Conserved themes but novel activities in recombinases and topoisomerases

OBJECTIVE: Hypertension is thought to play an important role in the pathogenesis of acromegalic cardiomyopathy. So far, hypertension has been defined by clinical measurement, with considerable variations reported concerning its prevalence in acromegalics. DESIGN: To determine the mean blood pressure (BP) values and the prevalence of hypertension in patients with active acromegaly according to non-invasive 24-hour ambulatory BP monitoring (ABPM) and to compare the data obtained with those provided by clinical measurement. PATIENTS: Forty patients with active acromegaly (22 women, 18 men, mean age 48.6 +/- 12.5 years) were included. Patients were in wash-out for antihypertensive treatment and none had been using any medical treatment for acromegaly for at least 3 months before the study. All were studied as outpatients. MEASUREMENTS: Clinical BP values were calculated as the mean of BP values obtained by standard sphygmomanometric measurement in three separate occasions. Mean 24-hour, daytime and night-time BP values were obtained by ABPM. RESULTS: The mean 24-hour BP values were lower than clinical BP values, the difference being significant for both systolic BP (SBP: 131.1 +/- 21.5 versus 136.1 +/- 16.3 mmHg, P < 0.02) and for diastolic BP (DBP: 74.6 +/- 10.6 versus 88.8 +/- 9.1 mmHg, P < 0.0001). ABPM values recorded during the daytime were 137.8 +/- 20.9 mmHg for SBP and 78.6 +/- 11.5 mmHg for DBP, the latter being significantly lower than the corresponding clinical BP values (P < 0.0001). About 60% of the patients considered hypertensive by clinical measurement were found to be normotensive by ABPM, thereby decreasing the prevalence of hypertension in this series from 42.5% to 17.5% according to ABPM (P < 0.02). In contrast, all patients defined as normotensive by clinical measurement were also normotensive by ABPM. CONCLUSIONS: Ambulatory blood-pressure monitoring indicated a lower prevalence of hypertension in acromegalic patients then usually reported, suggesting that the role of hypertension in the pathogenesis of acromegalic cardiomyopathy is commonly overestimated. We propose that ambulatory blood-pressure monitoring should be routinely proposed in acromegalics with high or borderline clinical blood pressure values although it is not useful in patients defined normotensive according to repeated clinical measurement.     

Stage I ovarian cancer by transvaginal color Doppler sonography: a report of 18 cases

PURPOSE: To evaluate the tolerability and 24 hours efficacy of a new anti-hypertensive drug: cilazapril. METHODS: In an open non comparative study 20 hypertensive patients (16 females, age from 30 to 60 years, average = 49.4) were followed for 6 weeks: 2 wash out and 4 treatment (5 mg OD). Blood pressure (BP) was measured by casual and ambulatory blood pressure monitoring (ABPM) readings. RESULTS: Comparing washout and treatment periods, ABPM averages both for systolic and diastolic BP (mmHg) showed significant decrease in 24 hours, during day and night sub periods. The decrease was not significant between averages considering the "early morning rising pressure" sub period. Heart rate averages showed significant reduction at all sub periods except during night. Adverse effects were mild and resolved spontaneously (n = 3, 15%). CONCLUSION: Cilazapril seems to be efficacious as antihypertensive. Tolerability is excellent. It preserved circadian rhythm despite significantly reducing blood pressure at all periods evaluated except early morning. A bradycardic effect observed mostly during day period should be better evaluated.     

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)     

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.     

