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Renal effects of losartan and amlodipine in hypertensive patients with non-diabetic nephropathy.

BACKGROUND: The objective of this study was to examine the effects of angiotensin II receptor blocker losartan versus the calcium channel blocker amlodipine on proteinuria, renal haemodynamics, glomerular sieving and tubular function in hypertensive patients with non-diabetic nephropathy. METHODS: The study design was a prospective, double blind, placebo controlled, randomized crossover trial with amlodipine and losartan. Renal parameters were measured at baseline and at the end of each 4-week active treatment period. Fifteen patients with a diagnosis of non-diabetic renal disease and hypertension were included. RESULTS: Mean arterial blood pressure decreased from 123+/-13 mmHg at baseline to 113+/-10 mmHg (P<0.01) on losartan and to 114+/-10 mmHg on amlodipine (P<0.01). Urinary albumin excretion significantly decreased from 3510+/-2586 mg/24 h at baseline to 2684+/-2051 mg/24 h (P<0.01) on losartan and increased non-significantly to 3748+/-3355 mg/24 h on amlodipine. Filtration fraction significantly decreased from a baseline value of 22.8+/-9.3% to 21.2+/-10.2% (P<0.05) on losartan and increased to 23.6+/-8.9% (ns) on amlodipine. Either drug did not significantly alter glomerular sieving of neutral dextrans. CONCLUSION: Our results demonstrate that losartan, but not amlodipine, decreased albumin excretion in hypertensive patients with non-diabetic nephropathy.

Adult↗

Evaluation of new computerized method for recording 7-day food intake in IDDM patients.

OBJECTIVE: To evaluate a new computerized method for recording 7-day food intake. RESEARCH DESIGN AND METHODS: Randomized crossover trial was conducted with patients recording the amount and type of every food and drink consumed during a week by either a computerized device (Food-meter) or recording the data in a diary. Each method was applied twice. Twenty-one insulin-dependent diabetic patients (mean +/- SD age 25 +/- 9 yr) were studied. RESULTS: The two methods showed very good agreement in the evaluation of the patients' diets (1792 +/- 408 vs. 1764 +/- 436 kcal/day, 84 +/- 19 vs. 82 +/- 21 g/day protein, 68 +/- 22 vs. 67 +/- 23 g/day fat, 210 +/- 60 vs. 207 +/- 58 g/day carbohydrate with the conventional and computerized methods, respectively). The variability between the methods and the variability within each method were of similar magnitude. CONCLUSIONS: The Food-meter represents a useful tool for computerizing the 7-day food record. The method is easy, reliable, and time saving. Moreover, it minimizes the risk of transcriptional errors.

Adult↗

Is combined therapy of sympathomimetics and theophylline indicated?

Bronchodilator effect and toxicity of theophylline 300 mg twice a day (R1), salbutamol 4 mg tid (R2), their combination in higher (200/4mg, R3), and lower doses (100/2mg R4), and placebo (calcium lactate 300 mg) tid (R5) were compared in 25 patients with bronchial asthma in a randomized crossover trial. Statistically significant improvement in forced expiratory volume in one second (FEV1) was observed in all the active treatment groups (R1 to R4) compared with placebo (R5). The mean improvement in FEV1 was 29.0%, 22.0%, 28.0%, 30.0%, and 0.73% in regimen R1, R2, R3, R4, and R5, respectively day 1, and corresponding improvement was 30.0%, 24.0%, 29.0%, 34.0%, and 4.4% on completion of one week therapy. On intergroup statistical comparison, mean improvement in pulmonary function test values were statistically significant or highly significant in regimens R1 to R4, as compared with placebo. However, improvement between any two regimens was not statistically significant in any of the regimens (R1-R4). Almost all the regimens were tolerated well and no patient showed major adverse reactions or cardiotoxicity necessitating withdrawal of the drug. On the other hand, minor adverse reactions were common and the high dose combination (R3) was found to have more adverse reactions than the low dose combination and either drug used alone.

Adolescent↗

Influence of home monitoring on compliance with a reduced sodium intake diet.

