A study of losartan, alone or with hydrochlorothiazide vs nifedipine GITS in elderly patients with diastolic hypertension

We conducted a randomised, double-blind, parallel design study comparing the efficacy and tolerability of the angiotensin II receptor antagonist, losartan, alone or with low-dose hydrochlorothiazide (HCTZ) to the dihydropyridine calcium channel blocker, nifedipine GITS (gastro-intestinal therapeutic system), in elderly patients (> or =65 years old) with a diastolic blood pressure (DBP) between 95 and 115 mm Hg. After a placebo wash out period, 140 patients were randomly assigned to receive either losartan 50 mg or nifedipine GITS 30 mg. Patients were evaluated at 4-week intervals during a 12-week treatment period. Patients receiving losartan had HCTZ 12.5 mg added and increased to 25 mg to reduce DBP <90 mm Hg. Patients receiving nifedipine GITS had their dose increased to 60 mg and 90 mg to reduce DBP <90 mm Hg. Efficacy, tolerability and quality of life were assessed during the 12 weeks on each regimen. Patients treated with the losartan regimen (n = 73) had reductions in trough sitting DBP of -10, -13, and -13 mm Hg after 4, 8, and 12 weeks of therapy, respectively. Patients receiving the nifedipine GITS regimen (n = 67) had DBP reductions of -14, -15, and -15 mm Hg, respectively. There were no significant differences in the DBP response between the treatment groups except at week 4 (P < 0.05). Similar reductions in systolic BP (SBP) between the two treatment groups were observed at all time points. The percentages of patients in the two treatment groups reaching goal DBP (<90 mm Hg or DBP > or =90 mm Hg with a reduction from a baseline of > or =10 mm Hg) were comparable (81% on the losartan regimen and 90% on the nifedipine GITS regimen). There were significantly more adverse events reported in patients receiving nifedipine GITS when compared to the losartan regimen (54% vs 36%, P < 0.05). A patient-reported symptom inventory also showed that swollen ankles was bothersome in significantly more patients treated with the nifedipine GITS regimen when compared to the losartan regimen (24% vs 5%, P = 0.001). Thus, in elderly patients with diastolic hypertension, a regimen of losartan alone or with HCTZ has similar efficacy to a regimen of nifedipine GITS with greater tolerability and less symptom bother due to swollen ankles.     

Efficacy and tolerability of extended-release felodipine and extended-release nifedipine in patients with mild-to-moderate essential hypertension

The efficacy and tolerability of extended-release felodipine (felodipine-ER) and nifedipine gastrointestinal therapeutic system (nifedipine GITS) were compared in a multicenter, prospective, open-label clinical trial of 277 patients with mild-to-moderate uncomplicated essential hypertension (sitting diastolic blood pressure [SiDBP] > or = 95 and < or = 115 mm Hg). After a 3-week washout period, patients were randomized to receive felodipine-ER (5 mg once daily) or nifedipine GITS (30 mg once daily); during a subsequent 6-week titration phase, the once-daily felodipine-ER dose could be increased to 10 mg and the nifedipine GITS dose to 60 or 90 mg in an attempt to achieve adequate blood pressure response (SiDBP < or = 90 mm Hg, or < 100 mm Hg with a > 10-mm Hg reduction from baseline, as measured 24 hours after dosing [trough]). At the end of titration, the mean daily doses of felodipine-ER and nifedipine GITS were 8 and 50 mg, respectively. Mean changes in sitting systolic blood pressure (SiSBP)/SiDBP were -14/-12 and -16/-13 mm Hg, respectively. All reductions were significant when compared with baseline (P < 0.01), but there were no significant differences between treatment groups. Adequate blood pressure response occurred in 77% of the felodipine-ER group and 80% of the nifedipine GITS group; this difference was not significant. Blood pressure changes were similar among sex and race subgroups. A higher percentage of older patients (> 55 years of age) than younger patients (< or = 55 years of age) reached goal SiDBP with both drugs. Patients with adequate SiDBP response continued receiving their assigned medication for an additional 6-week maintenance period. Reductions in SiDBP and SiSBP from baseline continued to be significant in both treatment groups. No clinically important changes in heart rate were noted. A total of 28 patients (15 in the felodipine-ER group and 13 in the nifedipine GITS group) withdrew from the study because of inadequate blood pressure response. At least one adverse experience occurred in 55% of the felodipine-ER group and 63% of the nifedipine GITS group, prompting withdrawal of 14 patients (10%) and 16 patients (11%), respectively. Headache and edema were the most common adverse experiences. The incidence and pattern of adverse experiences did not differ significantly between treatments. The results of this study demonstrate that once-daily felodipine-ER and nifedipine GITS are similarly highly effective and generally well tolerated in patients with essential hypertension.     

