Efficacy of benazepril monotherapy in moderate essential hypertension studied by automatic ambulatory blood pressure monitoring

Authors examined the effects of benazepril, regarding the length of effectiveness by ambulatory blood pressure monitoring (ABPM), drug tolerable, and the compliance of patients in mild to moderate essential hypertension. 14 patients were treated with benazepril monotherapy. Six of them were newly diagnosed, and the rest had already been treated for hypertension. At the start, after six and 12 weeks, 24-hour monitoring was performed. Casual blood pressure (BP) measurements and detection of side-effects were also performed at 3rd and 9th-week. Prior the study the average daytime BP measured by ABPM was 149.1 +/- 7.7/96.6 +/- 4.7 mmHg. 10 mg of benazepril was first administered in the morning. By the end of the sixth week the average BP was significantly decreased (daily average: 139.1 +/- 9.9/88.2 +/- 7.6 mmHg). The daytime diastolic average BP of 8 patients was lower than 90 mmHg and the other's daily dose was raised to 20 mg. During the 12th-week we found optimal tension in 11 patients, while in two others there was also a significant decrease. The daily average BP was 134.7 +/- 7.5/85.6 +/- 6.6 mmHg. In comparison the data at the beginning of the study here was significant decrease in the 24-hour, daytime and night-time BP, in the hypertension time-index and the hyperbaric impact, both in systolic and diastolic levels. During the 12th-week period the diurnal index was unchanged. The early morning BP decreased by the end of the 3rd month from 148.6 +/- 14.1/98.5 +/- 11.7 mmHg to 135.2 +/- 13.5/93.4 +/- 11.2 mmHg. Sustained side-effect did not occur. The patient's compliance to benazepril was excellent. Authors conclude that benazepril monotherapy lowered in 92.8%, and normalized in 78.5% the blood pressure of patients suffering from mild to moderate essential hypertension. The unchanged diurnal index, and the decrease in the early morning blood pressure suggest the 24-hour effect of benazepril.     

Low-dose amiodarone versus sotalol for suppression of recurrent symptomatic atrial fibrillation

The goal of this work is to study the consequences of the last on variations of the blood pressure (BP) in the course of 24 hours. From 1994 to 1997 we have selected 99 hypertensive patients and studied their BP profile. This study included 72 women and 27 men. Their age varies from 22 to 72 years (average 56.7 +/- 9 years). All these patients has an ambulatory blood pressure measurement (ABPM) before the fast and during Ramadan. Before Ramadan the period of the sleep goes from 10 pm +/- 1 h to 8 am +/- 1 h. During the month of Ramadan, the sleep lasts from 0 h +/- 1 to 9 am +/- 1 h. [table: see text] No statistically significant difference is noted between these 2 periods neither for the systolic BP (SBP) nor for the diastolic BP (DBP), for the BP of 24 hours, and the diurnal and nocturnal periods. We have then the compared the hourly average on 24 hours of the 99 patients. We observed that during the month of Ramadan the peak of the awakening is delayed by 2 hours and the nocturnal through is delayed by 1 hour. After this study, which is the first one to deal with variations of blood pressure during the fast of Ramadan we can confirm that in patients with essential hypertension without complications, the fast is well supported. The variations of BP are minimal and are related to the variations of the sleep, activity and eating pattern.     

The positive effect of pretreatment with serotonin and gangliosides on the development of early mouse embryos after cryopreservation

Blood pressure (BP) during siesta declines to levels similar to those of night time sleep. The objective of the study was to assess the effect of siesta on 24-h ambulatory BP (ABP) data. Two different approaches were employed for the definition of day and night periods: (1) actual patient reported day and night intervals (ACT) with siesta period analysed as a third time period; and (2) arbitrary day and night time intervals (ARB) with the presence of siesta being ignored. A total of 203 24-h ABP recordings were analysed, with a siesta during ABP monitoring reported in 154 of them. Mean siesta BP was very close to ACT night time BP. Among recordings with a siesta, ACT daytime BP was higher and night time BP lower than the corresponding ARB BPs (P < 0.001). The magnitude of night time BP drop was greater with ACT intervals, resulting in a lower percentage of non-dippers (P < 0.001). Among 49 recordings without a siesta, differences between ACT and ARB BPs were less pronounced for daytime but not for night time. Differences in the magnitude of nocturnal BP drop between ACT and ARB periods, although statistically significant, did not affect the prevalence of non-dippers. In conclusion, analysis of 24-h BP profiles by using ARB instead of ACT day and night intervals results in underestimation of the nocturnal BP drop and overestimation of the proportion of non-dippers. This bias is more pronounced in patients who take a siesta during ABP monitoring.     