To test the utility of a qualitative chloride titrator strip in facilitating compliance with a reduced sodium intake diet, we enrolled 32 patients into a randomized crossover trial comprising two study periods of four weeks each. The study periods were begun after the patients had undergone extensive instruction in the diet and the use of the strip. A high degree of correlation between the patient's and the laboratory's interpretation of the strip result was identified in 29 of the subjects. Ability to use the strip was not related to level of education. A total of 12 patients achieved compliance with the diet when using the strips. Of these, nine were able to achieve compliance without the strips. Ten patients (30%) had significantly lower sodium intake when using the strips than when they did not use them. We conclude that the use of the chloride titrator strip can be mastered by most patients and, in conjunction with dietary counseling, can facilitate compliance with a reduced sodium intake diet.

Adult↗

A new polyurethane anal plug in the treatment of incontinence after anal atresia repair.

UNLABELLED: 38 totally or partially incontinent patients following imperforate anus repair (age 6-15 years) tested a new polyurethane (PU) anal plug against another, widely used anal plug (PVA) in a randomized crossover trial. Plugs were tested 3 weeks each, data concerning bowel habits, handling and plug-related problems were collected by questionnaire before trial, at time of product change and after trial. RESULTS: 15 of 38 patients did not complete the protocol, among them 6 with anal canal diameters too small for the smallest plug. During plug use, patients experienced enhanced awareness of repletion and urge. Stool consistence did not change in 82% of patients. There were no changes in children constipated prior to study (n = 8/23). 12,123 children were absolutely clean during use of either plug. 15 patients (68%) using the PU plug and 10 (45%) using the PVA plug felt secure from soiling during plug use. 74% of patients preferred the PU plug. Painful plug insertion, a feeling of pressure inside the anal canal and painful plug removal were reported with both plugs, but were less frequent with the PU plug. CONCLUSION: Anal plugs, regardless of their make, offer absolute cleanliness for periods of several hours to 66% of our incontinent patients. The PU plug (Conveen, Coloplast) is preferred by the patients and offers greater security than the PVA plug.

Adolescent↗

Factors affecting the bioavailability of soy isoflavones in humans after ingestion of physiologically relevant levels from different soy foods.

The precise role that isoflavones play in the health-related effects of soy foods, and their potential for adverse effects are controversial. This may be due in part to a lack of basic knowledge regarding their bioavailability and metabolism, particularly as it relates to the soy source. To date, there is little information concerning possible differences in the bioavailability of isoflavones derived from natural soy foods consumed at physiologically relevant intakes and whether age- or gender-related differences influence that bioavailability. In the current study of healthy adults [premenopausal (n = 21) and postmenopausal (n = 17) women and a group of men (n = 21)], we examined the effect of age, gender, and the food matrix on the bioavailability of isoflavones for both the aglycon and glucoside forms that are naturally present in 3 different soy foods, soy milk, textured vegetable protein, and tempeh. The study was designed as a random crossover trial so that all individuals received each of the 3 foods. The dose of isoflavones administered to each individual as a single bolus dose was 0.44 mg/kg body weight. Pharmacokinetic parameters were normalized to mg of each isoflavone ingested per kilogram body weight to account for differences in daidzein and genistein content between the diets. Serum isoflavone concentrations in all individuals and groups increased rapidly after the ingestion of each soy food; as expected, genistein concentrations exceeded daidzein concentrations in serum. In this small study, gender differences in peak concentrations of daidzein were observed, with higher levels attained in women. Consumption of tempeh (mainly isoflavone aglycon) resulted in higher serum peak levels of both daidzein (P < 0.001) and genistein (P < 0.01) and the associated area under the curve (P < 0.001 and P < 0.03, respectively) compared with textured vegetable protein (predominantly isoflavone glucosides). However, soy milk was absorbed faster and peak levels of isoflavones were attained earlier than with the other soy foods. Only 30% of the subjects were equol producers and no differences in equol production with age or gender were observed.

Adult↗

Nebivolol: comparison of the effects of dl-nebivolol, d-nebivolol, l-nebivolol, atenolol, and placebo on exercise-induced increases in heart rate and systolic blood pressure.

