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Results for “randomized crossover trial”

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PubMed2003

Comparison of loss in lung volume with open versus in-line catheter endotracheal suctioning.

OBJECTIVE: Disconnecting the endotracheal tube from the ventilator causes significant loss in lung volume, which is further exacerbated by suctioning. In-line catheter suction systems have putative benefits over open catheter suction by maintaining positive pressure, thereby minimizing hypoxemia and hemodynamic instability. However, there is a theoretical risk of generating large negative airway pressures and auto-cycling of the ventilator with in-line catheter suction systems. We studied the effects on lung volume with both these techniques. DESIGN: Open, randomized, crossover, clinical trial. SETTING: Pediatric critical care unit. PATIENTS: Fourteen paralyzed patients, age 6 days to 13 yrs. INTERVENTIONS: Each patient, acting as his or her own control, was suctioned with an in-line catheter suction system and open catheter suction. Each suction maneuver was standardized. Changes in lung volume were measured by inductance plethysmography. Heart rate, blood pressure, and oxygen saturation were continuously monitored. MEASUREMENTS AND MAIN RESULTS: Total lung volume loss was greater with open catheter suction compared with in-line catheter suction systems (p = .008). The most significant amount of lung volume loss associated with open catheter suction appears to be related to ventilator disconnection, rather than actual suctioning. Patients with decreased pulmonary compliance (< 0.8 mL/cm H2O/kg) demonstrated a greater loss in lung volume, both absolute and relative, as a result of ventilator disconnection (p = .038 and .006, respectively). Patients suctioned with open catheter suction desaturated to a greater extent than patients suctioned with in-line catheter suction (p = .026). There was evidence of ventilator triggering during the actual suction maneuver in all patients during in-line catheter suctions. CONCLUSIONS: The most significant loss in lung volume during suctioning occurs primarily during ventilator disconnection. Hence, open catheter suction results in greater lung volume loss when compared with in-line catheter suction. We suggest that in-line catheter suction is preferable, especially in patients with significant lung disease and who require high positive end-expiratory pressures, to avoid alveolar derecruitment and exacerbating hypoxemia during endotracheal tube suctioning.

Adolescent↗

PubMed1998

Effects of a 5-lipoxygenase inhibitor, ABT-761, on exercise-induced bronchoconstriction and urinary LTE4 in asthmatic patients.

The novel 5-lipoxygenase (5-LO) inhibitor, ABT-761, was investigated for its effect on exercise-induced bronchoconstriction in asthmatic subjects. The relationship between 5-LO inhibition and effects on the response of the airways to exercise was examined. In a double-blind, randomized, crossover clinical trial, 10 patients with mild to moderate persistent asthma (who exhibited a fall in forced expiratory volume in one second (FEV1) > or = 20% following standardized exercise challenge) received 200 mg ABT-761 or matched placebo, orally, 5 h prior to exercise on two study days, 7-10 days apart. Lung function, urinary leukotriene E4 (LTE4) and ex vivo calcium ionophore-stimulated LTB4 release in whole blood were measured prior to dosing, prior to exercise and at various time points up to 4 h post-exercise. The mean (SD) maximal percentage fall in FEV1 after exercise was 27.1 (12)% on placebo and 19.9 (10)% on ABT-761 days, respectively (p<0.05). Post-exercise fall in FEV1 was significantly attenuated at 5, 10, 15 and 30 min after exercise and the mean area under curve, representing the overall effect of exercise from 0-45 min post-challenge, was also significantly attenuated by ABT-761 (p<0.001). Ex vivo LTB4 release was inhibited by more than 80% throughout the 4 h post-exercise period, indicating that 5-LO was extensively inhibited at all time points. Urinary LTE4 in the post-exercise period was significantly lower after ABT-761 day than after placebo (40.1 (17.6) versus 89.8 (58.2) pg x mg creatinine(-1); p<0.05). Inhibition of LTB4 release in ABT-761-treated patients correlated positively with the attenuation of post-exercise FEV1 decline (r=0.711; p<0.05). We conclude that ABT-761 is effective in suppressing exercise-induced bronchoconstriction and that this protection is related quantitatively to the degree of 5-lipoxygenase inhibition.

Adult↗

PubMed1992

Effect of a beta 2-agonist (broxaterol) on respiratory muscle strength and endurance in patients with COPD with irreversible airway obstruction.