Use of 201Thallium brain SPECT, image registration, and semi-quantitative analysis in the follow-up of brain tumors

BACKGROUND: Vasodilator drugs are increasingly being discussed as possible antiglaucomatous substances. Aim of the present study is to evaluate, from a hemodynamic point of view, the vasodilator drug isosorbide dinitrate (ISDN) regarding its suitability for glaucoma therapy. METHODS: 20 healthy subjects (mean age: 28 yrs) volunteered to participate in the study. In randomized order, each subject received one tablet containing 40 mg ISDN (sequels) or--in a second trial--one tablet placebo (+500 mg of the analgetic metamizol, respectively, for prophylaxis of nitrate headache). 1 h before as well as 1, 3, 5, and 7 hrs after medication, the following variables were determined using oculo-oscillo-dynamography: systolic ophthalmic artery pressure (SOAP), systolic ocular perfusion pressure (SOPP), ocular pulsation amplitude (OPA) and the product OPA x heart rate (HR). Intraocular pressure (IOP) as well as systolic and diastolic brachial artery pressures (SBAP, DBAP) were also measured. RESULTS: After administration of ISDN (+analgetic), the variables SBAP, SOAP and SOPP were significantly (p = 0.01) lowered compared to placebo (+analgetic), and also the IOP tended to be lower (p = 0.08). The maximum reduction was found 3-5 hrs after medication: SBAP 10.9 mm Hg (9%), SOAP 12.5 mm Hg (14%), SOPP 11.3 mm Hg (14.5%), and IOP 1.5 mm Hg (12%). The relation SOAP vs. SBAP was significantly (p = 0.0004) linear, the correlation coefficient amounted to 0.39. DBAP remained unchanged, HR was increased by 4-7 beats/min (p = 0.08). OPA and the product OPA x HR showed highly significant decreases by maximum values of 44% and 40%, respectively. CONCLUSION: ISDN (+analgetic) caused a reduction of SOAP and SOPP, which can be accounted for by the reduced systolic systemic blood pressure. In addition, there was a decrease of OPA and of the product OPA x HR (a measure of pulsatile ocular blood flow), which finding may be explained by a cardiac stroke volume reduction that is typical for nitrates. Due to these hemodynamic effects and due to the only weak IOP reduction, ISDN does not appear to be suitable for glaucoma therapy.     

Nifedipine gastrointestinal therapeutic system versus nifedipine coat-core: comparison of efficacy via 24-hour ambulatory blood pressure monitoring

OBJECTIVE: To assess the comparable efficacy and adverse effect profile of two extended-release preparations of nifedipine--gastrointestinal therapeutic system (GITS) and coat-core (CC)--in patients with mild-to-moderate hypertension. DESIGN: Single institution, single-blind, prospective study. SETTING: Dwight David Eisenhower Army Medical Center, Fort Gordon, GA. PATIENTS: Ninety-one patients who were taking nifedipine GITS as a sole antihypertensive agent were randomized to receive either GITS or CC. After 3 weeks, 24-hour ambulatory blood pressure monitoring was conducted and an adverse effect questionnaire was administered. The patients were then crossed over to the other treatment arm and monitoring was repeated after 3 weeks. MEASUREMENTS: Mean blood pressure, heart rates, and the percentage of readings exceeding 140 mm Hg systolic and 90 mm Hg diastolic were compared for the 24-hour period. Additionally, mean blood pressures at 4-hour intervals after drug administration and heart rate during the first 8 hours of the dosage interval were compared. RESULTS: Ninety-one patients enrolled, 79 completed the study, and 62 patients were included in the efficacy analysis. A statistically significant difference (p = 0.020) was shown only in the last 4-hour systolic blood pressure. However, this difference was small (122 +/- 15 mm Hg with GITS vs. 126 +/- 14 mm Hg with CC). There was no difference in the percentage of readings exceeding 140 mm Hg systolic or 90 mm Hg diastolic. Neither dosage nor treatment order had an effect on the results. Adverse effects were reported with a greater frequency during CC therapy (40 with CC vs. 22 with GITS; p = 0.006), but were generally transient. Discontinuation of the drug was necessary in 3 patients during the CC cycle. CONCLUSIONS: GITS and CC demonstrated clinically equivalent antihypertensive efficacy in the study population. The CC produce may have a higher rate of adverse effects, but drug discontinuation was uncommon.     

