Relationships between the antibacterial activity of sodium hypochlorite and treatment time and biofilm age in early Enterococcus faecalis biofilms.

AIM: To determine the relationships between the antibacterial activity of NaOCl and treatment time and biofilm age in early Enterococcus faecalis biofilms using a linear fitting procedure. METHODOLOGY: Enterococcus faecalis biofilms were formed on hydroxyapatite discs. To investigate the relationship between the antibacterial activity of NaOCl and biofilm age, 22-, 46-, 70- and 94-h-old biofilms were exposed to NaOCl (0-3%) for 5 min. To investigate the relationship between the antibacterial activity of NaOCl and treatment time, 70-h-old biofilms were exposed to NaOCl (0-3%) for 1, 3, 5 and 7 min. After treatment, colony-forming units (CFUs) were counted. To determine the relationships between these variables, linear fitting was performed. RESULTS: The change in the minimum biofilm eradication concentration (MBEC) of NaOCl followed a linear pattern of biofilm age (R = 0.941, R(2)  = 0.886) or treatment time dependence (R = -0.948, R(2)  = 0.898). Below the MBEC, the fitting lines for bacterial CFU count versus NaOCl concentration (R ≤ -0.973, R(2)  ≥ 0.948) in the 22-, 46-, 70- and 94-h-old biofilms implied that the antibacterial activity of NaOCl decreased as the biofilm age increased. The fitting lines for bacterial CFU count versus NaOCl concentration (R ≤ -0.970, R(2)  ≥ 0.942) in the 1-, 3-, 5- and 7-min treatments implied that the antibacterial activity of NaOCl increased with treatment time. CONCLUSIONS: These results suggest that the antibacterial activity of NaOCl against early E. faecalis biofilms in root canals may follow a linear pattern depending on biofilm age or treatment time.

Use of runs test to assess cardiovascular autonomic function in diabetic subjects.

OBJECTIVE: We suggest a simple, noninvasive method to assess the autonomic function in diabetic subjects. The method requires only a monitoring of heart rate (HR) with subjects in the sitting position. RESEARCH DESIGN AND METHODS: Sixty diabetic subjects, 44 men and 16 women, between 20-80 years of age, were recruited, chronologically, for this study. Subjects treated for high blood pressure were not included. Their autonomic function was assessed by the total score of five classical cardiovascular function tests. In the same subjects and in 44 healthy subjects, blood pressure and HR were determined from beat to beat by the Finapres system with subjects in the sitting position. We examined the randomness of the HR changes by calculating the zeta statistic of the runs test on 1,000 successive HR readings (the zeta value is low if the HR changes are random). When the HR changes are random, we consider that the autonomic control of HR is impaired. RESULTS: The zeta values of HR changes were significantly lower in diabetic subjects compared with normal subjects (2.98 +/- 0.97 vs. 3.54 +/- 0.97, P < 0.004). In diabetic subjects, the zeta value was closely correlated to the total score of disautonomy (r = -0.66, P < 0.0001, after correction for age effect) and to the office systolic blood pressure (r = -0.43, P < 0.001). CONCLUSIONS: The zeta value of HR changes might be a marker of the autonomic function in diabetic subjects.

Essential hypertension: an approach to clinical data by the use of models.

A new approach, based on animal circulatory models, was proposed for the study of clinical data in hypertension. Clinical data were identified with steady states in models. From the study of models, possible impairments, susceptible to account for the observed derivations of steady states in men, were analyzed. To be specific, the 1967-Guyton-Coleman model was confronted with a set of data on essential hypertension. The approach afforded a physiological interpretation for statistical results performed on clinical data.

Mechanical pressure versus intrinsic effects of hypertension on large arteries in humans.

