Evaluation of the antihypertensive effect of once-a-day trandolapril by 24-hour ambulatory blood pressure monitoring. The Italian Trandolapril Study Group.

The aim of this study was to evaluate the effects of trandolapril on 24-hour blood pressure in patients with mild-to-moderate essential hypertension. After a washout period of 4 weeks, 42 patients were randomized to receive 2 mg of trandolapril once daily and 20 to receive placebo in a double-blind fashion for 6 weeks. This was followed by a second washout period of 4 weeks. At the end of each period, clinic blood pressure was assessed at 24 hours after the last dose and 24-hour ambulatory blood pressure was measured noninvasively, taking blood pressure readings every 15 minutes during the day and every 20 minutes during the night. Two patients were dropped out before any blood pressure evaluation under treatment. Analysis of ambulatory blood pressure was performed in 48 patients who met the criteria for the minimal number of ambulatory blood pressure data (2 values per hour during the day and 1 value per hour in the night). In the trandolapril-treated group (n = 41) clinic systolic/diastolic blood pressures were 159.8 +/- 2.0/102.4 +/- 0.8, 146.8 +/- 2.3/94.8 +/- 1.1, and 155.7 +/- 2.0/99.2 +/- 0.7 mm Hg in the pretreatment, treatment, and post-treatment periods, respectively. The corresponding values for 24-hour mean blood pressure (n = 31) were 139.5 +/- 1.9/91.2 +/- 1.5, 131.0 +/- 2.0/84.3 +/- 1.2, and 139.7 +/- 1.8/90.9 +/- 1.1 mmHg. The differences between the lower treatment, versus the higher pre- and post-treatment, values were all statistically significant (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Left ventricular anatomy and function in normotensive young adults with hypertensive parents. Study at rest and during handgrip.

Using digitized M-mode echocardiograms, we evaluated left ventricular (LV) anatomy and function at rest and during handgrip in 24 normotensive young adults with both parents hypertensive (HP+), each matched for age, sex, body weight, and body surface area with one normotensive adult with both parents normotensive (HP-). LV parameters were within the normal range in all HP+ and HP-. At rest, HP+ as compared to HP- had higher systolic and diastolic blood pressure (BP), septal and posterior wall thickness, and LV mass; LV diastolic diameter and end-systolic wall stress were similar in the two groups. Modified midwall fractional shortening, peak shortening rate of LV diameter and peak thickening rate of LV posterior wall, indices of LV systolic function, and peak lengthening rate of LV diameter and peak thinning rate of LV posterior wall, indices of ventricular relaxation, were significantly higher in HP+. Handgrip induced significant (P < .001) and percent-comparable increases of systolic and diastolic BP, heart rate, and cardiac output in HP+ and HP-; peak shortening and lengthening rates of LV diameter and peak thickening and thinning rates of LV posterior wall increased significantly in HP-, whereas in HP+ the value of the four parameters, higher at rest as compared to HP-, did not show any further increase. In conclusion, normotensive young adults with high genetic risk for hypertension have higher BP and thicker and overactive LV as compared to subjects with normotensive parents. Handgrip stimulates LV function in offspring of normotensives, but not the already hyperkinetic LV of hypertensive offspring.

Ileal substitute of ureter with reflux-plasty by terminal intussusception of bowel: animal experiments and clinical experience.

The conflicting results reported after substitution of the ureter by isolated bowel segments suggest that the procedure is still hazardous. This induced us to check experimentally the performance of the ileal ureter with antireflux-plasty before using it clinically. The antireflux mechanism is constructed by intussuscepting the terminal 8 cm. of an isolated ileal segment into each other thus forming a nipple. After vesicoileostomy the nipple protrudes into the urinary bladder. In the pig vesicoileorenal reflux was prevented, and anterograde urinary flow from the kidney through the ileal ureter into the bladder was unobstructed. Finally, the case of a patient is recorded who was submitted to the same procedure successfully.

Endothelin in mild to moderate essential hypertension: relationship between ambulatory and clinic blood pressure values.