Development of a statistical model for the formation of poly [acryloyl hydroxyethyl starch] microspheres

Approximately 1 in 4 patients with systemic hypertension have a 24-hour blood pressure (BP) profile characterized by a blunted or absent nocturnal decline in pressure. We evaluated the effects of a chronotherapeutic delivery system of controlled-onset extended-release (COER) verapamil hydrochloride and placebo in 257 hypertensive patients according to their circadian BP pattern in an 8-week prospective, multicenter, randomized, and double-blind clinical trial. Patients were stratified into 193 dippers (>10% decline in BP during the period of 10 P.M. to 5 A.M. compared with the hours of 5 A.M. to 10 P.M.) and 64 nondippers (<10% decline in BP during nighttime). During daytime, placebo-subtracted BP was similarly decreased in dippers and nondippers by COER verapamil. During nighttime, the placebo increased nocturnal BP in dippers (baseline nocturnal BP, 133/78 mm Hg) by 3/3 +/- 2/2 mm Hg and reduced BP by -5/-3 +/- 2/2 mm Hg in nondippers (baseline nocturnal BP, 152/94 mm Hg) (p = NS between groups). After controlling for age, gender, ethnicity, and the regression to the mean observed on placebo for all doses, COER verapamil reduced nocturnal BP more in nondippers than dippers -5.8/-2.4 mm Hg, p <0.0001 for systolic BP and p = 0.09 for diastolic BP). Additionally, a significant dose-related reduction in systolic and diastolic nocturnal BP (r = 0.56, p <0.0001 for systolic BP and r = 0.62, p <0.0001 for diastolic BP) was observed with COER verapamil after controlling for baseline covariates. These data demonstrate that nocturnal BP is decreased by a greater extent in nondipper hypertensives than in dipper hypertensives following treatment with COER verapamil HCL.     

Plasmin, substilisin-like endoproteases, tissue plasminogen activator, and urokinase plasminogen activator are involved in activation of latent TGF-beta 1 in human seminal plasma

OBJECTIVES: To compare the effects of simulated and mild actual hemorrhage on parameters used traditionally to assess hemorrhaging patients: heart rate (HR), blood pressure (BP), and Shock Index (SI = HR/systolic BP), with stroke distance (SD) measured ultrasonically as an index of cardiac stroke volume. MATERIALS and METHODS: Hemorrhage was simulated in 19 healthy volunteers by the application of graded lower-body negative pressure (LBNP) (0, -20, -40, and -60 mm Hg) to pool blood in the lower body and reduce venous return. Measurements were also made before and after a standard blood donation (450 mL) in nine healthy volunteers. MEASUREMENTS and MAIN RESULTS: SD decreased significantly and progressively from the baseline level of 23.8+/-5.7 cm (mean+/-SD) at each level of LBNP: by 3.4+/-1.9, 7.4+/-2.5, and 11.8+/-3.2 cm at LBNP of -20, -40, and -60 mm Hg, respectively. Neither HR nor SI changed significantly at the lowest level of LBNP (-20 mm Hg), but they showed progressive, significant increases thereafter. Mean BP did not change significantly at any level of LBNP. Similarly, after a controlled hemorrhage of 450 mL, SD decreased significantly by 3.3+/-1.6 cm from 22.2+/-2.8 cm, whereas HR and SI remained unchanged and mean BP increased slightly. CONCLUSION: Changes in SD may provide an earlier indication of progressive blood loss than either HR or BP alone or in combination.     

Comparative effects of felodipine ER, amlodipine and nifedipine GITS on 24 h blood pressure control and trough to peak ratios in mild to moderate ambulatory hypertension: a forced titration study

