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Results for “randomized crossover trial”

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PubMed2004

Relative benefits of linear analogue and advanced digital hearing aids.

Speech recognition performance and self-reported benefit from linear analogue and advanced (digital) hearing aids were compared in 100 first-time hearing aid users with mild-to-moderate sensorineural hearing loss fitted monaurally with a behind-the-ear (BTE) hearing aid in a single-blind randomized crossover trial. Subjects used each aid for 5 weeks in turn, with aid order balanced across subjects. Three alternative models of digital hearing aid were assigned to subjects according to a balanced design. Aid type was disguised to keep subjects blind within practical limitations. Aided speech recognition performance in noise was measured at speech levels of 65 and 75dB at a speech-to-noise ratio (SNR) of +2dB for closed sets of single words. Self-rated benefit was measured using the Abbreviated Profile of Hearing Aid Benefit (APHAB) and the Glasgow Hearing Aid Benefit Profile (GHABP). Quality of life, hearing aid use and user preferences were also assessed. Speech recognition scores with the digital aids were significantly better at 75dB than with the analogue aids Self-reported benefit (APHAB, GHABP) and improvement in quality of life were generally not significantly different between analogue and digital aids, although aversiveness measured with the APHAB was significantly lower with digital aids, and satisfaction measured with the GHABP was greater. The digital aids were preferred significantly more often than the analogue aids, with 61 subjects choosing their digital aid, 26 choosing the analogue aid, and nine being equivocal. Overall, this study shows advantages for advanced digital over simple linear analogue aids in terms of both objective and subjective outcomes, although average differences are not large.

Adult↗

PubMed2002

Does oral folic acid lower total homocysteine levels and improve endothelial function in children with chronic renal failure?

BACKGROUND: Accelerated vascular disease is common in chronic renal failure (CRF) and accounts for significant mortality and morbidity. Elevated homocysteine levels may contribute by an effect on endothelial function. METHODS AND RESULTS: We performed a double-blind placebo-controlled randomized crossover trial of folic acid at 5 mg/m2 in 25 normotensive children 12+/-3 (7 to 17) years of age with CRF (glomerular filtration rate 26.8+/-13.2 mL/min per 1.73 m2) of noninflammatory etiology. Each subject underwent two 8-week periods of folic acid and placebo separated by an 8-week washout period. The effect of folic acid on homocysteine levels, LDL oxidation, and both endothelial-dependent and -independent vascular function were measured. After oral folic acid, serum folate levels rose from 11.7+/-4.25 to 635+/-519 microg/L (P=0.001), red cell folate levels rose from 364+/-195 to 2891+/-2623 microg/L (P<0.001), and total homocysteine levels fell from 10.28+/-4.16 to 8.62+/-2.32 micromol/L (P=0.03). In addition, there was a significant improvement in flow-mediated dilatation (FMD) (endothelial-dependent dilatation) from 7.21+/-2.8% to 8.47+/-3.01% (P=0.036) with no change in response to glyceryl trinitrate (endothelial-independent dilatation). There was no significant change in FMD or glyceryl trinitrate during the placebo phase. There was, however, no significant difference in final FMD after placebo or folic acid. Lag times for LDL oxidation were prolonged during the treatment phase (58.4+/-18.7 to 68.1+/-25.9 minutes, P=0.01). CONCLUSION: Folic acid supplementation in children with CRF may improve endothelial function with an increased resistance of LDL to oxidation.

Administration, Oral↗

PubMed1994

Gastroesophageal reflux with nasogastric tubes. Effect of nasogastric tube size.

