bluuebunny/crossref_metadata_2025 huggingface dataset:
The mixed company they keep: Potentially offensive sexual behaviours among adolescents
Authors: Lacasse Anne , Purdy Kelly T. , Mendelson Morton J.
Published: November 2003

This study investigated the incidence and tolerance of potentially offensive sexual behaviours in relation to the gender composition of adolescents’ friendship networks. High-school students (Grades 8 and 11) self-reported on the Sexual Experiences Questionnaire—High School and on the Social Network Form. Adolescents whose friendship network included a relatively greater proportion of other-sex friends tended to be those who experienced some form of potentially offensive sexual behaviours. However, tolerance (i.e., lack of upset) of these behaviours was not related to the gender composition of the friendship network. Moderate behaviours were perpetrated mostly by boys to both sexes, whereas severe behaviours were perpetrated by other-sex peers. The discussion addresses how sexual harassment in adolescence might be conceptualised.
Korean, Japanese, and US students’ judgments about peer exclusion: Evidence for diversity
Authors: Park Yoonjung , Killen Melanie , Crystal David S. , Watanabe Hirozumi
Published: November 2003

Children and adolescents (4th-, 7th-, and 10th-graders) from Korea ( N 1/4 553) were surveyed regarding their evaluations of peer group exclusion of atypical peers: aggressive behaviour, unconventional appearance, acting like a clown, cross-gender behaviour, slow runner, and sad personality. The data were compared to a previously collected data set from Japan ( N = 513), and the US ( N 1/4 542) using the identical assessment. It was hypothesised that differences between Korean and Japanese cultures would be found, which would support our proposal that Asian cultures should not be automatically grouped as one monolithic “collectivistic” culture. Further, it was expected that students’ judgments of exclusion, conformity, and self-perceived differences would vary by the context of exclusion in all three cultures as well as by age and gender of the participants. The results for the exclusion judgments confirmed our hypotheses regarding within-Asian cultural differences, and the findings for judgments about conformity and self-perceived differences provide a mixed picture of confirmation for our expectations. In general, the results support our theory of developmental social cognition in which multiple sources of influence have a significant effect on social decision-making involving the exclusion of others.
Similarities in outcomes for men and women after drug misuse treatment: results from the National Treatment Outcome Research Study (NTORS)
Authors: STEWART DUNCAN , GOSSOP MICHAEL , MARSDEN JOHN , KIDD TARA , TREACY SAMANTHA
Published: November 2003

The National Treatment Outcome Research Study (NTORS) is a prospective, multi‐site treatment outcome study of drug misusers in the UK. This paper reports the characteristics and problems of male and female clients at intake to treatment, and changes in substance use, health problems, and criminal behaviour at follow‐up. The sample comprised 753 subjects (552 men and 201 women) followed‐up 1 year after starting treatment in 54 programmes chosen to be representative of the main national treatment modalities. Men and women presented to treatment with different problems and characteristics. Women reported more frequent cocaine use, greater health problems, and were more likely to have a drug‐using partner and be responsible for children. Despite different profiles of problems, men and women both made significant reductions in their problem behaviours following treatment. At 1‐year follow‐up, men and women reported reductions in drug use, health problems and criminal behaviour. However, women did not reduce their alcohol consumption significantly, and improvements in crime were less pronounced than for men. After controlling for pretreatment differences, gender was not predictive of any of the outcome measures reported.
Enough! or too much. What is ‘excessive’ kava use in Arnhem Land?
Authors: CLOUGH ALAN
Published: November 2003