OBJECTIVE: To evaluate the 24 h antihypertensive efficacy and duration of action of felodipine extended release (ER) in comparison with two other long acting dihydropyridine calcium antagonists, amlodipine and nifedipine gastrointestinal therapeutic system (GITS), in patients with mild to moderate essential hypertension substantiated by ambulatory blood pressure (BP) monitoring. DESIGN: Randomized, forced titration, parallel group study. Clinic BP was measured at every patient's visit, and 24 h ambulatory BP was monitored at baseline and at the end of each dose-titration period. SETTING: Single centre: hypertension research unit in Quebec City, Quebec. PATIENTS: There were 89 patients enrolled into the study. Eighty-four eligible patients were randomized, and 83 completed the study and were included in the final efficacy analysis. INTERVENTIONS: Following a two-to four-week washout period (baseline), patients were randomly allocated to receive felodipine ER 5 mg, amlodipine 5 mg or nifedipine GITS 30 mg for four weeks (low dose). All study patients had their daily dose doubled to felodipine ER 10 mg, amlodipine 10 mg or nifedipine GITS 60 mg for a further four weeks (high dose). MAIN RESULTS: Significant (P < 0.001) and similar changes from baseline in clinic BP were observed in all treatment groups for low and high doses. Ambulatory BP profiles showed comparable blood pressure reductions with felodipine ER and amlodipine, and a trend towards a lesser reduction with nifedipine GITS during 24 h, daytime and night-time periods. BP loads were similarly reduced with the three treatments. Trough to peak ratios (T:Ps) were calculated from 24 h ambulatory BP curves according to two different approaches: for diastolic and systolic BP, respectively, the global approach produced T:Ps of 0.49 and 0.50 with felodipine ER 5 mg; 0.50 and 0.34 with felodipine ER 10 mg; 0.70 and 0.60 with amlodipine 5 mg; 0.88 and 0.82 with amlodipine 10 mg; 0.65 and 0.55 with nifedipine GITS 30 mg; 0.68 and 0.53 with nifedipine GITS 60 mg. T:Ps in the individual approach were 0.07 and 0.10 with felodipine ER 5 mg; 0.23 and 0.31 with felodipine ER 10 mg; 0.22 and 0.31 with amlodipine 5 mg; 0.45 and 0.58 with amlodipine 10 mg; 0.27 and 0.31 with nifedipine GITS 30 mg; and 0.24 and 0.40 with nifedipine GITS 60 mg. CONCLUSION: There was no evidence in this study of a difference among felodipine ER, amlodipine and nifedipine GITS in lowering ambulatory or clinic BP. Treatment based on ambulatory BP may be preferable to treatment guided by T:Ps because ambulatory BP is firmly established as a predictor of cardiovascular risk. Furthermore, there is no consensus on how to calculate T:Ps, and different methods of calculation may give divergent results.     

Rationale and design for the Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints (CONVINCE) Trial

The Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints (CONVINCE) Trial is a randomized, prospective, double-blind, parallel-group, two-arm, actively controlled, multicenter, international 5-year clinical trial involving 15,000 patients. CONVINCE will compare the incidence of fatal or nonfatal myocardial infarction (MI), fatal or nonfatal stroke, or cardiovascular-disease-related death in two antihypertensive treatment regimens. One treatment arm begins with controlled onset-extended release (COER)-verapamil, which has its major antihypertensive effect 6-12 hours after administration. The other arm (standard of care (SOC)) begins with either hydrochlorothiazide (HCTZ) or atenolol, one of which is preselected by the investigator for an individual patient prior to randomization. Secondary objectives include comparisons of the regimens for each of the components of the primary endpoint (separately), death or hospitalization related to cardiovascular disease, efficacy in lowering blood pressure to goal, primary events occurring between 6 am and noon, all-cause mortality, withdrawals from blinded therapy, cancer, and hospitalizations due to bleeding. Patients may be enrolled if they are hypertensive and at least 55 years of age and have an established second risk factor for cardiovascular disease. Initial medications include COER-verapamil (180 mg/d), HCTZ (12.5 mg/d), or atenolol (50 mg/d). Initial doses are doubled if blood pressure (BP) does not reach goal (systolic BP < 140 mm and diastolic BP < 90 mm Hg). If BP is not controlled by the higher dose of the initial medication, HCTZ is added to COER-verapamil, or the SOC choice not initially selected is added in the SOC arm. An ACE-inhibitor is recommended (although nearly any open-label medication is allowed) as the third step for patients whose BP is not adequately controlled or who have a contraindication to one of the two SOC medications. Patients take two sets of tablets daily, one in the morning and one in the evening. Although most patients switch from an established antihypertensive medication to randomized treatment, untreated patients with stages I-III hypertension (SBP between 140 and 190 or DBP between 90 and 110 mm Hg) are eligible. Outcomes are monitored by an independent Data and Safety Monitoring Board. Enrollment began during the third quarter of 1996, and follow-up is to be completed in the third quarter of 2002.     

Possible erythromelalgia-like syndrome associated with nifedipine in a patient with Raynaud's phenomenon

OBJECTIVE: To describe a patient who was diagnosed with Raynaud's phenomenon, was prescribed immediate-release nifedipine, and developed a possible erythromelalgia-like syndrome. CASE SUMMARY: A 24-year-old white woman with a history of esophageal spasms and Raynaud's phenomenon was prescribed nifedipine 10 mg po qid. Approximately 1 hour after the patient had taken the fourth dose of nifedipine, she experienced acute erythema and a burning sensation in her feet and lower limbs, light-headedness, and palpitations. Because of a reportedly abnormally low blood pressure, the patient took diphenhydramine 50 mg po and proceeded to the clinic. On arrival, abnormal vital signs were BP 140/48 mm Hg and HR 130 beats/min. Without any other medical intervention, approximately 30 minutes later her blood pressure and heart rate had returned to baseline at 122/60 mm Hg and 96 beats/min, respectively. The nifedipine was permanently discontinued and the patient's symptoms completely resolved over 24 hours. DISCUSSION: The characteristic symptoms of erythromelalgia include burning pain, increased skin temperature, and erythema of the extremities, usually to the feet, lower legs, and, less often, the hands. Erythromelalgia-like syndromes secondary to the administration of many medications have been reported. Several nifedipine-related reports describe an erythromelalgia-like syndrome similar to our reported case. CONCLUSIONS: Because the patient was not taking any other medications and the symptoms started with the administration of nifedipine and were relieved after its discontinuation, nifedipine was thought to be the cause of the erythromelalgia-like syndrome.     