Brachial artery diameter and compliance were measured in 23 normotensive control subjects and 49 hypertensive patients. The results were compared in isobaric conditions by a modeling analysis extrapolating from the measured data a short segment of the pressure-diameter and pressure-compliance curves in the artery. A logarithmic diameter-pressure function was used as well as measurements of brachial artery blood pressure and lumen diameter (by pulsed Doppler), and of brachial-to-radial pulse wave velocity (by mechanography). The measured values of diameter and compliance in the hypertensive patients were 109% and 63%, respectively, of the control group values. By extrapolating the data via the model at the same pressure level in all subjects (the average level of mean blood pressure of the two groups), the isobaric values of diameter and compliance in the hypertensive patients were 107% and 81%, respectively, of the control group values. Overall, measured isobaric diameters and measured compliance correlated with systolic, diastolic, and mean blood pressure values (p less than 0.001), whereas isobaric compliance correlated only with systolic (p less than 0.05) and pulse (p less than 0.01) pressure values. Thus, the increased diameter and reduced compliance of the brachial artery observed in hypertensive humans cannot be attributed solely to the stretching effect of elevated blood pressure, but also to intrinsic alteration of the arterial walls. These could represent either adaptative structural or functional changes secondary to the chronic increase in arterial pressure, or primary abnormalities of the vessel wall.

Rapid dextran infusion in essential hypertension.

Hemodynamic parameters were studied before and after rapid dextran infusion in 34 men including 17 patients with sustained essential hypertension and 17 normotensive controls. In both groups of patients, dextran infusion induced a significant increase (p less than 0.001) in central venous pressure (CVP), cardiac output (CO), and stroke volume. The percent change in stroke volume was significantly higher in hypertensives (p less than 0.001) than in controls. Three indices of volume expansion were calculated: 1) the ratio between the change in CO and the change in volume, which was significantly higher in hypertensives (p less than 0.025), 2) the ratio between the change in CO and the change in CVP, which was similar in both groups, and 3) the ratio between the change in volume and the change in CVP, which was significantly reduced in hypertensives (p less than 0.001). In the overall population, the latter ratio was negatively correlated with the change in CO (or in stroke volume) induced by expansion ( r = -0.75). The results provided evidence that: 1) the slope of the relationship between CO and blood volume was steeper in hypertensives than in normotensives, and 2) the steeper slope was due to a reduction in the effective compliance of the vascular bed, causing a greater elevation in CO per unit rise in volume.

Brachial artery hemodynamic response to acute converting enzyme inhibition by enalaprilat in essential hypertension.

To assess the vascular involvement of renin-angiotensin system inhibition in human hypertension, acute effects of intravenous enalaprilat on brachial artery diameter, blood flow, and blood velocity were investigated in hypertensive patients by pulsed Doppler technique and compared with effects of saline vehicle. Compared with saline vehicle, enalaprilat reduced blood pressure (P less than 0.001) and increased brachial arterial diameter (P less than 0.01) and brachial blood flow (P less than 0.01). Enalaprilat effect on arterial pulse pressure was dependent on preinjection pulse pressure (r = -0.76; P less than 0.001), but its effect on mean blood pressure was not dependent on preinjection mean blood pressure. On the other hand, enalaprilat effect on arterial blood flow was negatively correlated with preinjection blood pressure (r = -0.64; P less than 0.02). The findings point to different responses of large and small arteries to intravenous enalaprilat.

Ranitidine kinetics in normal subjects.

A 1-mg/kg IV bolus injection and a 150-mg (one tablet) oral dose of ranitidine were given to seven normal subjects. At least 1 wk separated the two doses. Ranitidine disappeared from plasma with a half-life of about 2.5 hr. Half of the oral dose was effectively absorbed and half of the absorbed amount was found unchanged in urine. Total body clearance was 10.1 ml/min/kg. Urinary clearance was the same after oral and intravenous doses (6.4 and 6.9 ml/min/kg, P greater than 0.10). Intravenous ranitidine kinetics included three phases, with a central distribution volume of 0.2 l/kg and a total distribution volume of 1.2 l/kg. Absorption kinetics were apparently order zero: of the 150-mg dose, 75 mg was absorbed during 5 hr at a constant rate of 15 mg/hr.

Ranitidine kinetics in chronic renal impairment.

