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Results for “randomized crossover trial”

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PubMed1991

Natriuretic effect of calcium-channel blockers in hypertensives.

This double-blind, randomized, crossover trial characterizes the acute natriuretic response to calcium-channel blockers (CCB) and investigates the role of hemodynamic and hormonal factors in mediating the natriuresis. Thirteen male subjects with essential hypertension received a single oral 20-mg dose of nifedipine or 120 mg of diltiazem. Renal functional and hemodynamic measurements were performed prior to and hourly for 4 hours following medication. Subjects then received these medications for 4 weeks at which time the above studies were repeated. Urinary sodium excretion increased within 60 minutes of CCB administration and the natriuresis was sustained for 4 hours. Cumulative sodium loss during the 4 hours of study was greater with nifedipine (43 +/- 12 mmol) than with diltiazem (18 +/- 6 mmol) (P less than 0.05). Despite natriuresis, urinary potassium excretion was decreased by both agents. Even though both drugs decreased the mean arterial pressure, inulin and paraaminohippurate (PAH) clearances were not altered. Plasma aldosterone concentrations decreased, plasma catecholamine concentrations increased, whereas plasma-renin activity was unchanged with both drugs. Body weight, glomerular filtration rate (GFR), renal plasma flow, plasma-renin activity, plasma aldosterone, and catecholamine concentrations were unchanged following 4 weeks of therapy. The acute natriuretic response after 4 weeks of therapy was similar to the response noted after the first dose. This study concludes that CCB are acutely natriuretic. Despite systemic hypotension, renal hemodynamics are unaltered during CCB therapy. Suppression of aldosterone as well as direct tubular effects of these drugs may mediate the natriuresis. Chronic therapy with CCB does not modify the acute natriuretic response to these agents.

Adult↗

PubMed1997

Grapefruit juice-terfenadine single-dose interaction: magnitude, mechanism, and relevance.

OBJECTIVE: To investigate the single dose-response effects of grapefruit juice on terfenadine disposition and electrocardiographic measurements. METHODS: Twelve healthy males received 250 ml water or regular- or double-strength grapefruit juice with 60 mg terfenadine in a randomized crossover trial. Plasma concentrations of the cardiotoxic agent terfenadine and the active antihistaminic metabolite terfenadine carboxylate were determined over 8 hours. The QTc interval was monitored. RESULTS: Terfenadine concentrations were measurable (> 1 ng/ml) in 27 (20%; p < 0.001) and 39 (30%; p < 0.001) samples from individuals treated with regular- and double-strength grapefruit juice, respectively, compared to only four (3%) samples with water. Terfenadine plasma peak drug concentration (Cmax) was also higher. Terfenadine carboxylate area under the plasma drug concentration-time curve (AUC), Cmax, and time to reach Cmax (tmax) were increased by both strengths of juice. However, terfenadine carboxylate apparent elimination half-life (t1/2) was not altered. The magnitude of the interaction of terfenadine carboxylate AUC and Cmax ranged severalfold and correlated among individuals for regular-strength (r2 = 0.87; p < 0.0001) and double-strength (r2 = 0.78; p < 0.0001) grapefruit juice. No differences in the pharmacokinetics of terfenadine and terfenadine carboxylate were observed between the two strengths of grapefruit juice. QTc interval was not altered. CONCLUSIONS: A normal amount of regular-strength grapefruit juice produced maximum single-dose effects on terfenadine and carboxylic acid metabolite pharmacokinetics. The mechanism likely involved reduced presystemic drug elimination by inhibition of more than one metabolic pathway. The extent of the interaction was not sufficient to produce electrocardiographic changes. However, the pharmacokinetic effects were highly variable among individuals. This study further enhances the awareness of the potential for a serious interaction between grapefruit juice and terfenadine.

Adult↗

PubMed1999

Impact of constant and breath-synchronized nebulization on inhaled mass of nebulized budesonide in infants and children.