The effect of broxaterol, a new beta 2-agonist, on respiratory muscle endurance and strength was studied in a double-blind, placebo-controlled, randomized crossover clinical trial in 16 patients with chronic obstructive pulmonary disease (COPD) with irreversible airway obstruction (FEV1 = 57.1 percent of predicted). One patient withdrew from the study because of acute respiratory exacerbation. Inspiratory muscle strength was assessed by maximal inspiratory pressure (MIP) and endurance time was determined as the length of time a subject could breathe against inspiratory resistance (target mouth pressure = 70 percent of MIP, Ti/Ttot = 0.4). Broxaterol (B) or placebo (P) was given orally for seven days at the dose of 0.5 mg three times a day with a washout period of 72 h between study treatments. Measurements were performed before administration of B or P and 2 h (six patients) or 8 h (nine patients) after the end of each treatment. No significant changes in FEV1 or FRC were observed after B or P suggesting that diaphragmatic length was maintained constant with each treatment. The MIP did not significantly change, while endurance time increased after B in the patients tested at 2 h (from 234.8 +/- 48.1 s to 284.0 +/- 48.0 s, p less than 0.05) and at 8 h (from 187.2 +/- 31.1 s to 258.2 +/- 40.4 s, p less than 0.005). No changes were observed after P. Minute ventilation, airway occlusion pressure (P0.1), integrated electromyographic activities of the diaphragm (Edi), and intercostal parasternals (Eic) (normalized to the value obtained during MIP) showed no change during the endurance run with different treatments. We conclude that in a group of COPD patients with irreversible airway obstruction, B significantly improves respiratory muscle endurance, and that this does not arise as a result of an effect on neuromuscular drive or pulmonary mechanics, but may be mediated by peripheral factors.

Adrenergic beta-Agonists↗

PubMed1998

The postoperative analgesic efficacy and safety of piroxicam (FDDF) and naproxen sodium.

The aim of the present study was to compare the analgesic efficacy of piroxicam-FDDF (fast dissolving dosage form) with naproxen sodium, following bilateral removal of impacted third molars. A double-blind, randomized, crossover, analgesic trial was carried out on 40 patients undergoing surgical removal of one lower third molar at each visit. The analgesic efficacy of a single dose regimen of piroxicam-FDDF (40 mg, Feldene Flash, Pfizer, Turkey) was compared with naproxen sodium (550 mg, Anaprotab, Sanli, Turkey). Pain intensity was measured on a category-rating scale during the 8-h period after drug administration. Each patient evaluated the efficacy of the study medication at 15, 30, 45, 60, 90 and 120 min, and then hourly for up to 8 h of drug ingestion. Additional key efficacy measures were also determined (pain intensity difference [PID], sums of pain intensity difference [SPID], total pain relief [TOTPAR], peak pain relief, number of observations at which pain was half-relieved, overall evaluation of study medication effectiveness, and time to medication with a back-up analgesic). The data were analyzed by paired Student's t-test and one-way analysis of variance (ANOVA). Results are expressed as means +/- SEM, and p < 0.05 was taken as statistically significant. The PID and pain relief scores of the piroxicam-FDDF group were significantly greater than those for the naproxen sodium group at 15, 30, 45 and 60 min (p < 0.01). After 90 min to 8 h, no statistical significance was revealed among the two test groups (p > 0.05). The peak pain relief, maximal analgesic effect, SPID, TOTPAR values, adjusted mean number of observations with pain at least half-relieved, and the final overall evaluation records were all superior for piroxicam-FDDF (p < 0.05). The results of this study clearly show that the analgesic efficacy of piroxicam-FDDF is superior to naproxen sodium in the treatment of pain following oral surgery for the removal of impacted third molars.

Adolescent↗

PubMed2001

Nutritional supplements used in weight-reduction programs increase intestinal gas in persons who malabsorb lactose.

OBJECTIVE: To determine if ingestion of 2 doses of milk-based dietary supplements produce gaseous symptoms in subjects who malabsorb lactose. DESIGN: Randomized, controlled, crossover trial. SUBJECTS/SETTING: Ten community-based subjects who malabsorb lactose. INTERVENTION: Ingestion of 2 standard servings of milk-based supplements (a powder reconstituted in fat-free milk or a ready-to-drink preparation) or low-lactose control preparations. MAIN OUTCOME MEASURES: Frequency of flatus passage and subjective impression of bloating, flatulence, and abdominal discomfort. STATISTICAL ANALYSIS: Wilcoxon signed-rank test. RESULTS: The high lactose content (27 g) of 2 servings of the powder-based supplement ingested without other food resulted in a marked increase in daily flatus passages from the basal level of 9.7+/-8.2 to 30+/-14 (mean+/-SD), and a significant increase in the subjects' perception of gas. In contrast, the lower lactose content (18.4 g) of 2 servings of a ready-to-drink supplement resulted in a flatus frequency of 17+/-10 (P=.14 vs baseline) and no significant increase in the perception of increased gas. Neither supplement resulted in a significant increase in bloating, abdominal pain, or diarrhea. The lactose content of the liquid supplement was reduced by 80% following overnight incubation with an over-the-counter lactase preparation. APPLICATIONS/CONCLUSIONS: Persons who malabsorb lactose should be aware that sizable increases in rectal gas commonly occur when milk-based powders reconstituted in milk are used as meal replacements. In contrast, gas problems probably will be minor following ingestion of 2 doses of a ready-to-drink, milk-based supplement. The lactose content of these supplements can be markedly reduced by overnight incubation with over-the-counter lactase preparations, and this manipulation should be beneficial for subjects troubled by the increased gas caused by the consumption of lactose-containing supplements.