Continuous ambulatory measurement of blood pressure in children--personal experience

Ambulatory blood pressure monitoring (ABPM) during normal daily activities and during night, when the patient is asleep, is a new method of measuring blood pressure (BP) in children, used for better diagnosis and treatment of hypertension. Compared to casual BP measurements, it documents normal daily BP variations, BP during sleep, the influence of emotional and physical stress on BP and is a better predictor of hypertension associated with end-organ damage. However, the experience in ABPM in children is still limited. In our country ABPM has been used since recently, and first results are referred to children with end-stage renal failure. SUBJECTS AND METHODS: ABPM was performed in two groups of children: group A consisted of 61 children, aged 14.3 +/- 2.9 (mean +/- SD) yrs in whom intermittent outpatient BP measurements (for at least 3 months) suggested the diagnosis of hypertension (according to the data of Second Task Force); group B consisted of 52 patients (pts), aged 12.8 +/- 4.6 yr with renal disease. Four pts from group A (6.6%) and 20 pts from group B (38.5%) received antihypertensive therapy (captopril, nifedipine, furosemide and propranolol ). All children from group A and half of the children from group B had normal renal function. Eighteen pts from group B were on chronic haemodialysis (34.6%). Blood pressure was recorded during a 24-hour period except in haemodialyzed pts (48 h) (Table 1). Results of BP measurements are presented as the mean values of BP during a 24-hour period, during normal daily activities and during sleep. We used the age- and gender-appropriate 95th percentile from the Task Force Study as the daytime upper-limit of normal and 10% lower for the upper-limit at night. According to BP load (the percentage of BPs exceeding the upper limits of normal for age), children were assumed to have mild-to-moderate hypertension (BP load between 20% and 40%) or severe hypertension (BP load more than 40%). The success of antihypertensive therapy was evaluated after 1-3 months in 11 pts (twice in 10 pts and three times in one pt). RESULTS: In group A 39.4% of pts were normotensive and 36.1% were without antihypertensive therapy, 58.4% of normotensive and 40.5% of hypertensive pts had blunted circadian BP rhythm (nocturnal BP reduction of less than 10% of diurnal values) (Graph. 1). In group B 38.5% of pts were normotensive and 27% were without antihypertensive therapy. In the group of normotensive pts alteration of circadian BP rhythm was found in 40% of pts with normal renal function, 80% of pts with chronic renal failure and in 100% of pts with terminal renal failure, while in the hypertensive group, altered circadian BP rhythm had 68%, 100% and 92% of pts, respectively (Graph 2). Mild-to-moderate hypertension had 54% of hypertensive pts from group A and 37.5% of hypertensive pts from group B. Severe hypertension was more frequent in group B (62.5%) comparing to group A (46%). The effectiveness of antihypertensive therapy was assessed in 11 pts. In 69.2% of pts BP became normal or was significantly decreased, in 23.1% of pts BP was not changed and 7.7% of pts had higher values of BP. DISCUSSION: ABPM is very useful for diagnosing white coat hypertension. Like other authors, we have pointed out that more than one third of pts who were hypertensive according to usual BP measurements had normal 24-hour BP and we classified them as white coat hypertensives. More than a half of the pts had blunted circadian BP rhythm, and as it is not certain whether they will become hypertensive in adulthood they should be periodically controlled. There are several proofs that results of ABPM have a better correlation with hypertensive end-organ damage; therefore ABPM is used for assessing the severity of hypertension. In our former work, we showed excellent correlation of BP with left ventricular mass index in children with end-stage renal failure. (ABSTRACT TRUNCATED)     

Ambulatory blood pressure and risk factors for coronary heart disease in black and Indian medical students