The objective of the study was to describe parameters for use in monitoring health, social and economic effects of kava use in Arnhem Land Aboriginal communities in the Northern Territory (NT). Kava has been used mainly in eight communities (population > 200), and in smaller associated homeland areas since 1982 with a total population of approximately 6800, using cross‐sectional description and comparison using data from three kava‐using communities. Interview data combined with health worker assessments were compiled using: (1) a sample (n = 136) aged 16–34 years in one community in 2001–02; (2) a sample (n = 101) aged 16 years and over in 2000 where physical assessments and biochemical and haematological data were also collected; (3) participant‐observation in one community (133 people aged 18 years and over) during 1989–91. Kava, supplied illegally, was still being used in Arnhem Land in 2001–02. In 2000 dermopathy characteristic of heavy use, abnormally low body mass index (BMI), low blood lymphocytes and abnormally high γ‐glutamyl transferase (GGT) occurred more frequently with increased kava use. These acute effects emerge at average consumption levels of from 310–440 g/week of kava powder. When kava users in one community began to consume it at an average of 240–425 g/week from mid‐1990, 19% of available cash resources were spent on kava with 11% of cash resources leaving the local community economy. The proportion of men drinking kava reached 70% and women 62% from mid‐1990, with 20% of the population spending unprecedented amounts of time (14 + hours/week) in activities where kava was consumed. These parameters may be useful to monitor kava's adverse health, social and economic effects. Their association with increased kava use suggests that approaches to minimizing harm from its abuse may begin fruitfully with controlling supply.
Comparison of disulfiram and placebo in treatment of alcohol dependence of adolescents
Authors: NIEDERHOFER HELMUT , STAFFEN WOLFGANG
Published: November 2003

About 50% of alcoholic patients relapse within 3 months of treatment. Previous studies have suggested that disulfiram may help to prevent such relapse. The aim of our study was to assess the efficacy and safety of long‐term disulfiram treatment in alcohol dependence of adolescents. In this double‐blind, placebo‐controlled study we recruited 26 adolescents, aged 16–19 years, with chronic or episodic alcohol dependence. Patients were allocated treatment randomly with disulfiram (200 mg daily) or placebo for 90 days. Patients were assessed on the day treatment started and on days 30 and 90 by interview, self‐report, questionnaire and laboratory screening. Patients were classified as abstinent, relapsing or non‐attending. Time to first treatment failure (relapse or non‐attendance) was the primary outcome measure. The disulfiram (n = 13) and placebo (n= 13) groups were well matched in terms of baseline demographic and alcohol‐related variables. Thirteen disulfiram‐treated and 13 placebo‐treated patients completed the treatment phase; seven (1 vs. 6) relapsed, five (3 vs. 2) refused to continue treatment, three (1 vs. 2) had concurrent illness and two (1 vs. 1) had adverse side effects. At the end of treatment, seven disulfiram‐treated and two placebo‐treated patients had been abstinent continuously (p = 0.0063). Mean cumulative abstinence duration was significantly greater in the disulfiram group than in the placebo group [68.5 (SD 37.5) vs. 29.7 (19.0) days; p = 0.012]. Apart from occasional diarrhoea, there was no difference in side effects between groups. In some cases, disulfiram may be an effective and well‐tolerated pharmacological adjunct to psychosocial and behavioural treatment programmes for treatment of adolescent alcohol‐dependent patients.
A prototype screening instrument for cannabis use disorder: the Cannabis Use Disorders Identification Test (CUDIT) in an alcohol‐dependent clinical sample
Authors: ADAMSON SIMON J. , SELLMAN J. DOUGLAS
Published: November 2003

The Cannabis Use Disorders Identification Test (CUDIT) was used for the first time as part of a randomized controlled trial for brief interventions in mild to moderate alcohol‐dependent out‐patients. This sample may be seen as a population at increased risk of cannabis use disorder. The CUDIT was developed by modifying the Alcohol Use Disorders Identification Test (AUDIT). The ability of the CUDIT to accurately screen for cannabis abuse or dependence was examined in the portion of the sample who reported some cannabis use over the preceding 6 months (n = 53), as was self‐reported frequency of cannabis use in the preceding 6 months. The CUDIT was superior to the frequency measure, achieving positive predictive power of 84.6% and sensitivity of 73.3% at a cut‐off of 8, compared to positive predictive power of 81.8% and sensitivity of 60.0% for 80 or more cannabis use‐days. These results indicate the viability of a screening measure for identifying cannabis use disorder in at risk populations.
A systematic review of the effectiveness of brief interventions with substance using adolescents by type of drug
Authors: TAIT ROBERT J. , HULSE GARY K.
Published: November 2003