Pulmonary aspiration of gastric contents results initially from reflux of stomach contents into the esophagus. Small-bore enteral feeding tubes are thought to result in less pulmonary aspiration and less reflux. We prospectively investigated the effect of nasogastric tube size upon gastroesophageal (GE) reflux in normal volunteers in a randomized crossover trial. Reflux was assessed by gastroesophageal scintiscanning, a radioisotopic technique that detects and quantitates GE reflux. A total of 11 subjects were studied three times: control, no nasogastric tube, small-bore (8F) nasogastric tube, and large-bore (14F) nasogastric tube. Reflux was assessed in each subject under each experimental condition by provocative testing in which abdominal pressure was increased from 0 to 100 mm Hg by 20-mm Hg increments with an abdominal pressure device. GE reflux indices were calculated for each measurement and the groups compared. A positive indicator of reflux was defined as a > or = 4% reflux index. Gastroesophageal reflux was not detected at any level of abdominal pressure regardless of the presence or size of a nasogastric tube. With maximum 100 mm Hg abdominal pressure, the reflux index was control, 1.75 +/- 0.45%; small-bore tube, 1.67 +/- 0.28%; and large-bore tube, 1.88 +/- 0.35% (NS). The reflux index was not different between small-bore and large-bore nasogastric tubes. Our data suggest the size of a nasogastric tube is not an important determinant of GE reflux in normal subjects during short-term intubation. Large-bore tubes did not cause more reflux than small-bore tubes. The presence of a nasogastric tube did not cause reflux in normal subjects. These data suggest that factors other than the size of nasogastric tube are more important in GE reflux in normal subjects.

Abdomen↗

PubMed2005

Relationships between the concentrations of prostaglandins and the nonsteroidal antiinflammatory drugs indomethacin, diclofenac, and ibuprofen.

STUDY OBJECTIVES: To study the concentration-effect relationships of the nonsteroidal antiinflammatory drugs (NSAIDs) indomethacin, diclofenac, and ibuprofen; to investigate whether standard doses of these drugs inhibit prostaglandin concentrations to a similar extent, determined by measuring the concentration of a surrogate marker of prostaglandin E 2 (PGE 2 ); and to determine the extent to which dose increases produce analogous increases in prostaglandin inhibition. DESIGN: Single-dose, randomized, crossover trial with a 1-week washout period. SETTING: University biopharmaceutics and pharmacokinetics laboratory. SUBJECTS: Eight healthy adult volunteers younger than 35 years old. INTERVENTION: Subjects were administered two different standard doses of regular formulations (not enteric coated) of each NSAID on separate occasions. MEASUREMENTS AND MAIN RESULTS: Plasma samples were collected for determination of drug and 13,14-dihydro-15-keto-PGE 2 (PGEM; the surrogate marker of PGE 2 ) concentrations at regular intervals after administration of each NSAID dose. Statistically significant linear correlations were found between the percent reduction in PGEM concentration and the concentrations of diclofenac, indomethacin, and ibuprofen in plasma (R 2 = 0.992-0.999). The PGEM plasma concentrations correlated inversely with NSAID plasma concentrations, indicating maximum inhibition when the highest NSAID plasma concentrations were achieved. Statistically significant differences in the percent inhibition of PGEM concentrations were observed between the two doses for each NSAID (p<0.05), but not between subjects for each NSAID. Doubling the dose (100% increase) of diclofenac and indomethacin produced a 60-65% increase in maximum inhibition of PGEM concentrations, whereas a 50% increase in dose produced a 44% increase in the maximum effect of ibuprofen. CONCLUSION: Prostaglandin inhibition, as measured by changes in PGEM concentrations, correlated significantly with NSAID concentrations in plasma and differed significantly between high and low NSAID doses. Measurement of PGEM plasma concentrations appears to be a promising marker for estimation of relative potency of NSAIDs.

Administration, Oral↗

PubMed1994

Angiotensin II receptor blockade with single doses of valsartan in healthy, normotensive subjects.