The effects of moderate to severe renal impairment on kinetics of the H2-blocker ranitidine were investigated in 16 patients divided into two groups. Mean inulin clearance (ClIn) was 35 +/- 18.3 ml/min/1.73 m2 in group I and 7.4 +/- 3.5 ml/min/1.73 m2 in group II. Each patient received a single 150-mg oral dose of ranitidine. Values determined were maximum plasma concentration (MC) and time of occurrence, AUC, elimination t 1/2 (t 1/2 beta), total amount of unchanged ranitidine recovered in urine, and ranitidine renal clearance (ClR). MC values were higher and longer delayed than values reported in subjects with normal renal function. The t 1/2 beta was longer in group I and group II and correlated with the degree of renal impairment. The amount of ranitidine excreted within the first 24 hr decreased (18% of the dose in group I and 6% of the dose in group II), and ClR correlated strongly with ClIn, indicating that the observed changes in ranitidine kinetics are mainly related to changes in its renal excretion.

Prazosin kinetics in essential hypertension.

Prazosin kinetics were studied in 8 hypertensive patients (4 male and 4 female) with normal renal function. Intravenous data showed a 3-phase distribution. As a result, a linear 3-compartment model with elimination from the central compartment was proposed to describe the drug kinetics. Prazosin disappeared from plasma with a terminal half-life t1/2 of about 3 hr and had a central distribution volume of about 0.18 1/kg. Only a negligible fraction of the dose was found unchanged in urine. The oral data showed that, of the 2-mg dose, about 1 mg was effectively absorbed. This fraction was almost entirely absorbed in 2 hr. Absorption kinetics were apparently linear with a t1/2 of about 30 min.

Pindolol availability in hypertensive patients with normal and impaired renal function.

Intravenous and oral pharmacokinetics of pinlolol were studied in 18 hypertensive patients-9 with normal renal function and 9 with impaired renal function. Analysis of data showed that a linear two-compartment model was suitable to describe the pindolol kinetics. Compared with patients with normal renal function, patients with chronic renal failure exhibited: (1) unchanged transfer rate constants and distribution volumes and (2) decreased total body clearance with decreased renal clearance and unchanged nonrenal clearance. Analysis of oral data by the Loo-Riegelman method showed that the pindolol absorption kinetic was not first order. Compared with patients with normal renal function, patients with chronic renal failure exhibited decreased fraction of dose effectively absorbed and increased initial rate of absorption. The initial rate of absorption was inversely correlated with the creatinine clearance. The study disclosed evidence that absorption was modified in chronic renal failure.

Inverse relationship between upright plasma renin activity and twenty-four hour blood pressure variability in borderline hypertension.

Office, i.e. measured by the physician at rest, and 24 h ambulatory systolic (SBP) and diastolic (DBP) blood pressures, heart rate, supine and upright plasma renin activities, supine and upright aldosterone concentrations and plasma and urine sodium and potassium were measured in 61 young male subjects aged 19-25 years, including 40 normotensive subjects (office DBP less than or equal to 90 mmHg and office SBP less than or equal to 140 mmHg) and 21 borderline hypertensive subjects (non-normal blood pressures with office DBP less than or equal to 95 mmHg and office SBP less than or equal to 160 mmHg). No significant differences were found in the plasma or urine K+ or Na+, upright or supine plasma renin activity or aldosterone concentration between normotensives and borderline hypertensive subjects. No correlation was detected between plasma and urine K+ or Na+, upright and supine aldosterone concentration or supine plasma renin activity and blood pressure. In contrast, significant inverse correlations were observed between upright plasma renin activity and blood pressure. The correlations were approaching statistical significance when upright plasma renin activity was related to office SBP and office DBP (r = -0.22, P = 0.097 and r = -0.25, P = 0.049, respectively), and were more significant when plasma renin activity was related to 24 h mean DBP (r = -0.32, P = 0.013) and to SBP and DBP standard deviations (r = -0.37, P = 0.004 and r = -0.26, P = 0.04, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Short-term representatives of daytime and night-time ambulatory blood pressures.