Effects of amlodipine on 24-hour ambulatory blood pressure profiles, electrocardiographic monitoring, and left ventricular mass and function in black patients with very severe hypertension

In a 3-month, open-label study, 54 consecutive black patients with very severe hypertension were treated with amlodipine. Very severe hypertension was defined as an average sitting diastolic blood pressure (BP) > or = 115 mmHg and < or = 140 mmHg as a mean of 10 readings over a 30-minute period using an automatic BP measuring device and a mean 24-hour diastolic ambulatory blood pressure (ABP) > or = 110 mmHg and < or = 140 mmHg). Serial changes in 24-hour ABP and electrocardiographic monitoring, left ventricular (LV) mass index, and LV systolic function were evaluated. Mean 24-hour ABP was reduced from 181 +/- 14/119 +/- 6 to 140 +/- 15/92 +/- 9 mmHg at 3 months (P < 0.0001). Target BP (mean 24-hour diastolic ABP < 90 mmHg) was achieved in 35% of the patients. The reduction in BP was sustained for 24 hours after drug administration. Simultaneous BP measurements using the automatic BP measuring device were significantly different from the ABP measurements before and after treatment, suggesting a marked "white coat" pressor effect. At baseline, frequent or complex ventricular arrhythmias (> 30 ventricular extrasystoles per hour, ventricular couplets) were present in 2 (4%) patients, with no significant change after treatment. Left ventricular mass index regressed from 140 +/- 50 to 111 +/- 30 g/m2 at 3 months (P < 0.03); LV performance was not adversely affected. Adverse effects were few and tended to disappear during the treatment period. All of the clinical laboratory parameters tested remained unchanged. In this group of patients, treatment with amlodipine showed a marked and sustained antihypertensive action as demonstrated by 24-hour ABP monitoring, and was well tolerated and associated with LV mass regression without adverse effect on systolic cardiac function. Further, a low rate of complex ventricular arrhythmias was documented.     

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.     

A case report of two siblings with familial leukoencephalopathy in normotensive male adults with alopecia and lumbago

The aim of the study was to examine the hypotensive efficacy and tolerance of bisoprolol in elderly patients. Sixty patients (40 <65 years and 20 >65 years) with mild-to-moderate essential hypertension (diastolic blood pressure (DBP) between 95 and 109 mm Hg) were included in the study. After a 2-week run-in period on placebo, patients began bisoprolol therapy (5 mg/d) for 12 weeks. After 4 weeks the dose was increased to 10 mg/d in those with a DBP > or =95 mm Hg. Additionally, in 10 patients over 65 years old, 24-h ambulatory BP monitoring (ABPM) was performed, after placebo and after bisoprolol (5 mg) administration. The hypotensive efficacy of bisoprolol in the elderly and younger patients was similar. Before and after treatment the mean difference of systolic BP (SBP) was 19.6 +/- 12.5 mm Hg and DBP 9.6 +/- 6.2 mm Hg in the younger patients and 16.1 +/- 13.6 mmHg and 9.5 +/- 6.0 mmHg in the elderly patients. Bisoprolol produced a similar reduction in heart rate (23.1% vs 17.1%) in the estimated groups. The tolerance of bisoprolol was good in both groups. There were no significant differences in adverse drug reactions between the groups.     

Association between blood pressure and circulating hormonal factors with left ventricular mass in patients with essential hypertension older than 55 years of age

BACKGROUND: The prevalence of left ventricular hypertrophy (LVH) is higher in elderly patients with hypertension than in normotensive patients. The factors relationed herewith are not well known. The first purpose was to analyse the relationship between the levels of blood pressure (BP) recorded by ambulatory blood pressure monitoring (ABPM) and the left ventricular mass index (LVMI) in a group of untreated patients older than 55 years with essential hypertension. Our second purpose was to observe the relationship between the concentration of several circulating hormones and the left ventricular mass index. SUBJECTS AND METHODS: The study included 31 untreated patients with mild to moderate essential hypertension and 37 healthy normotensives. Both groups were of similar age, sex and body mass index. We determined for both groups the casual arterial pressure (CAP), ambulatory BP monitoring (ABPM) throughout 24 h, daytime (07.00-23.00 h), nighttime (23.00-07.00 h), left ventricular mass index (LVMI) (following Devereux's formula) and circulating levels of endothelin-1, aldosterone, renine, free adrenaline and noradrenaline. RESULTS: The ILVM in hypertensive patients was 139.6 +/- 35.9 g/m2 and in 124.0 +/- 31.8 g/m2 in normotensive (p < 0.05). The percentage of patients with LVH was 63 and 43%, respectively (p < 0.05). The LVMI in hypertensive patients was correlated with the diastolic CAP (97 +/- 7 mmHg) (r = 0.41; p < 0.05), unlike with the systolic CAP (164 +/- 18 mmHg). The ILVM in normotense patients was not associated neither with the systolic CAP (126 +/- 10 mmHg) nor with the diastolic (79 +/- 6 mmHg). In hypertensive patients we found a slight association between the LVMI and the systolic ABPM (130 +/- 14 mmHg) during nighttime (r = 0.41; p < 0.05). The rest of average ambulatory BP and the hormonal values at study did not show a correlation with the LVMI in both groups. CONCLUSIONS: A slight correlation exists between BP (casual and determined with ambulatory blood pressure monitoring throughout 24 hours) and the left ventricular mass index in mild to moderate untrated hypertensive patients older than 55 years. We did not observe correlations between the circulating levels of endothelin-1, renin, aldosterone, free adrenaline and noradrenaline and the left ventricular mass. The average ventricular mass and the number of subjects with ventricular hypertrophy was significantly increased in hypertensives than in normotensives.     