Valsartan (CGP 48933), a specific blocker of the angiotensin II (Ang II) receptor subtype 1 (AT1 receptor) was administered in single, oral doses of 40 mg and 80 mg to six healthy, normotensive male volunteers in a double-blind, placebo-controlled, randomized crossover trial. The aims of the study were a) to assess the extent, time course and dose-dependency of inhibition of the pressor effect of exogenous Ang II; and b) to attempt to correlate AT1 receptor blockade with the drug levels in plasma and with other markers of biological activity of the trial drug such as plasma renin activity (PRA). Using the Finapres device and i.v. bolus injections of exogenous Ang II, AT1 receptor blockade was assessed by measuring blood pressure (BP) and heart rate (HR) on a beat-by-beat basis. A dose-response curve for Ang II was obtained for each subject before and at 2, 4, 6, 8 and 24 h after administration of placebo and of the two doses of valsartan. PRA was measured with a conventional radioimmunoassay method. Data evaluation included a) descriptive analysis of the changes of the Ang II dose-response curves after valsartan, as compared to the curve on placebo; b) calculation of the pressor dose D30 of Ang II at each time-point, using linear regression; c) assessment of the effect of 4 micrograms Ang II on systolic BP and HR and the calculation of the percentage inhibition of these effects after valsartan; d) description of the relationship between drug levels in plasma and the measures of AT1 blockade, including pharmacokinetic-pharmacodynamic modeling with an Emax model for the percentage inhibition of systolic BP and HR.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed2004

Copper, selenium, zinc, and thiamine balances during continuous venovenous hemodiafiltration in critically ill patients.

BACKGROUND: Acute renal failure is a serious complication in critically ill patients and frequently requires renal replacement therapy, which alters trace element and vitamin metabolism. OBJECTIVE: The objective was to study trace element balances during continuous renal replacement therapy (CRRT) in intensive care patients. DESIGN: In a prospective randomized crossover trial, patients with acute renal failure received CRRT with either sodium bicarbonate (Bic) or sodium lactate (Lac) as a buffering agent over 2 consecutive 24-h periods. Copper, selenium, zinc, and thiamine were measured with highly sensitive analytic methods in plasma, replacement solutions, and effluent during 8-h periods. Balances were calculated as the difference between fluids administered and effluent losses and were compared with the recommended intakes (RI) from parenteral nutrition. RESULTS: Nineteen sessions were conducted in 11 patients aged 65 +/- 10 y. Baseline plasma concentrations of copper were normal, whereas those of selenium and zinc were below reference ranges; glutathione peroxidase was in the lower range of normal. The replacement solutions contained no detectable copper, 0.01 micromol Se/L (Bic and Lac), and 1.42 (Bic) and 0.85 (Lac) micromol Zn/L. Micronutrients were detectable in all effluents, and losses were stable in each patient; no significant differences were found between the Bic and Lac groups. The 24-h balances were negative for selenium (-0.97 micromol, or 2 times the daily RI), copper (-6.54 micromol, or 0.3 times the daily RI), and thiamine (-4.12 mg, or 1.5 times the RI) and modestly positive for zinc (20.7 micromol, or 0.2 times the RI). CONCLUSIONS: CRRT results in significant losses and negative balances of selenium, copper, and thiamine, which contribute to low plasma concentrations. Prolonged CRRT is likely to result in selenium and thiamine depletion despite supplementation at recommended amounts.

Acute Kidney Injury↗

PubMed1990

A project in diabetes education for children.

Forty-eight families with children less than 13 years old attending a paediatric diabetic clinic volunteered for a 2-year randomized crossover trial to determine whether an informal education programme (diabetic club) could improve diabetic control. Group A attended the diabetic club for 10 afternoons of informal education in the first year, while Group B continued at the routine clinic (5 visits per year). For the second year Group A returned to the clinic, Group B attended the club. Glycosylated haemoglobin (HbA1) remained stable while attending the club but rose significantly (p less than 0.01) while attending the clinic in both groups (HbA1 at baseline, 1 year, and 2 years: Group A, 9.6 (SD 1.2), 9.6(1.4), 10.7(2.1)%; Group B 8.9(1.3), 10.4(1.4), 10.5(1.4)% (normal reference range 4.7-7.9%)). Other indices of control were unchanged. Diabetic problem-solving scores of parents improved (p less than 0.01) but their knowledge of diabetes did not correlate with their child's HbA1. Dietary intake showed a reduction in percentage of energy taken as fat (40% vs 37.7%, p less than 0.05) during club attendance. The percentage of parents reporting helpful social contact between families increased during their club year (Group A 50 to 78%, Group B 32 to 57%, p less than 0.001). Psychological measurements remained unchanged. An education programme for diabetic children may stabilize diabetic control in the short term but this effect is not sustained. The main benefit was the support provided by increased social contact with families of other diabetic children within the informal framework of the diabetic club.