Abdominal Pain↗

PubMed1997

Predictors of response to exercise training in severe chronic congestive heart failure.

We prospectively assessed whether baseline central hemodynamics and exercise capacity can predict improvement of VO2 at ventilatory threshold (VT) after exercise training in patients with severe chronic congestive heart failure. Eighteen patients (mean +/- SEM; age 52 +/- 2 years), half of them listed for transplant, underwent 3 weeks of exercise training (interval cycle and treadmill walking; 5 x/week) and 3 weeks of activity restriction in a random-order crossover trial. Baseline data were not significantly different for groups with exercise training first and activity restriction first: cardiac index at rest (2.1 +/- 0.1 L/m2/min), maximum cardiac index (3.1 +/- 0.2 L/m2/min) (Fick), and echocardiographic ejection fraction (21 +/- 1%). The same was true for cardiopulmonary exercise data (cycle ergometry; up 12.5 W/min): VO2 at VT (9.3 +/- 0.4 ml/kg/min), maximum VO2 (12.2 +/- 0.7 ml/kg/min), VT in percentage of predicted maximum VO2 (31 +/- 2%), heart rate at VT (95 +/- 4 beats/min), and decrease of dead space-to-tidal volume ratio from rest to VT (33 +/- 1 --> 29 +/- 1). Improvement of VO2 at VT after training (2.2 +/- 0.4 ml/kg/min; p <0.001) was not related to baseline central hemodynamics (r = <0.10 for each), but was greater in patients with a lower baseline VO2 at VT (r = -0.65; p <0.01), peak VO2 (r = -0.66; p <0.01), VT in percentage of predicted maximum VO2 (r = -0.74; p <0.001), heart rate at VT (r = -0.63; p <0.01), and smaller decrease of dead space-to-tidal volume ratio from rest to VT (r = 0.65; p <0.01). Ejection fraction after exercise training (24 +/- 2%) and activity restriction (23 +/- 2%) did not differ significantly compared with baseline, and patient status (heart failure and cardiac rhythm) remained stable. Three parameters accounted for 84% of the variance of improvement in VO2 at VT: VO2 at VT in percent predicted maximum VO2, decrease of dead space-to-tidal volume ratio, and heart rate at VT. The findings suggest that there was a greater increase in VO2 at VT after exercise training in patients with greater peripheral deconditioning at baseline. The improvement was unrelated to central hemodynamics. Clinically stable patients with severe chronic congestive heart failure, potential heart transplant candidates, and those awaiting transplantation may benefit from involvement in a short-term exercise training program.

Exercise↗

PubMed1993

Physical training improves skeletal muscle metabolism in patients with chronic heart failure.

OBJECTIVES: This study investigated the effects of physical training on skeletal muscle metabolism in patients with chronic heart failure. BACKGROUND: Skeletal muscle metabolic abnormalities in patients with chronic heart failure have been associated with exercise intolerance. Muscle deconditioning is a possible mechanism for the intrinsic skeletal muscle metabolic changes seen in chronic heart failure. METHODS: We used phosphorus-31 nuclear magnetic resonance spectroscopy to study muscle metabolism during exercise in 12 patients with stable ischemic chronic heart failure undergoing 8 weeks of home-based bicycle exercise training in a randomized crossover controlled trial. Changes in muscle pH and concentrations of phosphocreatine and adenosine diphosphate (ADP) were measured in phosphorus-31 spectra of calf muscle obtained at rest, throughout incremental work load plantar flexion until exhaustion and during recovery from exercise. Results were compared with those in 15 age-matched control subjects who performed a single study only. RESULTS: Before training, phosphocreatine depletion, muscle acidification and the increase in ADP during the 1st 4 min of plantar flexion exercise were all increased (p < 0.04) compared with values in control subjects. Training produced an increase (p < 0.002) in incremental plantar flexion exercise tolerance. After training, phosphocreatine depletion and the increase in ADP during exercise were reduced significantly (p < 0.003) at all matched submaximal work loads and at peak exercise, although there was no significant change in the response of muscle pH to exercise. After training, changes in ADP were not significantly different from those in control subjects, although phosphocreatine depletion was still greater (p < 0.05) in trained patients than in control subjects. The phosphocreatine recovery half-time was significantly (p < 0.05) shorter after training, although there was no significant change in the half-time of adenosine diphosphate recovery. In untrained subjects, the initial rate of phosphocreatine resynthesis after exercise (a measure of the rate of oxidative adenosine triphosphate [ATP] synthesis) and the inferred maximal rate of mitochondrial ATP synthesis were reduced compared with rates in control subjects (p < 0.003) and both were significantly increased (p < 0.05) by training, so that they were not significantly different from values in control subjects. CONCLUSIONS: The reduction in phosphocreatine depletion and in the increase in ADP during exercise, and the enhanced rate of phosphocreatine resynthesis in recovery (which is independent of muscle mass) indicate that a substantial correction of the impaired oxidative capacity of skeletal muscle in chronic heart failure can be achieved by exercise training.

