Double-blind Randomized Manner Research Articles

Capacitive Neuromodulation via Material-Based Passive Interaction: Efficacy in Motor Function Improvement in Parkinson Disease.

A non-invasive and non-pharmacological approach is evaluated for the proprioceptive and postural improvement of PD subjects. The authors evaluated the effectiveness of a class I medical device according to EU regulation 745/2017 designed to develop the mechanism of action based on the modulation of action potentials, which occurs in prevalent pathways of the afferent peripheral nervous system efferent in subjects with spasticity. The present observational study, structured in a double-blind randomized manner, therefore, had the main aim of evaluating the ability of the device to improve on the motor and proprioceptive function of PD patients. This study was based on the instrumented gait analysis performed according to the Timed Up and Go (TUG) test procedure, as well as using a fall risk assessment in accordance with the Berg Balance Scale (BBS) procedures. This study involved 25 participants in the active group (no placebo) and 25 in the non-active group (placebo), the latter to whom non-functional devices were applied, but in every respect identical to the functional devices applied to the 25 patients in the no placebo group. Data analysis was conducted using statistical methodologies for statistics, the statistical significance of the results for the observed samples and the interdependence between the measured variables. The study of the mechanism of action based on the remodulation of action potentials was preliminary conducted through numerical modeling of the Hodgkin-Huxley axon, modified by introducing the influence of the capacitive device applied in clinical tests into the validated model to target the dielectric properties of materials constituting the passive sensor. The use of the neuromodulation device promises observable improvements in motor function among PD patients, including increased limb mobility and greater postural stability.

Comparison of Monopolar Review to Fixed Parameter Fractionation in Deep Brain Stimulation.

Technological advancements in deep brain stimulation (DBS) require methodological changes in programming. Fractionalization poses significant practical challenges for the most common approach for assessing DBS efficacy, monopolar review (MR). Two DBS programming methods: MR and fixed parameter vertical and horizontal fractionalization (FPF) were compared. A two-phase process of vertical and horizontal FPF was performed. MR was conducted thereafter. After a short wash-out period, both optimal configurations determined by MR and FPF were tested in a double-blind randomized manner. Seven PD patients were enrolled, providing 11 hemispheres to compare the two conditions. In all subjects, the blinded examiner selected a directional or fractionalization configuration. There was no significant difference in clinical benefits between MR and FPF. FPF was the preferred method for initial programming as selected by subject and clinician. FPF programming is a viable and efficient methodology that may be incorporated into clinical practice.

Effects of Caffeine Intake on Endurance Running Performance and Time to Exhaustion: A Systematic Review and Meta-Analysis.

Caffeine (1,3,7-trimethylxanthine) is one of the most widely consumed performance-enhancing substances in sport due to its well-established ergogenic effects. The use of caffeine is more common in aerobic-based sports due to the ample evidence endorsing the benefits of caffeine supplementation on endurance exercise. However, most of this evidence was established with cycling trials in the laboratory, while the effects of the acute intake of caffeine on endurance running performance have not been properly reviewed and meta-analyzed. The purpose of this study was to perform a systematic review and meta-analysis of the existing literature on the effects of caffeine intake on endurance running performance. A systematic review of published studies was performed in four different scientific databases (Medline, Scopus, Web of Science, and SportDiscus) up until 5 October 2022 (with no year restriction applied to the search strategy). The selected studies were crossover experimental trials in which the ingestion of caffeine was compared to a placebo situation in a single- or double-blind randomized manner. The effect of caffeine on endurance running was measured by time to exhaustion or time trials. We assessed the methodological quality of each study using Cochrane’s risk-of-bias (RoB 2) tool. A subsequent meta-analysis was performed using the random effects model to calculate the standardized mean difference (SMD) estimated by Hedges’ g and 95% confidence intervals (CI). Results: A total of 21 randomized controlled trials were included in the analysis, with caffeine doses ranging between 3 and 9 mg/kg. A total of 21 studies were included in the systematic review, with a total sample of 254 participants (220 men, 19 women and 15 participants with no information about gender; 167 were categorized as recreational and 87 were categorized as trained runners.). The overall methodological quality of studies was rated as unclear-to-low risk of bias. The meta-analysis revealed that the time to exhaustion in running tests was improved with caffeine (g = 0.392; 95% CI = 0.214 to 0.571; p < 0.001, magnitude = medium). Subgroup analysis revealed that caffeine was ergogenic for time to exhaustion trials in both recreational runners (g = 0.469; 95% CI = 0.185 to 0.754; p = 0.001, magnitude = medium) and trained runners (g = 0.344; 95% CI = 0.122 to 0.566; p = 0.002, magnitude = medium). The meta-analysis also showed that the time to complete endurance running time trials was reduced with caffeine in comparison to placebo (g = −0.101; 95% CI = −0.190 to −0.012, p = 0.026, magnitude = small). In summary, caffeine intake showed a meaningful ergogenic effect in increasing the time to exhaustion in running trials and improving performance in running time trials. Hence, caffeine may have utility as an ergogenic aid for endurance running events. More evidence is needed to establish the ergogenic effect of caffeine on endurance running in women or the best dose to maximize the ergogenic benefits of caffeine supplementation.