BACKGROUND: Coronary heart disease (CHD) has reached 'epidemic' proportions in South Africa. CHD is uncommon in the black population of South Africa, yet the prevalence of hypertension in the adult black population is high. DESIGN: This study compared the blood pressure profile in 154 medical students of which 83 were Indians (1), 71 were black (B), 87 were male (50 I, 37 B), and 67 were female (33 I, 34 B) age 21 (SD+/-1.6), using the cuff method and 24 h ambulatory blood pressure monitoring (ABPM). METHODS: All students underwent ABPM. Biochemical studies for CHD risk factors were done. Electrocardiography (ECG) was performed in all participants and echocardiography in 90. RESULTS: ABPM showed that black students had higher systolic and diastolic blood pressure throughout the day, night and critical time periods compared with the Indian students. Blood pressure load was higher in black (40.8%) than in Indian participants (29.6%; P<0.05) and there was less dipping at night Left ventricular mass was significantly higher in black than in Indian participants (29.6%; P<0.05) and there was less dipping at night. Left ventricular mass was significantly higher in black than in Indian participants. Risk factors leading to CHD were more common in Indian than in black participants. Those with borderline hypertension (blood pressure > or = 130/85 and < or = 140/90 mmHg) had statistically higher serum triglyceride and left ventricular mass than normotensives. CONCLUSIONS: Young black people had higher blood pressure readings than young Indian participants in the absence of metabolic abnormalities and had greater cardiac involvement Borderline hypertension is not innocuous. Metabolic risk factors for CHD in Indian people are apparent at an early age. This study emphasizes the need for prevention of risk factors leading to CHD at an early age.     

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.     

Mortality of aerospace workers exposed to trichloroethylene

We assessed the differential effects of a chronotherapeutic agent (controlled-onset extended release [COER] verapamil), administered at bedtime versus a conventional, homeostatic therapy (nifedipine gastrointestinal therapeutic system [GITS]) taken in the morning, on early morning and 24-hour blood pressure (BP), heart rate (HR), and the HR x systolic BP product. The study was a multicenter (n = 51), randomized, double-blind prospective clinical trial with a 10-week treatment period. Dose titration was performed by study investigators based on systolic and diastolic BP values at the doctor's office. Ambulatory BP monitoring was performed at placebo baseline, after 4 weeks of stable double-blind therapy, and at end of the study. Twenty-four-hour BP profiles were studied in 557 hypertensive patients. Changes in BP, HR, slope of the rate of rise of BP and HR, and the HR-systolic BP product during the 4 hours from 1 hour before to 3 hours after awakening were evaluated. The study was powered to show equivalence between the 2 regimens, predefined as a difference between treatment groups in mean change from baseline in early morning BP of +/- 5 mm Hg systolic and +/- 3 mm Hg diastolic. Changes in the early morning BP fell within the definition of equivalence for the 2 treatment strategies (-12.0/-8.2 mm Hg for COER-verapamil and -13.9/-7.3 mm Hg for nifedipine GITS). Changes in both the early morning HR and rate-pressure product were significantly greater following COER-verapamil therapy versus nifedipine GITS (HR, -3.8 beats/minute vs +2.6 beats/minute, p < 0.001 and HR-systolic BP product, -1,437 beats/min x mm Hg vs -703 beats/min x mm Hg, respectively, p < 0.001). Changes in ambulatory BP demonstrated clinically similar reductions for the awake period, but nifedipine GITS lowered systolic BP to a greater extent than COER-verapamil during sleep (-11.0 vs -5.8 mm Hg, p < 0.001). COER-verapamil and nifedipine GITS had equivalent effects (+/- 5/3 mm Hg) on early morning BP. In addition, both extended-release calcium antagonists effectively lowered 24-hour BP. However, COER-verapamil had greater effects than nifedipine GITS on early morning hemodynamics (HR, HR-systolic BP product, rate of rise of BP and HR) and lesser effects during sleep due to its intrinsic pharmacologic properties and chronotherapeutic delivery system.     

Changes in blood pressure 24 hour monitoring data and quality of life in patients with systolic hypertension treated with arifon

AIM: The study of quality of life and 24-h monitoring blood pressure data in elderly patients with isolated systolic hypertension (SH) on arifon monotherapy. MATERIALS AND METHODS: 22 patients over 65 (mean age 69.8 +/- 1.3 years) suffering from SH entered the open trial. 24-h monitoring of blood pressure was performed at least 2 weeks after discontinuation of the previous antihypertensive treatment and after 4 weeks of arifon monotherapy (2.5 mg once a day). Quality of life was evaluated according to the standard SIP questionnaire. RESULTS: Arifon 4-week treatment resulted in a significant fall of systolic pressure for 24 hours, day and night (by 16.2, 13.7 and 17.4%, respectively; p < 0.001). Variability of blood pressure did not change much. 24-h index for systolic and diastolic blood pressure increased 2-fold and by 46%, respectively. Moreover, the rate of the systolic pressure growth in the morning hours decreased by 36.7% (p < 0.05). Psychosomatic status by SIP questionnaire changed for the best. CONCLUSION: Arifon is an effective treatment of SH and improves quality of life.     