The aim of this paper is to evaluate the effectiveness of brief interventions (BI) with adolescents (mean age < 20) in reducing alcohol, tobacco or other drug (ATOD) use by means of a systematic review of BI for adolescent substance use in the English language literature up to 2002. We identified 11 studies involving 3734 adolescents. Follow‐up ranged from 6 weeks to 24 months. Motivational interviewing was the predominant approach, underpinning eight studies: the remaining three provided personalized health information. Seven papers reported outcomes for alcohol interventions and four involved other substances (including one with separate alcohol outcomes). The overall effect size was d= 0.126 with borderline homogeneity (Q = 14.9, df = 9, p = 0.09). The effect size from the eight alcohol interventions (n = 1075) was classified as significant but “small” (d = 0.275). The remaining non‐alcohol studies were considered separately as interventions involving tobacco or multiple substance use. The two interventions with tobacco involved a substantial sample (n = 2626) but had a very small effect (d = 0.037), while the two interventions addressing multiple substances involved few participants (n = 110) but had a medium — large effect (d = 0.78). Across a diverse range of settings (dental clinic, schools, universities, substance treatment centres) and, therefore, probably diverse clients, BI conferred benefits to adolescent substance users. BI had a small effect on alcohol consumption and related measures. The data for tobacco interventions suggested a very small reduction, particularly with general community interventions. The effect of BI with multiple substances appears substantial but the small sample cautions against expansive generalization.
Groin tissue necrosis requiring skin graft following parenteral abuse of buprenorphine tablets
Authors: FEENEY G. F. X. , FAIRWEATHER P.
Published: November 2003

In May 2002 Buprenorphine (Subutex®) was listed on the Australian Pharmaceutical Benefits Schedule for treatment in opioid dependence. In addition to broadening treatment options, buprenorphine has the advantage of an improved safety profile. The risk of overdose is lessened but other risks remain due to diversion. French experience reports widespread deviation of buprenorphine sublingual tablets to intravenous injection. We report a case of attempted parenteral administration of buprenorphine tablets. Stringent protocols for dispensing are appropriate.
Developmental Considerations of Sperm Protein 17 Gene Expression in Rheumatoid Arthritis Synoviocytes
Authors: Takeoka Yuichi , Kenny Thomas P. , Yago Hisashi , Naiki Mitsuru , Gershwin M. Eric , Robbins Dick L.
Published: November 2003

Rheumatoid arthritis (RA) is an autoimmune disease characterized by proliferative synovial tissue. We used mRNA differential display and library subtraction to compare mRNA expression in RA and osteoarthritis (OA) synoviocytes. We initially compared the mRNA expression patterns in 1 female RA and 1 OA synovia and found a differentially expressed 350 bp transcript in the RA synoviocytes which was, by sequence analysis, 100% homologous to sperm protein 17 (Sp17). Moreover, the Sp17 transcript was found differentially expressed in a RA synovial library that was subtracted with an OA synovial library. Using specific primers for full length Sp17, a 1.1 kb transcript was amplified from the synoviocytes of 7 additional female RA patients, sequenced and found to 100% homologous to Sp17. Thus, we found the unexpected expression of Sp17, a thought to be gamete‐specific protein, in the synoviocytes of 8/8 female RA patients in contrast to control OA synoviocytes. Interestingly, Sp17′s structural relationship with cell‐binding and recognition proteins, suggests that Sp17 may function in cell‐cell recognition and signaling in the RA synoviocyte. Further, Sp17 could have a significant regulatory role in RA synoviocyte gene transcription and/or signal transduction. Thus, Sp17 could have an important role in RA synoviocyte proliferation or defective apoptosis. Finally, the presence of Sp17 in synoviocytes has interesting developmental considerations.
Autoimmune Cholangitis in the SJL/J Mouse is Antigen Non‐specific
Authors: Sasaki Motoko , Allina Jorge , Odin Joseph A. , Thung Swan N. , Coppel Ross , Nakanuma Yasuni , Gershwin M. Eric
Published: November 2003