Hydrochlorothiazide is superior to isradipine for reduction of left ventricular mass: results of a multicenter trial. The Isradipine Study Group

OBJECTIVES: We sought to determine the efficacy of isradipine in reducing left ventricular (LV) mass and wall thickness in hypertensive patients. BACKGROUND: LV hypertrophy on the echocardiogram is a strong predictor of cardiovascular events. Reduction of LV mass may be a desirable goal of drug therapy for hypertension. However, although thiazide diuretic drugs have been advocated as first-line therapy for hypertension, their efficacy in reducing LV mass has been questioned. METHODS: Patients with mild to moderate diastolic hypertension and LV mass in excess of 1 SD of normal values were randomized to isradipine (n = 89) or hydrochlorothiazide therapy (n = 45). Evaluations were obtained at baseline, after 3 and 6 months of treatment and 2 weeks after treatment was stopped. RESULTS: At 6 months, LV mass decreased by 43 +/- 45 g (mean +/- SD) with hydrochlorothiazide (p < 0.001) but only by 11 +/- 48 g with isradipine (p = NS; between-group comparison, p < 0.001). Two weeks after drug therapy was stopped, LV mass remained 24 +/- 41 g lower than that at baseline in the hydrochlorothiazide group (p = 0.003) but only 7 +/- 50 g lower in the isradipine group (p = NS). Septal and posterior wall thicknesses were significantly and equally reduced with both isradipine and hydrochlorothiazide. Greater LV mass reduction with hydrochlorothiazide was related to a 2.8 +/- 3.3-mm reduction of LV cavity size with hydrochlorothiazide but no reduction with isradipine. At 6 months of treatment, diastolic blood pressure (BP) by design was equally reduced in both treatment groups. At 3 months, systolic BP was reduced by 17 +/- 15 mm Hg with isradipine and by 26 +/- 15 and 25 +/- 17 mm Hg at 3 and 6 months, respectively, with hydrochlorothiazide (p = 0.003, between-group comparison). However, on stepwise multivariable regression analysis, treatment selection (partial r2 = 0.082, p = 0.001), change in average 24-h systolic BP (partial r2 = 0.032, p = 0.029) and change in average sitting systolic BP (partial r2 = 0.017, p = 0.096) were predictive of LV mass reduction. CONCLUSIONS: Despite an equivalent reduction of diastolic BP, 6 months of therapy with hydrochlorothiazide is associated with a substantial reduction of LV mass, greater than that with isradipine. The superior efficacy of hydrochlorothiazide for LV mass reduction is associated with a greater reduction of systolic BP as well as drug selection itself. These data may have important therapeutic implications.     