Epidemiology of extrapulmonary tuberculosis among persons with AIDS in the United States

We compared the antihypertensive efficacy of once-daily amlodipine (AM) versus nitrendipine (NTR) by 24-h ambulatory blood pressure monitoring (24-h ABPM) in 32 patients with mild to moderate essential hypertension (EH). After a 2-week single-blind, placebo run-in period, patients were randomized in a double-blind, parallel fashion: 14 received AM 5 mg and 18 NTR 10 mg. After 2 weeks, dose was adjusted if necessary (AM 10 mg or NTR 20 mg) and continued for another 6-week period. At the end of the placebo period and during the last week of treatment, patients underwent 24-h ABPM. Initial office BP mean values were similar in both groups (169.8 +/- 14/102.5 +/- 6 vs. 167.1 +/- 14/98.7 +/- 5 mm Hg, respectively, p = NS). A comparable decrease in office mean values of systolic BP (SBP, -22.3 +/- 13 vs. -19.1 +/- 16 mm Hg) and diastolic BP (DBP, -12.0 +/- 5 vs. -8.1 +/- 8 mm Hg) was observed. Nevertheless, 24-h ABPM mean values differed significantly between patients treated with AM or NTR with regard to 24-h SBP (120.0 +/- 10 vs. 132.5 +/- 1 mm Hg, p = 0.01). Moreover, the average decrease in 24-h SBP (-19.3 +/- 6 vs. -5.2 +/- 11 mm Hg, p = 0.0036) and 24-h DBP (-10.7 +/- 4 vs. -3.7 +/- 6 mm Hg, p = 0.0047) was higher in the AM group, with no changes in 24-h heart rate (HR). At equivalent once-daily dosage, AM was more effective than NTR in decreasing BP assessed by 24-h ABPM.     

Long-term reproducibility and usefulness of daytime recording of noninvasive 24-hour ambulatory blood pressure monitoring in borderline hypertension: a two-year follow-up study

We investigated the long-term reproducibility of noninvasive 24-hour ambulatory blood pressure monitoring (ABPM) compared with casual blood pressure measurements in 54 individuals (47 +/- 11 years) with borderline hypertension. ABPM and casual blood pressure measurements were obtained 3 times over 2 year period. ABPM data were analyzed to determine the average 24-hour blood pressure (24-BP), the average blood pressure during the waking hours (Day-BP), and the average blood pressure from the time the subject went to bed until he awoke (Night-BP). ABPM measurements were similar for Year 1, 2, and 3 (24-BP: Year 1; 130 +/- 10/79 +/- 6 mmHg; Year 2; 130 +/- 10/79 +/- 7 mmHg; and Year 3; 130 +/- 10/78 +/- 7 mmHg). Bland-Altman analysis and standard deviation of the difference also indicated the reproducibility of 24-BP was better than casual pressure. The 24-BP was significantly correlated with both Day-BP and Night-BP for each year. Day-BP showed the stronger correlation. Our results suggest that Day-BP provides reproducible estimation in subjects with borderline hypertension.     

Valsartan, a new angiotensin II antagonist: antihypertensive effects over 24 hours

This study was done to assess the antihypertensive efficacy of once-daily valsartan 20 mg, 80 mg, 160 mg, and 320 mg over 24 hours using ambulatory blood pressure monitoring (ABPM). A total of 217 adult outpatients with uncomplicated essential hypertension (office mean sitting diastolic blood pressure [DBP] of > or = 95 to < or = 115 mm Hg) participated in this multicenter, double-masked, placebo-controlled study. Patients were randomized to receive valsartan 20 mg, 80 mg, 160 mg, 320 mg, or placebo for 8 weeks. Twenty-four-hour ABPM was done at baseline and after 8 weeks of treatment. All valsartan doses produced significant decreases in average ambulatory systolic blood pressure (SBP) and DBP over 24 hours compared with placebo. A trend to greater reductions compared with placebo was observed for doses of valsartan 80 mg and greater (80 mg, -6.61 mm Hg DBP, -11.04 mm Hg SBP; 160 mg, -5.51 mm Hg DBP, -10.61 mm Hg SBP; 320 mg, -8.44 mm Hg DBP, -14.34 mm Hg SBP) compared with valsartan 20 mg (-3.52 mm Hg DBP, -5.92 mm Hg SBP). Valsartan produced consistent reductions compared with placebo during both day (> 6 AM to < or = 10 PM) and night (> 10 PM to < or = 6 AM). However, in all groups, the circadian pattern of blood pressure over 24 hours was preserved and was similar to that observed at baseline (but shifted into the normotensive range in a parallel fashion). The data show that single daily doses of valsartan 80 mg and greater provide effective control of both DBP and SBP over a 24-hour period without loss of diurnal variation.     