We investigated in a post hoc analysis the relationship between plasma endothelin (ET-1) levels (immunoreactive ET-1-like material: ir-ET-1) with both casual and noninvasive 24h ambulatory blood pressure monitoring (24h ABPM) values in EH. Fifteen uncomplicated EH patients (casual supine DBP > or = 100 mmHg), 10 males, age 54 +/- 6 years, 13 previously treated, enrolled in an antihypertensive drug trial (casual DBP > or = 100 mmHg), were evaluated. After a four week single-blind placebo wash-out period, measurements of supine casual SBP and DBP (three consecutive readings) and a 24h ABPM (Spacelabs 90207; automatic reading every 15 minutes) were carried out. Plasma ir-ET-1 was measured by radioimmunoassay kit (Amersham, UK). Pearson correlation coefficient tests were used for statistical evaluations. Mean (SD) casual SBP/DBP values were 166(5)/104(2) mmHg. The 24h ABPM mean values were 148(7)/87(3) mmHg. Daytime (07.00-23.00h) and nighttime (23.00-07.00h) SBP/DBP were 153(7)/91(3) and 137(10)/78(5) mmHg, respectively. Plasma ir-ET-1 levels were 0.9(0.5) pmol/l (range 0.3-2.1 pmol/l). Plasma ir-ET-1 was not correlated with casual SBP and DBP, age, serum creatinine and duration of EH. Positive and significant correlations were observed with 24h SBP (r = 0.59), daytime SBP (r = 0.58), nighttime SBP (r = 0.53) and DBP (r = 0.60). Unlike casual BP, ABPM mean values correlate positively with plasma ir-ET-1 in mild to moderate EH.

Fixed combination of benazepril and very low dose hydrochlorothiazide in the treatment of mild to moderate essential hypertension: evaluation by 24-hour non invasive ambulatory blood pressure monitoring.

A double-blind, crossover, placebo-controlled study was undertaken in order to assess the antihypertensive efficacy of a fixed combination of benazepril and hydrochlorothiazide in two different dosages by ambulatory blood pressure monitoring (ABPM). After a three-week placebo wash-out period, 18 patients with mild to moderate essential hypertension, all males, aged 41-60 years, were randomized to receive benazepril 5 mg + hydrochlorothiazide 6.25 mg, benazepril 10 mg + hydrochlorothiazide 12.5 mg or placebo, all given once daily for 4 weeks, according to a 3 crossover period, arranged in a 3 x 3 latin square design. Patients were checked after the wash-out period and every 4 weeks thereafter. At each visit, 24-hour ABPM was performed by a non-invasive device (Spacelabs 90202); causal BP (by mercury sphygmomanometer) and HR were also measured. Both dosages of the fixed combination were equally effective in reducing systolic and diastolic BP values throughout the 24-hour period as compared to the placebo. The antihypertensive effect of the drug could be observed to a similar extent both during the day and night and was still significant 24-hour post-dosing. In addition, the fixed combination did not affect the normal BP circadian variability.

[Evaluation of neuropsychological parameters in a group of metal mechanics occupationally exposed to radio frequencies]. / Valutazione di alcuni parametri neuropsicologici in un gruppo di lavoratori metalmeccanici professionalmente esposti a radiofrequenze.

In view of the increasing interest in electromagnetic fields, the effects on behaviour were studied in a group of foundry workers following prolonged exposure to radiofrequencies. The results of behavioural tests revealed significant differences between the exposed and control groups as regards neuropsychological performance. Anxiety and depression tests, however, indicated no pathological alterations, in contrast to previous observations. Nevertheless, the results need to be confirmed by further, more detailed studies.

The urethral pressure profile recorded by means of CO2-perfusion at high flow rates.

The urethral pressure profile (UPP) is recorded by CO2-perfusion of the urethra at a rate of 120 ml/min. The curves are reproducible. Their features are practically identical with the shape of profiles written by liquid perfusion. The curves are absolutely calibrated. High flow perfusion and calibration make it possible to compare CO2-curves with each other and even with graphs executed by other methods.

[Antihypertensive effect and tolerability of slow-release nicardipine]. / Effetto antipertensivo e tollerabilità di nicardipina a rilascio graduale.

In order to evaluate the antihypertensive efficacy and tolerability of a new nicardipine formulation, 26 mild-to-moderate essential hypertensive patients were given slow-release nicardipine, 40 mg, twice daily for 6 weeks. Systolic (SBP) and diastolic (DBP) blood pressure were measured after a 1 week single-blind placebo run-in period and after 1, 2, 4 and 6 weeks of active treatment, just before the morning administration. After 1 week, nicardipine induced a significant blood pressure reduction (p less than 0.01), with a decrease in mean SBP/DBP values of -15/-11 mmHg (from baseline values of 165/104 to 150/93 mmHg) in supine and of -16/-12 mmHg (from 158/110 to 142/98 mmHg) in standing position. After 6 weeks the decrease was of -15/-12 mmHg in supine and of -15/-14 mmHg in standing position. The responder rate (DBP decrease of at least 10 mmHg) was 62% (16/26). Normalization rate (DBP less than 95 mmHg with a concomitant decrease of at least 10 mmHg) was 54% (14/26). Eleven patients reported adverse events (headache, peripheral oedema, palpitations, nausea, constipation, flush, dizziness and asthenia). Due to an improved pharmacokinetic profile, the slow-release formulation prolongs to 12 hours the antihypertensive effect of nicardipine, thus facilitating patient's compliance.

Comparative effects of celiprolol, propranolol, oxprenolol, and atenolol on respiratory function in hypertensive patients with chronic obstructive lung disease.

