough plot slopes. The height of the cusum plot, which reflects pressure alteration extent and duration, may also be used as a measure of circadian pattern. The modified cusums technique and cusum-derived statistics are illustrated using ambulatory blood pressure profiles of hypothetical and actual hypertensive subjects. Independence from fixed time periods improves precision and reproducibility. Cusum-derived statistics are simply calculated from raw ambulatory data and should prove useful in the quantitative analysis of circadian blood pressure profiles. The cumulative sums (cusums) technique is among the simplest statistical methods available. -19 It makes possible rapid and powerful assessments of changes in means or in the slopes of trends from data collected at intervals of time. In this technique, an arbitrary but relevant line is drawn across a plot of the data. Successive deviations of the data from that line are then summed and plotted. Sustained higher or lower values than the reference line produce positively and negatively sloping lines, respectively. The magnitude of the slope of the line depends on the difference of the values from the reference value. Changes in the cusum reveal changes in the trend of data from the baseline much more sensitively than do the data themselves. The use of cusums in ambulatory blood pressure data has previously been confined to merely detecting the precise points of change of successive measurements. 20 However, taking mean 24-hour blood pressure as the reference value and multiplying pressure deviations by time permits the adaptation of cusums to quantify nocturnal dipping with independence from fixed time periods.In this study, we used both hypothetical blood pressure profiles and repeated 24-hour ambulatory blood pressure measurements from a group of 22 hypertensive subjects to illustrate this modification of cusums methodology and also to assess its precision in the characterization of circadian blood pressure patterns.
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