Child↗

PubMed1999

Near-patient test for C-reactive protein in general practice: assessment of clinical, organizational, and economic outcomes.

BACKGROUND: The benefits of near-patient, point-of-care tests have not been fully examined. We have assessed the clinical, organizational, and economic outcomes of implementing a near-patient test for C-reactive protein (CRP) in general practice. METHODS: In a randomized crossover trial during intervention periods, general practitioners (GPs) were allowed to measure CRP within 3 min, using NycoCard(R) CRP. During control periods, they had to mail blood samples for CRP measurements to the hospital laboratory and received test results 24-48 h later. Twenty-nine general practice clinics participated (64 GPs), and 1853 patients were included in the study. Results were evaluated at both the level of participating GPs and the level of included patients. RESULTS: For participating GPs, the overall use of erythrocyte sedimentation rates (ESRs) decreased by 8% (95% confidence interval, 1-14%) during intervention periods, and the number of blood samples mailed to the hospital laboratory decreased by 6% (1-10%). No reduction in the prescription of antibiotics was seen. The proportion of study patients having a follow-up telephone consultation was reduced from 63% to 53% (P = 0. 0001), and patients with CRP concentrations >50 mg/L had their antibiotic treatments started earlier when CRP was measured in general practices (P = 0.0161). CONCLUSION: The implementation of the near-patient CRP test was cost-effective mainly on the basis of a reduction in the use of services from the hospital laboratory by GPs. If the implementation is followed by education and clinical guidelines, opportunities exist for additional reduction in the use of ESR and for a more appropriate use of antibiotics.

Anti-Bacterial Agents↗

PubMed1983

Increased exercise tolerance after nitroglycerin oral spray: a new and effective therapeutic modality in angina pectoris.

The prophylactic antianginal efficacy of nitroglycerin (NTG) oral spray was assessed in 20 patients with angiographically documented coronary disease and stable angina pectoris. The evaluation was by a randomized crossover trial involving treadmill exercise testing. On study day 1, a control treadmill exercise test was performed, followed 30 minutes later by a second exercise test 2 minutes after administration of either placebo (group A, 10 patients) or NTG spray 0.8 mg (group B, 10 patients). One week later, on study day 2, the patients again underwent control treadmill exercise testing followed by a second exercise test after either NTG spray (group A) or placebo (group B). NTG spray delayed the onset of anginal pain during exercise by a mean of 100 +/- 64 seconds (p less than 0.001) in 13 patients and prevented pain entirely in seven. Placebo did not significantly delay the appearance of angina and prevented chest pain in only one patient. NTG spray increased treadmill exercise duration by 31% before the onset of angina (p less than 0.001); placebo did not significantly alter the duration of exercise. NTG spray abolished in six patients and delayed in 14 patients the onset of exercise-induced ST-segment depression of 1 mm (p less than 0.001). Patients achieved a higher heart rate at peak exercise with NTG spray, and yet the maximal exercise-induced ST-segment depression of 2.1 +/- 1.0 mm during the control study declined to 1.3 +/- 0.9 mm on NTG spray (p less than 0.001). Placebo had no effect on exercise ST-segment depression. These data indicate that the oral NTG spray is an effective prophylactic for exercise-induced angina.

Administration, Oral↗

PubMed1992

Effect of conventional and intensified insulin therapy on free-insulin profiles and glycemic control in NIDDM.