Maternal-fetal transfers: indications, appropriateness, and cost

The objective of this study was to assess the indications, appropriateness, and cost of maternal-fetal transfers to a tertiary care facility in an era of managed care. Our perinatal database was reviewed from January 1, 1996 through June 30, 1997 to determine maternal and fetal indications for transfer, referring institution characteristics, utilization of tertiary level services, and cost of transfer. There were 273 transfers from 53 referring hospitals ranging in distance from <20 miles (n = 102) to >100 miles (n = 41). Thirty-one patients were transferred by air (average cost $7656), 238 by ground (average cost $920), 4 by private car. The referring diagnosis was preterm premature rupture of membranes (PPROM) (n = 80), preterm labor (n = 76), preeclampsia (n = 42), medical complications (n = 25), or other (n = 50). Mean gestational age (GA) at transfer was 28.5+/-5.5 weeks. Patients were referred from hospitals with a self-designated nursery level I (n = 115), II (n = 111), III (n = 45), or none (n = 2). In 42 patients, (15%) no maternal or fetal indication for hospital transfer was identified after evaluation at the tertiary center. The most common referring misdiagnoses were preterm labor (n = 25), PPROM (n = 10) and preeclampsia (n = 3). One hundred and sixty-five patients delivered during transfer admission (mean GA = 29.6+/-4.8 weeks); 79 infants (48%) required admission to a level III, and 52 (31%) to a level II nursery. Most patients require the services of a tertiary facility after maternal fetal transfer. If delivered during transfer admission, the majority of neonates require care in an intermediate or intensive care nursery.     

Prevalence and profile of renovascular disease in type II diabetic patients with severe hypertension

The aim of this study was to determine the prevalence and profile of renal artery stenosis (RAS) in NIDDM population with severe hypertension. 60 consecutive NIDDM with severe HT (> or = 3 hypotensive drugs), 42 F/18 M (SR: 2.8), mean age: 66.6 +/- 6.5 years, diabetes duration: 14.1 +/- 6 years have had metabolic, ABPM and renal investigations: color duplex scan (CDS) (with renal us): n = 60, and/or arteriography: n = 17). 13 (21.5%) renal artery stenosis > or = 70%: 8 unilateral/5 bilateral were proved by arteriography. We compared classic HT (n = 47) versus renovascular HT (n = 13). There was no difference for age (years): 64.8 +/- 8 versus 70.6 +/- 6.4, HT duration (years): 11.6 +/- 6.8 versus 12.3 +/- 6. B.M.I.: 31.5 +/- 6 versus 27.6 +/- 3.3, HBA1C (%): 8.9 +/- 2.2 versus 8.8 +/- 0.9, cholesterol (mmol/L): 5.7 +/- 1.3 versus 5.5 +/- 0.6. Significant difference (p < 0.05) was noticed for S.R. (F/M): 2.9 versus 1.16, diabetes duration (years): 11.7 +/- 5 versus 16.5 +/- 8, frequency of retinopathy (%): 30 versus 61, smoking (%): 10 versus 40, triglycerides (mmol/L): 1.9 +/- 1.1 versus 2.6 +/- 1.1, and (p < 0.01) for blood pressure level (mmHg) (SBP: 142 +/- 20 vs 155 +/- 7, DBP: 81 +/- 13 vs 87 +/- 10, MBP: 103 +/- 16 vs 111 +/- 6), frequency (%) of HT escape (> or = 140/SBP, > or = 90/DBP) on ABPM: 40 versus 75 and 24 versus 40, insulin requirence (%): 36 versus 69, macroangiopathy (%): 51 versus 100 (coronaropathy: 34 vs 61, legs arteritis: 21 vs 69, carotid stenosis: 17 vs 30) and for renal function: frequency (%) of micro-macroalbuminuria: 36 versus 92 creatinaemia (mmol/L): 80 +/- 24 versus 124 +/- 44, creatinaemia clearance (mmL/min): 65 +/- 30 versus 40 +/- 12 while are found 5 renal insufficiencies (> or = 120 mmol/L). In NIDDM population with severe HT, renovascular HT is frequent (21.5%), and RAS must be evocated in unstable HT and/or renal injury with macro angiopathy, old NIDDM (> 15 years), requiring insulin. Colour duplex scan (+ renal US) mays lead to arteriography to confirm renal artery stenosis.     