Adenosine Diphosphate↗

PubMed1998

Randomized crossover study comparing the phosphate-binding efficacy of calcium ketoglutarate versus calcium carbonate in patients on chronic hemodialysis.

The objective of the study was to evaluate the phosphate-binding efficacy, side effects, and cost of therapy of calcium ketoglutarate granulate as compared with calcium carbonate tablets in patients on chronic hemodialysis. The study design used was a randomized, crossover open trial, and the main outcome measurements were plasma ionized calcium levels, plasma phosphate levels, plasma intact parathyroid hormone (PTH) levels, requirements for supplemental aluminum-aminoacetate therapy, patient tolerance, and cost of therapy. Nineteen patients on chronic hemodialysis were treated with a dialysate calcium concentration of 1.25 mmol/L and a fixed alfacalcidol dose for at least 2 months. All had previously tolerated therapy with calcium carbonate. Of the 19 patients included, 10 completed both treatment arms. After 12 weeks of therapy, the mean (+/-SEM) plasma ionized calcium level was significantly lower in the ketoglutarate arm compared with the calcium carbonate arm (4.8+/-0.1 mg/dL v 5.2+/-0.1 mg/dL; P = 0.004), whereas the mean plasma phosphate (4.5+/-0.3 mg/dL v 5.1+/-0.1 mg/dL) and PTH levels (266+/-125 pg/mL v 301+/-148 pg/mL) did not differ significantly between the two treatment arms. Supplemental aluminum-aminoacetate was not required during calcium ketoglutarate treatment, while two patients needed this supplement when treated with calcium carbonate. Five of 17 (29%) patients were withdrawn from calcium ketoglutarate therapy within 1 to 2 weeks due to intolerance (anorexia, vomiting, diarrhea, general uneasiness), whereas the remaining 12 patients did not experience any side effects at all. The five patients with calcium ketoglutarate intolerance all had pre-existing gastrointestinal symptoms; four of them had received treatment with cimetidine or omeprazol before inclusion into the study. Calculations based on median doses after 12 weeks showed that the cost of the therapy in Denmark was 10 times higher for calcium ketoglutarate compared with calcium carbonate (US$6.00/d v US$0.65/d). Calcium ketoglutarate may be an effective and safe alternative to treatment with aluminum-containing phosphate binders in patients on hemodialysis who are intolerant of calcium carbonate or acetate because of hypercalcemia. However, care must be exercised when dealing with patients with pre-existing gastrointestinal discomfort. Due to the high cost of the therapy, calcium ketoglutarate should be used only for selected patients.

Adult↗

PubMed2003

Treatment of chronic constipation with colchicine: randomized, double-blind, placebo-controlled, crossover trial.

OBJECTIVE: Refractory constipation is a common GI complaint seen by physicians in all practice settings. We have previously shown that p.d. colchicine (0.6 mg t.i.d.) increases the number of spontaneous bowel movements, hastens GI transit, and improves GI symptoms in patients with chronic constipation during an 8-wk, open-label therapeutic trial. The aim of this study was to determine if p.d. colchicine will increase spontaneous bowel movements and accelerate colonic transit in patients with idiopathic chronic constipation in a randomized, placebo-controlled, crossover trial. METHODS: A total of 16 patients (15 women, one man) with a mean age of 47 yr (age range 25-89) with chronic idiopathic constipation who were refractory to standard medical therapy participated in the study. Patients randomly received either colchicine 0.6 mg p.o. t.i.d. or an identical placebo p.o. t.i.d. for a total of 4 wk in a double-blind, crossover fashion. Patients recorded their daily number of bowel movements and daily symptoms of daily nausea, abdominal pain, and bloating. Mean colonic transit was calculated at baseline, weeks 6 and 12. RESULTS: Colchicine increased the number of bowel movements and accelerated colonic transit compared with baseline and placebo conditions. There were no significant differences between conditions on ratings of nausea and bloating. During colchicine administration, mean abdominal pain was greater than the baseline or placebo conditions, however, the pain decreased significantly by the last week the patient was on colchicine. CONCLUSION: Colchicine increases the frequency of bowel movements and hastens colonic transit in patients with chronic constipation. Colchicine may be an effective agent available to practitioners to treat a subset of patients with chronic constipation who are refractory to standard medical therapy.