OBJECTIVE: To investigate the effects on 24-h insulin and glucose profiles of two- and four-dose insulin regimens in patients with non-insulin-dependent diabetes mellitus (NIDDM) who have failed oral agent therapy. RESEARCH DESIGN AND METHODS: Ten patients with NIDDM and 10 matched nondiabetic control subjects took part in the study, a randomized crossover trial with 8-wk treatment periods. We determined 24-h profiles of blood glucose and free insulin in control subjects and patients when they were taking oral agents and at the end of each treatment period. The two-dose regimen was mixed (15% regular, 85% NPH) insulin given before breakfast and dinner, and the four-dose regimen was regular insulin given before meals and NPH given at 2200. RESULTS: Patients taking oral agents had higher mean blood glucose than control subjects (mean +/- SE 12.6 +/- 0.6 vs. 4.5 +/- 0.1 mM, P less than 0.0001) and similar 24-h insulin concentrations but lower postprandial insulin concentrations (at breakfast, 87.6 +/- 13.8 vs. 228.6 +/- 29.4 pM, P less than 0.01). Mean 24-h insulin concentrations were the same on two- and four-dose regimens, and both regimens caused basal hyperinsulinemia. Glycemic control also improved. Postprandial insulin peaks were higher at lunch and dinner on the four-dose regimen, and postprandial blood glucose was lower. Fasting proinsulin was elevated in patients compared with the control subjects (25.1 +/- 4.7 pM vs. 5.0 +/- 0.9 pM, P less than 0.001) and was suppressed to normal during insulin treatment. CONCLUSIONS: Two- and four-dose insulin regimens can achieve similar glycemic control. Both regimens cause basal hyperinsulinemia but normalize the hyperproinsulinemia observed during failure of oral agent therapy. Four-dose insulin regimens offer few advantages to the glycemic control achieved with two-dose regimens but may be more physiological.

Blood Glucose↗

PubMed2003

Acute double-blind, placebo-controlled sleep laboratory and clinical follow-up studies with a combination treatment of rr-L-dopa and sr-L-dopa in restless legs syndrome.

In a double-blind, placebo-controlled randomized crossover trial, the acute efficacy of a combination treatment of 100 mg regular-release (rr) and 100 mg sustained-release (sr) L-dopa/benserazide in RLS was investigated by means of sleep laboratory methods, with a subsequent open clinical follow-up for 4 weeks. 21 RLS patients classified according to ICSD and IRLSSG criteria were included; 18 completed the study. Objective sleep quality was determined by polysomnography (PSG) in 3 subsequent nights (adaptation/screening, placebo and drug night), subjective sleep and awakening quality was evaluated by rating scales, objective awakening quality by psychometric tests. Clinical follow-up consisted of daily ratings of subjective sleep and awakening quality (SSA) and VAS for RLS symptomatology ratings, completion of the RLS (IRLSSG) Scale weekly and the Zung Depression (SDS) and Anxiety (SAS) Scale, Quality of Life Index, Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale before and after therapy. Acute L-dopa/benserazide significantly (p < 0.001) and markedly (75%) decreased the target variable PLM/h of sleep as well as all other RLS/PLM variables, but failed to improve objective sleep efficiency and subjective sleep quality in comparison to placebo. After 4 weeks of therapy, however, subjective sleep and awakening quality also improved significantly. While RLS/PLM measures showed an immediate significant and marked response to the combination therapy subjective sleep quality only improved after chronic treatment.

Adult↗

PubMed2001

Simplified citrate anticoagulation for high-flux hemodialysis.

In a randomized crossover trial, we compared a simple citrate anticoagulation protocol for high-flux hemodialysis with standard anticoagulation by low-molecular-weight heparin (dalteparin). Primary end points were urea reduction rate (URR), Kt/V, and control of electrolyte and acid-base homeostasis. Secondary end points were bleeding time at vascular puncture sites and markers of activation of platelets, coagulation, and fibrinolysis. Solute removal during citrate dialysis was excellent (URR, 0.71 +/- 0.06; Kt/V, 1.55 +/- 0.3) and similar to results of conventional bicarbonate hemodialysis anticoagulation with dalteparin (URR, 0.72 +/- 0.04; Kt/V, 1.56 +/- 0.2). Electrolyte control was effective with both anticoagulation regimens, and total and ionized calcium, sodium, potassium, and phosphate concentrations at the end of dialysis did not differ. Alkalemia was less frequent after citrate than conventional dialysis (pH 7.5 in 25% versus 62% of patients; mean pH at end of dialysis, 7.46 +/- 0.06 versus 7.51 +/- 0.07; P < 0.01). Bleeding time at puncture sites was shorter by 30% after citrate compared with dalteparin anticoagulation (5.43 +/- 2.80 versus 7.86 +/- 2.93 minutes; P < 0.001). Activation of platelets, coagulation, and fibrinolysis was modest for both treatments and occurred mainly within the dialyzer during dalteparin treatment and in the vascular-access region during citrate anticoagulation. Citrate-related adverse events were not observed. We conclude that citrate anticoagulation for high-flux hemodialysis is feasible and safe using a simple infusion protocol.

