bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics of Propofol Infusions in Critically Ill Neonates, Infants, and Children in an Intensive Care Unit
Authors: Rigby-Jones Ann E. , Nolan Judith A. , Priston Melanie J. , C. Wright Peter M. , Robert Sneyd J. , Wolf Andrew R. 
Published: August 2004

Background
Propofol is a commonly used anesthetic induction agent in pediatric anesthesia that, until recently, was used with caution as an intravenous infusion agent for sedation in pediatric intensive care. Few data have described propofol kinetics in critically ill children.

Methods
Twenty-one critically ill ventilated children aged 1 week to 12 yr were sedated with 4-6 mg. kg(-1).h(-1) of 2% propofol for up to 28 h, combined with a constant morphine infusion. Whole blood concentration of propofol was measured at steady state and for 24 h after infusion using high-performance liquid chromatography.

Results
A propofol infusion rate of 4 mg. kg(-1).h(-1) achieved adequate sedation scores in 17 of 20 patients. In 2 patients the dose was reduced because of hypotension, and 1 patient was withdrawn from the study because of a increasing metabolic acidosis. Mixed-effects population models were fitted to the blood propofol concentration data. The pharmacokinetics were best described by a three-compartment model. Weight was a significant covariate for all structural model parameters; Cl, Q2, Q3, V1, and V2 were proportional to weight. Estimates for these parameters were 30.2, 16.0, and 13.3 ml. kg(-1).min(-1) and 0.584 and 1.36 l/kg, respectively. The volume of the remaining peripheral compartment, V3, had a constant component (103 l) plus an additional weight-related component (5.67 l/kg). Values for Cl were reduced (typically by 26%) in children who had undergone cardiac surgery.

Conclusions
Propofol kinetics are altered in very small babies and in children recovering from cardiac surgery. Increased peripheral distribution volume and reduced metabolic clearance following surgery causes prolonged elimination.
Both Local Anesthetics and Salbutamol Pretreatment Affect Reflex Bronchoconstriction in Volunteers with Asthma undergoing Awake Fiberoptic Intubation
Authors: Groeben Harald , Schlicht Markus , Stieglitz Sven , Pavlakovic Goran , Peters Jürgen 
Published: August 2004

Background
Awake tracheal intubation may evoke reflex bronchoconstriction in asthmatics. Whether this effect is altered by the choice of the local anesthetic used or by pretreatment with a beta2-adrenoceptor agonist is unknown. Therefore, we assessed the effect of awake fiberoptic intubation after lidocaine or dyclonine inhalation with or without pretreatment with salbutamol on lung function in asthmatic volunteers.

Methods
Bronchial hyperreactivity was verified by an inhalational histamine challenge. On four different days in a randomized, double blind fashion the volunteers (n = 10) inhaled either dyclonine or lidocaine with or without salbutamol pretreatment. FEV1 was measured at baseline, following salbutamol or saline inhalation, after lidocaine or dyclonine inhalation, while intubated, and after extubation. Lidocaine and dyclonine plasma concentrations were also measured.

Statistics
Two-way ANOVA, post hoc tests with Bonferroni correction, results are presented as mean +/- SD.

Results
Neither lidocaine nor dyclonine inhalation changed FEV1 significantly from baseline compared with placebo inhalation (4.43 +/- 0.67 l vs. 4.29 +/- 0.72 l, and 4.53 +/- 0.63 l vs. 4.24 +/- 0.80 l, respectively). Salbutamol slightly but significantly increased FEV1 (4.45 +/- 0.76 l vs. 4.71 +/- 0.61 l, P = 0.0034, and 4.48 +/- 0.62 l vs. 4.71 +/- 0.61 l, P = 0.0121, respectively). Following awake intubation FEV1 significantly decreased under lidocaine topical anesthesia (4.29 +/- 0.72 l to 2.86 +/- 0.87 l) but decreased even more under dyclonine anesthesia (4.24 +/- 0.80 l to 2.20 +/- 0.67 l; P < 0.0001). While salbutamol pretreatment significantly attenuated the response to intubation, it did not eliminate the difference between the effects of lidocaine and dyclonine. Only minutes after extubation FEV1 was similar compared with baseline.