Population pharmacokinetic-pharmacodynamic modeling of moxonidine using 24-hour ambulatory blood pressure measurements

OBJECTIVES: To develop a model for 24-hour ambulatory blood pressure measurements (ABPM) that can be applied in a pharmacokinetic-pharmacodynamic model. METHODS: Four different data sets were prepared from 2 studies to accommodate different modeling strategies. In study A, a double-blind placebo-controlled study in 47 patients, 24-hour ABPM profiles (74 to 99 measurements per profile) were obtained during the placebo run-in phase and after 3, 5, and 11 weeks during the treatment. Three to 5 plasma samples were taken. Cosine and polynomial models were evaluated to describe the circadian rhythm in blood pressure based on 3 data sets (1: only run-in data; 2: only placebo data; 3: all data). In study B, a double-blind placebo-controlled study in 94 patients, two 24-hour ABPM profiles per patient (during placebo run-in and after 8 weeks) were recorded and randomly reduced to 15 measurements per profile to evaluate the robustness of the baseline model. RESULTS: The mean moxonidine clearance was 35 L/h, and the volume of distribution was 132 L. The final baseline model consisted of 2 cosine terms with fixed-effect parameters for rhythm-adjusted 24-hour mean blood pressure, amplitude, phase, and period; random-effect parameters for interindividual variability in rhythm-adjusted 24-hour mean, amplitude, and clock time; and interoccasion variability in rhythm-adjusted 24-hour mean and clock time. The final baseline model was combined with an Emax model for the drug effect. An effect compartment was used (kco = 0.198 h-1). The maximum decrease in diastolic blood pressure (Emax) was 16.7%, and EC50 was 0.945 microgram/L. CONCLUSION: The pharmacokinetic-pharmacodynamic model for 24-hour ABPM can be used to estimate the concentration-effect relationship of antihypertensive drugs.     

Morning and Monday: critical periods for the onset of acute myocardial infarction. The GISSI 2 Study experience

The onset of acute myocardial infarction (AMI) is unevenly distributed over the 24 h and the week. While presence of a morning peak is generally agreed upon, contrasting results had been obtained regarding other periods of the day, probably due to differences of origin, size and composition of the populations. The 24 h and weekly distributions were studied within 6 h from the beginning of the symptoms in a population following a Latin life-style, who were enrolled in the GISSI 2 Study (n = 11472). Subgroups (smokers, the elderly (> 65 years), diabetics, hypertensives) were also considered. Six hour periods starting at midnight were tested for uniformity. Circadian non-uniformity was found. Events increased in the morning hours and reduced during the night regardless of the day of the week. The night and day difference was attenuated in smokers and diabetics. Non-uniformity of the events was also found among the days of the week. AMI significantly increased in non-smokers on Monday. We suggest that there is a night-day gradient (characterized by the short time interval between the two frequency extremes) in the time of onset of AMI. The different distribution in smokers stresses the possible unfavourable and masking effect of a heightened sympathetic tone during the day while the general protective role of the night hours is preserved. Moreover, the increased incidence of events on Monday may suggest the importance of the shift from a period of non-scheduled to scheduled activity.     

The use of ambulatory pressure monitoring for evaluating antihypertensive treatment in clinical practice