Age-dependent eradication of Helicobacter pylori with dual therapy

BACKGROUND: Combined treatment using an acid-inhibiting drug with antibiotics can cure Helicobacter pylori infection. However, eradication rates are highly variable, especially if a proton pump inhibitor is used with amoxycillin. Therefore it is important to define factors/predictors of the clinical outcome. METHODS: In a single-blind study, 60 H. pylori-positive patients prospectively matched for diagnosis (erosive gastritis, duodenal and gastric ulcer), age (above and below 50 years) and smoking habits were randomly treated (each group n = 20) for 2 weeks with amoxycillin (1 mg b.d.) and either omeprazole (20 mg b.d.), lansoprazole (30 mg b.d.) or ranitidine (300 mg b.d.). Intragastric pH and plasma levels of the administered drugs were monitored over a dosing interval of 12 h. RESULTS: The overall eradication rates were 45% (intention-to-treat, ITT, 27/60) or 47% (per protocol 27/58); they did not differ (ITT) between omeprazole (50%), lansoprazole (40%) and ranitidine (45%). Median pH and time at which intragastric pH was above 4 was slightly lower for ranitidine (4.0 +/- 1.7; 51 +/- 25%) than for omeprazole (5.4 +/- 1.1: 77 +/- 25%; P < 0.05) or lansoprazole (4.4 +/- 1.6: 68 +/- 32%). Plasma concentrations of amoxycillin were comparable in all three treatment groups. Post-treatment H. pylori status was not dependent on those levels, or the drug-induced extent or duration of increased intragastric pH. However, H. pylori-eradicated patients were significantly (P < 0.05) older (56 +/- 13 years) than patients still H. pylori-positive (47 +/- 14 years). In addition, in patients older than 50 years (n = 33), eradication was higher (P < 0.01) than in patients (n = 25) below 50 years (65 vs. 24%). Eradication rate was highest (75-83%) in subgroups of patients (> 50 years and history of peptic ulcer or smokers). Neither activity/grade of peptic ulcer or erosive gastritis nor initial diagnosis were predictors for clinical outcome. CONCLUSION: The age of patients must be regarded as a major determinant of H. pylori eradication rate and may represent an important factor contributing to the highly variable clinical results.     

Single-center randomized trial comparing tacrolimus (FK506) and cyclosporine in the prevention of acute myocardial rejection

BACKGROUND: To compare the efficacy and safety of tacrolimus and cyclosporine in heart transplantation, this single-center, prospective, randomized, open-label clinical trial was undertaken. METHODS: Seventy-three adult patients were randomly assigned at the time of transplantation to receive either tacrolimus (n=43) or cyclosporine (n=30) as the primary immunosuppressant. Ten of the 43 patients in the tacrolimus group received the drug intravenously in the perioperative period; all other patients received only oral tacrolimus. RESULTS: With a mean follow-up of 27 months, patient survival rates (tacrolimus 83%, cyclosporine 81%) were similar. Fewer patients experienced acute rejection in the tacrolimus group (79%) than in the cyclosporine group (100%), but the difference was not statistically significant. The number of infections and dialysis and insulin requirements were similar for the 2 treatment groups, but the proportion of patients requiring multidrug antihypertensive regimens was lower in the tacrolimus group (12.5% vs 50.0% at month 6; p=.025). The interpatient variance in pharmacokinetic parameters in a subset of 10 patients was much higher after the first oral dose of tacrolimus than at steady-state (eg, first-dose time at which maximal concentration is reached (t(max)): 3.5+/-2.5h, steady-state t(max): 2.0+/-0.7h), and patients treated with intravenous tacrolimus (n=13) rather than oral tacrolimus (n=30) reached target concentrations faster and with less interpatient variability (eg, at day 0: 9.72+/-10.9 ng/mL intravenously vs 3.31+/-8.1 orally). CONCLUSIONS: Tacrolimus was associated with similar efficacy and safety profiles compared with cyclosporine. The higher interpatient variance in absorption associated with oral tacrolimus during the first few days after transplantation would suggest that intravenous tacrolimus should be used during the perioperative period.     