Conclusion
In asthmatics, awake fiberoptic intubation evokes a more than 50% decrease in FEV1 following dyclonine inhalation. Using lidocaine for topical anesthesia the decrease in FEV1 is significantly mitigated (35%) and can be even further attenuated by salbutamol pretreatment. Therefore, combined treatment with lidocaine and salbutamol can be recommended for awake intubation while the use of dyclonine, despite its excellent and longer lasting topical anesthesia, may be contraindicated in patients with bronchial hyperreactivity.
Effects of Bupivacaine on Mitochondrial Energy Metabolism in Heart of Rats following Exposure to Chronic Hypoxia
Authors: Nouette-Gaulain Karine , Forestier François , Malgat Monique , Marthan Roger , Mazat Jean-Pierre , Sztark François 
Published: August 2004

Background
Adaptation to chronic exposure to hypoxia alters energy metabolism in the heart, particularly in the left ventricle, which undergoes a loss in oxidative capacity. Highly lipophilic local anesthetics interfere with mitochondrial energy metabolism. The purpose of this study was to compare the effects of bupivacaine on mitochondrial energy metabolism in heart of rats subjected to normoxic or hypoxic environments.

Methods
Male Wistar rats (n = 10) were subjected to hypobaric hypoxia (simulated altitude = 5,000 m, 380 mmHg) for 2 weeks. Control rats (n = 10) were maintained in an ambient normoxic environment. Mitochondrial metabolism (oxygen consumption and adenosine triphosphate synthesis) was assessed using saponin-skinned ventricular fibers. Bupivacaine (0-5 mM) was tested on both left and right ventricles of normoxic or hypoxic heart.

Results
In animals exposed to hypobaric hypoxia for 14 days, cardiac mass significantly increased, and the right-to-left ventricular ratio was approximately twofold (0.48 +/- 0.11 vs. 0.22 +/- 0.04, P < 0.05). Oxygen consumption and adenosine triphosphate synthesis were significantly lower in the hypoxic left ventricles but not in the right ones. The uncoupling effect of bupivacaine was more pronounced in the left ventricle from hypoxic heart than in the right ventricle; the bupivacaine-induced decrease in the adenosine triphosphate synthesis rate and in the adenosine triphosphate-to-oxygen ratio was significantly greater in the hypoxic left ventricle than in the normoxic one.

Conclusions
Chronic hypoxia impairs cardiac energy metabolism in left ventricles and enhances the depressant effects of bupivacaine on mitochondrial functions.
Desflurane Improves Neurologic Outcome after Low-flow Cardiopulmonary Bypass in Newborn Pigs
Authors: Loepke Andreas W. , Priestley Margaret A. , Schultz Steven E. , McCann John , Golden Jeffrey , Kurth C. Dean 
Published: August 2004

Background
Despite improvements in neonatal heart surgery, neurologic complications continue to occur from low-flow cardiopulmonary bypass (LF-CPB) and deep hypothermic circulatory arrest (DHCA). Desflurane confers neuroprotection against ischemia at normothermia and for DHCA. This study compared neurologic outcome of a desflurane-based with a fentanyl-based anesthetic for LF-CPB.

Methods
Thirty piglets aged 1 week received either fentanyl-droperidol (F/D), desflurane 4.5% (Des4.5), or desflurane 9% (Des9) during surgical preparation and CPB. Arterial blood gases, glucose, heart rate, arterial pressure, brain temperature, and cerebral blood flow (laser Doppler flowmetry) were recorded. After CPB cooling (22 degrees C brain) using pH-stat strategy, LF-CPB was performed for 150 min followed by CPB rewarming, separation from CPB, and extubation. On postoperative day 2, functional and histologic outcomes were assessed.

Results
Cardiovascular variables were physiologically similar between groups before, during, and after LF-CPB. Cerebral blood flow during LF-CPB (13% of pre-CPB value) did not differ significantly between the groups. Functional disability was worse in F/D than in Des9 (P = 0.04) but not Des4.5 (P = 0.1). In neocortex, histopathologic damage was greater in F/D than in Des4.5 (P = 0.03) and Des9 (P = 0.009). In hippocampus, damage was worse in F/D than in Des9 (P = 0.01) but not Des4.5 (P = 0.08). The incidences of ventricular fibrillation during LF-CPB were 90, 60, and 10% for F/D, Des4.5 (P = 0.06), and Des9 (P = 0.0002), respectively.