OBJECTIVE: To describe the clinical experience of our Centre in the assessment of antihypertensive therapy with 24-hour ambulatory blood pressure monitoring (ABPM). DESIGN AND PATIENTS: We retrospectively studied all the 241 out-patients on antihypertensive therapy submitted to ABPM (SpaceLabs 90207, USA) between March 1992 and March 1993 for clinical purposes. We evaluated: 1) the clinical indications for the test; 2) the modifications of drug treatment suggested by the ABPM results; 3) the referring physicians' acceptance of these suggestions; 4) the changes of office BP measured before and 3-6 months after ABPM. RESULTS: 1) The indications for ABPM were: resistant or poorly controlled hypertension (n = 170-71%); suspected "white coat effect" (n = 51-21%); assessment of symptoms (n = 20-8%). 2) The analysis of ABPM suggested to modify drug treatment in 51% of the patients; a "white-coat effect" was found in 18% of the patients. 3) The ABPM suggestions about treatment were accepted by the referring physicians in 89% of the patients. 4) Office BP decreased from 163 +/- 18/99 +/- 9 mm Hg (before ABPM) to 151 +/- 13/91 +/- 7 (3-6 months after ABPM), (p < 0.001). CONCLUSIONS: The use of ABPM in our Centre, which is based on specific clinical indications, provided indications to modify the drug treatment in a high percentage of patients.     

Effect of evening versus morning benazepril on 24-hour blood pressure: a comparative study with continuous intraarterial monitoring

In a single-blind, in-patient, crossover study, the influence on the circadian blood pressure (BP) profile of the 9:00 a.m. versus the 9:00 p.m. acute administration of a single dose of benazepril 10 mg, a new angiotensin-converting-enzyme inhibitor, was assessed in 10 hypertensive patients by means of 24-hour intraarterial ambulatory BP monitoring. Mean 24-hour BP for the three treatments (placebo, benazepril a.m., benazepril p.m.) were 155/93, 131/83 and 138/86 mmHg, respectively. No significant differences between the two benazepril schedules were found in terms of either 24-hour or day-time and night-time mean BP values. However, hourly averages showed that benazepril a.m. had a more sustained antihypertensive effect than benazepril p.m., where a loss of efficacy was observed 19 hours after the administration. BP responses to static and dynamic exercise and to cold pressor test were unchanged after both benazepril schedules, as were BP peaks. These results demonstrate that acute benazepril administration markedly reduces systolic and diastolic BP. The morning administration is preferable because it more effectively covers the whole 24 hours than an evening dose.     

Feelings of anxiety and associated variables in a very elderly population

The effect of octreotide on morning hyperglycemia and GH levels was evaluated in eight insulin-dependent diabetic patients. Octreotide (50 mcg) was administered through subcutaneous injections at different hours (20:00, 22:00 and 24:00 h) or through continuous subcutaneous night infusion from midnight to 08:00 at increasing rate between 03:00 and 08:00 h. After octreotide injection at midnight we noticed a sharp decrease of both glycemia (p < 0.005) and GH (p < 0.05) at 04:00 h, but not at 08:00 h. Only the night continuous infusion at increasing rate was able to reduce glycemia and GH at 04:00 and at 08:00 h (p < 0.001 and p < 0.01 respectively). The injections of octreotide at 20:00 and 22:00 h lowered GH values at 24:00 h (p < 0.01 and p < 0.05 vs insulin alone) but did not show any significant effect on blood glucose levels and GH at 04:00 and 08:00 h. In conclusion, only the continuous subcutaneous night infusion of octreotide at increasing rate during the last hours of the night was able to reduce simultaneously morning hyperglycemia and GH levels in insulin-dependent diabetic patients, whereas evening subcutaneous injections at different times did not show any appreciable effect.     

Human evoked potentials to long duration vibratory stimuli: role of muscle afferents

The aim of this study was to evaluate the reproducibility of the circadian blood pressure (BP) change in normal healthy volunteers. The subjects were 32 healthy, young, normotensive volunteers who underwent 24 h ambulatory BP monitoring on two occasions, at least 4 weeks apart. Data were analysed using standard definitions of day and night (i.e. 07.00-22.00 for daytime and 22.00-07.00 for night time), event diaries to identify individual's day and night time and a time independent method (cusum analysis). Intraindividual variations of BP were assessed using the coefficient of variation (CV). The mean 24 h BP was very reproducible with a CV of 4.7%. Using the fixed definition of day and night, mean night time systolic blood pressure (SBP) was significantly reduced on the second visit compared to the first (P < 0.001). Using fixed times for day and night, day-night difference was poorly reproducible, with a CV of 52% for SBP and 59% for diastolic blood pressure (DBP), however this improved using diary based day-night to 40/41% and cusum analysis to 24.6/28.1%. We recommend that circadian BP changes are studied using individual definitions of day and night or time independent methods such as cusum analysis.     