Changes in Lipid Profile, Liver Enzymes and Inflammatory Factors Following Oral Supplementation with Propolis in Patients with Type 2 Diabetes

Objective: Nutritional ingredients with anti-inflammatory and antioxidant properties such as flavonoids and phenolic acids have been reported in propolis. The present study investigated the effect of propolis supplements on lipid metabolism, liver enzymes, and inflammatory factors in patients with type 2 diabetes. Materials and methods: This clinical trial was performed in a double-blind randomized manner with two parallel intervention (n = 30) and placebo (n = 30) groups. Each group received a capsule (propolis or placebo) of 500 mg 3 times a day for 8 weeks. The lipid profile, liver enzymes, and inflammatory factors were measured at the beginning and end of the study. Statistical analysis was performed by using SPSS software. Results: The mean of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL) levels decreased significantly at the end of the study in the intervention group (p &lt; 0.05). Also, the serum high-density lipoprotein cholesterol (HDL) level increased significantly in this group (p &lt; 0.05). Propolis supplementation significantly decreased C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α) (p &lt; 0.05). Also, propolis decreased the mean of aspartate transaminase (AST) and alanine transaminase (ALT) levels, but it was not significant (p &gt; 0.05). Conclusions: Propolis supplementation can be helpful as a dietary supplement in patients with type 2 diabetes by improving status of lipid profile and inflammatory factors in diabetic patients.

Affective modulation of the associative-limbic subthalamic nucleus: deep brain stimulation in obsessive\u2013compulsive disorder

Affective states underlie daily decision-making and pathological behaviours relevant to obsessive–compulsive disorders (OCD), mood disorders and addictions. Deep brain stimulation targeting the motor and associative-limbic subthalamic nucleus (STN) has been shown to be effective for Parkinson’s disease (PD) and OCD, respectively. Cognitive and electrophysiological studies in PD showed responses of the motor STN to emotional stimuli, impairments in recognition of negative affective states and modulation of the intensity of subjective emotion. Here we studied whether the stimulation of the associative-limbic STN in OCD influences the subjective emotion to low-intensity positive and negative images and how this relates to clinical symptoms. We assessed 10 OCD patients with on and off STN DBS in a double-blind randomized manner by recording ratings of valence and arousal to low- and high-intensity positive and negative emotional images. STN stimulation increased positive ratings and decreased negative ratings to low-intensity positive and negative stimuli, respectively, relative to off stimulation. We also show that the change in severity of obsessive–compulsive symptoms pre- versus post-operatively interacts with both DBS and valence ratings. We show that stimulation of the associative-limbic STN might influence the negative cognitive bias in OCD and decreasing the negative appraisal of emotional stimuli with a possible relationship with clinical outcomes. That the effect is specific to low intensity might suggest a role of uncertainty or conflict related to competing interpretations of image intensity. These findings may have implications for the therapeutic efficacy of DBS.

Structural similarity networks predict clinical outcome in early-phase psychosis.