The aim of the present study was to compare the output of a breath-synchronized jet nebulizer to a conventional constant output nebulizer over a fixed period of time in terms of inhaled mass of budesonide, i.e., the amount of budesonide deposited on a filter interposed between the nebulizer and the face mask. One hundred and sixty-five asthmatic children (103 boys) were enrolled in this open, randomized, crossover trial. Their age ranged from 6 months to 7.9 years, height from 69 to 132 cm, and weight from 8.2 to 31.3 kg. Their duration of asthma ranged from less than 1 to 7 years. Budesonide suspension, 0.5 mg mL-1, 2 mL, was used. With 5 min of constant output nebulization, the mean inhaled mass of budesonide in percent of the nominal dose was 11.4% in the youngest children and 14.9% in the 7-year-old children. Expressed in percent of the total output of budesonide, i.e., the amount that left the nebulizer as an aerosol, the inhaled mass ranged from 34.6-48.6%. Thus, 51.4-65.4% of the total output was deposited on the expiratory filter. With 5 min of breath-synchronized nebulization, the mean inhaled mass ranged from 10.5-14.9% of the nominal dose. For the youngest patients less than 3-4 years of age, it was approximately 80-90% of the total output. For the older patients the inhaled mass was approximately 95% of the total output, i.e., only small amounts of budesonide were deposited on the expiratory filter. For both modes of nebulization the between-subject variation in inhaled mass was large: up to 6-fold in the young children and 3-4-fold in the older ones. The results of the present study showed that the inhaled mass of budesonide was significantly age-dependent with both modes of nebulization, i.e., the inhaled mass was less in younger children. Breath-synchronized nebulization resulted in reduced waste of drug during expiration.

Administration, Inhalation↗

PubMed2000

Safety and acceptability of a baggy latex condom.

A total of 104 couples participated in a randomized crossover trial to compare a new baggy condom with a straight-shaft condom produced by the same manufacturer. Participants completed a coital log after using each condom. All couples used five condoms of each type. Among 102 couples who did not report major deviations from the protocol, the breakage rate was eight of 510 (1.6%) for the baggy condom, and six of 510 (1.2%) for the standard condom (rate difference, RD = 0. 4%, 95% confidence interval of the RD, CI = -1.0%; +1.8%). Slippage was reported in 50 baggy condom logs and in 58 standard condom logs; the slippage rate was 50 of 510 (9.8%) for the baggy condom, and 58 of 510 (11.4%) for the standard condom (RD = -1.6%, 95% CI = -5.4%; +2.2%). Slippage was most often partial (<1 inch) and may not indicate condom failure. Severe slippage rates were 11 of 510 (2.2%) for the baggy condom, and 18 of 510 (3.5%) for the standard condom (RD = -1.4%, 95% CI = -3.4%; +0.7%). The findings support the conclusion that the two condoms are equivalent with respect to breakage and slippage. The participants appeared to prefer the baggy condom, suggesting that the new product may be more acceptable to the public than the traditional straight-shaft condoms, and may be easier to use consistently over long time periods.

Adolescent↗

PubMed2004

Electronic pain diary: a randomized crossover study.

Electronic pain diaries and palm-top computers have become increasingly important in clinical research and practice. In a randomized crossover trial, 24 patients suffering from chronic cancer and non-cancer pain completed both the electronic and the paper version of a pain diary based on the Minimal Documentation System (MIDOS) for pain and symptom assessment. This includes daily assessment of pain on an 11-point numeric rating scale and weekly documentation of a short quality-of-life questionnaire. Of 52 patients seen during the baseline phase of this study, 28 could be enrolled and only 24 patients completed both diary versions. The other patients were either physically or intellectually unable to use a palm-top computer or unwilling to participate in this study. After a total of four weeks, patient satisfaction was remarkably higher for the electronic palm-top version, even though a high number of patients were lacking experience in the use of computers. Obvious differences were observed between the versions. There were higher numbers of missing values in the electronic data, and patients tended to retrospectively fabricate information in the paper version. No significant difference between the electronic and paper diary could be found assessing the documented pain and symptom intensity. The electronic diary was used more frequently and patients said its use supported a more regular pharmacotherapy. We conclude that the use of electronic pain diaries is a valid and feasible method for documenting patients' pain perception, though some patients may not be able to operate such a diary version. Electronic palm-top pain diaries provide a high degree of patient satisfaction and can ease data collection for clinical research and practice.

Adolescent↗

PubMed1996

The effects of albuterol on the lung function of hospitalized patients with cystic fibrosis.