Primary biliary cirrhosis (PBC) is an autoimmune disease characterized by intrahepatic bile duct destruction and the production of anti‐mitochondrial antibodies (AMA). The absence of an animal model has been a striking impedance in defining the molecular basis of disease. Previous work has suggested that SJL/J mice immunize with the pyruvate dehydrogenase complex (PDC‐E2), the major mitochondrial autoantigen of PBC, leads to the development of lymphoid cell infiltration in portal tracts and a model system coined autoimmune cholangitis. We hypothesized that this pathology would be augmented if immunization occurred in the presence of IFN‐γ injections. Accordingly, SJL/J mice were immunized with PDC‐E2 and, for purpose of control, α‐casein. Subgroups of mice were also treated with exogenous IFN‐γ. As expected, mice immunized with PDC‐E2, with or without IFN‐γ, developed high titer AMAs. In contrast, mice immunized with α‐casein, develop antinuclear antibodies. More importantly, the livers from mice immunized with PDC‐E2 and/or those immunized with α‐casein all displayed lymphoid cell infiltration to the portal tracts, irrespective of bile duct size. Indeed, there was no significant difference between the experimental and the control groups by histologic analysis. Thus, autoimmune cholangitis in these mice is antigen non‐specific.
ROCK-generated contractility regulates breast epithelial cell differentiation in response to the physical properties of a three-dimensional collagen matrix
Authors: Wozniak Michele A. , Desai Radhika , Solski Patricia A. , Der Channing J. , Keely Patricia J.
Published: November 2003

Breast epithelial cells differentiate into tubules when cultured in floating three-dimensional (3D) collagen gels, but not when the cells are cultured in the same collagen matrix that is attached to the culture dish. These observations suggest that the biophysical properties of collagenous matrices regulate epithelial differentiation, but the mechanism by which this occurs is unknown. Tubulogenesis required the contraction of floating collagen gels through Rho and ROCK-mediated contractility. ROCK-mediated contractility diminished Rho activity in a floating 3D collagen gel, and corresponded to a loss of FAK phosphorylated at Y397 localized to 3D matrix adhesions. Increasing the density of floating 3D collagen gels also disrupted tubulogenesis, promoted FAK phosphorylation, and sustained high Rho activity. These data demonstrate the novel finding that breast epithelial cells sense the rigidity or density of their environment via ROCK-mediated contractility and a subsequent down-regulation of Rho and FAK function, which is necessary for breast epithelial tubulogenesis to occur.
Spatial and temporal expression of heparan sulfate in mouse development regulates FGF and FGF receptor assembly
Authors: Allen Benjamin L. , Rapraeger Alan C.
Published: November 2003

Heparan sulfate (HS) interacts with diverse growth factors, including Wnt, Hh, BMP, VEGF, EGF, and FGF family members, and is a necessary component for their signaling. These proteins regulate multiple cellular processes that are critical during development. However, a major question is whether developmental changes occur in HS that regulate the activity of these factors. Using a ligand and carbohydrate engagement assay, and focusing on FGF1 and FGF8b interactions with FGF receptor (FR)2c and FR3c, this paper reveals global changes in HS expression in mouse embryos during development that regulate FGF and FR complex assembly. Furthermore, distinct HS requirements are identified for both complex formation and signaling for each FGF and FR pair. Overall, these results suggest that changes in HS act as critical temporal regulators of growth factor and morphogen signaling during embryogenesis.
Defective flagellar assembly and length regulation in LF3 null mutants in Chlamydomonas
Authors: Tam Lai-Wa , Dentler William L. , Lefebvre Paul A.
Published: November 2003

Four long-flagella (LF) genes are important for flagellar length control in Chlamydomonas reinhardtii. Here, we characterize two new null lf3 mutants whose phenotypes are different from previously identified lf3 mutants. These null mutants have unequal-length flagella that assemble more slowly than wild-type flagella, though their flagella can also reach abnormally long lengths. Prominent bulges are found at the distal ends of short, long, and regenerating flagella of these mutants. Analysis of the flagella by electron and immunofluorescence microscopy and by Western blots revealed that the bulges contain intraflagellar transport complexes, a defect reported previously (for review see Cole, D.G., 2003. Traffic. 4:435–442) in a subset of mutants defective in intraflagellar transport. We have cloned the wild-type LF3 gene and characterized a hypomorphic mutant allele of LF3. LF3p is a novel protein located predominantly in the cell body. It cosediments with the product of the LF1 gene in sucrose density gradients, indicating that these proteins may form a functional complex to regulate flagellar length and assembly.
Calcium mobilization from mitochondria in synaptic transmitter release
Authors: Rizzuto Rosario
Published: November 2003