Despite recent advances, there is still a major need for prediction of treatment success in schizophrenia, a condition long considered a disorder of dysconnectivity in the brain. Graph theory provides a means to characterize the connectivity in both healthy and abnormal brains. We calculated structural similarity networks in each participant and hypothesized that the "hubness", i.e., the number of edges connecting a node to the rest of the network, would be associated with clinical outcome. This prospective controlled study took place at an academic research center and included 82 early-phase psychosis patients (23 females; mean age [SD] = 21.6 [5.5] years) and 58 healthy controls. Medications were administered in a double-blind randomized manner, and patients were scanned at baseline prior to treatment with second-generation antipsychotics. Symptoms were assessed with the Brief Psychiatric Rating Scale at baseline and over the course of 12 weeks. Nodal degree of structural similarity networks was computed for each subject and entered as a predictor of individual treatment response into a partial least squares (PLS) regression. The model fit was significant in a permutation test with 1000 permutations (P = 0.006), and the first two PLS regression components explained 29% (95% CI: 27; 30) of the variance in treatment response after cross-validation. Nodes loading strongly on the first PLS component were primarily located in the orbito- and prefrontal cortex, whereas nodes loading strongly on the second PLS component were primarily located in the superior temporal, precentral, and middle cingulate cortex. These data suggest a link between brain network morphology and clinical outcome in early-phase psychosis.

The Effect of a Dietary Nitrate Supplementation in the Form of a Single Shot of Beetroot Juice on Static and Dynamic Apnea Performance.

The purpose of the present study was to assess the effects of acute nitrate ([Formula: see text])-rich beetroot juice (BRJ) supplementation on peripheral oxygen saturation (SpO2), heart rate (HR), and pulmonary gas exchange during submaximal static and dynamic apnea. Nine (six males and three females) trained apneists (age: 39.6 ± 8.2years, stature: 170.4 ± 11.5cm, and body mass: 72.0 ± 11.5kg) performed three submaximal static apneas at 60%, 70%, and 80% of the participant's current reported personal best time, followed by three submaximal (∼75% or personal best distance) dynamic apneas following the consumption of either a 70-ml concentrated BRJ (7.7mmol [Formula: see text]) or a [Formula: see text]-depleted placebo (PLA; 0.1mmol [Formula: see text]) in double-blind randomized manner. HR and SpO2 were measured via fingertip pulse oximetry at the nadir, and online gas analysis was used to assess pulmonary oxygen uptake ([Formula: see text]) during recovery following breath-holds. There were no differences (p < .05) among conditions for HR (PLA = 59 ± 11bpm and BRJ = 61 ± 12bpm), SpO2 (PLA = 83% ± 14% and BRJ = 84% ±9%), or [Formula: see text] (PLA = 1.00 ± 0.22L/min and BRJ = 0.97 ± 0.27L/min). The consumption of 7.7mmol of beetroot juice supplementation prior to a series of submaximal static and dynamic apneas did not induce a significant change in SpO2, HR, and [Formula: see text] when compared with placebo. Therefore, there is no apparent physiological response that may benefit free divers as a result of the supplementation.

The effect of intravenous magnesium sulfate infusion on sensory spinal block and postoperative pain score in abdominal hysterectomy.

Aim. The aim of this study was to investigate the effect of i.v. infusion of magnesium sulphate during spinal anesthesia on duration of spinal block and postoperative pain. Methods. Forty ASA physical status I and status II, aged between 18 and 65, female patients undergoing abdominal hysterectomy under spinal anesthesia were enrolled in this study. Patients in the magnesium group (Group M, n = 20) received magnesium sulphate 65 mg kg−1 infusion in 250 mL 5% dextrose at 3.5 mL/min rate, and control group (Group C, n = 20) received at the same volume of saline during operation in a double-blind randomized manner. Duration of sensory and motor block, systolic, diastolic, and mean arterial blood pressures, heart rates, pain scores (VAS values), and side effects were recorded for each patient. Blood and CSF samples were taken for analysis of magnesium concentrations. Results. Regression of sensorial block was longer in Group M when compared with that in Group C (175 ± 39 versus 136 ± 32 min) (P < 0.01). The VAS scores were lower in Group M than those in Group C at the 2 time points postoperatively (P < 0.01). Conclusion. 65 mg kg−1 of magnesium sulphate i.v. infusion under spinal anesthesia prolongs spinal sensorial block duration and decreases pain VAS scores without complication in patients undergoing abdominal hysterectomy.