The aim of the study was to compare the pulmonary effects of four beta-blockers with different ancillary properties: propranolol (non-beta 1 selective without ISA), oxprenolol (non-beta 1 selective with ISA), atenolol (beta 1 selective), and celipropol (beta 1 selective with mild beta 2-agonist and alpha 2-antagonist activity) in hypertensive patients with chronic obstructive lung disease. Ten asthmatic patients, all males, aged 50-66 years were studied. Entry criteria were a) DBP greater than or equal to 95 mmHg and less than or equal to 115 mmHg; b) FEV1 less than 70% of the theoretical values; c) FEV1 increase of at least 20% after salbutamol inhalation (200 micrograms). After a 2-week washout period on placebo, each patient received propranolol (80 mg/day), oxprenolol (80 mg/day), atenolol (100 mg/day), and celiprolol (200 mg/day) for 1 week, according to a randomized, cross-over design. At the end of the washout and of each treatment period, airway function, assessed by FEV1, FVC, and FEV1%, was evaluated by spirometry both in the basal condition and after salbutamol inhalation. Unlike propranolol and oxprenolol, which significantly reduced FEV1 and inhibited the bronchodilator response to inhaled salbutamol, atenolol and celiprolol did not significantly affect respiratory function and did not antagonize salbutamol effects. Celiprolol more closely approached placebo in its respiratory effects than did atenolol, although the differences were not statistically significant.

Community control of hypertension at the worksite in a metallurgical factory: results of 1-year follow-up.

This study was designed to assess advantages and cost-effectiveness of community control of hypertension at the worksite in a metallurgical factory in Pavia. Under consent of managers and trade-unionists, a screening program was undertaken. 2701 subjects (95% of the total number of employees) were screened: 277 (10.2%) were hypertensive, 101 (38%) did not know to be hypertensive, 56 (22%) knew to be hypertensive but they were untreated and only 20 (8%) of those under treatment were adequately treated. Of the 277 essential hypertensives, 262 (94%) adhered to the program. They were assigned to beta-blocking or diuretic treatment following WHO rules. Then an aggressive follow-up was started (the hypertensives were periodically called to control at the worksite). 257 (98%) were participants 1 year later. Our worksite hypertension control program allowed us to identify many cases of undiagnosed or untreated hypertension and to start an early treatment. One year after entry, the percentage of hypertensives achieving a normal blood pressure (85%) was almost twice as that obtained by conventional clinical approach employing the same type of treatment. Besides, more than 95% of hypertensives remained under control at 1 year. Regarding the costs, it is difficult to generalize, but our study suggests that, if there is the will, it is possible to realize programs of hypertension community control at a very low cost (in our experience: 43 dollars per hypertensive per year).

[Arterial hypertension: adenocarcinoma of the kidney or bilateral renal artery stenosis$]. / Arterielle Hypertonie: Adenokarzinom der Niere oder bilaterale Nierenarterienstenose$

In a 71-year-old female with severe hypertension, bilateral renal artery stenosis and renal adenocarcinoma, a renal vein renin study revealed suppressed renin secretion from the kidney with carcinoma and contralateral ischemia. The hypertension was not cured by surgical removal of the kidney with carcinoma. Hypertension is frequently noted in patients with renal adenocarcinoma (28% of 603 patients reported in the literature). This type of hypertension is frequently improved after removal of the tumor (83% of 36 surgically treated patients). In certain patients the pathogenesis of hypertension associated with renal adenocarcinoma may be related to renin secretion from the tumor or to renin activation due to regional ischemia caused by vascular compression. In other patients the renin-angiotensin system does not appear to play a pathogenic role in the development of hypertension associated with renal adenocarcinoma.

Effects of nifedipine and indomethacin on cough induced by angiotensin-converting enzyme inhibitors: a double-blind, randomized, cross-over study.

Prostaglandins (PG) have been suggested to play a role in the genesis of cough induced by angiotensin-converting enzyme inhibitors (ACE-I) and that inhibition of PG synthesis can reduce or abolish the incidence of this side effect. Moreover, experimental and clinical data suggest that nifedipine, a dihydropyridine Ca antagonist, can inhibit PG synthesis. Therefore, we wished to determine whether nifedipine can reduce cough induced by ACE-I as compared with indomethacin, a known inhibitor of PG synthesis. Fourteen hypertensive patients who developed cough during captopril chronic therapy randomly received slow-release nifedipine 20 mg twice daily (b.i.d.), indomethacin 50 mg b.i.d., and placebo b.i.d. for 1 week in a double-blind, cross-over design. At the end of each treatment phase, cough was evaluated by a self-administered questionnaire containing an ordinal scale for daily cough intensity and frequency. Indomethacin abolished or markedly reduced cough induced by ACE-I, whereas nifedipine reduced it but to a lesser degree. These findings suggest that PG can play a role in cough caused by ACE-I, and a dihydropyridine Ca antagonist can reduce the occurrence of this side effect.