OBJECTIVE: To see whether measurements of ambulatory blood pressure during short-term daytime and night-time periods can represent complete daytime and night-time pressures accurately. DESIGN: Short-term measurements would be less uncomfortable for patients, easier to perform and could lead to fewer missing values, outliers or artefacts than full-day measurements, especially when repeated monitorings are required. METHOD: Ambulatory blood pressure was measured every 15 min for 24 h in 254 subjects with normal or borderline office blood pressure. Each pressure profile included at least 80 valid readings. Mean blood pressures for different 1-, 2-, 3-, 4-, 5- and 6-h spans were calculated and compared with mean daytime and night-time values using paired Student's t-test. RESULTS: One or two-hour spans of daytime blood pressure poorly represented mean daytime pressure. In contrast, 4-h readings, selected between 1000-2200 h represented daytime blood pressure with good accuracy. Over the total sample, 4-h mean blood pressure readings from 1000-2200 h differed from daytime readings by less than 2 mmHg and 2-h mean readings from 0300-0700 h differed from mean night-time readings by less than 1 mmHg. CONCLUSION: We suggest that 4-h measurements of ambulatory blood pressure during the daytime and 2-h measurements at night (with time spans selected as indicated as above) may be of value.

Active ambulatory blood pressures and urinary electrolytes in young male subjects with normal blood pressure or borderline hypertension.

OBJECTIVES: To examine the relationship between ambulatory blood pressure (ABP) and 24-h urinary electrolytes in young subjects with normal blood pressure or borderline hypertension. DESIGN: ABP shows a circadian profile. We question whether high- and low-level pressure spans might have a relationship with urinary salt output. METHODS: ABP was monitored by the SpaceLabs 5200 system in 182 young male subjects (aged 17-25 years) with normal or borderline office blood pressure. In all subjects, 24-h urinary sodium, potassium and chloride were measured. The mean values and SD of ABP during 24 h, or during the daytime (0900-2100 h) and night-time (2115-0845 h), were estimated. In addition, using a 'cumulative sum' method, 'active' (high-level) and 'passive' (low-level) spans of APB were identified in each subject. RESULTS: No relationship was found between 24-h urinary sodium, potassium or chloride and office systolic blood pressure. Also, no relationship was found between the electrolytes and mean value or SD of ABP during 24 h, daytime or night-time. In contrast, significant positive correlations were found between 24-h urinary sodium and active systolic and diastolic blood pressure. The present study suggests that the active blood pressure span is associated with salt intake in normal and borderline blood pressure groups.

Home blood pressure: variability, comparison with office readings and proposal for reference values. Groupe de la Mesure, French Society of Hypertension.

PURPOSE: A multicentre study was performed on 390 healthy subjects (210 male, 180 female) to evaluate home blood pressure versus office blood pressure. METHODS: The patients, aged 20-59 years, not on antihypertensive treatment, were not preselected by blood pressure levels. Blood pressure was measured in the doctor's office, using a mercury manometer at the fifth, sixth and seventh minute of rest, and at home by self-measurement using a validated electronic oscillometric device at the fifth, sixth and seventh minute of rest, in the morning and evening, on three consecutive days. RESULTS: The analysis of office and home measurements at the fifth, sixth and seventh minute of rest showed a significant decrease in blood pressure, mostly between the fifth and sixth minute. There was no significant variation in home pressure over the three consecutive days of measurement. Blood pressures were significantly higher in the evening than in the morning; the mean differences were 3 mmHg for systolic and 1.5 mmHg for diastolic blood pressure. Compared with office blood pressure measurement, home measurement provided significantly lower systolic and diastolic blood pressure means. Of the subjects, 78% showed a higher systolic and 69.9% a higher diastolic blood pressure with office measurement than with home measurement. Systolic and diastolic blood pressure differences were non-significantly higher for females than for males and did not differ with age. CONCLUSIONS: The comparison of the office and home measurement distributions allowed us to propose reference values for home blood pressure measurement. These were established by choosing blood pressure at the identical percentile for home measurement as we found for office measurement using the World Health Organization criteria (140/90 and 160/95 mmHg). Using this approach, the upper limit for normotension by home measurement would be 127/83 mmHg and for hypertension 147/86 mmHg. Although this approach has no prognostic value, it could be useful for the interpretation of home blood pressure.