Mitochondria can rapidly accumulate and release Ca2+ upon cell stimulation. A paper by Yang and coworkers in this issue reports an unusual form of synaptic potentiation, dependent on Ca2+ release from mitochondria through the Na+/Ca2+ exchanger and triggered by Na+ entry through voltage-gated channels (Yang et al., 2003).
Human Chest Wall Function while Awake and during Halothane Anesthesia
Authors: Warner David O. , Warner Mark A.
Published: November 2003

Background

Changes in the distribution of respiratory drive to different respiratory muscles may contribute to respiratory depression produced by halothane. The aim of this study was to examine factors that are responsible for halothane-induced depression of the ventilatory response to carbon dioxide rebreathing.

Methods

In six human subjects, respiratory muscle activity in the parasternal intercostal, abdominal, and diaphragm muscles was measured using fine-wire electromyography electrodes. Chest wall motion was determined by respiratory impedance plethysmography. Electromyography activities and chest wall motion were measured during hyperpnea produced by carbon dioxide rebreathing while the subjects were awake and during 1 MAC halothane anesthesia.

Results

Halothane anesthesia significantly reduced the slope of the response of expiratory minute ventilation to carbon dioxide (from 2.88 +/- 0.73 (mean +/- SE) to 2.01 +/- 0.45 l.min-1.mmHg-1). During the rebreathing period, breathing frequency significantly increased while awake (from 10.3 +/- 1.4 to 19.7 +/- 2.6 min-1, P < 0.05) and significantly decreased while anesthetized (from 28.8 +/- 3.9 to 21.7 +/- 1.9 min-1, P < 0.05). Increases in respiratory drive to the phrenic motoneurons produced by rebreathing, as estimated by the diaphragm electromyogram, were enhanced by anesthesia. Anesthesia attenuated the response of parasternal electromyography and accentuated the response of the transversus abdominis electromyography to rebreathing. The compartmental response of the ribcage to rebreathing was significantly decreased by anesthesia (from 1.83 +/- 0.58 to 0.48 +/- 0.13 l.min-1.mmHg-1), and marked phase shifts between ribcage and abdominal motion developed in some subjects. However, at comparable tidal volumes, the ribcage contribution to ventilation was similar while awake and anesthetized in four of the six subjects.

Conclusions

Halothane anesthesia enhances the rebreathing response of neural drive to the primary respiratory muscle, the diaphragm. These findings provide direct evidence that, at the dose examined in this study, halothane-induced respiratory depression is caused by alterations in the distribution and timing of neural drive to the respiratory muscles, rather than a global depression of respiratory motoneuron drive.
Quantitative Assessment of Differential Sensory Nerve Block after Lidocaine Spinal Anesthesia
Authors: Liu Spencer , Kopacz Dan J. , Carpenter Randall L.
Published: November 2003

Background

Recent technology allows for quantitative and selective measurement of A beta, A delta, and C fiber nerve transmission. To gain further insight into the physiology of differential block after lidocaine spinal anesthesia, the function of these different fibers was quantitatively measured over time, and these measurements were correlated with regression of anesthesia to pinprick, touch, cold, and tolerance of tetanic electrical current (equivalent to surgical incision).

Methods

Six volunteers received lidocaine spinal anesthesia with 50 mg lidocaine (5% in dextrose). Cutaneous current perception thresholds at 2,000, 250, and 5 Hz, which stimulate A beta, A delta, and C fibers, respectively, were determined at L2-L3 (medial aspect above knee) before and every 10 min after spinal anesthesia. Dermatomal levels to pinprick, touch, and cold were assessed every 5 min after spinal anesthesia. Tolerance to tetanic electrical stimulus was assessed at L2-L3 every 10 min after spinal anesthesia.