The effects of racemic nebivolol, 2.5, 5.0, and 10.0 mg; d-nebivolol, 2.5 mg; l-nebivolol, 2.5 mg; atenolol, 50 mg; and placebo, each given once daily for 7 days, on exercise-induced increases in heart rate and systolic blood pressure were compared in a seven-way double-blind randomized crossover trial in 14 healthy male volunteers. Observations on these variables were made 3 and 24 hours after dosing on the first and last days of therapy. Similar effects on both exercise-induced tachycardia and increases in systolic blood pressure were seen with nebivolol 5.0 mg and with d-nebivolol 2.5 mg; l-nebivolol 2.5 mg was no different from placebo. These data show that the beta-blocking effects of nebivolol reside in the d-isomer. A dose-related response was evident with racemic nebivolol in inhibiting exercise-induced tachycardia over the range of doses studied. Whereas the effects of atenolol on both exercise-induced tachycardia and increases in systolic blood pressure were fully evident on the first day of treatment, those of nebivolol, especially with regard to heart rate, and, to a lesser degree, systolic pressure, were greater on the final than on the first day. Nebivolol had a clearly superior trough-to-peak efficacy ratio than atenolol.

Adrenergic beta-Antagonists↗

Evaluation of the bioequivalence and pharmacokinetics of two lisinopril tablet formulations after single oral administration in healthy volunteers.

An open, two-period, randomized, crossover trial of two lisinopril (1-[N2-[(S)-1-carboxyl-3-phenylpropyl]-L-lysil]-L-proline, CAS 76547-98-3) formulations (Adicanil as test and another commercially available preparation as reference) was performed in 24 healthy volunteers. A single 20 mg oral dose of lisinopril was administrated and pharmacokinetic parameters were compared. Lisinopril plasma concentrations were measured by a fully validated LC-MS method. The parametric 90% confidence intervals of the geometric mean values of the test/reference ratios were 95.38% to 105.94% (point estimate: 100.52%) for AUC(0-last), 94.01% to 103.47% (point estimate: 98.63%) for AUC(0-infinity) and 92.34% to 103.97% (point estimate: 97.98%) for Cmax, being within the acceptance criteria for bioequivalence (80%-125%). T(1/2), k(el) and Tmax values were also tested and the difference was not statistically significant. Therefore, it is concluded that the test and the reference lisinopril formulations are bioequivalent both in the extent and the rate of absorption.

Adult↗

Preliminary study of the effect of low-intensity home-based physical therapy in chronic stroke patients.

This study was a preliminary examination of the effect of low-intensity home-based physical therapy on the performance of activities of daily living (ADL) and motor function in patients more than 1 year after stroke. Twenty patients were recruited from a community stroke register in Nan-Tou County, Taiwan, to a randomized, crossover trial comparing intervention by a physical therapist immediately after entry into the trial (Group I) or after a delay of 10 weeks (Group II). The intervention consisted of home-based physical therapy once a week for 10 weeks. The Barthel Index (BI) and Stroke Rehabilitation Assessment of Movement (STREAM) were used as standard measures for ADL and motor function. At the first follow-up assessment at 11 weeks, Group I showed greater improvement in lower limb motor function than Group II. At the second follow-up assessment at 22 weeks, Group II showed improvement while Group I had declined. At 22 weeks, the motor function of upper limbs, mobility, and ADL performance in Group II had improved slightly more than in Group I, but the between-group differences were not significant. It appears that low-intensity home-based physical therapy can improve lower limb motor function in chronic stroke survivors. Further studies will be needed to confirm these findings.

Activities of Daily Living↗

Antianginal effects of amlodipine at a single dose on exertional angina patients using treadmill exercise testing--a randomized crossover study in comparison with placebo.

With eight cases of stable exertional angina as subjects, the antianginal action and sustained effects of single 10 mg oral doses of new calcium antagonists amlodipine were assessed by treadmill exercise tests in randomized crossover trials with respect to a placebo. Exercise tests were conducted before as well as 4, 8, and 24 hours after administration, and plasma amlodipine concentration was investigated at the same times. The maximal exercise time was 299 +/- 43 seconds before as compared with 346 +/- 49 seconds 4 hours after administration and 368 +/- 50 seconds 8 hours after administration, a significant prolongation in each case (p < 0.01). Moreover, the exercise time elapsed until 1 mm of ST-segment depression, as well as the ST-segment depression measured at the same time, were both significantly improved as compared with the placebo results. The plasma amlodipine concentration reached a peak 8 hours after administration and displayed an effective level even 24 hours after administration. The value of delta PRP measured at the same time during the exercise test was also significantly reduced as compared with the placebo results, even 24 hours after administration of amlodipine. These findings supported the conclusion that single 10-mg doses of amlodipine provide stable antianginal action over a 24-hour period.