Twenty-four hospitalized patients with cystic fibrosis were enrolled into a 2-d, double-blind, placebo-controlled, randomized crossover trial comparing albuterol inhalation aerosol with a saline placebo. Aerosols were administered with the first three of four chest physiotherapy sessions given 4 h apart. Spirometry was measured before and 45 min after 7:00 A.M. and 3:00 P.M. therapy and before therapy at 7:00 P.M. and 7:00 A.M. the next morning. The mean percent change in FVC, FEV1, and FEF25-75% at 7:00 A.M. was 10.7, 14.8, and 19.6% with albuterol versus 2.4, 1.0, and -0.8% with placebo (p = 0.0012, < 0.0001, and = 0.003, respectively). A greater than 8% change in FEV1 separated changes with albuterol versus placebo with 96% specificity and occurred in 75% of all patients with albuterol; 71% at 7:00 A.M. versus 24% at 3:00 P.M. The reduction in response at 3:00 P.M. (p < 0.01) was presumably due to prolonged effects of morning therapy ( > 4 h). Individual changes in spirometry were significantly more positive and homogeneous with albuterol versus placebo at both 7:00 A.M. and 3:00 P.M. The mean percent change for the FVC, FEV1, and FEF25-75 across the day (7:00 A.M. pretherapy to 7:00 P.M. pretherapy) was 8.1, 10.1, and 9.7% with albuterol versus 3.9, 3.5 and 2.6% with placebo (p = 0.029, 0.036, and 0.232, respectively). The more positive and homogeneous changes in spirometry with albuterol, along with greater changes in these measures across the day when compared with placebo, suggest that albuterol improves pulmonary function in a majority of hospitalized patients with cystic fibrosis.

Adolescent↗

PubMed2000

Absorption of phenytoin from rectal suppositories formulated with a polyethylene glycol base.

STUDY OBJECTIVE: To compare phenytoin pharmacokinetics following administration of an oral suspension and a rectal suppository formulated with a polyethylene glycol base. DESIGN: Unblinded, single-dose, randomized, crossover trial. SETTING: University-affiliated pharmacokinetics and biopharmaceutics laboratory. SUBJECTS: Six healthy subjects. INTERVENTION: Subjects were given a single 200-mg dose of phenytoin as an oral suspension and a rectal suppository separated by a 1-week washout. MEASUREMENTS AND MAIN RESULTS: Blood for plasma phenytoin concentrations was obtained at baseline and 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours after administration. Plasma was analyzed by high-performance liquid chromatography (coefficient of variation < 6%) for total phenytoin concentration. Phenytoin maximum concentration (Cmax), time to Cmax (Tmax), time to first measurable concentration (Tlag), and area under the curve from time zero to time of last measurable concentration (AUClast) were estimated for oral and rectal administration by WinNonlin (v 1.1) and compared using Wilcoxon's signed rank test (p<0.05 for statistical significance). Two subjects did not have detectable plasma phenytoin concentrations after rectal administration. For the other four subjects, median rectal Cmax was significantly lower than oral Cmax (0.4 vs 1.9 microg/ml, p=0.028), median rectal Tmax did not differ from oral Tmax (11.9 vs 8.0 hrs, p=0.465), and median rectal AUClast, although highly variable, was significantly lower than oral AUClast (5.4 vs 36.2 microg x hr/ml, p=0.046). No Tlag was seen after oral administration, but with rectal administration the median Tlag was 2 hours. The estimated relative bioavailability of rectal phenytoin suppositories based on AUC0-24 was 4.7%, with individual values ranging from 0-58.3%. CONCLUSION: It appears that absorption of phenytoin from polyethylene glycol rectal suppositories in healthy subjects is highly variable and unpredictable. Thus this formulation is not recommended.

Administration, Rectal↗

PubMed1996

Cardiorespiratory effects of a 5HT2 antagonist (R51703) in awake and anesthetized dogs.