Effect of Antioxidant Supplementation on Exercise-Induced Cardiac Troponin Release in Cyclists: A Randomized Trial

BackgroundCardiac troponin is the biochemical gold standard to diagnose acute myocardial infarction. Interestingly however, elevated cardiac troponin concentrations are also frequently observed during and after endurance-type exercise. Oxidative stress associated with prolonged exercise has been proposed to contribute to cardiac troponin release. Therefore, the aim of this study was to assess the effect of 4 week astaxanthin supplementation (a potent cartenoid antioxidant) on antioxidant capacity and exercise-induced cardiac troponin release in cyclists.MethodsThirty-two well-trained male cyclists (age 25±5, weight 73±7 kg, maximum O2 uptake 60±5 mL·kg−1·min−1, Wmax 5.4±0.5 W·kg−1; mean ± SD) were repeatedly subjected to a laboratory based standardized exercise protocol before and after 4 weeks of astaxanthin (20 mg/day), or placebo supplementation in a double-blind randomized manner. Blood samples were obtained at baseline, at 60 min of cycling and immediately post-exercise (≈ 120 min).ResultsThe pre-supplementation cycling trial induced a significant rise of median cardiac troponin T concentrations from 3.2 (IQR 3.0–4.2) to 4.7 ng/L (IQR 3.7–6.7), immediately post-exercise (p<0.001). Four weeks of astaxanthin supplementation significantly increased mean basal plasma astaxanthin concentrations from non-detectable values to 175±86 µg·kg−1. However, daily astaxanthin supplementation had no effect on exercise-induced cardiac troponin T release (p = 0.24), as measured by the incremental area under the curve. Furthermore, the elevation in basal plasma astaxanthin concentrations was not reflected in changes in antioxidant capacity markers (trolox equivalent antioxidant capacity, uric acid, and malondialdehyde). Markers of inflammation (high-sensitivity C-reactive protein) and exercise-induced skeletal muscle damage (creatine kinase) were equally unaffected by astaxanthin supplementation.ConclusionDespite substantial increases in plasma astaxanthin concentrations, astaxanthin supplementation did not improve antioxidant capacity in well-trained cyclists. Accordingly, exercise-induced cardiac troponin T concentrations were not affected by astaxanthin supplementation.Trial registrationClinicalTrials.gov NCT01241877

Preexercise Galactose and Glucose Ingestion on Fuel Use during Exercise

This study determined the effect of ingesting galactose and glucose 30 min before exercise on exogenous and endogenous fuel use during exercise. Nine trained male cyclists completed three bouts of cycling at 60% W(max) for 120 min after an overnight fast. Thirty minutes before exercise, the cyclists ingested a fluid formulation containing placebo, 75 g of galactose (Gal), or 75 g of glucose (Glu) to which (13)C tracers had been added, in a double-blind randomized manner. Indirect calorimetry and isotope ratio mass spectrometry were used to calculate fat oxidation, total carbohydrate (CHO) oxidation, exogenous CHO oxidation, plasma glucose oxidation, and endogenous liver and muscle CHO oxidation rates. Peak exogenous CHO oxidation was significantly higher after Glu (0.68 ± 0.08 g.min(-1), P < 0.05) compared with Gal (0.44 ± 0.02 g.min(-1)); however, mean rates were not significantly different (0.40 ± 0.03 vs. 0.36 ± 0.02 g.min(-1), respectively). Glu produced significantly higher exogenous CHO oxidation rates during the initial hour of exercise (P < 0.01), whereas glucose rates derived from Gal were significantly higher during the last hour (P < 0.01). Plasma glucose and liver glucose oxidation at 60 min of exercise were significantly higher for Glu (1.07 ± 0.1 g.min(-1), P < 0.05, and 0.57 ± 0.08 g.min(-1), P < 0.01) compared with Gal (0.64 ± 0.05 and 0.29 ± 0.03 g.min(-1), respectively). There were no significant differences in total CHO, whole body endogenous CHO, muscle glycogen, or fat oxidation between conditions. The preexercise consumption of Glu provides a higher exogenous source of CHO during the initial stages of exercise, but Gal provides the predominant exogenous source of fuel during the latter stages of exercise and reduces the reliance on liver glucose.