Administration, Oral↗

Effects of inspired hypoxic and hypercapnic gas mixtures on cerebral oxygen saturation in neonates with univentricular heart defects.

BACKGROUND: Neonates with functional single ventricle often require hypoxic or hypercapnic inspired gas mixtures to reduce pulmonary overcirculation and improve systemic perfusion. Although the impact of these treatments on arterial oxygen saturation has been described, the effects on cerebral oxygenation remain uncertain. This study examined the effect of these treatments on cerebral oxygen saturation and systemic hemodynamics. METHODS: Neonates with single ventricle mechanically ventilated with room air were enrolled in a randomized crossover trial of 17% inspired oxygen or 3% inspired carbon dioxide. Each treatment lasted 10 min, followed by a 10-20-min washout period. Cerebral and arterial oxygen saturation were measured by cerebral and pulse oximetry, respectively. Cerebral oxygen saturation, arterial oxygen saturation, and other physiologic data were continuously recorded. RESULTS: Three percent inspired carbon dioxide increased cerebral oxygen saturation (56 +/- 13 to 68 +/- 13%; P < 0.01), whereas 17% inspired oxygen had no effect (53 +/- 13 to 53 +/- 14%; P = 0.8). Three percent inspired carbon dioxide increased the mean arterial pressure (45 +/- 8 to 50 +/- 9 mmHg; P < 0.01), whereas 17% inspired oxygen had no effect. And 3% inspired carbon dioxide decreased arterial pH and increased arterial carbon dioxide and oxygen tensions. CONCLUSIONS: Inspired 3% carbon dioxide improved cerebral oxygenation and mean arterial pressure. Treatment with 17% inspired oxygen had no effect on either.

Brain Chemistry↗

Acute effects on insulin sensitivity and diurnal metabolic profiles of a high-sucrose compared with a high-starch diet.

Decreased insulin sensitivity is associated with diabetes mellitus, ischemic heart disease, and hypertension, both independently and in association as what is called the metabolic syndrome. Although the negative effects of obesity, sedentary lifestyles, and high-fat diets on insulin sensitivity are well established, the influence of type and quantity of dietary carbohydrate is more controversial. This study aimed to assess the acute (24 h) effects of a high-sucrose compared with a high-starch diet on insulin sensitivity and to identify changes in blood metabolites that might lead to altered insulin sensitivity. Eight healthy adults consumed high-sucrose or high-starch diets (50% of dietary energy) in a randomized, crossover trial. Insulin sensitivity was assessed by a short insulin tolerance test the following morning. No differences were detected in insulin sensitivity, either for glucose metabolism [Kitt(glucose) (the rate constant for the decline in blood glucose concentrations) for sucrose diet = 3.86%/min, for starch diet = 3.72%/min; pooled SEM = 0.23] or for lipid metabolism [Kitt(NEFA) (the rate constant for the decline in blood fatty acid concentrations) for sucrose diet = 12.9%/min, for starch diet = 11.4%/min; pooled SEM = 1.18]. Profiles for blood glucose and serum insulin concentrations revealed higher peaks and lower troughs with the high-sucrose diet whereas area under the curve for glucose was higher with the high-starch diet (6780 +/- 245 mmol x L/min) than with the high-sucrose diet (6290 +/- 283 mmol x L/min) (P < 0.001). Plasma fatty acid concentrations showed a late postprandial rise with the sucrose-rich diet relative to the starch-rich diet, which was mirrored with a fractionally later peak in triacylglycerol concentrations.

Adult↗

Is the time of dosing of a potent long-acting H2-receptor antagonist critical? Twenty-four-hour pH measurements with SKF-94482.