To investigate cardiorespiratory effects of an experimental 5-hydroxytryptamine receptor antagonist (R51703) with sedative properties, intramuscular doses of the drug were studied in 6 awake dogs of mixed breed, and in 6 anesthetized beagles. Two doses (0.2 and 0.4 mg/kg) of R51703 and a saline control were studied in the awake dogs using a randomized crossover trial. Subsequently, the higher dose of R51703 was included as a component of halothane anesthesia to determine whether the halothane sparing effect of R51703 produced a beneficial alteration of hemodynamic function. Data were obtained at equipotent halothane/R51703 (H/R) and halothane/saline (H/S) doses equivalent to 1.0, 1.5 and 2.0 MAC. In awake dogs, heart rates tended to be lower in dogs sedated with R51703, significantly so at 30 min for both doses, and at 90 and 120 min for the 0.2 and 0.4 mg/kg doses, respectively (P < 0.05). The cardiac index (CI) was lower at 60 min with both doses compared to the saline control group. Both doses of R51703 reduced mean blood pressure at 30, 90 and 120 min, and diastolic pressure at 30 and 90 min after administration; however, systolic blood pressure (SBP) was not altered. Overall, the cardiovascular alterations were minimal in conscious dogs and there was no evidence of respiratory depression. In the anesthetized dogs, at equipotent MAC, CI tended to be lower with H/R than with H/S, though the difference was not significant. Heart rate and stroke volume index also tended to be lower in the dogs treated with R51703, while systemic vascular resistance tended to be higher: these changes were not significant. Mean and SBP were higher at each MAC multiple in the H/R group. It was concluded that the halothane sparing effect of R51703 did not substantially improve hemodynamic function compared to the use of halothane alone at equipotent doses.

Anesthetics, Inhalation↗

PubMedDate not supplied

Responses of plasma lipoproteins and sex hormones to the consumption of lean fish incorporated in a prudent-type diet in normolipidemic men.

OBJECTIVE: The effects of lean fish on plasma lipoproteins, postheparin plasma lipolytic activities and sex hormones were examined in 11 normolipidemic male subjects. METHODS: This study was a randomized crossover trial of two isoenergetic prudent-type diets, lean fish diet and beef, pork, veal, eggs and milk (nonfish) diet. Experimental diets provided approximately 11800 kJ--18% as proteins, 50% as carbohydrates, 32% as lipids [ratio of polyunsaturated to saturated fatty acids (P:S) of 1:1 compared with 0.5:1 in preexperimental diet], and 260 mg cholesterol/day. RESULTS: Compared with the nonfish diet, the lean fish diet induced higher plasma total and LDL apolipoprotein (apo) B and apo B:apo A-1 ratio, indicating that the substitution of lean fish for beef, veal, pork, eggs and milk provides little benefits with regard to plasma apo B concentrations in a low-fat high P:S diet. Moreover, triglycerides:apo B and cholesterol:apo B ratios of VLDL were lower following the lean fish diet than the nonfish diet, suggesting the presence of smaller very low-density lipoprotein (VLDL) particles following the consumption of lean fish. Higher plasma concentrations of sex hormone-binding globulin (SHBG), HDL2 cholesterol and HDL2:HDL3 cholesterol ratio were found with the lean fish diet compared with the nonfish diet. Negative correlations between plasma postheparin lipoprotein lipase (LPL) activity and VLDL triglycerides (n = 11, r = -0.53, p = 0.02), and between plasma postheparin LPL activity and VLDL triglycerides:apo B ratio (n = 11, r = -0.64, p = 0.02) were also observed following the lean fish diet. CONCLUSION: These results suggest that the effects of substituting lean fish for beef, veal, pork, eggs and milk on plasma lipoproteins may be partly associated with variations in plasma sex hormone status and plasma LPL activity in normolipidemic men.

Adult↗

PubMed1999

Effect of age on the exercise response in normal postmenopausal women during estrogen replacement therapy.

Postmenopausal estrogen replacement therapy (ERT) has been associated with a reduced risk of coronary artery disease (CAD). Whether this apparent cardioprotective effect is mediated by a cardiovascular benefit during exercise, however, has not been clearly defined. To evaluate rest and exercise variables with and without ERT, a randomized crossover trial was conducted in 23 postmenopausal women, ranging in age from 44 to 75 years, mean age 57+/-8 years. The rest and exercise variables were compared on ERT and during a drug-free period. The baseline measure was compared to the effects after 4 weeks of ERT and after 4 drug-free weeks. Echocardiographic treadmill exercise variables of heart rate (HR), blood pressure, rate-pressure product (RPP), and cardiac dimensions were determined at baseline and at the end of each treatment period. In response to ERT, there was a decrease in low-density lipoprotein (LDL) cholesterol (drug-free: 142+/-40 mg/dl, ERT: 124+/-34 mg/dl) and an increase in high-density lipoprotein (HDL) cholesterol (drug-free: 52+/-14 mg/dl, ERT: 62+/-15 mg/dl, both p<0.01). At rest, the study population had no overall significant change in HR, blood pressure, RPP, or left ventricular end-systolic and end-diastolic diameters when ERT was compared to the drug-free period. However, subjects with the fastest baseline resting HR had the greatest decrease in HR with ERT relative to the drug-free period (p<0.05). During exercise, ERT effected no change in peak HR, blood pressure, or RPP, although end-systolic diameter decreased slightly (p<0.05). With ERT, subject age correlated negatively with systolic blood pressure (p<0.05) and RPP (p<0.01); both blood pressure and RPP decreased in older subjects. In conclusion, ERT has differential effects dependent on baseline HR and age.