Adult↗

PubMed1997

Pharmacokinetics of an oral solution of the microemulsion formulation of cyclosporine in maintenance pediatric liver transplant recipients.

BACKGROUND: A comparison of the oral bioavailability of cyclosporine from the original formulation (CsA) and from the new formulation, cyclosporine for microemulsion (CsA-ME), was made in pediatric maintenance liver transplant patients within two age groups (group 1, ages 1-5 years; group 2, ages 6-17 years) in an open-label, multicenter, randomized crossover trial. All patients were at least 6 months past transplantation and were receiving CsA maintenance therapy. METHODS: In study period 1 (days 1 through 14), patients were administered either CsA or CsA-ME at the same b.i.d. dosage as their maintenance therapy. Upon entry into period 2 (days 15 through 28), patients were converted to the alternate formulation at a 1:1 mg dose ratio. On day 29, all patients returned to the CsA treatment administered at study entry, with follow-up on day 35. Dosage adjustments were not allowed with either CsA or CsA-ME. Twelve-hour pharmacokinetic profiling was performed at the end of periods 1 and 2. RESULTS: Both the mean area under the concentration-versus-time curve and the mean maximum blood concentration of cyclosporine-both normalized for dose-were significantly increased: by 66% and 109%, respectively, in patients receiving CsA-ME compared with those receiving CsA in group 1 and by 39% and 75%, respectively, in group 2. During this study, liver function remained stable, and serum creatinine and blood pressure did not differ significantly between treatment groups. CONCLUSIONS: This study shows increased bioavailability in all patients converted to CsA-ME, with the greatest increase seen in patients with the lowest initial cyclosporine bioavailability. The tolerability was similar between the two formulations during this study.

Absorption↗

PubMed1998

No interaction between ciprofloxacin and an oral contraceptive.

Several antibiotics have been reported to lessen the ovarian suppression produced by oral contraceptive agents, as a result of drug interactions. The present investigation was designed to study the likelihood of the occurrence of any such interaction between the fluoroquinolone antibiotic ciprofloxacin (Ciproxin) at a dosage of 500 mg twice a day and the "low-dose" oral contraceptive Marvelon (30 microgram of ethinyl estradiol [EE] plus 150 microgram of desogestrel). Twenty-four healthy female volunteers were studied in a double-blind, placebo-controlled, randomized crossover trial. There were no significant differences between measurements of the area under the concentration-time curve of EE up to 24 h after oral contraceptive intake during placebo and ciprofloxacin administration on days 11 and 16 of the cycles, indicating the absence of pharmacokinetic interaction. Similarly, no clinically significant differences in the levels of sex hormone binding globulin were found between the placebo and ciprofloxacin cycles, indicating no major variation in EE levels during ciprofloxacin and placebo treatment. Ten subjects in each of the placebo and ciprofloxacin groups had early-follicular-phase levels of 17-beta estradiol (<184 ng/liter) at one or more points during their cycles, but none had values above the early-follicular-phase range, indicating no significant ovarian activity. In addition, all subjects had progesterone levels of <2 ng/ml, indicating the absence of ovulation. Only two subjects, who received the placebo, had evidence of sustained follicular growth to a potentially ovulatory follicle ( approximately 18 mm). We conclude that ciprofloxacin does not interfere with the ovarian suppression produced by the low-dose oral contraceptive Marvelon.

Adult↗

PubMed2003

High-fiber rye bread and insulin secretion and sensitivity in healthy postmenopausal women.