Benazepril at incremental doses in essential hypertension.

The antihypertensive effect of the new non-sulphydryl ACE-inhibitor benzepril was studied in 30 patients (16 men, 14 women; mean age 50 +/- 7 years) with essential hypertension at WHO stage I or II. After a 2-week placebo treatment, patients with lying diastolic blood pressure (DBP) greater than or equal to 95 mmHg were given benzepril 10 mg once daily for 2 weeks. At the end of this period, patients with lying DBP less than 95 mmHg continued with the same dosage, while those with lying DBP greater than or equal to 95 mmHg were blindly up-titrated to benazepril 20 mg once daily. In both cases treatment was continued for further 4 weeks. BP was measured every two weeks 24-26 h after last drug administration. After the run-in period, mean group lying BP was 160/104 +/- 8/5 mmHg. Benazepril significantly reduced systolic blood pressure (SBP) and DBP, both supine and standing (p less than 0.01), while heart rate (HR) did not change. After the first 2 weeks, 13 patients (43%) had lying DBP less than 95 mmHg ("fast responders"), while 17 patients (57%) had DBP greater than or equal to 95 mmHg. By increasing the dosage to 20 mg, a further 5 patients became responder and mean group blood pressure in patients up-titrated with benazepril dropped significantly (-16/-10 mmHg from baseline; p less than 0.01, "slow responders"). Fast responders were younger (47 +/- 5 vs 54 +/- 8 years), had lower baseline BP (160/99 +/- 4/3 vs 173/107 +/- 7/3) and had shorter duration of hypertension (20 +/- 14 vs 61 +/- 27 months) than "slow responders".(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of celiprolol on the blood lipid profile in hypertensive patients with high cholesterol levels.

The aim of this study was to compare the effects of chronic antihypertensive therapy with either celiprolol or atenolol on plasma lipids in patients with hypercholesterolemia. Forty-six patients with essential hypertension and a total cholesterol (TC) concentration greater than 220 mg/dl were studied. After 1 month on placebo, patients were stratified into five classes on the basis of their plasma TC levels and then randomized to receive atenolol 100 mg/day or celiprolol 400 mg/day for 1 year. Blood pressure (BP), heart rate (HR), and blood samples for evaluation of TC, HDL cholesterol (HDL-C), LDL cholesterol (LDL-C), and triglycerides (TG) were taken before and after the placebo period, and every 6 months from the beginning of the active treatment. Celiprolol and atenolol caused similar reduction in BP. Both atenolol and celiprolol decreased TC. Atenolol significantly reduced HDL-C, while celiprolol increased it (p less than 0.01 at 12 months), and the difference between the two drugs was statistically significant in this regard. LDL-C levels were not significantly affected by atenolol, but were progressively reduced by celiprolol (p less than 0.05 at 6 months, p less than 0.01 at 12 months). TG rose under atenolol but was reduced by celiprolol (p less than 0.05). The results of this study show that the celiprolol-induced changes in plasma lipids may be favorable and suggest that, in hypertensive patients with high cholesterol levels, beta-blocker therapy with celiprolol may be effective in lowering BP without worsening the lipid profile.

Beta-blocker effects on plasma lipids in antihypertensive therapy: importance of the duration of treatment and the lipid status before treatment.

The aim of this study was to evaluate the effects of long-term monotherapy with four beta-blockers provided with different pharmacological properties on plasma lipids in both normocholesterolemic and hypercholesterolemic hypertensive patients. After a 1-month run-in period on placebo, 70 hypertensive patients with basal total cholesterol (TC) < or = 220 mg/dl were treated for 3 years with propranolol 160 mg/day or atenolol 100 mg/day or bisoprolol 10 mg/day or mepindolol 10 mg/day, while 59 hypertensive patients with basal TC > 220 mg/dl were given the same beta-blockers at the same dosage for 6 months. In both normocholesterolemic and hypercholesterolemic hypertensive patients. HDL-C and triglyceride (TG) levels showed significant changes that appeared to be related to the type of beta-blocker used and to the duration of therapy. Nonselective, non-ISA (intrinsic sympathomimetic activity) propranolol caused the most pronounced changes, decreasing HDL-C and increasing TG concentrations; beta1-selective atenolol and bisoprolol had similar, but less remarkable effects; even more discrete changes were observed on mepindolol (with ISA). The variations in HDL-C and TG values reached their peak in 6-12 months of beta-blocker therapy; then, after a plateau phase, they showed a progressive trend toward pretreatment levels. In hypercholesterolemic patients, the percent change in both HDL-C and TG values was lower compared to normocholesterolemic patients.