Adult↗

PubMed2002

Animal versus plant protein meals in individuals with type 2 diabetes and microalbuminuria: effects on renal, glycemic, and lipid parameters.

OBJECTIVE: To determine, for individuals with type 2 diabetes and microalbuminuria, the effects of 6 weeks of meals containing plant-based protein (PP) versus meals with predominantly animal-based protein (AP) on renal function and secondarily on glycemia, lipid levels, and blood pressure. RESEARCH DESIGN AND METHODS: In a randomized crossover trial, we compared 6 weeks of meals containing only PP with meals containing primarily AP (60% animal, 40% plant) in 17 subjects with type 2 diabetes and microalbuminuria treated with diet and/or oral antidiabetic agents. Protein content was equivalent to the average American diet, and calories provided weight maintenance. Nutrients were equivalent between the two diets. Meals were prepared and packaged by a metabolic kitchen staff and were sent home weekly. At the beginning and end of each 6-week period, subjects were studied for 36 h on a metabolic unit. RESULTS: There were no significant differences between diets for glomerular filtration rate, renal plasma flow, albumin excretion rate, total cholesterol, HDL cholesterol, triglyceride area under the curve (AUC), glucose and insulin AUC, HbA(1c,) blood pressure, or serum amino acids. For both diets, at the end of the treatment periods as compared with baseline, total cholesterol was significantly lower (PP and AP: from 4.75 to 4.34 mmol/l, P < 0.01), HbA(1c) had significantly improved (PP: from 8.1 to 7.5%, P < 0.01; AP: from 7.9 to 7.4%, P < 0.01), and diastolic blood pressure was significantly lower (PP: from 83 to 80 mmHg, P < 0.02; AP: from 82 to 78, P < 0.02). CONCLUSIONS: There is no clear advantage for the recommendation of diets containing only PP rather than diets containing protein that is primarily animal-based for individuals with type 2 diabetes and microalbuminuria. There are, however, potential lipid, glycemic, and blood pressure benefits for following a carefully constructed, weight-maintaining, healthy diet, regardless of protein source.

Adult↗

PubMed2004

Bronchodilator response to formoterol after regular tiotropium or to tiotropium after regular formoterol in COPD patients.

We conducted a randomized, crossover trial with tiotropium 18 microg once daily (group A), and formoterol 12 microg twice daily (group B) over a 5-day period for each drug, with a 10-day washout, in 20 COPD patients. At the end of each period, patients inhaled both drugs separated by 180 min in alternate sequence (group A: tiotropium 18 microg+formoterol 12 microg; group B: formoterol 12 microg+tiotropium 18 microg). FEV1 and FVC were measured at baseline and after 30, 60, 120, 180, 210, 240, 300 and 360 min. FEV1 and FVC further improved after crossover with both sequences. The mean maximal change in FEV1 over baseline was 0.226 L (0.154-0.298) after tiotropium+formoterol and 0.228 L (0.165-0.291) after formoterol+tiotropium; the mean maximal change in FEV1 over pre-inhalation the second drug value was 0.081 L (0.029-0.133) after tiotropium+formoterol and 0.054 L (0.016-0.092) after formoterol+tiotropium. The mean maximal change in FVC over baseline was 0.519 L (0.361-0.676) after tiotropium+formoterol and 0.495 L (0.307-0.683) after formoterol+tiotropium; the mean maximal change in FVC over pre-inhalation of the second drug value was 0.159 L (0.048-0.270) after tiotropium+formoterol and 0.175 L (0.083-0.266) after formoterol+tiotropium. The FEV1 AUCs(0-360 min) were 62.70 (45.67-79.74) after tiotropium+formoterol and 69.20 (50.84-87.57) after formoterol+tiotropium, the FEV1 AUCs(0-180 min) were 24.70 (18.19-31.21) after tiotropium+formoterol and 29.74 (21.02-38.46) after formoterol+tiotropium, whereas the FEV1 AUCs(180-360 min) were 15.70 (10.88-20.52) after tiotropium+formoterol and 11.71 (7.21-16.21) after formoterol+tiotropium. Differences between the two treatments were not statistically significant (P>0.05). The addition of second different long-acting bronchodilator to a regularly administered long-acting bronchodilator seems to be to patient's advantage.