Conclusions
Desflurane improved neurologic outcome following LF-CPB compared with F/D in piglets, indicated by less functional disability and less histologic damage, especially with Des9. Desflurane may have produced cardiac protection, suggested by a lower incidence of ventricular fibrillation.
Fetal and Maternal Effects of Phenylephrine and Ephedrine during Spinal Anesthesia for Cesarean Delivery
Authors: Cooper David W. , Carpenter Mark , Mowbray Paul , Desira William R. , Ryall David M. , Kokri Manmohan S. 
Published: August 2004

Background
In our routine practice, we observed a reduced incidence of fetal acidosis (umbilical artery pH < 7.20) at cesarean delivery during spinal anesthesia when a combination of phenylephrine and ephedrine was used as first line vasopressor therapy, compared with using ephedrine alone.

Methods
The study was randomized and double blind. It compared phenylephrine 100 microg/ml (phenylephrine group), ephedrine 3 mg/ml (ephedrine group), and phenylephrine 50 microg/ml combined with ephedrine 1.5 mg/ml (combination group), given by infusion, to maintain maternal systolic arterial pressure at baseline during spinal anesthesia for elective cesarean delivery.

Results
Fetal acidosis was less frequent in the phenylephrine group (1 of 48) (P = 0.004) and less frequent in the combination group (1 of 47) (P = 0.005) than in the ephedrine group (10 of 48). The mean systolic arterial pressure was similar for the three groups: Phenylephrine group median 98% (IQR 94-103) of baseline, ephedrine group 100% (96-106) and combination group 101% (97-108) (P = 0.11). The mean heart rate was higher in the ephedrine group (median 107% [IQR 99-118] of baseline) than in the phenylephrine group (88% [82-98]) (P < 0.0001), or the combination group (96% [86-102]) (P < 0.0001). Nausea and vomiting were less frequent in the phenylephrine group (nausea 17%, vomiting 0%) than in the ephedrine group (nausea 66%, vomiting 36%) (P < 0.0001), or the combination group (nausea 55%, vomiting 18%) (P < 0.0001).

Conclusions
Giving phenylephrine alone by infusion at cesarean delivery was associated with a lower incidence of fetal acidosis and maternal nausea and vomiting than giving ephedrine alone. There was no advantage to combining phenylephrine and ephedrine because it increased nausea and vomiting, and it did not further improve fetal blood gas values, compared with giving phenylephrine alone.
Functional μ Opioid Receptors Are Reduced in the Spinal Cord Dorsal Horn of Diabetic Rats
Authors: Chen Shao-Rui , Sweigart Kristi L. , Lakoski Joan M. , Pan Hui-Lin 
Published: August 2004

Background
The mechanisms of decreased spinal analgesic potency of morphine in neuropathic pain are not fully known. Agonist-stimulated [35S]GTPgammaS receptor autoradiography has been used to measure receptor activation of G proteins in vitro. Using this technique, we determined changes in the functional mu opioid receptors in the spinal dorsal horn in diabetic rats.

Methods
Rats were rendered diabetic with an intraperitoneal injection of streptozotocin. The lumbar spinal cord was obtained from age-matched normal and diabetic rats 4 weeks after streptozotocin treatment. [D-Ala2,N-MePhe4,Gly5-ol]-enkephalin (DAMGO, 10 microm)-stimulated [35S]GTPgammaS binding was performed in both tissue sections and isolated membranes.

Results
The DAMGO-stimulated [35S]GTPgammaS binding in the spinal dorsal horn was significantly reduced (approximately 37%) in diabetic rats compared with normal rats. However, [35S]GTPgammaS bindings in the spinal dorsal horn stimulated by other G protein-coupled receptor agonists, including [D-Pen2,D-Pen5]-enkephalin, R(-)N6-(2-phenylisopropyl)-adenosine, and WIN-55212, were not significantly altered in diabetic rats. The basal [35S]GTPgammaS binding in the spinal dorsal horn was slightly (approximately 13%) but significantly increased in diabetic rats. Western blot analysis revealed no significant difference in the expression of the alpha subunits of G(i) and G(o) proteins in the dorsal spinal cord between normal and diabetic rats.