Preliminary findings on the interactive effects of IV ethanol and IV nicotine on human behavior and cognition: a laboratory study.

There are mixed reports on nicotine's effects on alcohol-induced impairment in cognitive performance and behavior in humans. The main objective of this study was to characterize the interactive effects of acute intravenous (IV) alcohol and nicotine administration on behavior and cognition in healthy nonsmokers. Healthy subjects aged 21-44 years participated in 3 test days. On each test day, they received in a double-blind randomized manner one of three IV alcohol infusion conditions using a "clamp": placebo, targeted breathalyzer of 40 mg%, or targeted breathalyzer of 80 mg%. Alcohol infusion was delivered over 20 min and lasted for 120 min. They also received both placebo and active nicotine in a fixed order delivered intravenously. Placebo nicotine was delivered first over 10 min at the timepoint when the breath alcohol was "clamped"; active nicotine (1.0 mcg/kg/min) was delivered for 10 min, 70 min after the alcohol infusion was clamped. Subjective effects of alcohol were measured using the Biphasic Alcohol Effects Scale and the Number of Drinks Scale. Cognitive inhibition and attention were measured by the Continuous Performance Task-Identical Pairs and working memory by the Rey Auditory Verbal Learning Task (RAVLT). Nicotine significantly reversed subjective intoxication and sedation of alcohol at the low dose. Alcohol impaired performance on the RAVLT, and nicotine further impaired verbal learning and recall at both doses of alcohol. The data showed that nicotine had an effect on subjective alcohol effects but did not reverse and actually worsened alcohol-induced deficits in memory.

Prospective randomized double-blind trial of bilateral thalamic deep brain stimulation in adults with Tourette syndrome

The severity of Tourette syndrome (TS) typically peaks just before adolescence and diminishes afterward. In some patients, however, TS progresses into adulthood, and proves to be medically refractory. The authors conducted a prospective double-blind crossover trial of bilateral thalamic deep brain stimulation (DBS) in five adults with TS. Bilateral thalamic electrodes were implanted. An independent programmer established optimal stimulator settings in a single session. Subjective and objective results were assessed in a double-blind randomized manner for 4 weeks, with each week spent in one of four states of unilateral or bilateral stimulation. Results were similarly assessed 3 months after unblinded bilateral stimulator activation while repeated open programming sessions were permitted. In the randomized phase of the trial, a statistically significant (p < 0.03, Friedman exact test) reduction in the modified Rush Video-Based Rating Scale score (primary outcome measure) was identified in the bilateral on state. Improvement was noted in motor and sonic tic counts as well as on the Yale Global Tic Severity Scale and TS Symptom List scores (secondary outcome measures). Benefit was persistent after 3 months of open stimulator programming. Quality of life indices were also improved. Three of five patients had marked improvement according to all primary and secondary outcome measures. Bilateral thalamic DBS appears to reduce tic frequency and severity in some patients with TS who have exhausted other available means of treatment.

Prospective randomized double-blind trial of bilateral thalamic deep brain stimulation in adults with Tourette syndrome

Object The severity of Tourette syndrome (TS) typically peaks just before adolescence and diminishes afterward. In some patients, however, TS progresses into adulthood, and proves to be medically refractory. The authors conducted a prospective double-blind crossover trial of bilateral thalamic deep brain stimulation (DBS) in five adults with TS. Methods Bilateral thalamic electrodes were implanted. An independent programmer established optimal stimulator settings in a single session. Subjective and objective results were assessed in a double-blind randomized manner for 4 weeks, with each week spent in one of four states of unilateral or bilateral stimulation. Results were similarly assessed 3 months after unblinded bilateral stimulator activation while repeated open programming sessions were permitted. Results In the randomized phase of the trial, a statistically significant (p < 0.03, Friedman exact test) reduction in the modified Rush Video-Based Rating Scale score (primary outcome measure) was identified in the bilateral on state. Improvement was noted in motor and sonic tic counts as well as on the Yale Global Tic Severity Scale and TS Symptom List scores (secondary outcome measures). Benefit was persistent after 3 months of open stimulator programming. Quality of life indices were also improved. Three of five patients had marked improvement according to all primary and secondary outcome measures. Conclusions Bilateral thalamic DBS appears to reduce tic frequency and severity in some patients with TS who have exhausted other available means of treatment.