Ambulatory blood pressure monitoring: a critical review of the current methods to handle outliers.

OBJECTIVES: To examine the methods to handle marginal readings in the analysis of ambulatory blood pressure. DESIGN: Data obtained from automatic ambulatory blood pressure monitoring include several 'outliers', i.e. readings at the frontier of physiologically acceptable ranges. Several methods have been used to handle these readings. We need to know whether using different methods to reject outliers leads to different results in the analysis of the data. If so, then it is important that a common method be used by different authors. METHODS: Ten reported methods to handle outliers were selected and applied to a large set of unpublished blood pressure profiles (Novacor Diasys system). We compared the effects of data rejection by these methods on the mean values and standard deviations (calculated over 24 h, daytime and night-time) of the remaining data. RESULTS: The different methods had quite different effects on the same data set. Depending on the method used, the discarded data varied from 1 to 17% of the total number of readings. Among the rejected data, readings that occurred in the daytime varied from 14 to 56%. Also, 'high-value' outliers varied from 1 to 60% of the rejected data. On average over the total sample, the rejection of outliers had only a small effect on the mean values of blood pressure. In contrast, it may strongly reduce the standard deviation of the readings. CONCLUSION: The study emphasized the need to use a common method to handle outliers in the analysis of ambulatory blood pressure data.

Unrelated responses of brachial artery hemodynamics and renin-angiotensin system to acute converting enzyme inhibition by enalaprilat in essential hypertension.

The simultaneous acute effects of converting enzyme inhibition by intravenous enalaprilat on the circulating renin-angiotensin system and on the brachial artery were studied in 12 hypertensive patients by a double-blind comparison with saline effects in 14 hypertensive patients. The brachial artery was investigated in terms of arterial section (measured by pulsed Doppler technique) and wall rigidity (assessed by pulse wave velocity). Arterial and biochemical parameters were measured in baseline before injection and at 20 to 40 minutes (t1) and 80 to 100 minutes (t2) after saline and drug injections. Compared with the saline vehicle, enalaprilat significantly decreased angiotensin enzyme converting activity (p less than 0.001), increased plasma renin activity (p less than 0.01) and decreased plasma aldosterone concentrations (p less than 0.01). The drug reduced blood pressure (p less than 0.01) and increased the brachial artery section (p less than 0.01), but did not change pulse wave velocity. In the enalaprilat group, significant postinjection relations were observed between: (1) enalaprilat concentration and plasma angiotensin converting enzyme activity (r = -0.72, p less than 0.001); (2) plasma renin activity and mean blood pressure (r = -0.46, p less than 0.02); (3) plasma enalaprilat concentration and pulse wave velocity (r = -0.50, p less than 0.01) and (4) pulse wave velocity and brachial artery section (r = 0.42, p less than 0.05). Thus, the brachial artery effects of enalaprilat were not directly related to the blockade of the renin-angiotensin system in plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of nicorandil on arterial and venous vessels of the forearm in systemic hypertension.

The effects of a single oral dose of 20 mg of nicorandil were evaluated in 12 untreated patients with mild to moderate essential hypertension. Serial measurements of arterial pressures were obtained by means of an automatic device (Dynamap) up to 120 minutes after drug administration. Forearm hemodynamics were determined with a pulsed Doppler velocimeter, or strain gauge mecanography and plethysmography enabling measurement of the diameter, velocity and flow of the brachial artery as well as the arterial pulse wave velocity and forearm venous tone. In addition, local vascular resistance, compliance and impedance were deduced. Nicorandil administration produced a significant decrease in systolic and diastolic blood pressure, from 18 minutes after dosing which lasted up to the end of the study (i.e., 120 minutes after drug administration) (p less than 0.01). This decrease in blood pressure was not associated with reflex tachycardia. The brachial artery diameter increased significantly (p less than 0.01) with no change in brachial artery blood flow. A decrease in brachial-radial pulse wave velocity and arterial impedance (p less than 0.01) and an increase in arterial compliance were observed. Thus, this study demonstrated an antihypertensive activity of a single oral administration of nicorandil without baroreflex activation. This decrease in blood pressure was associated with a dilation of peripheral large arteries leading to an increase in arterial compliance. Thus, clinical testing to evaluate the antianginal activity of nicorandil, especially in hypertensive patients with coronary heart disease, should be encouraged.