Conclusions
These data suggest that the functional mu opioid receptors in the spinal cord dorsal horn of diabetic rats are reduced. The impaired functional mu opioid receptors in the spinal cord may constitute one of the mechanisms underlying the reduced spinal analgesic effect of mu opioids in diabetic neuropathic pain.
Alcohol, Estrogen Replacement Therapy, and Visuospatial Processes in Postmenopausal Women
Authors: Tivis Laura J. , Green Michelle D. , Nixon Sara Jo , Tivis Rick D. 
Published: August 2004

Background: Studies suggest that moderate drinking may benefit cognition and the effect may favor women. This study investigated effects of moderate drinking on visuospatial functioning in postmenopausal women. Visuospatial processes are sensitive to alcohol abuse and are thought to be sensitive to hormonal fluctuations. Three questions were posed in order to: explore visuospatial processes in moderate‐drinking and abstaining postmenopausal women, assess visuospatial differences in women using no estrogen replacement therapy (No‐ERT), ERT alone (ERT‐only), and ERT with progestin (ERT+Pro), and identify alcohol/ERT interactions associated with visuospatial performance.Methods: Two hundred fourteen postmenopausal women participated (75 No‐ERT; 63 ERT‐only; 76 ERT+Pro. All were moderate drinkers or teetotalers and all received the Block Design test from the Wechsler Adult Intelligence Scale–Revised. A raw score was calculated and progress at 30‐sec intervals was assessed.Results: ANOVA revealed an alcohol main effect [F (3,202) = 4.74; p < 0.004] on 60‐ to 120‐sec change scores. Teetotalers had significantly smaller change scores (less improvement) compared with all levels of drinkers. ANOVA on design 9 (the most difficult trial) revealed an ERT main effect [F (3,202) = 4.37; p < 0.02]. ERT nonusers scored significantly lower than ERT‐only and ERT+Pro groups. A design 9 trend toward an alcohol × ERT interaction was noted [F (6,202) = 1.93; p < 0.08], and a design 9 time × alcohol interaction was revealed [F (6,404) = 2.65; p < 0.02].Conclusions: These data suggest that moderate drinking may be positively associated with visuospatial processes in postmenopausal women. They also suggest that ERT, alone and with progestin, is positively associated with visuospatial processes, but only when the task is difficult. These findings support Kaplan's assertion that subtle performance deficits may not be detectible with traditional endpoint measures. A provocative alcohol × ERT trend suggests that alcohol consumption should be considered in studies of ERT effects on cognitive ability.
A 6‐Month Controlled Naltrexone Study: Combined Effect With Cognitive Behavioral Therapy in Outpatient Treatment of Alcohol Dependence
Authors: Balldin J. , Berglund M. , Borg S. , Månsson Marianne , Bendtsen P. , Franck J. , Gustafsson L. , Halldin J. , Nilsson L.‐ H. , Stolt G. , Willander A. 
Published: August 2004

Background: In several studies, patients with alcohol dependence treated with the opioid antagonist naltrexone have shown fewer relapses to heavy drinking than those receiving placebo. An interaction between the naltrexone effect and the type of psychological therapy has been observed.Methods: A 6‐month, double‐blind, placebo‐controlled, parallel‐group study was performed at 10 different investigation sites. After a placebo run‐in period of 1 week, 118 patients were randomized into 4 treatment groups—50 mg of naltrexone daily or placebo in combination with either cognitive behavioral therapy (CBT) or supportive therapy. The CBT was performed over nine sessions according to the manual of Project MATCH (Matching Alcoholism Treatments to Client Heterogeneity). The supportive therapy was defined as “the treatment as usual.” Alcohol consumption, craving, carbohydrate‐deficient transferrin, medication compliance by tablet count, and adverse clinical events were assessed at all visits. Other liver enzymes and psychiatric symptoms were also determined.Results: Ninety‐one (77%) patients completed the study, and 92 (78%) were 80% compliant with the medication regimen. A lower percentage of heavy‐drinking days was shown in the naltrexone group (p= 0.045) compared with the placebo group, as was a lower craving score (p= 0.029). These results are supported by the lower levels of liver enzyme activities (p < 0.010 for aspartate aminotransferase, alanine aminotransferase, and γ‐glutamyltransferase), but not by the carbohydrate‐deficient transferrin levels, in the naltrexone group. The mean time period before the first day of heavy drinking was longer for the group treated with CBT (p= 0.010), especially in combination with naltrexone (p= 0.007). Naltrexone was well tolerated, and no patients discontinued the study due to side effects.Conclusions: This study supports the effect of naltrexone in outpatient treatment of alcohol dependence and suggests that a beneficial interaction effect with CBT can be expected.
Auditory P3 in Female Alcoholics
Authors: Suresh Sudha , Porjesz Bernice , Chorlian David B. , Choi Keewhan , Jones Kevin A. , Wang Kongming , Stimus Arthur , Begleiter Henri 
Published: August 2004