Adult↗

PubMed2006

Influence of posture and muscle length on stretch reflex activity in poststroke patients with spasticity.

OBJECTIVE: To investigate the influence of different positions on stretch reflex activity of knee flexors and extensors measured by electromyography in poststroke patients with spasticity and its expression in the Ashworth Scale. DESIGN: Crossover trial with randomized order of positioning. SETTING: Outpatient rehabilitation center in the Netherlands. PARTICIPANTS: Poststroke patients (N = 19) with lower-limb spasticity. INTERVENTION: Changing position: sitting versus supine. MAIN OUTCOME MEASURES: Root mean square (RMS) values of muscle activity and goniometric parameters, obtained during the pendulum test and passive knee flexion and extension, and Ashworth scores. RESULTS: RMS values of bursts of rectus femoris activity were significantly higher in the supine compared with the sitting position (P = .006). The first burst of vastus lateralis activity during the pendulum test (P = .049) and semitendinous activity during passive stretch (P = .017) were both significantly higher in the supine versus the sitting position. For both the pendulum test and passive movement test, the duration and amplitude of the cyclic movement of the lower leg changed significantly as well. In the supine position, we found significantly higher Ashworth scores for the extensors (P = .001) and lower scores for the flexors (P = .002). CONCLUSIONS: The outcome of clinical and neurophysiologic assessment of spasticity is influenced considerably by subject positioning.

Cross-Over Studies↗

PubMed2003

Medium-chain triglycerides increase energy expenditure and decrease adiposity in overweight men.

OBJECTIVE: The objectives of this study were to compare the effects of diets rich in medium-chain triglycerides (MCTs) or long-chain triglycerides (LCTs) on body composition, energy expenditure, substrate oxidation, subjective appetite, and ad libitum energy intake in overweight men. RESEARCH METHODS AND PROCEDURES: Twenty-four healthy, overweight men with body mass indexes between 25 and 31 kg/m(2) consumed diets rich in MCT or LCT for 28 days each in a crossover randomized controlled trial. At baseline and after 4 weeks of each dietary intervention, energy expenditure was measured using indirect calorimetry, and body composition was analyzed using magnetic resonance imaging. RESULTS: Upper body adipose tissue (AT) decreased to a greater extent (p < 0.05) with functional oil (FctO) compared with olive oil (OL) consumption (-0.67 +/- 0.26 kg and -0.02 +/- 0.19 kg, respectively). There was a trend toward greater loss of whole-body subcutaneous AT volume (p = 0.087) with FctO compared with OL consumption. Average energy expenditure was 0.04 +/- 0.02 kcal/min greater (p < 0.05) on day 2 and 0.03 +/- 0.02 kcal/min (not significant) on day 28 with FctO compared with OL consumption. Similarly, average fat oxidation was greater (p = 0.052) with FctO compared with OL intake on day 2 but not day 28. DISCUSSION: Consumption of a diet rich in MCTs results in greater loss of AT compared with LCTs, perhaps due to increased energy expenditure and fat oxidation observed with MCT intake. Thus, MCTs may be considered as agents that aid in the prevention of obesity or potentially stimulate weight loss.

Adipose Tissue↗

PubMed2003

Beneficiary effect of dietary soy protein on lowering plasma levels of lipid and improving kidney function in type II diabetes with nephropathy.