BACKGROUND: Fiber and whole-cereal intakes may protect against hyperinsulinemia and the risk of type 2 diabetes. OBJECTIVE: The aim was to study whether the long-term use of high-fiber rye bread and white-wheat bread modifies glucose and insulin metabolism in healthy postmenopausal women. DESIGN: The study was a randomized crossover trial consisting of 8-wk test and 8-wk washout periods. The subjects were 20 postmenopausal women [macro x +/- SD age: 59 +/- 6.0 y; body mass index (in kg/m(2)): 27.5 +/- 2.9; baseline fasting serum cholesterol: 6.5 +/- 0.8 mmol/L], of whom 3 had impaired glucose tolerance as determined by a 2-h oral-glucose-tolerance test. The test breads were high-fiber rye and white-wheat breads, planned to make up > or =20% of energy. Fasting blood samples were collected for the measurement of plasma glucose and insulin at the beginning and at the end of both bread periods. The frequently sampled intravenous-glucose-tolerance test was performed at the run-in and at the end of both bread periods. The acute insulin response, insulin sensitivity, and glucose effectiveness were calculated. RESULTS: The rye bread made up 23.4 +/- 4.3% and wheat bread 26.7 +/- 8.2% of total energy intake. Compared with that during the run-in period, the acute insulin response increased significantly more during the rye bread period (9.9 +/- 24.2%) than during the wheat bread period (2.8 +/- 36.3%; P = 0.047). Other measured variables did not change significantly during the study. CONCLUSIONS: Modification of carbohydrate intake by high-fiber rye bread did not alter insulin sensitivity in postmenopausal, hypercholesterolemic women. High-fiber rye bread appears to enhance insulin secretion, possibly indicating improvement of b cell function.

Area Under Curve↗

PubMed1993

Cardiorespiratory consequences of expiratory chest wall compression during mechanical ventilation and severe hyperinflation.

OBJECTIVES: To measure and compare the effects of manual expiratory compression of either the rib cage or abdomen on cardiac output, end-expiratory lung volume, and other cardiorespiratory variables in an animal model that mimics the severe pulmonary hyperinflation and hemodynamic impairment occurring in patients with severe acute asthma during mechanical ventilation. DESIGN: Prospective, randomized, crossover trial. SETTING: Research laboratory. SUBJECTS: Seven cross-bred, anesthetized, supine dogs. INTERVENTIONS: The following sequence was employed: a) spontaneous breathing without pulmonary hyperinflation; b) positive-pressure ventilation with severe pulmonary hyperinflation (produced by an external variable expiratory flow resistor); c) approximately 7 mins of manual expiratory compression of either the rib cage or abdomen during positive-pressure ventilation-hyperinflation. This sequence was then repeated, incorporating the alternative type of expiratory compression. MEASUREMENTS AND MAIN RESULTS: Cardiac output (measured by thermodilution), aortic pressure, pleural (esophageal) pressure, and changes in end-expiratory lung volume were measured. The decrease in cardiac output due to mechanical ventilation with pulmonary hyperinflation was exacerbated by rib cage compression (p < .001; spontaneous breathing 2.9 +/- 0.2 L/min, hyperinflation 1.5 +/- 0.1 L/min, and rib cage compression 1.0 +/- 0.1 [SEM] L/min). However, the positive-pressure ventilation-hyperinflation-induced decrease in cardiac output was attenuated by abdominal compression (p < .001; spontaneous breathing 3.3 +/- 0.2 L/min, hyperinflation 1.4 +/- 0.1 L/min, and abdominal compression 2.1 +/- 0.1 L/min). Mean aortic pressure returned to prehyperinflation levels during abdominal compression (p < .001; spontaneous breathing 126 +/- 2 mm Hg, hyperinflation 75 +/- 5 mm Hg, and abdominal compression 120 +/- 3 mm Hg). Both types of compression were similarly effective (p > .75) in increasing mean expiratory pleural pressure, so that end-expiratory lung volume was similarly (p > .25) reduced (0.45 +/- 0.05 and 0.40 +/- 0.05 L for rib cage and abdominal compressions, respectively) in this non-air flow, limiting animal model. CONCLUSIONS: The cardiorespiratory effects of manually compressing the rib cage or abdomen during expiration in this animal study suggest that these techniques should be carefully evaluated in mechanically ventilated patients with severe acute asthma.