Reduction of daytime as well as nighttime acidity is important in the healing of duodenal ulceration and reflux oesophagitis. The importance of the time of dosing of potent, long-acting H2 blockers for optimal suppression of intragastric acidity is unknown. The efficacy of different oral dosage regimens of SKF-94482, a new, competitive and long-acting H2-receptor antagonist, in reducing daytime and nighttime intragastric acidity was studied with 24-h pH-monitoring in 3 double-blind, randomized, crossover trials in 45 fed, healthy subjects. In study A 200 mg, 400 mg, or 600 mg SKF-94482 or placebo was given at 0830 h for 6 days. In study B the above doses were taken at 1830 h. In study C 200 mg or 300 mg of SKF-94482 or placebo was given at 0830 and 1830 h for 6 days. SKF-94482, 400 mg, was the most effective dose, and twice daily dosing was of no additional pharmacodynamic benefit. When 400 mg SKF-94482 was given at 0830 h, the median 24-h, day (0800-1800 h) and night (1800-0800 h) pH (interquartile range) were 2.6 (2.2-3.2), 2.3 (2.1-3.8), and 2.6 (1.8-3.6), respectively. When the time of dosing was 1830 h with 400 mg SKF-94482, median 24-h, day and night pH were 3.4 (2.5-4.0), 3.4 (3.1-4.3), and 3.7 (2.8-5.9), respectively. Early-evening dosing of this long-acting H2 antagonist resulted in substantially greater suppression of intragastric acidity than morning dosing.

Administration, Oral↗

The effect of zinc supplementation on plasma lipids and low-density lipoprotein oxidation in males.

Recent studies in animals and in vitro support the hypothesis that zinc, an essential micronutrient, possesses antioxidant properties. The aims of this study were to determine whether zinc provides antioxidant protection in humans by decreasing low-density lipoprotein (LDL) oxidizability and to determine the effect of zinc supplementation on plasma lipid and its distribution among lipoproteins. Ten healthy male volunteers were recruited to participate in a randomized crossover trial. Subjects were asked to consume 50 mg zinc as 220 mg zinc sulphate (equivalent to 4 x recommended dietary intake, or RDI) daily for 4 weeks, followed by placebo, and vice versa. Venous blood samples were collected at 2-week intervals for the determination of plasma lipids and the in vitro oxidizability of LDL in the presence of copper ions. No changes in the oxidizability of LDL or the plasma concentrations of total cholesterol, high-density lipoprotein (HDL) cholesterol and its subfractions, LDL cholesterol, or triacylglycerol were observed following zinc supplementation compared to placebo. Plasma zinc concentrations were increased significantly, indicating that the lack of effect was not due to poor compliance. The antioxidant effect of zinc in relation to LDL was not demonstrated in humans at this dose, and higher doses are unlikely to be effective given the adverse interaction with copper metabolism and the potential decrease in the activity of superoxide dismutase, a free radical quenching enzyme. The findings of this study suggest that zinc provides little, if any, antioxidant protection against LDL oxidation in humans.

Adult↗

Clinical evaluation of the use of low-intensity ultrasound in the treatment of recurrent aphthous stomatitis.

OBJECTIVE: The purpose of this study was to assess the efficacy of low-intensity ultrasound in the treatment of recurrent aphthous stomatitis. STUDY DESIGN: Fifty patients with recurrent aphthous stomatitis were enrolled, and 35 patients completed this randomized crossover trial. The ultrasound was self-administered by twice daily use of an ultrasonic toothbrush. The level of aphthous ulcer activity was first observed for each patient with the use of either an ultrasonic or placebo toothbrush over a 6 month period. Patients were then observed for a 2 to 4 month period while using the alternate toothbrush. The level of ulcer activity was calculated as a numeric index: the total duration of sores divided by the period of observation. Statistical analysis was performed with the Student's t test. RESULTS: During the initial study period, the level of aphthous ulcer activity was lower for patients in the ultrasonic toothbrush group than for those in the placebo group (0.58 versus 0.78). This difference was not statistically significant. However, when the patients who used the placebo switched to the ultrasonic toothbrush, the level of aphthous ulcer activity dropped by 46% (O.81 to 0.44; p < 0.05). Those patients who started with the ultrasonic toothbrush worsened slightly after switching to the placebo. CONCLUSION: Routine use of low intensity ultrasound appears to have a modest beneficial effect on recurrent aphthous stomatitis.