A double-blind, randomized study on platelet aggregation in patients treated with a daily dose of 150 or 75 mg of clopidogrel for 30 days

We sought to test whether an increase in the clopidogrel maintenance dose results in increased inhibition of platelet aggregation. Sixty patients after pre-treatment with 600 mg of clopidogrel and within 12 h after successful PCI were included in this trial. They were allocated to receive one of two clopidogrel daily maintenance doses (75 or 150 mg) for 30 days in a double-blind randomized manner. Platelet function was evaluated 30 days after the intervention with optical aggregometry and with a new point-of-care test (VerifyNowtrade mark P2Y12 assay). Maximal 5 microM ADP-induced platelet aggregation 30 days after PCI in the group treated with 150 mg/day clopidogrel (45.1 +/- 20.9%) was significantly lower than in the group treated with 75 mg/day (65.3 +/- 12.1%; P < 0.001). The VerifyNowtrade mark P2Y12 assay also indicated a higher degree of platelet function inhibition in the group treated with 150 mg/day (60.0 +/- 72.0 P2Y12 Reaction Units) than in the group treated with 75 mg/day (117.0 +/- 64.3 P2Y12 Reaction Units; P = 0.004). Administration of a 150 mg oral maintenance dose of clopidogrel results in more intense inhibition of platelet aggregation than administration of the currently recommended 75 mg maintenance dose.

The effects of Botulinum Toxin type A on capsaicin-evoked pain, flare, and secondary hyperalgesia in an experimental human model of trigeminal sensitization

The trigeminovascular system is involved in migraine. Efficacy of Botulinum Toxin type A (BoNT-A) in migraine has been investigated in clinical studies but the mechanism of action remains unexplored. It is hypothesized that BoNT-A inhibits peripheral sensitization of nociceptive fibers and indirectly reduces central sensitization. We examined the effect of intramuscular injection of BoNT-A on an experimental human model of trigeminal sensitization induced by intradermal capsaicin injection to the forehead. BoNT-A (BOTOX ®) or saline was injected intramuscularly in precranial, neck and shoulder muscles to 32 healthy male volunteers in a double blind-randomized manner. Intradermally capsaicin-induced pain, flare and secondary hyperalgesia were obtained before and 1, 4 and 8 weeks after the above treatments. A significant suppressive effect of BoNT-A on pain, flare and hyperalgesia area was observed. The pain intensity area was significantly smaller in BoNT-A group (9.16 ± 0.83 cm × s) compared to saline group (15.41 ± 0.83 cm × s) ( P = 0.011). The flare area was also reduced significantly in BoNT-A group (29.81 ± 0.69 cm 2) compared to saline group (39.71 ± 0.69 cm 2) ( P < 0.001). Similarly, the mean area of secondary hyperalgesia was significantly smaller in BoNT-A group (4.25 ± 0.91 cm 2) compared to saline group (7.03 ± 0.91 cm 2) ( P = 0.040). Post hoc analysis showed significant differences across the trials with a remarkable suppression effect of BoNT-A on capsaicin-induced sensory and vasomotor reactions as early as week1 ( P < 0.001). BoNT-A presented suppressive effects on the trigeminal/cervical nociceptive system activated by intradermal injection of capsaicin to the forehead. The effects are suggested to be caused by a local peripheral effect of BoNT-A on cutaneous nociceptors.