Administration, Inhalation↗

PubMed1997

Temperature circadian rhythms during the menstrual cycle and sleep deprivation in premenstrual dysphoric disorder and normal comparison subjects.

The aim of this study was to test the hypothesis that the circadian rhythm of core body temperature is altered in premenstrual dysphoric disorder (PMDD) subjects compared to that in normal comparison (NC) subjects and that it is normalized in PMDD subjects after treatment with early night partial sleep deprivation (ESD) or late night partial sleep deprivation (LSD). A total of 23 subjects meeting DSM-IV criteria for PMDD and 18 NC subjects had 24-h core body temperature recordings taken during the following conditions: (1) baseline midfollicular (preovulatory) and (2) late luteal (postovulatory) menstrual cycle phases and after a randomized crossover trial in subsequent luteal phases of (3) ESD, in which subjects slept from 03:00 to 07:00 h, followed by (4) a night of recovery sleep (ESD-R: sleep 22:30 to 06:30 h), and (5) LSD, in which subjects slept from 21:00 to 01:00 h, also followed by (6) a night of recovery sleep (LSD-R: sleep 22:30 to 06:30 h). Temperature amplitudes were significantly decreased in the luteal phase compared to those in the follicular menstrual cycle phase and increased after nights of recovery sleep. Compared to the baseline late luteal phase, during LSD, temperature amplitude increased in PMDD subjects but decreased in NC subjects. During ESD, the temperature acrophase was delayed in PMDD subjects but was advanced in NC subjects; during LSD, the temperature acrophase was advanced in PMDD subjects but was delayed in NC subjects compared to the late luteal baseline. Nocturnal temperature and temperature maxima and mesors tended to be higher in PMDD subjects than in NC subjects; when not reduced during sleep deprivation interventions, these were not associated with therapeutic effects. Alterations in both phase and amplitude of temperature circadian rhythms characterize PMDD subjects as contrasted with NC subjects in response to sleep deprivation. The changes in phase reflected more shifts in temperature acrophase in response to shifts in sleep in PMDD subjects. This realignment of the timing of sleep and temperature in addition to the enhancement of blunted amplitude rhythms during recovery nights of sleep may provide corrective mechanisms that contribute to the therapeutic effects of sleep deprivation.

Adult↗

PubMed1996

Effects of increased liver blood flow on the kinetics and dynamics of recombinant tissue-type plasminogen activator.

OBJECTIVE: To investigate the influence of increased liver blood flow on the pharmacokinetics and pharmacodynamics of recombinant tissue-type plasminogen activator (rt-PA) and to study the changes in endogenous urokinase-type plasminogen activator (u-PA). METHODS: This open, randomized, crossover trial was carried out in a clinical research unit. Eight healthy, nonsmoking volunteers received linear infusions of 24 mg rt-PA and 92 mg indocyanine green over 160 minutes. Sixty minutes after the infusions were started, the subjects consumed a standardized meal to increase liver blood flow on one occasion and abstained from taking food on the other occasion. Plasma concentrations of indocyanine green, tissue-type plasminogen activator (t-PA) antigen, t-PA activity, total u-PA antigen, plasmin-activatable single-chain u-PA (scu-PA), active two-chain u-PA (tcu-PA), fibrinogen, total fibrin, and fibrinogen/fibrin degradation products (TDP), and alpha 2-antiplasmin were measured. RESULTS: After the consumption of the meal, the area under the curve (AUC) was 35% (95% confidence interval [CI]: 25%, 43%) lower for indocyanine green, 15% (CI: 6%, 24%) lower for t-PA antigen, and 11% (CI: 2%, 19%) lower for t-PA activity compared to the AUC after subjects abstained from food. No changes were observed in fibrinogen, TDP, or alpha 2-antiplasmin concentrations that were attributable to the intake of food. The infusion of rt-PA caused a fivefold increase in the concentration of active tcu-PA and a concomitant decrease in scu-PA concentrations by more than 50%. CONCLUSIONS: Increased liver blood flow results in an increase in t-PA clearance. The conversion of the inactive zymogen scu-PA to the active tcu-PA is increased by an infusion of rt-PA, but total u-PA antigen concentrations remain unchanged.