Body fatness and bioelectrical impedance in non-obese pre-menarcheal girls: comparison to anthropometry and evaluation of predictive equations

This study investigated the period of time that blood pressure (BP) should be measured at home in older patients in order to obtain steady BP values. Thirty-six men and 38 women (> or =60 years) were recruited at one family practice. At one office visit the family physician measured supine, sitting and standing BPs three times consecutively in each position. During 10 consecutive days, BP was measured at home five times daily. The supine and standing BPs were measured once in the morning and in the evening and the sitting BP once at noon. These home BP values were averaged over the first day (1-day), over the first 3 days (3-day) and all 10 days (10-day) of measurements. In both the supine (-5.1 mm Hg) and sitting (-3.8 mm Hg) positions the 10-day average systolic home BP was significantly lower than the corresponding office BP. The opposite was observed for the 10-day average standing home BP values (+7.3/+3.4 mm Hg). Comparison of the 3-day and 10-day average home BP values showed only a significantly lower 10-day than 3-day systolic BP level in the supine position (-1.1 mm Hg, 95% CI -1.9 to -0.2 mm Hg). Repeated measures ANOVA, showed a small but significant decrease over time only for the supine systolic home BP (-0.29 mm Hg per day, 95% CI -0.49 to -0.08 mm Hg per day). We conclude that in older subjects, 3 days of home measurements may suffice to obtain steady values for the sitting and standing BPs. A longer interval might be required for the supine BP.     

Indomethacin does not attenuate the hypotensive effect of trandolapril

This is a randomised, double-blind, placebo-controlled, four-way crossover study to determine if indomethacin attenuates the hypotensive effect of trandolapril. Twenty-three hypertensive patients (diastolic blood pressure (DBP) 95-115) requiring NSAID were recruited. Seventeen completed the study. Three week treatment periods: trandolapril 2 mg od and indomethacin 25 mg tds, trandolapril 2 mg and placebo, indomethacin and placebo, placebo and placebo. Clinic and ambulatory BP after 3 weeks of each treatment. Study had 85% power to detect a 5 mm Hg difference in BP (s.d. 7 mm Hg). End of treatment clinic BPs were: 152.9/98 mm Hg (95% CI 147.2, 158.6/95.8, 101.4) with placebo and placebo; 150.4/94.9 mm Hg (95% CI 144.7, 156.1/92.1, 97.7) with trandolapril and indomethacin; 148.2/96.5 mm Hg (95% CI 142.5, 153.9/93.7, 99.3) with trandolapril and placebo; and 156.6/97.4 mm Hg (95% CI 150.9, 162.3/94.6, 100.2) with indomethacin and placebo. There were no significant interactions between trandolapril and indomethacin for clinic systolic BP (SBP) (P = 0.79) or clinic DBP (P = 0.87). When trandolapril treatments (placebo or with indomethacin) were compared to treatments without trandolapril (placebo or indomethacin), trandolapril lowered clinic SBP by 5.4 mm Hg (P = 0.047) and DBP by 2.3 mm Hg (P = 0.08). Mean ambulatory BP was: 140.6/88.2 mm Hg (trandolapril and placebo); 142.8/89.7 mm Hg (trandolapril and indomethacin); 149.6/95.0 mm Hg, (indomethacin and placebo); 147.7/94.0 mm Hg (placebo and placebo). Compared with placebo, trandolapril and placebo lowered BP by 6.5/7.5 mm Hg (P < 0.001, SBP; P < 0.001, DBP). Compared with indomethacin, trandolapril and indomethacin lowered BP by 5.0/5.5 mm Hg (P = 0.001, SBP; P < 0.001, DBP). In the present study trandolapril 2 mg lowered clinic SBP and ambulatory BP, but indomethacin did not attenuate this. Indomethacin had no significant effect on either clinic or ambulatory BP. The antihypertensive effects of trandolapril in this study were modest. Patient selection factors may have contributed to the observed responses, but it seems unlikely from these data that a clinically important drug interaction has occurred.     