Abdomen↗

PubMed1996

Inverse nonlinear pharmacokinetics of total and protein unbound drug (oxaprozin): clinical and pharmacokinetic implications.

The nonsteroidal antiinflammatory drug oxaprozin is extensively bound to plasma proteins in a concentration-dependent manner. This study demonstrates for the first time the inverse nonlinear pharmacokinetics of total and unbound oxaprozin and presents clinical implications of this phenomenon. A total of 71 healthy volunteers participated in single- and multiple-dose studies. In study I, 0.6-, 1.2-, and 1.8-gm doses of oxaprozin were given on an empty stomach in a randomized, crossover trial (n = 35). In studies II and III, 1.2- and 1.8-gm doses, respectively, were given once a day for 8 days (n = 12 and 24, respectively). Serial blood samples for total and unbound drug assays were taken over a 240-hour period in study I and for a 24-hour period on days 1, 5, and 8 in studies II and III. After administration of 1.2 gm once daily, steady-state conditions were established by day 5. Actual average steady-state plasma concentrations (Cavg) were lower than those predicted from the single-dose study based on linear kinetics for the total drug, but higher for the unbound drug. Nonlinear changes in Vd/F were also noted with multiple-dose administration. Vd/F increased by 47% for total drug but decreased by 61% for unbound drug relative to single-dose values. Half-lives after single-dose administration for total and unbound drug determined from 24 to 240 hours and from 24 to 72 hours, respectively, were dose independent for total drug, but dose dependent for unbound drug. Half-lives after multiple-dose administration measured from 24 to 48 hours in study II decreased further. In conclusion, oxaprozin clearance for the total drug was increased while that of the unbound drug was decreased after repetitive dosing. This inverse pharmacokinetic behavior has been attributed to the two noncompensatory kinetic effects: concentration-dependent protein binding and saturable metabolism of oxaprozin.

Adult↗

PubMed1995

Rheumatoid arthritis treated with tenidap and piroxicam. Clinical associations with cytokine modulation by tenidap.

OBJECTIVE: To compare the effects of tenidap and piroxicam on acute-phase protein and cytokine levels in the blood of rheumatoid arthritis (RA) patients and to explore their associations with clinical disease activity. METHODS: A double-blind, randomized, crossover trial in 49 patients with active RA compared 6 weeks of treatment with tenidap (120 mg/day) versus 6 weeks of treatment with piroxicam (20 mg/day). RESULTS: Median values for C-reactive protein (CRP), Westergren erythrocyte sedimentation rate (ESR), serum amyloid A (SAA) protein, and interleukin-6 (IL-6) were significantly lower after tenidap treatment compared with piroxicam treatment, even in the presence of stable background treatment with prednisone, methotrexate, or prednisone plus methotrexate. The median within-patient treatment differences (after tenidap minus after piroxicam) in the CRP, ESR, SAA, and IL-6 values were -1.7 mg/dl, -10.0 mm/hour, -22.0 micrograms/ml, and -3.7 pg/ml, respectively, and represent -60.4%, -17.7%, -35.5%, and -26.1% of the respective baseline levels. IL-6 levels were positively correlated with CRP and SAA. Plasma IL-1 beta was generally below the level of detection. Tumor necrosis factor alpha levels were similar after tenidap and after piroxicam. Treatment differences for 4 of 7 clinical parameters favored tenidap, but did not reach statistical significance. IL-6, CRP, and ESR were significantly correlated with clinical treatment differences. Tenidap and piroxicam toleration were similar, although tenidap-treated patients exhibited a reversible increase in urinary protein excretion. CONCLUSION: Tenidap was differentiated from piroxicam by lower levels of acute-phase proteins, ESR, and IL-6 after tenidap treatment. These treatment differences were significantly correlated with clinical parameters.

Anti-Inflammatory Agents, Non-Steroidal↗