OBJECTIVE: Heart and renal diseases are two major problems in diabetic patients. Hyperlipidemia is one of the main risk factors of cardiovascular complications in diabetes. The type of protein consumed also affects the changes in renal blood flow, glomerular resistance and renal function in these patients. Hence, this study was undertaken to show the effect of soy protein consumption on lipid profiles and kidney function of diabetic patients with nephropathy, who attended an educational university hospital as well as a private kidney disease clinic in Tehran. SUBJECTS AND METHODS: This crossover randomized clinical trial was conducted on 14 patients who were free of any uncontrolled condition or other renal diseases. The patients were asked to follow a usual nephropathy diet (0.8 g/kg protein, 70% animal and 30% vegetable protein) for 7 weeks. After a washout period of 4 weeks consuming the prestudy diet, subjects were readmitted to repeat the same cycle with a similar diet containing 35% soy protein and 30% vegetable protein. Paired t-test, carryover effect and period effect were used for statistical analysis. RESULT: : There were 10 men and four women whose mean (s.d.) of weight was 70.6 (10.3) kg. Significant reductions were seen in total cholesterol (P<0.01), triglyceride (P<0.002) and LDL-c (P<0.04), urinary urea nitrogen and proteinuria (P<0.001) after soy vs animal protein consumption. There were no significant changes in HDL-c, LDL-c/HDL-c levels. We also saw a favorable effect on renal function. CONCLUSION: Soy inclusion in the diet can modify the risk factors of heart disease and improve kidney function in these patients.

Cardiovascular Diseases↗

PubMed2001

Add-on angiotensin receptor blockade with maximized ACE inhibition.

BACKGROUND: Prolonged angiotensin-converting enzyme (ACE) inhibitor therapy leads to angiotensin I (Ang I) accumulation, which may "escape" ACE inhibition, generate Ang II, stimulate the Ang II subtype 1 (AT1) receptor, and exert deleterious renal effects in patients with chronic renal diseases. We tested the hypothesis that losartan therapy added to a background of chronic (>3 months) maximal ACE inhibitor therapy (lisinopril 40 mg q.d.) will result in additional Ang II antagonism in patients with proteinuric chronic renal failure with hypertension. METHODS: Sixteen patients with proteinuric moderately advanced chronic renal failure completed a two-period, crossover, randomized controlled trial. Each period was one month with a two-week washout between periods. In one period, patients received lisinopril 40 mg q.d. along with other antihypertensive therapy, and in the other, losartan 50 mg q.d. was added to the previously mentioned regimen. Hemodynamic measurements included ambulatory blood pressure monitoring (ABP; Spacelabs 90207), glomerular filtration rate (GFR) with iothalamate clearances and cardiac outputs by acetylene helium rebreathing technique. Supine plasma renin activity and plasma aldosterone and 24-hour urine protein were measured in all patients. RESULTS: Twelve patients had diabetic nephropathy, and four had chronic glomerulonephritis. The mean age (+/- SD) was 53 +/- 9 years. The body mass index was 38 +/- 5.7 kg/m(2), and all except two patients were males. Seated cuff blood pressure was 156 +/- 18/88 +/- 12 mm Hg. The pulse rate was 77 +/- 11 per min, and the cardiac index was 2.9 +/- 0.5 L/min/m(2). Mean log 24-hour protein excretion/g creatinine or overall ABPs did not change. Mean placebo subtracted, losartan-attributable change in protein excretion was +1% (95% CI, -20% to 28%, P = 0.89). Similarly, the change in systolic ambulatory blood pressure (ABP) was 4.6 mm Hg (-5.7 to 14.9, P = 0.95), and diastolic ABP was 1.5 mm Hg (-4.5 to 7.6, P = 0.59). No change was seen in cardiac output. However, there was a mean 14% increase (95% CI, 3 to 26%, P = 0.017) in GFR attributable to losartan therapy. A concomitant fall in plasma renin activity by 32% was seen (95% CI, -15%, - 45%, P = 0.002). No hyperkalemia, hypotension, or acute renal failure occurred in the trial. These results were not attributable to sequence or carryover effects. CONCLUSIONS: Add-on losartan therapy did not improve proteinuria or ABP over one month of add on therapy. Improvement of GFR and fall in plasma renin activity suggest that renal hemodynamic and endocrine changes are more sensitive measures of AT1 receptor blockade. Whether add-on AT1 receptor blockade causes antiproteinuric effects or long-term renal protection requires larger and longer prospective, randomized controlled trials.

Adolescent↗

PubMed2002

Add-on angiotensin II receptor blockade lowers urinary transforming growth factor-beta levels.