Adult↗

PubMed1998

Role of calcium carbonate administration timing in relation to food intake on its efficiency in controlling hyperphosphatemia in patients on maintenance dialysis.

A study has claimed that at an equal elemental calcium dose, CaCO3 was not less but equally as efficient in controlling predialysis hyperphosphatemia as calcium acetate, provided both calcium salts were ingested 5 min before meals instead of during meals because the higher acidity of the fasting gastric juice would allow for better dissociation of CaCO3. However, this study did not directly demonstrate that the efficiency of CaCO3 in controlling hyperphosphatemia was actually greater when it was administered before a meal than during a meal. To examine this point, we performed a 3 month randomized crossover trial in 12 reliable and stable patients maintained on chronic hemodialysis. Their plasma concentrations of calcium, protein, phosphate, bicarbonate, urea, and creatinine were measured before the first dialysis of each week and the amount of intact parathyroid hormone (PTH) at the beginning and at the end of each of the 3 months. Comparison of the plasma concentrations measured during the 2 modes of administration showed no significant differences in creatinine, urea, bicarbonate, or intact PTH. The mean (+/-SD) plasma concentration of PO4 was not significantly lower (1.88+/-0.50 vs. 1.74+/-0.41 mM) whereas the corrected level of plasma Ca was significantly lower (2.30+/-0.17 vs. 2.38+/-0.16 mM; p < 0.04) when CaCO3 was given before meals than during meals. In conclusion, the administration of CaCO3 before a meal does not increase its efficiency in controlling hyperphosphatemia because the level of plasma PO4 was actually slightly higher with this timing of administration whereas the comparison of the creatinine and urea levels suggested a stability of phosphate intake and the comparison of the PTH and bicarbonate levels suggested the stability of osteolysis and of the transcellular membrane shift of phosphate. Also, administration of CaCO3 before a meal is associated with significantly lower plasma corrected calcium, suggesting less absorption of calcium, which may be an advantage but only in hypercalcemic patients. There is no reason other than the prevention of its hypercalcemic effect to recommend the administration of CaCO3 just before meals rather than during meals.

Absorption↗

PubMed2003

Cost-utility analysis of intravenous immunoglobulin and prednisolone for chronic inflammatory demyelinating polyradiculoneuropathy.

The aim of this study was to provide an incremental cost-effectiveness analysis comparing intravenous immunoglobulin (IVIg) and prednisolone treatment for chronic inflammatory demyelinating polyradiculoneuropathy. Patients were recruited to a double-blind randomized crossover trial from nine European centres and received either prednisolone or IVIg during the first 6-week treatment period on which the economic evaluation was based. A societal perspective was adopted in measuring service use and costs, although the costs of lost employment were not included. The main outcome measure in the economic evaluation was the number of quality adjusted life years (QALYs) gained, with change in a 11-point disability scale used to measure clinical outcomes. Service use and quality of life data were available for 25 patients. Baseline costs were controlled for using a bootstrapped multiple regression model. The cost difference between the two treatments was estimated to be euro 3754 over the 6-week period. Health-related quality of life, as measured by the EuroQol EQ-5D instrument, increased more in the IVIg group but the difference was not statistically significant. Using a net-benefit approach it was shown that the probability of IVIg being cost-effective in comparison with prednisolone was 0.5 or above (i.e. was more likely to be cost-effective than cost-ineffective) only if one QALY was valued at over euro 250 000. The cost-effectiveness of IVIg is greatly affected by the price of IVIg and the amount administered. The impact of later side-effects of prednisolone on long-term costs and quality of life are likely to reduce the cost per QALY of IVIg treatment.