Results

Differential block was demonstrated by the sequential return of sensation to touch, pinprick, and cold at L2-L3. Recovery of function of A beta, A delta, and C fibers correlated with return of sensation to touch (R2 = 0.7, p = 0.03), pinprick (R2 = 0.75, p = 0.02), and cold (R2 = 0.67, p = 0.04) respectively. Loss of tolerance of surgical anesthesia corresponded to return of A beta current perception thresholds to baseline, whereas current perception thresholds for A delta and C fibers were still increased to greater than baseline (p = 0.025).

Conclusions

Differential sensory block during spinal anesthesia is due to different recovery profiles of A beta, A delta, and C fibers. Return of A beta current perception thresholds to baseline correlated with duration of surgical anesthesia as assessed with an electrical stimulation model.
Carbachol, Norepinephrine, and Hypocapnia Stimulate Phosphatidylinositol Turnover in Rat Tracheal Slices
Authors: Shibata Osamu , Makita Tetsuji , Tsujita Toshiya , Tomiyasu Shiro , Fujigaki Toru , Nakamura Harumasa , Sumikawa Koji
Published: November 2003

Background

The intracellular mechanisms involved in the alpha-adrenoceptor- or hyperventilation-induced bronchoconstriction remain unknown. Because there is a direct relationship between phosphatidylinositol (PI) metabolism and airway smooth muscle contraction induced by muscarinic agonists, the authors examined the effects of carbachol (CCh), norepinephrine (NE), and hypocapnia on PI turnover in the airway smooth muscle.

Methods

Rat tracheal slices were incubated in Krebs-Henseleit solution containing LiCl and [3H]myo-inositol in the presence of NE, CCh, or neither. The PCO2 in the solution was 36 +/- 3 mmHg (normocapnia), 19 +/- 2 mmHg (moderate hypocapnia), or 5 +/- 2 mmHg (severe hypocapnia), respectively. [3H]inositol monophosphate (IP1) formed was counted with a liquid scintillation counter.

Results

Basal IP1 formed was greater at severe hypocapnia than at normocapnia. Norepinephrine- and CCh-induced IP1 formation were also greater at hypocapnia than at normocapnia.

Conclusions

These results indicate that CCh, NE, and hypocapnia stimulate PI turnover in the airway smooth muscle, which would cause bronchoconstriction, and hypocapnia also augments NE- and CCh-induced PI turnover, which could cause worsening of exercise-induced asthma and vagotonic asthma, respectively.
Halothane Impairs the Hemodynamic Influence of Endothelium-derived Nitric Oxide
Authors: Sigmon David H. , Florentino-Pineda Ivan , Van Dyke Russell A. , Beierwaltes William H.
Published: November 2003

Background

The endogenous vasodilator endothelium-derived nitric oxide (EDNO) contributes to the regulation of vascular tone and organ perfusion. It has been suggested that some volatile anesthetics may diminish the influence of EDNO and thereby decrease regional blood flow.

Methods

Radioactive microspheres were used to determine regional hemodynamics in rats. The authors tested the hypothesis that halothane inhibits EDNO and, therefore, should diminish the response to nitric oxide synthesis inhibition by NW-nitro-L-arginine methyl ester (L-NAME) compared with either conscious or barbiturate-anesthetized rats.