The cardiovascular and subjective effects of thyrotropin releasing hormone (TRH) and a stable analogue, dimethyl proline-TRH, in healthy volunteers

1. The cardiovascular effects of TRH 0.5 mg and 1 mg and a stable TRH analogue, dimethylproline-TRH (RX77368) 1 mg, infused intravenously over 1 min were assessed in healthy volunteers in two randomised, double-blind, placebo controlled crossover studies. 2. Both doses of TRH produced significant but transient increases in blood pressure (peak delta systolic: 0.5 mg = 9.2 mm Hg, 1.0 mg = 5.2 mm Hg; peak delta diastolic: 0.5 mg = 6.4 mm Hg, 1.0 mg = 5.4 mm Hg). 3. Beat-to-beat Finapres monitoring demonstrated a rapid onset of effects of RX77368 1 mg, with significant blood pressure effects by 45-60 s from the start of the infusion (delta systolic BP: 14.2 mm Hg, delta diastolic BP: 15.8 mm Hg and delta heart rate: 8.9 mm Hg at 60 s). 4. The pressor effects of RX77368 1 mg recorded by Dinamap (peak delta systolic: 14.3 mm Hg; peak delta diastolic: 11.8 mm Hg) were sustained, with diastolic pressure still elevated (delta diastolic: 8.2 mm Hg) at 60 min. Heart rate was more transiently elevated (peak delta heart rate: 9.0 beats min-1) during the first 6 min post infusion. 5. Mild apprehension was reported for the first 6 min after RX77368 1 mg, whereas paraesthesiae were noted after TRH. Otherwise both drugs were similar in the type (flushing, nausea, acid taste, urethral sensations) and duration of subjective effects.     

Stress-induced left ventricular outflow tract obstruction: a potential cause of dyspnea in the elderly

OBJECTIVES: We sought to identify the pattern of disturbed left ventricular physiology associated with symptom development in elderly patients with effort-induced breathlessness. BACKGROUND: Limitation of exercise tolerance by dyspnea is common in the elderly and has been ascribed to diastolic dysfunction when left ventricular cavity size and systolic function appear normal. METHODS: Dobutamine stress echocardiography was used in 30 patients (mean [+/-SD] age 70 +/- 12 years; 21 women, 9 men) with exertional dyspnea and negative exercise test results, and the values were compared with those in 15 control subjects. RESULTS: Before stress, left ventricular end-diastolic and end-systolic dimensions were reduced, fractional shortening was increased, and the basal septum was thickened (2.3 +/- 0.5 vs. 1.4 +/- 0.2 cm, p < 0.001, vs. control subjects) in the patients, but posterior wall thickness did not differ from that in control subjects. Left ventricular outflow tract diameter, measured as systolic mitral leaflet septal distance, was significantly reduced (13 +/- 4.5 vs. 18 +/- 2 mm, p < 0.001). Isovolumetric relaxation time was prolonged, and peak left ventricular minor axis lengthening rate was reduced (8.1 +/- 3.5 vs. 10.4 +/- 2.6 cm/s, p < 0.05), suggesting diastolic dysfunction. Transmitral velocities and the E/A ratio did not differ significantly. At peak stress, heart rate increased from 66 +/- 8 to 115 +/- 20 beats/min in the control subjects, but blood pressure did not change. Transmitral A wave velocity increased, but the E/A ratio did not change. Left ventricular outflow tract velocity increased from 0.8 +/- 0.1 to 2.0 +/- 0.2 m/s, and mitral leaflet septal distance decreased from 18 +/- 2 to 14 +/- 3 mm, p < 0.001. In the patients, heart rate rose from 80 +/- 12 to 132 +/- 26 beats/min and systolic blood pressure from 143 +/- 22 to 170 +/- 14 mm Hg (p < 0.001 for each), but left ventricular dimensions did not change. Peak left ventricular outflow tract velocity increased from 1.5 +/- 0.5 m/s (at rest) to 4.2 +/- 1.2 m/s; mitral leaflet septal distance fell from 13 +/- 4.5 to 2.2 +/- 1.9 mm (p < 0.001); and systolic anterior motion of mitral valve appeared in 24 patients (80%) but in none of the control subjects (p < 0.001). Measurements of diastolic function did not change. All patients developed dyspnea at peak stress, but none developed a new wall motion abnormality or mitral regurgitation. CONCLUSIONS: Although our patients fulfilled the criteria for "diastolic heart failure," diastolic dysfunction was not aggravated by pharmacologic stress. Instead, high velocities appeared in the left ventricular outflow tract and were associated with basal septal hypertrophy and systolic anterior motion of the mitral valve. Their appearance correlated closely with the development of symptoms, suggesting a potential causative link.     