Centralized i.v. team provides inpatient and home-care treatment

AIM: The study of the effects of the inhibitor of angiotensin converting enzyme ramipril (tritace) on the 24-h profile of blood pressure (BP) in patients with mild and moderate arterial hypertension. MATERIALS AND METHODS: Ramipril was given to 21 males aged 45-68 years with essential hypertension stage II (WHO criteria) with stable elevated diastolic blood pressure (95-114 mm Hg) in a single dose 2.5-10 mg/day. Captopril controls received 100 mg twice a day. BP was monitored using "SpaceLabs Medical" unit (model 90207, USA). RESULTS: Compared to placebo, ramipril lowered systolic and diastolic blood pressure both for the 24-h period and in the day time; captopril lowered only diastolic BP in the day time. Side effects of long-term application of ramipril occurred 2 times less frequently than in application of captopril. CONCLUSION: Long-term treatment with ramipril in the above regimen provides more effective control of BP than captopril in the above doses in patients with mild and moderate hypertension.     

Twenty-four hour time and frequency domain variability of systolic blood pressure and heart rate in an experimental model of arterial hypertension plus obesity]

Modifications of heart rate (HR) and systolic blood pressure (SBP) variabilities (V) have been reported in the human syndrome arterial hypertension plus insulin-resistance. The aim of this study was to characterize the 24 h SBPV and HRV in both time and frequency domains during weight increase in dogs fed ad libitum with a high fat diet. Implantable transmitter units for measurement of blood pressure and heart rate were surgically implanted in five beagle male dogs. BP and HR were continuously recorded using telemetric measurements during 24 hours, before and after 6 and 9 weeks of hypercaloric diet in quiet animals submitted to a 12h light-dark cycle. To study nychtemeral cycle of SBP and HR, two periods were chosen: day (from 6.00 h to 19.00 h) and night (from 23.00 h to 6.00 h). Spontaneous baroreflex efficiency was measured using the sequence method. Spectral variability of HR and SBP was analyzed using a fast Fourier transformation on 512 consecutive values and normalized units of low (LF: 50-150 mHz, reflecting sympathetic activity) and high (HF: respiratory rate +/- 50 mHz, reflecting parasympathetic activity) frequency bands were calculated. The energy of total spectrum (from 0.004 to 1 Hz) was also studied. Body weight (12.4 +/- 0.9 vs 14.9 +/- 0.9 kg, p < 0.05). SBP (132 +/- 1 vs 147 +/- 1 mmHg, p < 0.05) significantly increased after 9 weeks of hypercaloric diet. A nycthemeral HR rhythm was present at baseline (day: 79 +/- 1 vs night: 71 +/- 1 bpm) but not after 9 weeks (day: 91 +/- 4 bpm ; night: 86 +/- 2 bpm). Concomitantly, the efficiency of spontaneous baroreflex decreased at 6 weeks (36 +/- 1 vs 42 +/- 2 mmHg/ms, p < 0.05). A significant decrease in HF energy of HRV was found after 6 but not after 9 weeks. LF energy of SBPV was increased at 6 but not at 9 weeks (table). [table: see text] In conclusion, this study shows that an hyperlipidic and hypercaloric diet induces transient variations in autonomic nervous system activity which could be the physiopathological link between obesity, insulin-resistance and arterial hypertension.     

Pattern of messenger ribonucleic acid expression of tissue inhibitors of metalloproteinases (TIMPs) during testicular maturation in male mice lacking a functional TIMP-1 gene

We attempted to characterize circadian variations in pharmacokinetic parameters of a new formulation of cyclosporine (CsA) in nine cardiac allograft recipients. A secondary objective was to determine the sampling time that correlated best with exposure of patients to the drug. This was a two-period study with each period lasting 12 hours. All patients received two equal doses of a new microemulsion of CsA 12 hours apart. Blood samples to measure drug levels were obtained at administration and 1, 2, 3, 4, 6, 9, and 12 hours after each dose. We found no statistically significant difference in pharmacokinetic parameters (areas under the curve, minimum blood concentration, oral clearance) measured during the day and during the night. However, maximum blood concentrations during the day were 30% higher than those at night (p<0.05). We found a good correlation between minimum concentrations in the morning and overall exposure of patients to CsA (r=0.89). This new microemulsion appears to have few circadian variations of blood concentrations in cardiac transplant recipients. The clinical significance of higher maximum blood concentration during daytime remains to be elucidated. Our results support the most widely accepted method for monitoring CsA, which is based on minimum concentrations in the morning.