Results

NW-nitro-L-arginine methyl ester decreased blood flow to the brain by 23% (P < 0.005) in conscious rats to a level similar to that seen with either anesthetic agent. In both conscious and barbiturate-anesthetized rats, L-NAME increased blood pressure (BP) by 24 +/- 2 (P < 0.001) and 20 +/- 1 (P < 0.001) mmHg and total peripheral resistance (TPR) by 132% (P < 0.001) and 105% (P < 0.001), respectively. In contrast, during halothane anesthesia, both the pressor response (only 7 +/- 1 mmHg) and the increase in TPR (only 22%) were greatly diminished (P < 0.001). NW-nitro-L-arginine methyl ester decreased cardiac output (CO) by 47% (P < 0.001) and heart rate (HR) by 28% (P < 0.001) in conscious rats. In barbiturate-anesthetized rats, L-NAME decreased CO by 38% (P < 0.005) and HR by 13% (P < 0.001). In halothane-anesthetized rats, L-NAME changed neither CO nor HR. Thus halothane anesthesia largely eliminated the systemic response to EDNO synthesis inhibition. In conscious rats, L-NAME decreased blood flow to the heart (30%) and kidneys (47%). In barbiturate-anesthetized rats, L-NAME did not alter blood flow to the heart but decreased renal blood flow by 35% (P < 0.005). In halothane-anesthetized rats, L-NAME did not alter blood flow to either the heart or the kidneys. Overall, halothane blunted or blocked the systemic and regional hemodynamic responses to EDNO synthesis inhibition seen in conscious and barbiturate-anesthetized rats.

Conclusions

Halothane anesthesia greatly diminished or eliminated all systemic and regional hemodynamic responses to L-NAME. These data indicate that halothane anesthesia inhibits EDNO-mediated regulation of systemic and organ hemodynamics.
Effects of Opioid Microinjections in the Nucleus of the Solitary Tract on the Sleep-Wakefulness Cycle States in Cats
Authors: Reinoso-Barbero Francisco , de Andres Isabel
Published: November 2003

Background

Previous studies have shown that the region of the nucleus of the solitary tract (NST) is involved in the control of electrocortical activity and in sleep mechanisms. It also is well known that this region contains the highest concentration of opioid receptors within the medullary brainstem. The involvement of the NST opioid system in sleep-wakefulness states were evaluated.

Methods

Ten cats were implanted with electrodes for chronic polygraphic recordings of their sleep-wakefulness states and provided with an implanted guide cannula stereotaxically aimed at the NST region. Microinjections of saline, morphine sulfate, morphiceptin (specific mu agonist), D-pen-2-D-pen-5-enkephalin (delta agonist), and U-50488H (kappa agonist) were given to the freely moving animals (doses 0.8-2.4 x 10(-9) M, in a volume of 0.05 microliters of saline). After microinjections, sleep-wakefulness recordings were obtained for 8 h.

Results

Morphine microinjections in NST provoked a dose-dependent enhancement of all the polygraphic and behavioral manifestations of slow wave sleep. This effect was blocked by the prior intraperitoneal administration of naloxone. The mu and delta agonists also produced a hypnotic effect by enhancing slow wave sleep. By contrast, the kappa agonist caused no changes in sleep-wakefulness states.

Conclusions

These results indicate that endogenous opioids could be involved in controlling electrocortical activity generated by NST and that activation of mu and delta NST opioid receptors enhanced the electroencephalographic synchronization associated with behavioral slow wave sleep in cats.
The Effects of Halothane on Cardiovascular Responses in the Neuraxis of Cats
Authors: Farber Neil E. , Samso Enric , Kampine John P. , Schmeling William T.
Published: November 2003

Background

This study examined the effects of halothane on arterial pressure after central nervous system (CNS) pressor site stimulation in anesthetized cats, cats rendered unconscious by midcollicular transection, and conscious cats.

Methods

Two anesthetized groups and two nonanesthetized groups were used. Cats were anesthetized with either alpha-chloralose and urethane or pentobarbital. Nonanesthetized groups were cats with midcollicular transections or conscious cats with chronically implanted electrodes. Stimulating electrodes were placed into vasomotor areas of the hypothalamus (HYP), reticular formation (RF), and medulla, and arterial pressure responses to increasing stimulus currents were examined during different halothane concentrations. Two groups of cats were also anesthetized with either pentobarbital or urethane and underwent bilateral carotid artery occlusion.