Algorithms↗

PubMed1995

Urinary isoflavonoid phytoestrogen and lignan excretion after consumption of fermented and unfermented soy products.

OBJECTIVE: To compare the effects of consumption of fermented and unfermented soy products on excretion of urinary isoflavonoid phytoestrogens and lignans in healthy men. DESIGN: A randomized, crossover trial consisting of two 9-day feeding periods following 5 days of baseline data collection. SUBJECTS: Healthy men, aged 20 to 40 years, were recruited from the University of Minnesota Twin Cities community. Of the 22 subjects who began the study, 17 completed all feeding periods. INTERVENTIONS: Fermented soy product (112 g tempeh) or unfermented soy (125 g soybean pieces) was consumed during each controlled feeding period. MAIN OUTCOME MEASURE: Urine samples collected while subjects consumed their habitual diets and on the last 3 days of each feeding period were analyzed for isoflavonoid and lignan content by isotope dilution gas chromatography-mass spectrometry. STATISTICAL ANALYSIS PERFORMED: Comparisons of isoflavonoid and lignan excretion were analyzed using the general linear model procedure. Orthogonal contrasts were used to determine treatment differences of interest. RESULTS: Urinary excretion of isoflavonoids (equol, O-desmethylangolensin [O-DMA], daidzein, genistein) was higher and excretion of lignans (enterodiol, enterolactone) was lower when subjects consumed soy-supplemented diets than when they consumed their habitual diets (P < .05). Urinary isoflavonoid excretion and lignan excretion were similar when subjects consumed tempeh and soybean pieces diets; however, recovery of daidzein and genistein was significantly higher when subjects consumed the tempeh diet than when they consumed the soybean pieces diet (P < .002). When fed soy, 5 of 17 subjects excreted high amounts of equol. These five subjects tended to excrete less O-DMA and daidzein than the 12 subjects who excreted low amounts of equol (P < .06). CONCLUSIONS: Fermentation of soy decreased the isoflavone content of the product fed but increased the urinary isoflavonoid recovery. This finding suggests that fermentation increases availability of isoflavones in soy.

4-Butyrolactone↗

PubMed1997

Modification of cardiopulmonary and intestinal motility effects of xylazine with glycopyrrolate in horses.

Xylazine (XYL) administration in horses is accompanied by significant cardiovascular depression characterized by a 25-35% decrease in cardiac output (CO) which is likely to compromise tissue oxygen delivery (DO2), and usually vagally mediated bradycardia is an important cause of this reduced cardiovascular performance. To examine the possible benefit of preventing the bradycardiac response, 6 healthy horses were treated with intravenous (IV) saline (SAL) or 2.5 micrograms/kg glycopyrrolate (GLY) in a blinded, randomized, crossover trial. Fifteen minutes later, 1 mg/kg XYL was administered IV and systolic, diastolic and mean blood pressures (SBP, DBP, and MBP, respectively), central venous pressure (CVP), mean pulmonary artery pressure, heart rate (HR), CO, and arterial and mixed venous blood gases were measured at the following times: baseline, 2, 5, and 10 min post-SAL or GLY; and 2, 5, 10, 15, 30, 45 and 60 min post-XYL. Determination of cardiac index (CI), stroke index (SI), left ventricular work, systemic vascular resistance (SVR), DO2, oxygen uptake, and oxygen extraction ratio were made at the same time. Gastrointestinal (GI) motility was evaluated by four-quadrant auscultation for 24 h post-XYL. Statistical analysis of continuous variables was carried out using ANOVA for repeated measures and Wilcoxon's rank-sum test for non-parametric data. In GLY treated horses, HR, SBP, MBP, DBP, CI, DO2 and mixed venous oxygen tension were significantly higher up to 30 min after XYL (P < or = 0.02) while CVP and SI were significantly lower 2 and 5 min post-XYL, respectively. In both groups, GI motility as assessed by auscultation was virtually abolished for an hour, with a non-significant tendency for the decrease in motility to last longer in the GLY/XYL group. None of the treated horses developed abdominal discomfort. No significant difference was observed in the other variables. The study shows that 2.5 micrograms/kg GLY premedication reduces the cardiovascular depression caused by 1 mg/kg XYL, without adversely affecting GI motility.

Adjuvants, Anesthesia↗