Background:The P3 (P300) has been considered to be a phenotypical marker of the risk for alcoholism. Although reductions in visual P3 in male and female alcoholics have been replicated, studies of auditory target P3 have been inconsistent. Our objective was to study the magnitude of auditory P3 reduction in female alcoholics and to establish the association between P3 reduction and alcoholism while taking into account comorbid depression and psychoactive drug dependence. The characteristics of P3 reduction were further examined by studying the reduction in family history–positive and –negative individuals.Methods:Auditory target P3s recorded from 61 scalp electrodes in female alcoholics (n= 71) were compared with P3s from female controls (n= 159) ranging in age from 18 to 50 years. The amplitudes and latencies were statistically analyzed, by using repeated‐measures ANOVA, in six regional electrode arrays and at representative electrode sites, with age and comorbid depression as covariates. The effects of family density and clinical variables such as depression and drug dependence were also examined with correlation analysis.Results:Alcoholic women had significantly lower P3 amplitudes in all six regions and at midline electrode sites. The reductions were not associated with comorbid depression, as shown by low correlations and similar P3 amplitudes at Pz in female alcoholics with and without depression. The P3 amplitudes in women with a high family density were smaller than those in women with a low family density of alcohol dependence. Drug dependency did not influence P3 amplitude, as shown by similar responses in drug‐dependent and non–drug‐dependent alcoholic women.Conclusions:These findings highlight the significance of P3 reductions associated with alcoholism in women, independently of comorbid depression. Family density effects further support the evidence that these findings are heritable. These results suggest that P3 can be considered as a phenotypical marker of vulnerability to alcoholism in women.
The Search for Genes Related to a Low‐Level Response to Alcohol Determined by Alcohol Challenges
Authors: Wilhelmsen Kirk C. , Schuckit Marc , Smith Tom L. , Lee James V. , Segall Samantha K. , Feiler Heidi S. , Kalmijn Jelger 
Published: August 2004

Background: A low level of response (LR) to alcohol seems to relate to a substantial proportion of the risk for alcoholism and to have significant heritability.Methods: This report describes the results of a genome‐wide segregation analysis for the first 139 pairs of full siblings by using an alcohol challenge protocol as a direct measure of LR. Subjects from 18 to 29 years old were selected if the original screen indicated they had an alcohol‐dependent parent, reported a personal history of drinking but had no evidence of alcohol dependence, and had a full sibling with similar characteristics. Body sway and Subjective High Assessment Scale scores were measured at baseline and at regular intervals after the administration of a measured dose of alcohol. Participants and available parents were genotyped for 811 microsatellite markers, and resulting data were analyzed with a variance component method.Results: Nine chromosome regions with logarithm of the odds ratio (LOD) between 2.2 and 3.2 were identified; several had previously been implicated regarding phenotypes relevant to alcoholism and the LR to alcohol. Several regions identified in the previous linkage study by using a retrospective self‐report questionnaire were potentially confirmed by this study. The strongest evidence was on chromosomes 10, 11, and 22.Conclusions: Several chromosomal areas seem to relate to the low LR to alcohol as a risk factor for alcohol dependence.
Moderators of the Relationship Between Alcohol Dependence and Suicide and Medically Serious Suicide Attempts: Analyses of Canterbury Suicide Project Data
Authors: Conner Kenneth R. , Beautrais Annette L. , Conwell Yeates 
Published: August 2004

Background: Preliminary data indicate that age, gender, and mood disorder moderate the association of alcohol dependence and suicide. The purpose of this study was to evaluate potential moderators of the relationship between alcohol dependence and suicide and medically serious suicide attempts by using case‐control data gathered in the Canterbury region of New Zealand for the Canterbury Suicide Project.Methods: Data on 193 suicide decedents, 240 medically serious suicide attempters, and 984 community controls, all age 18 and over, were gathered by using psychological autopsy methodology. Multinomial logistic analyses were used to compare the two case groups to controls on demographic and diagnostic variables. Moderating effects were evaluated based on significant statistical interactions of predictors with alcohol dependence.Results: The association of alcohol dependence and suicide (but not medically serious attempts) was amplified with increased age. Neither mood disorder nor gender moderated the relationship between alcohol dependence and suicide. Increased age amplified the association of mood disorder and suicide, whereas decreased age strengthened the association of mood disorder and medically serious suicide attempts.Conclusions: Older age may serve as a marker for a construct (e.g., aggression/impulsivity) that underlies the failure to mature out of alcoholism, or a late‐onset subtype of alcoholism prone to negative affect, accounting for the association of older age and suicide in this population. Older age also may merely reflect longer duration of the deleterious effects of alcoholism.