Adult↗

Mobilization of peripheral blood stem cells by granulocyte-colony stimulating factors: comparison of a standard dose of glycosylated and mutated granulocyte-colony stimulating factor in non-Hodgkin's lymphoma patients following CHOP therapy.

The effects of granulocyte-colony stimulating factor (G-CSF) have been studied in several clinical settings. G-CSFs are widely used to stimulate the production of granulocytes and are well known to mobilize peripheral blood stem cells (PBSCs). However, very few studies have examined differences among G-CSFs. The aim of this study was to compare the mobilization of PBSCs induced by a standard dose of two G-CSFs following biweekly cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) therapy. Using a standard dose of G-CSF, we conducted a randomized, crossover trial that compared the efficacy of two kinds of G-CSF, glycosylated [lenograstim (2 micrograms/kg)] and mutated [nartograstim (1 microgram/kg)], on PBSC mobilization in 10 patients with non-Hodgkin's lymphoma after biweekly CHOP chemotherapy. Lenograstim (2 micrograms/kg) was more effective in shortening the duration of neutropenia than nartograstim (1 microgram/kg) (3.8 days vs. 5.0 days, p < 0.05, the number of days for the neutrophil count to reach 5 x 10(9)/l from nadir). The number of CD34+ cells and granulocyte-macrophage colony forming units (GM-CFU) was higher for lenograstim but no statistically significant difference between the two groups was found. Glycosylated G-CSF is more effective than mutated G-CSF in shortening the duration of neutropenia. As for the mobilization of CD34+ cells and the number of CFU-GM, there was a tendency to increase in the lenograstim group but no statistically significant differences were found.

Adult↗

The effect of exercise episode duration on blood pressure.

OBJECTIVE: To investigate the effect on blood pressure for 10-min compared with 40-min episodes of physical activity for 4 days. DESIGN AND METHODS: The design used a randomized crossover trial of two exercise episode durations, involving 17 subjects, which were performed in a university setting. The intervention was exercise on a stationary bicycle for four consecutive days, at 50% of maximal oxygen uptake (determined by heart rate), for episode durations of 10 or 40 min. A rest period of 10 days followed before exercise for the alternative duration was performed. The main outcome measure was blinded assessment of blood pressure 24 h after the last exercise episode. RESULTS: Significant reductions were found in systolic and diastolic blood pressure after 4 days of 40 min but not after 4 days of 10 min stationary cycling. The reduction in blood pressure was significant for both systolic and diastolic blood pressure for 4 days of 40 min of exercise episodes. CONCLUSION: Exercise of moderate intensity on a stationary bicycle for 10 min for 4 days is not effective in lowering blood pressure in comparison with the same exercise for 40 min for 4 days. The experimental design employed in the present study has potential for monitoring the effects of exercise on blood pressure.

Blood Pressure↗

Flumazenil may attenuate some subjective effects of nitrous oxide in humans: a preliminary report.

Two double-blind, randomized, crossover trials were conducted to study whether the benzodiazepine antagonist, flumazenil, would interact with the subjective and psychomotor effects of nitrous oxide in healthy volunteers. In both experiments, eight subjects inhaled 30% nitrous oxide in oxygen for 35 min and were challenged, 10 min into the inhalation, with flumazenil. Experiment 1 tested a range of flumazenil doses used clinically (0, 0.25, 0.5, and 1.0 mg/70 kg) whereas Experiment 2 tested a supraclinical flumazenil dose (0 and 5.0 mg/70 kg). Nitrous oxide increased mood ratings of "high," "drunk," and "tingling," and decreased psychomotor performance as assessed by the Digit Substitution Test. Flumazenil, at the supraclinical dose, significantly lowered the mood rating of "high." Decreases, though not significant (p < 0.10), were also obtained on the ratings "drunk," "elated," and "drug liking". Flumazenil, in both experiments, did not interact with the psychomotor effects of nitrous oxide. It appears that flumazenil, at a dose higher than that used clinically, may antagonize some of the subjective effects produced by nitrous oxide in humans.

Adult↗