Familial ligand-defective apolipoprotein B-100: simultaneous detection of the ARG3500-->GLN and ARG3531-->CYS mutations in a French population

BACKGROUND: Flask pulmonary edema (FPE) may be a manifestation of renovascular hypertension (RVHTN) and unresponsive to antihypertensive therapy. METHODS: Response to antihypertensive therapy and perioperative outcomes were determined in 5 consecutive patients with FPE. RESULTS: A mean of 2.3 admissions for the treatment of FPE were observed despite a mean cardiac ejection fraction of 60%. Preoperative treatment was attempted for 12 days and included ventilatory support (n = 3) and hemodialysis (n = 2). Total decreased renal perfusion was demonstrated by arteriography and radionuclide scans, no patient having a functional, contralateral kidney. Renal revascularizations were not associated with mortalities; 1 patient experienced atalectasis requiring bronchoscopy. All patients were extubated within 48 hours of surgery. A significant reduction in blood pressure (BP, 46%) and serum creatinine (Cr, 53%, P < or = 0.05) was observed. A mean of 1 antihypertensive medication was required at discharge compared with 3.4 on admission. At follow-up (mean 57 months) all patients remain cured of FPE. CONCLUSIONS: Medical management was unsuccessful in the treatment of FPE. Renal revascularization was associated with low morbidity and mortality, control of BP, restoration of renal function, and cure of FPE. These data suggest surgical intervention is the optimal mode of treatment of RVHTN associated with FPE.     

Morphogenesis of the lateral nasal wall from 6 to 36 weeks

Salt intake, and the sensitivity of blood pressure (BP) to excessive salt intake is thought to contribute to the pathogenesis of essential hypertension in some patients. This study was designed to ascertain whether salt sensitivity of BP is a determinant of BP and renal vascular responsiveness to angiotensin converting enzyme (ACE) inhibition. In 24 patients with essential hypertension, ranging in age from 30 to 68 years, renin status, renal hemodynamics, and sensitivity of BP to steady state changes in salt intake were assessed. Twenty-four hour ambulatory BP monitoring (ABPM) was employed to measure baseline BP and BP response to 4 weeks' treatment with benazepril at 20 or 40 mg/day. Benazepril induced a highly-significant reduction in BP (P < .001) and increase in renal plasma flow (530 +/- 17 to 580 +/- 19 mL/min/1.73 m2; P < .001). Systolic BP fell from 143 +/- 2 to 129 +/- 2 mm Hg (P < .001), and diastolic BP fell from 91 +/- 1.6 to 80 +/- 2 mm Hg (P < .001). The magnitude of the BP and renal vascular response to ACE inhibition was not influenced by the sensitivity of BP to salt intake. In a multivariate analysis neither body mass index nor age influenced the BP response to ACE inhibition or the relationships between salt intake and a BP response to ACE inhibition. We conclude that the factors that influence sensitivity of BP to salt intake do not influence the systemic or renal hemodynamic response to ACE inhibition.     

Blood pressure outcome of angioplasty in atherosclerotic renal artery stenosis: a randomized trial. Essai Multicentrique Medicaments vs Angioplastie (EMMA) Study Group

Data for the effects on blood pressure of renal artery balloon angioplasty are mostly from uncontrolled studies. The aim of this study was to document the efficacy and safety of angioplasty for lowering blood pressure in patients with atherosclerotic renal artery stenosis. Patients were randomly assigned antihypertensive drug treatment (control group, n = 26) or angioplasty (n = 23). Twenty-four-hour ambulatory blood pressure, the primary end point, was measured at baseline and at termination. Termination took place 6 months after randomization or earlier in patients who developed refractory hypertension. In those allocated angioplasty, antihypertensive treatment was discontinued after the procedure but was subsequently resumed if hypertension persisted. Secondary end points were the treatment score and the incidence of complications. Two patients in the control group and 6 in the angioplasty group suffered procedural complications (relative risk, 3.4; 95% confidence interval, 0.8 to 15.1). Early termination was required for refractory hypertension in 7 patients in the control group. Antihypertensive treatment was resumed in 17 patients in the angioplasty group. Mean ambulatory blood pressure at termination did not differ between control (141+/-15/84+/-11 mm Hg) and angioplasty (140+/-15/81+/-9 mm Hg) groups. Angioplasty reduced by 60% the probability of having a treatment score of 2 or more at termination (relative risk, 0.4; 95% confidence interval, 0.2 to 0.7). There was 1 case of dissection with segmental renal infarction and 3 of restenosis in the angioplasty group. No patient suffered renal artery thrombosis. In unilateral atherosclerotic renal artery stenosis, angioplasty is a drug-sparing procedure that involves some morbidity. Previous uncontrolled and unblinded assessments of angioplasty overestimated its potential for lowering blood pressure.     