Acute hemodynamic changes during carotid artery stenting

To determine the clinical significance of acute hemodynamic disturbances during stenting in the carotid sinus region, we assessed the relation between intraprocedural changes in heart rate (HR) and blood pressure (BP) and adverse neurologic and cardiac outcomes. Eighteen patients underwent carotid stenting with the Wallstent (Schneider Inc). Suitable candidates had at least 60% diameter stenosis of the carotid artery by angiography. Initial and nadir HR and BP were recorded during the predilatation, stent delivery, and postdilatation periods. Bradycardia was defined as HR < or =60 beats/min and hypotension as systolic BP < or =100 mm Hg. Nineteen Wallstents were successfully deployed in all 19 carotid arteries. Some degree of bradycardia or hypotension occurred in 68% of carotid stent procedures, but administration of vasoactive medications was necessary in only 7 patients (37%) with more persistent hemodynamic disturbances. Hypotension or the need for continuous vasopressor therapy was significantly more common during postdilatation (32%) than in the predilatation period (5%) (p = 0.02). Bradycardia was not reduced by prophylactic atropine. In 1 patient the hemodynamic response to stenting may have contributed to an adverse neurologic and cardiac outcome. Thus, despite frequent fluctuations in HR and BP, most carotid stenting procedures were performed with excellent overall results, even in patients at high risk.     

Medication use in nursing homes for elderly people

The aim of this cross-sectional study which took place in a hypertension clinic at a district general hospital in Denmark was to make a pragmatic definition of white coat hypertension. A total of 420 patients were referred consecutively from general practice with newly diagnosed untreated essential hypertension and 146 normal subjects were drawn at random from the Danish national register. The following measurements were taken: office blood pressure; 24-h ambulatory blood pressure (BP) monitoring; echocardiography with determination of left ventricular mass index and relative wall thickness; and early morning urine albumin/creatinine ratios. Four different cut-off levels were studied. An ambulatory daytime BP of 135.6/90.4 mm Hg was found to correspond to an office BP of 140/90 mm Hg in normal controls; used as a cut-off level in patients with newly diagnosed hypertension it separated 19% as white coat hypertensives. The end-organ involvement of these white coat hypertensives differed significantly from those with established hypertension but not from the normal controls. Lower cut-off levels were less efficient in this respect, as was the case when the systolic BP was not taken into account. In conclusion a pragmatic definition of white coat hypertension should--apart from well-established hypertensive office measurements--include a cut-off level close to 135/90 mm Hg ambulatory daytime BP.     

Stress-management training for essential hypertension: a controlled study

Forty three patients with essential hypertension participated in a study on the effectiveness of stress-management training for essential hypertension. After 6-9 clinic and 48 self-measured readings of systolic and diastolic blood pressures (SBP and DBP), 22 patients were treated with a program based on education, relaxation, and problem-solving training; and another 21 patients were assigned to a waiting list control group. At post-treatment, mean reductions of clinic BP (17/13 mm Hg vs. 6.9/4.7 mm Hg for SBP/DBP), percentages of subjects who achieved at least a 5 mm Hg reduction (86/86% vs. 48/48% for SBP/DBP) and percentages of subjects who in addition achieved a normotensive level (59/68% vs. 29/14% for SBP/DBP) were significantly higher in the treated group than in the control group. Concerning self-measured BP, the effectiveness of the stress-management training was not so considerable (mean reductions of 3.6/2.4 mm Hg and percentages of subjects who achieved a 5 mm Hg reduction of 52/38% for SBP/DBP), but it was significant and maintained in a 4-month follow-up assessment (mean reductions of 4/2 mm Hg and percentages of subjects who achieved a 5 mm Hg reduction of 48/33% for SBP/DBP). It is suggested that stress-management training can be beneficial for treatment of essential hypertension.     

Self-awareness, task failure, and disinhibition: how attentional focus affects eating

Prolonged continuous blood pressure (BP) and heart rate (HR) recordings from neonates of 35 to 42 weeks gestation were studied during and after ECMO. Data segments with significant deviation of BP were extracted for further analysis. The simultaneous changes in BP and HR were compared and the slope of the regression determined baroreflex sensitivity (BRS). Of 464 BP deviations, 98% produced curves with a negative slope consistent with the presence of a baroreflex. The average BRS was -1.0 +/- 0.8 bpm/mmHg (mean +/- S.D.) and curves were steeper during rising BP than falling BP (-1.1 +/- 0.9 beats/min per mmHg versus -0.9 +/- 0.6, P = 0.001). The baroreflex was more sensitive during ECMO than after ECMO to both rising BP (-1.0 +/- 0.5 beats/min per mmHg versus -0.7 +/- 0.5, P = 0.004) and falling BP (-1.0 +/- 0.6 beats/min/mmHg versus -0.7 +/- 0.5, P = 0.04). HR response curves obtained during different BP fluctuations on the same recording had varying threshold, consistent with acute resetting. One infant demonstrated chronic baroreceptor resetting over 3 days to a rise in resting BP. The near-term, critically ill neonate has an active baroreflex which is capable of resetting. ECMO was associated with accentuation of the baroreflex response.     