Progression of renal failure, despite renoprotection with angiotensin-converting enzyme (ACE) inhibitors in patients with proteinuric nephropathies, may be caused by persistent renal production of transforming growth factor-beta1 (TGF-beta1) through the angiotensin II subtype 1 (AT1) receptors. We tested the hypothesis that AT1-receptor blocker therapy added to a background of chronic maximal ACE inhibitor therapy will result in a reduction in urinary TGF-beta1 levels in such patients. Sixteen patients completed a two-period, crossover, randomized, controlled trial, details of which have been previously reported. All patients were administered lisinopril, 40 mg/d, with either losartan, 50 mg/d, or placebo. Blood pressure (BP) was measured using a 24-hour ambulatory BP monitor. Overnight specimens of urine were analyzed for urine TGF-beta1, protein, and creatinine concentrations. Mean age of the study population was 53 +/- 9 (SD) years; body mass index, 38 +/- 5.7 kg/m2; seated BP, 156 +/- 18/88 +/- 12 mm Hg; and urine protein excretion, 3.6 +/- 0.71 g/g of creatinine. Twelve patients had diabetic nephropathy, and the remainder had chronic glomerulonephritis. At baseline, urinary TGF-beta1 levels were significantly increased in the study population compared with healthy controls (13.2 +/- 1.2 versus 1.7 +/- 1.1 ng/g creatinine; P < 0.001). There was a strong correlation between baseline urine protein excretion and urinary TGF-beta1 level (r2 = 0.53; P = 0.001), as well as systolic BP and urinary TGF-beta1 level (r2 = 0.57; P < 0.001). After 4 weeks of add-on losartan therapy, there was a 38% (95% confidence interval [CI], 16% to 55%) decline in urinary TGF-beta1 levels (13.3 [95% CI, 11.4 to 15.5] to 8.2 pg/mg creatinine [95% CI, 6.2 to 10.7]). The reduction in urinary TGF-beta1 levels occurred independent of changes in mean urinary protein excretion or BP. Thus, proteinuric patients with renal failure, despite maximal ACE inhibition, had increased urinary levels of TGF-beta1 that improved over 1 month of add-on therapy with losartan. We speculate that dual blockade with losartan and an ACE inhibitor may provide additional renoprotection by decreasing renal production of TGF-beta1.

Angiotensin Receptor Antagonists↗

PubMed2000

Skin irritation and dryness associated with two hand-hygiene regimens: soap-and-water hand washing versus hand antisepsis with an alcoholic hand gel.

OBJECTIVE: To compare the frequency of skin irritation and dryness associated with using an alcoholic-hand-gel regimen for hand antisepsis versus using soap and water for hand washing. DESIGN: Prospective randomized trial with crossover design. Irritation and dryness of nurses' hands were evaluated by self-assessment and by visual assessment by a study nurse. Epidermal water content of the dorsal surface of nurses' hands was estimated by measuring electrical capacitance of the skin. SETTING: Miriam Hospital, a 200-bed university-affiliated teaching hospital. PARTICIPANTS: Thirty-two nurses working on three hospital wards participated in the trial, which lasted 6 weeks. RESULTS: Self-assessment scores of skin irritation and dryness decreased slightly during the 2 weeks when nurses used the alcoholic-hand-gel regimen (mean baseline score, 2.72; mean final score, 2.0; P=.08) but increased substantially during the 2 weeks when nurses used soap and water (mean baseline score, 2.0; mean final score, 4.8; P<.0001). Visual assessment scores by the study nurse of skin irritation and dryness did not change significantly when the alcoholic-hand-gel regimen was used (mean baseline and final scores were both 0.55), but scores increased substantially when nurses used soap and water (baseline score, 0.59; mean final score, 1.21; P=.05). Epidermal water content of the dorsal surface of nurses' hands changed little when the alcoholic-hand-gel regimen was used (mean+/-standard deviation baseline electrical capacitance reading, 24.8+/-6.8; mean final reading, 25.7+/-7.3), but decreased significantly (skin became dryer) with soap-and-water hand washing (mean baseline, 25.9+/-7.5; mean final reading, 20.5+/-5.4; P=.0003). CONCLUSIONS: Hand antisepsis with an alcoholic-hand-gel regimen was well tolerated and did not result in skin irritation and dryness of nurses' hands. In contrast, skin irritation and dryness increased significantly when nurses washed their hands with the unmedicated soap product available in the hospital. Newer alcoholic hand gels that are tolerated better than soap may be more acceptable to staff and may lead to improved hand-hygiene practices.

Antisepsis↗

PubMed2004

Midodrine appears to be safe and effective for dialysis-induced hypotension: a systematic review.