Divergent effects of ACE-inhibition and calcium channel blockade on NO-activity in systemic and renal circulation in essential hypertension

OBJECTIVE: Nitric oxide is a vasodilating and blood pressure lowering substance. To investigate whether calcium antagonists or angiotensin-converting enzyme (ACE) inhibitors increase vascular nitric oxide activity, we assessed systemic and renal vascular sensitivity to nitric oxide synthase inhibition in hypertensives on and off medication. METHODS: Ten essential hypertensive patients, aged 22-51 years, were studied 3 times: > or = 4 weeks off medication, after 3 weeks treatment with enalapril 20 mg twice a day and after 3 weeks nifedipine 60 mg/day. Each time, 24-h blood pressure registration was performed, followed by a clearance study to obtain a 3-h dose-response curve for intravenously infused NG-monomethyl-L-arginine (L-NMMA, respectively 0.75, 1.5 and 3.0 mg/kg/h). RESULTS: L-NMMA dose-dependently increased mean arterial pressure with 5 +/- 2 mmHg and systemic vascular resistance with 24 +/- 5% at maximum dose, whereas cardiac output decreased (all P < 0.001). Enalapril and nifedipine treatment decreased blood pressure, while the L-NMMA-induced increase in systemic vascular resistance was potentiated (enalapril: 45 +/- 7% and nifedipine: 46 +/- 8%; both P < 0.01). L-NMMA also dose-dependently decreased renal blood flow by 58 +/- 8% at maximum dose (P < 0.001), but neither drug potentiated these effects. CONCLUSION: These results indicate that, in essential hypertensives, antihypertensive therapy with enalapril or nifedipine increases nitric oxide dependency of systemic vascular tone, which may play a role in the blood pressure lowering effect of these drugs. However, this phenomenon cannot be observed in the renal circulation, suggesting a different regulation of endothelium-dependent vasomotion in the hypertensive kidney.     

An autopsy case of primary squamous cell carcinoma of the liver associated with hepatitis C virus antibody positive liver cirrhosis

An increase in potassium (K) intake may lower blood pressure (BP), but inconsistent results have been obtained in clinical trials. We studied the effects of K supplementation in hypertensive patients with monitoring of home and ambulatory BP. Fifty-five patients with essential hypertension (26 men, 29 women, 36-77 years old) participated in this study. A 4-week K supplementation period and 4-week control period were assigned in a randomized crossover manner. During the K period, the subjects were given 64 mmol/day of K as slow-release KCl tablets. Office, home, and 24-h BP, as well as serum and urinary electrolytes, were measured at the end of each period. In the control period, office, home, and 24-h BP were 151 +/- 2/88 +/- 1 (mean +/- SE), 138 +/- 1/83 +/- 1, and 137 +/- 1/81 +/- 1 mm Hg, respectively. Serum K increased from 4.15 +/- 0.04 to 4.42 +/- 0.05 mmol/L, and urinary K increased from 54 +/- 2 to 96 +/- 3 mmol/day with the K supplementation. Office, home, and 24-h BP were significantly lower in the K period than in the control period, although the differences were small (2.7 +/- 1.1/1.4 +/- 0.6, 3.6 +/- 0.9/1.7 +/- 0.5, 3.4 +/- 1.0/1.2 +/- 0.5 mm Hg, respectively). Changes in home and 24-h systolic BP with K supplementation were highly significant (P < .001), compared with office BP (P < .05). The change in 24-h systolic BP was correlated negatively with baseline BP and urinary Na/K ratio, and positively with baseline urinary K excretion. The changes in daytime and nighttime BP were comparable. These results indicate that increasing K intake lowers BP in hypertensive subjects, especially in those with higher BP and lower K intake. Our study supports the usefulness of K supplementation in the treatment of hypertension, although its antihypertensive effect may be small.     