The Cardiovascular Effects of Thoracic Bolus Epidural Injection of Lidocaine, Morphine and Fentanyl during Sevoflurane General Anesthesia

Background: Sevoflurane is an inhalational anesthetic that produces rapid induction, emergence and little cardiovascular depression. Elevated sympathetic activity during surgery produces undesirable effects on the cardiovascular system, such as hypertension, tachycardia or arrhythmias. So combined general and epidural anesthesia have been used recently for the operation, especially the abdominal surgery. This study was performed to evaluate the cardiovascular effects of thoracic epidural anesthesia during sevoflurane general anesthesia. Methods: Forty patients of ASA class 1-2 undergoing elective subtotal gastrectomy were divided into 5 groups. Thoracic epidural bolus injection was administered via an epidural catheter during sevoflurane general anesthesia in a double-blind random manner: Group 1; normal saline (N/S) 10 ml (placebo), Group 2; morphine 0.1 mg/kg mixed with N/S in 10 ml, Group 3; fentanyl 1 mcg/kg mixed with N/S in 10 ml, Group 4; 1% lidocaine 10 ml, and Group 5; 1% lidocaine 10 ml mixed with morphine 0.1 mg/kg and fentanyl 1 mcg/kg. Systolic and diastolic blood pressures, pulse rates, peripheral oxygen saturation levels (Sp) and end-tidal carbon dioxide partial pressures (ETC) were measured every 5 minutes. Results: Systolic and diastolic blood pressures were significantly reduced from 10 minutes after epidural bolus injection in groups 4 and 5, but these decreases in blood pressure were not severe enough to require treatment in either group. Pulse rates were significantly decreased from 10 minutes after injection in groups 3, 4, and 5, but these decreases in pulse rate were not so severe enough to require treatment in 3 groups. Sp and ETC were stable, and arrhythmia was not observed. Conclusions: The thoracic epidural injection of 1% lidocaine mixed with morphine 0.1 mg/kg and fentanyl 1 mcg/kg can be safely used during sevoflurane anesthesia without severe cardiovascular complications during upper abdominal surgery in ASA 1-2 patients.

PARTICIPATION IN ANESTHESIA DRUG TRIALS DOES NOT DECREASE PARENTS' SATISFACTION WITH THE SURGICAL EXPERIENCE

S297 INTRODUCTION: Pediatric drug trials are essential to establish the safety, efficacy and dosing guidelines of new anesthetics in children. When parents are invited to enroll in a research study, they have to understand and agree to all the conditions of the protocol. Even in the absence of a significant increase in the medical risk to the child, there are often the potential inconveniences of needing to spend extra time in the facility, answer questionnaires, undergo extra testing, etc. Following some highly-publicized negative media reports, some surgeons expressed concern that recruiting children for anesthesia research studies may make the institution less appealing to parents. This study examines the effect of participating in a typical anesthetic drug trial on parental satisfaction with their child's overall surgical experience. METHODS: A questionnaire was sent to the parents of 62 children who had participated in a phase III, double blind, randomized anesthesia drug trial of a new opioid at a major pediatric institution within the previous year. Parents were questioned about their overall satisfaction of the whole surgical experience and specifically about their child's experience of being a research subject. The same questionnaire was mailed to a matched group of parents whose children underwent similar procedures, but were not involved in any research protocols. RESULTS: Sixty-one percent of the parents whose children were research subjects answered the questionnaire (vs. 47% of the matched controls). There was no difference in the number of parents who reported "good" or "very good" over-all experience with the way the child received anesthesia care between those who participated in the study (97.4%) and those who did not (93.1%) (P=0.1). Of those who participated, 89% continued to be pleased with their decision, and would consider participating again (or recommend the same to a friend) if the child requires similar surgery in the future. DISCUSSION: There is little information in the literature regarding the consequences of participating in clinical anesthesia research on the patients or parents perception of their surgical experience. In spite of the potential inconveniences and the "more-than-minimal" risk of receiving a new drug in a double-blind randomized manner, involved parents felt that their overall experience was very good. Various factors may have contributed to this positive outcome. Patients who participate in clinical trials receive extra attention from having a research nurse with them at all times and are made to feel special along the way. Some parents believe that care in the research setting is better than the less specialized care they would receive in the community. It is concluded that recruiting children for anesthesia drug trials does not decrease parents' satisfaction with the surgical experience.