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.     

Pain description and severity of chronic orofacial pain conditions

The Finapres non-invasive blood pressure (BP) monitor uses the method of Penaz to indirectly record the arterial waveform; studies on its accuracy have suggested little systematic bias vs intra-arterial pressure (IAP) but substantial variability. Inconsistency between studies, in respect of the magnitude, direction and variance of bias, was described in the validation studies against the direct IAP. We have employed a novel re-sampling statistical method to combine the data from 20 published studies; a robust overall estimate of the accuracy and precision of the Finapres was thereby obtained. Based on 449 patients and 4490 re-samples, the average Finapres systolic bias (IAP- Finapres) was 2.2 mm Hg (s.d.+/-12.4) with limits of agreement (bias+/-2 s.d.) of -22.6 and 26.9 mm Hg. The average precision was 12.1 mm Hg (s.d.+/-8.4). The Finapres diastolic bias was -0.3 mm Hg (s.d.+/-7.9) with the limits of agreement of -16.1 and 15.5 mm Hg. The average precision was 7.6 mm Hg (s.d.+/-5.3). The average Finapres mean arterial pressure bias was 2.1 mm Hg (s.d.+/-8.6) with precision of 7.6 mm Hg (s.d.+/-5.3). The calculated percentage of Finapres systolic values expected to fall within +/-5 or +/-10 of the direct intra-arterial pressure was 35.9% and 73.1%, respectively. The calculated precision of the Finapres systolic pressure between 0-5 mm Hg was 1.6% and between 0-10 mm Hg 36.4%. The comparable values for Finapres diastolic BP for accuracy were 63.5% and 92.8% and for precision 23.1% and 79.2%. The Finapres device can provide an accurate estimate of diastolic and mean arterial pressure compared with the intra-arterial record; the apparent inaccuracy of the Finapres systolic pressure may have a physiological explanation. When the Finapres device is used in experimental or in clinical situations, then calibration against a reliable reference arterial pressure is desirable to obviate the possibility of an 'offset' error.     

Social health evolution in Vall d''Uixó. Application of multivariate analysis as a new health status indicator method

The present study aimed to investigate the influence of the angiotensin-converting enzyme (ACE)-inhibitor captopril and the Ca-antagonist nifedipine on endothelium-dependent vasodilation (EDV) in the forearm of hypertensive patients. Twenty-three middle-aged untreated hypertensive patients underwent evaluation of EDV and endothelium-independent vasodilation (EIDV) in the forearm, by means of local intra-arterial infusions of methacholine (MCh, evaluating EDV) and sodium-nitroprusside (SNP, evaluating EIDV), before and 1 h after intake of either captopril (25 mg) or nifedipine (10 mg) in a randomised, double-blind fashion. A matched normotensive control group was investigated at baseline conditions only. Five of the hypertensives were also evaluated after 3 months of treatment with captopril 25 mg twice daily in an open pilot study. First, the vasodilation induced by methacholine (MCh), but not SNP, was significantly attenuated in the hypertensive patients compared to the normotensive controls (P < 0.001 at MCh 4 microg/min). Second, although the two drugs induced a similar decline in blood pressure (BP) 1 h after administration (-11 to 10 mm Hg/-8 to 7 mm Hg), captopril significantly potentiated the vasodilator response to MCh (+32+/-13%, MCh 4 micr og/min, P < 0.01) but not SNP, while nifedipine did not significantly alter the response to either MCh or SNP. The improvement in vasodilator response to MCh induced by captopril was closely related to the reduction in BP (r = 0.72, P < 0.01). Third, in the pilot study, 3 months of captopril treatment induced a significant potentiation of the vasodilator response to MCh (+34+/-17%, MCh 4 microg/min, P < 0.05) in parallel with a significant BP reduction (-22+/-24/13+/-13 mm Hg, P < 0.05), while the response to SNP was unchanged. In conclusion, the present study confirmed that essential hypertension is associated with a defect in EDV. Furthermore, an improvement in EDV was seen in hypertensive patients shortly after administration of captopril, but not nifedipine. In addition, a significant beneficial effect on EDV was seen in a small pilot study during long-term treatment with captopril.