Control of cardiac output in essential hypertension.

Cardiac and renal hemodynamics and cardiopulmonary and total blood volume were determined in 202 men, 101 with normotension and 101 of the same age with chronic essential hypertension, normal renal function and balanced sodium intake and urinary output. Cardiac output was identical in the two groups, whereas blood pressure and total peripheral resistance were significantly different. The two groups exhibited strong differences in the correlation study: (1) Correlations of blood pressure with, respectively, heart rate, cardiopulmonary blood volume and total blood volume were significant in the normotensive group but not in the hypertensive group. (2) Correlations of cardiac output with, respectively, heart rate, cardiopulmonary blood volume and total blood volume were significant in both groups. (3) Correlations of renal blood flow with, respectively, cardiac output, blood pressure and total blood volume were significant in the hypertensive group but not in the normotensive group. This study provides evidence that: (1) the volume and neural control of blood pressure are disrupted in hypertension whereas control of cardiac output is maintained; and (2) adaptive mechanisms involving renal function are necessary to the maintenance of normal cardiac output in patients with essential hypertension.

Ambulatory blood pressure in diabetic subjects.

Ambulatory blood pressure (ABP) was measured every 15 min for 24 h in 82 diabetic subjects aged 35 to 79 years and in 66 healthy controls having the same age and office blood pressure. The autonomic control in diabetic subjects was evaluated by the total score of five cardiovascular function tests (a high score means an autonomic neuropathy). The diurnal cycle of BP was assessed by the difference of BP between daytime and nighttime (delta BP = BP in the day - BP in the night). The variability of BP was evaluated by the standard deviations of the readings. Compared with control subjects, diabetic subjects had the same 24-h mean level of BP, a smaller delta BP, and an increased variability during the daytime; however, the differences were in the limit of statistical significance. Clearcut results were obtained in diabetic subjects with autonomic neuropathy. In the latter, the score of autonomic neuropathy was (1) negatively correlated to delta SBP (systolic) and delta DBP (diastolic) (r = 0.44, P = .0004 and r = 0.46, P = .0004, respectively) and (2) positively correlated to the variability of SBP and DBP during the daytime (r = 0.46, P .0004 and r = 0.29, P = .03, respectively). In diabetic subjects, mean level and variability of ABP were positively correlated to urinary microalbumin. The relationships were the most significant when one relates microalbuminuria to the level of SBP in the night (r = 0.42, P < .0003) and to the variability of SBP in the day (r = 0.32, P = .008).(ABSTRACT TRUNCATED AT 250 WORDS)

Use of nonlinear methods to assess effects of clonidine on blood pressure in spontaneously hypertensive rats.

In spontaneously hypertensive rats (SHR), chronic infusion of clonidine failed to decrease blood pressure and blood pressure variability. We used nonlinear methods to get a deeper insight on the effects of clonidine on blood pressure dynamics. For 24 h and 4 wk, clonidine (0.1 mg . kg-1 . day-1 sc) was infused by minipumps in the conscious SHRs, and, for comparison, a vehicle was infused in SHRs and in Wistar-Kyoto rats. Blood pressure was recorded for 30 min before and after treatments. We used the Lyapunov exponent, approximated by the inverse of the lmax index derived from the recurrence plot method, to characterize nonlinear dynamics. Before treatment, lmax index of blood pressure was lower (P < 0.01) in the SHRs than in the Wistar-Kyoto rats. Clonidine significantly increased lmax (P < 0.01) to the level observed in normotensive rats, at 24 h and up to 4 wk after infusion. We conclude that clonidine has a significant chronic effect on blood pressure dynamics, as evidenced by nonlinear methods. Our study also suggests that the mechanisms governing blood pressure variations are nonlinear.