Effect of a nitric oxide synthase inhibitor and a glucocorticosteroid on exhaled nitric oxide.

Nitric oxide (NO) is produced by a variety of cells within the respiratory tract, including inflammatory epithelial cells. NO has been detected in the exhaled air of normal human subjects, and its concentration is raised in asthmatic patients. To study whether exhaled NO arises from the respiratory tract, we administered a NO synthase (NOS) inhibitor, NG-monomethyl-L-arginine (L-NMMA), by inhalation (490 mg) in a double-blind randomized manner in nine normal and six asthmatic subjects. Because exhaled NO may arise from an inducible isoform of NO synthase that may be inhibited by glucocorticosteroids, we also studied the effects of oral prednisolone (30 mg orally for 3 d) in seven normal and six asthmatic subjects in a separate double-blind crossover study with matched placebo. After nebulized L-NMMA, there was a significant fall in peak exhaled NO compared with saline control values, with a mean fall of 43.6 +/- 5.6% in normal subjects (p < 0.01) and of 39.7 +/- 6.5% (p < 0.01) in asthmatic subjects, which persisted for 4 h. There were no effects of L-NMMA inhalation on heart rate, blood pressure, or FEV1 in either normal or asthmatic patients. Administration of oral prednisolone (30 mg) resulted in a fall in exhaled NO concentrations in asthmatic subjects by 21.6 +/- 5.0% at 48 h (p < 0.01) but no significant change in normal subjects. These data suggest that NOS inhibitors may be safely given in normal and asthmatic patients and that the increased exhaled NO seen in asthmatic patients is likely to be caused by induction of inducible NOS.

Comparison of the hemodynamic responses to molsidomine and isosorbide dinitrate in congestive heart failure

To evaluate the mechanisms involved in nitrate tolerance, we randomized 23 patients with congestive heart failure resulting from coronary artery disease to an isosorbide dinitrate or a molsidomine infusion. The drugs were titrated to decrease pulmonary capillary wedge pressure by ≥30% or ≥10 mm Hg. Then isosorbide dinitrate, molsidomine, or placebo was infused in a double-blind randomized manner for 24 hours. In all patients, treatment with enalapril was begun ≥48 hours before the begining of the protocol and was continued throughout the study to avoid renin-angiotensin activation. The pulmonary capillary wedge pressure remained significantly decreased at 24 hours during molsidomine infusion only. No significant increase in catecholamines occurred. Because molsidomine differs from organic nitrates by its property of directly stimulating guanylate cyclase without depending on thiol group availability, these results suggest that impaired biotransformation of nitrates is involved in tolerance induced by high doses of isosorbide dinitrate in congestive heart failure.

Aminophylline and respiratory muscle interaction in normal humans.

The effects of intravenous infusion of aminophylline on respiratory muscle interaction were examined in seven normal subjects breathing at rest. Rib cage (RC-Ap) and abdominal (AB-Ap) volume displacements, pleural (Ppl), gastric (Pg), and transdiaphragmatic (Pdi) pressure swings, and electromyographic activity of the diaphragm (Edi) and the parasternal (Eps) muscles were measured under control and during infusion of either aminophylline or placebo in a double-blind randomized manner. Compared with placebo, aminophylline induced an increase in ventilation (p < 0.01) that was mainly accounted for by an increase in tidal volume (p = 0.01). Aminophylline induced a significant and similar increase in RC-Ap and AB-Ap as associated with increased Ppl and Pg swings (p = 0.002, and p < 0.01, respectively). On the contrary, no changes in end-expiratory RC and AB volume and in Ppl and Pg at end-expiration were observed, indicating that expiratory muscles did not contribute to the increase in tidal volume. Edi and Eps increased significantly with aminophylline, whereas Pdi/Edi ratio remained unchanged. We conclude that in normal humans breathing at rest: (1) aminophylline increases ventilation, promoting larger tidal volume; (2) this effect is due to increased neural drive to inspiratory muscles; (3) aminophylline does not promote any appreciable expiratory muscle recruitment and distortion in the pattern of chest wall motion.