BACKGROUND: Dialysis-induced hypotension is an important complication of haemodialysis. Midodrine is an oral alpha-1 agonist that has been used in several small studies to prevent intradialytic hypotension (IDH). METHODS: The authors searched MEDLINE, EMBASE, ASN conference proceedings, and references of potentially relevant articles, and contacted industry (Shire Pharmaceuticals) for unpublished data. Observational studies, randomized controlled trials, crossover studies and pre- and post-intervention design studies with >/=5 haemodialysis patients were included. Study outcomes assessed were: hypotensive symptoms, changes in systolic and/or diastolic blood pressure, dry weight and length of stay after treatment. Data were abstracted on: study design, patient characteristics, intradialytic changes in blood pressure, nadir blood pressure and symptom improvement with midodrine. Thirty-seven full text articles were retrieved and nine met the selection criteria, in addition to one unpublished study. Midodrine dosing regimens ranged from 2.5 to 10 mg of midodrine given 15-30 min before dialysis. RESULTS: Post-dialysis systolic blood pressure was higher by 12.4 mmHg [95% confidence interval (CI) 7.5-17.7] and diastolic pressure was higher by 7.3 mmHg (95% CI 3.7-10.9) during midodrine treatment vs control. Likewise, the nadir systolic blood pressure was higher by 13.3 mmHg (95% CI 8.6-18.0), with a difference in nadir diastolic pressure of 5.9 mmHg (95% CI 2.7-9.1). Six of 10 studies report improvement in symptoms of IDH, and there were no reported serious adverse events ascribed to midodrine. CONCLUSIONS: This systematic review would suggest that midodrine has a role in the therapy of haemodialysis patients experiencing IDH. This conclusion must be viewed with caution, however, given the quality and sample size of the studies included in this review.

Adrenergic alpha-Agonists↗

PubMed2001

Airway pressure release ventilation in pediatrics.

OBJECTIVES: The purpose of this study was to determine the effectiveness of airway pressure release ventilation in children. DESIGN: Prospective, randomized, crossover clinical trial. SETTING: This study was conducted in our 33-bed pediatric intensive care unit at The Children's Hospital of Philadelphia. PATIENTS: Patients requiring mechanical ventilatory support and weighing >8 kg were considered for enrollment. Patients were excluded if they required mechanical ventilatory support for >7 days or required >.50 Fio(2) for >7 days before enrollment. Patients with documented obstructive airway disease and congenital or acquired heart disease were excluded as well. INTERVENTIONS: Each patient received both volume-controlled synchronized intermittent mechanical ventilation (SIMV) and airway pressure release ventilation (APRV) via the Drager Evita ventilator (Drager, Lubeck, Germany). Measurements were obtained after the patient was stabilized on each ventilation mode. Stabilization was defined as oxygenation, ventilation, hemodynamic variables, and patient comfort within the acceptable range for each patient as determined by the bedside physician. After measurements were obtained on the initial mode of ventilation, the subjects crossed over to the alternative study mode. Stabilization was again achieved, and measurements were repeated. After completion of the second study measurements, patients were placed on the ventilation modality preferred by the bedside clinician and were followed through weaning and extubation. Measurements: Vital signs, airway pressures, minute ventilation, Spo(2), and E(T)CO(2) were recorded at enrollment and at each study condition. MAIN RESULTS: APRV provided similar ventilation, oxygenation, mean airway pressure, hemodynamics, and patient comfort as SIMV. Inspiratory airway pressures were lower with APRV when compared with SIMV. CONCLUSIONS: Using APRV in children with mild to moderate lung disease resulted in comparable levels of ventilation and oxygenation at significantly lower inspiratory peak and plateau pressures. Based on these findings, we plan to evaluate APRV in children with significant lung disease.

Journal Article↗

PubMed2003

Testosterone increases in men after a low dose of alcohol.

BACKGROUND: Heavy acute alcohol drinking decreases blood testosterone in men due to an effect on the testicular level. An acute increase in blood testosterone levels after a low alcohol dose has, however, recently been reported in women. The objective of this investigation was to study the effect of a low alcohol dose on testosterone in men and further elucidate the mechanism behind the effect by using 4-methylpyrazole, an inhibitor of alcohol metabolism. METHODS: A double-blind placebo-controlled interventional crossover trial in random order (n = 13). RESULTS: After intake of alcohol (0.5 g/kg, 10% w/v), an acute increase in plasma testosterone (from 13.5 +/- 1.2 nmol/liter to 16.0 +/- 1.6 nmol/liter, mean +/- SEM; p < 0.05), a decrease in androstenedione (from 5.1 +/- 0.4 nmol/liter to 4.0 +/- 0.3 nmol/liter; p < 0.05), and an increase in the testosterone:androstenedione ratio (from 2.8 +/- 0.3 to 4.2 +/- 0.4; p < 0.01) were observed. The effects were not observed during pretreatment with 4-methylpyrazole (10-15 mg/kg orally), which inhibited the ethanol elimination rate by 37 +/- 3%. CONCLUSIONS: Alcohol intake affects the androgen balance in men through an effect mediated by the alcohol-induced change in the redox state in the liver.

Adult↗