Role of spinal NO in antiallodynic effect of intrathecal clonidine in neuropathic rats

BACKGROUND: In the presence of elevated cardiac filling pressures, the decline of blood pressure (BP) during the straining phase of a Valsalva manoeuvre is blunted or absent. We compared the use of non-invasively measured BP response to a Valsalva manoeuvre with clinical assessment and bioimpedance measurements to identify haemodialysis patients at risk of acute congestive heart failure (CHF). METHODS: Continuous BP response (Finapres) to a Valsalva manoeuvre, clinical assessment by nephrologists, and bioimpedance estimations of extracellular fluid volume were determined before and after haemodialysis, once every week during a 5-week period. Acute CHF was defined according to preset clinical and radiological criteria. RESULTS: Participants (age 60+/-19 years, six females, nine males) had an average predialysis weight of 66.8+/-11.8 kg. Patients were dialysed for 3.8+/-0.8 h with a mean ultrafiltration of 2.4+/-1.1 litres. Valsalva systolic BP ratios (phase 2 to 1) decreased significantly during dialysis from 0.81+/-0.11 to 0.73+/-0.10 (P<0.05). Five patients experienced an episode of acute CHF. The Valsalva BP ratios for these patients before and after dialysis (0.89+/-0.05 and 0.78+/-0.05 respectively) were higher than for the remaining ten patients (0.77+/-0.10 and 0.70+/-0.11, respectively) (P<0.05). A cutoff Valsalva BP ratio of 0.82 resulted in positive and negative predictive values for CHF of 62 and 100% respectively. No differences in clinical assessment or bioimpedance parameters were found, with the exception of postdialysis diastolic BP and predialysis ankle oedema. After treatment of CHF, Valsalva BP ratios decreased significantly without changes in the other hydration parameters. CONCLUSIONS: Non-invasive assessment of the BP response to a Valsalva manoeuvre appears to be a potential tool for identifying patients at risk of acute CHF during maintenance haemodialysis.     

The effectiveness and safety of low dose pravastatin in elderly hypertensive hypercholesterolemic subjects on antihypertensive therapy

To evaluate the efficacy and safety of low dose (10 mg) pravastatin in hypercholesterolemic, hypertensive elderly subjects undergoing antihypertensive treatment, a randomized, double-blind, placebo-controlled 6-month trial was conducted. The subjects had a total plasma cholesterol of at least 250 mg/dL and had been, for at least 3 months, consuming a standard lipid-lowering diet (American Heart Association Step 1 Diet). Sixty elderly hypertensive patients randomly received placebo (n = 30) or pravastatin (n = 30) treatment. The dosage consisted of 10 mg of pravastatin daily during the 6-month trial. Over that period, in the pravastatin group, plasma levels of total cholesterol and LDL-cholesterol significantly (P < .01) dropped (-20% and -25%, respectively) compared to the placebo group. The plasma level of HDL-cholesterol increased (+5%) while triglycerides slightly decreased (-8%) (P < .05). No serious side effects occurred, and pravastatin was generally tolerated. Fasting hyperinsulinemia (11.0 +/- 0.8 v 9.3 +/- 0.7 microU/mL; P = .06) also improved, although not significantly, after 6 months of pravastatin therapy. Results from this study confirmed that a low dose (10 mg) of pravastatin daily is a safe and effective method of reducing plasma total and LDL-cholesterol in hypercholesterolemic, hypertensive elderly patients who are on concurrent antihypertensive drug therapy.