Results

Stimulation at each CNS site produced increases in arterial pressure and heart rate. Halothane attenuated pressor responses evoked by stimulation of all loci in all groups of cats. The inhibition by halothane on these cardiovascular responses was greatest at HYP and RF sites, while the medulla was more resistant to the effects of halothane in the anesthetized animals. Midcollicular transection decreased this medullary resistance. The inhibition of pressor responses by halothane was also greater in pentobarbital-than chloralose urethane-anesthetized animals. In contrast, pressor responses elicited by bilateral carotid occlusion were attenuated by halothane similarly in both anesthetic groups. Reticular formation stimulation in conscious animals resulted in "altering responses" in addition to pressor effects, both of which were attenuated by halothane.

Conclusions

Modulation of CNS cardiovascular control centers contribute to halothane-induced hemodynamic alterations. Baseline anesthesia, CNS stimulation site, and the suprabulbar system influence the effects of halothane.
Halothane Inhibits Signaling through m1 Muscarinic Receptors Expressed in Xenopus Oocytes
Authors: Durieux Marcel E.
Published: November 2003

Background

Interactions between volatile anesthetics and muscarinic acetylcholine receptors have been studied primarily in binding assays or in functional systems derived from tissues or cells, often containing multiple receptor subtypes. Because interactions with muscarinic signaling systems may explain some effects and side effects of anesthetics and form a model for anesthetic-protein interactions in general, the author studied anesthetic inhibition of muscarinic signaling in an isolated system.

Methods

mRNA encoding the m1 muscarinic receptor subtype was prepared in vitro and expressed in Xenopus oocytes. Effects of halothane on methylcholine-induced intracellular Ca2+ release was measured. Angiotensin II receptors were expressed to evaluate anesthetic effects on intracellular signaling.

Results

m1 Receptors expressed in oocytes were functional, and could be inhibited by atropine and pirenzepine. Halothane depressed m1 muscarinic signaling in a dose-dependent manner: half-maximal inhibition of 10(-7) M methylcholine was obtained with 0.3 mM halothane. The effect was reversible and could be overcome by high concentrations of muscarinic agonist. Angiotensin II signaling was unaffected by 0.34 mM halothane.

Conclusions

m1 Muscarinic signaling is inhibited by halothane, and lack of halothane effect on angiotensin signaling indicates that the intracellular signaling systems of Xenopus oocytes are unaffected. Therefore, the most likely site of halothane action is the receptor and/or G protein. Oocytes provide a versatile system for detailed investigation into the molecular mechanism of anesthetic-protein interactions.
Cerebral Metabolism during Propofol Anesthesia in Humans Studied with Positron Emission Tomography
Authors: Alkire Michael T. , Haier Richard J. , Barker Steven J. , Shah Nitin K. , Wu Joseph C. , Kao James Y.
Published: November 2003

Background

Although the effects of propofol on cerebral metabolism have been studied in animals, these effects have yet to be directly examined in humans. Consequently, we used positron emission tomography (PET) to demonstrate in vivo the regional cerebral metabolic changes that occur in humans during propofol anesthesia.

Methods

Six volunteers each underwent two PET scans; one scan assessed awake-baseline metabolism, and the other assessed metabolism during anesthesia with a propofol infusion titrated to the point of unresponsiveness (mean rate +/- SD = 7.8 +/- 1.5 mg.kg-1.h-1). Scans were obtained using the 18fluorodeoxyglucose technique.

Results

Awake whole-brain glucose metabolic rates (GMR) averaged 29 +/- 8 mumoles.100 g-1.min-1 (mean +/- SD). Anesthetized whole-brain GMR averaged 13 +/- 4 mumoles.100 g-1.min-1 (paired t test, P < or = 0.007). GMR decreased in all measured areas during anesthesia. However, the decrease in GMR was not uniform. Cortical metabolism was depressed 58%, whereas subcortical metabolism was depressed 48% (P < or = 0.001). Marked differences within cortical regions also occurred. In the medial and subcortical regions, the largest percent decreases occurred in the left anterior cingulate and the inferior colliculus.

Conclusion

Propofol produced a global metabolic depression on the human central nervous system. The metabolic pattern evident during anesthesia was reproducible and differed from that seen in the awake condition. These findings are consistent with those from previous animal studies and suggest PET may be useful for investigating the mechanisms of anesthesia in humans.
The Effect of Pentoxifylline on Acid-induced Alveolar Epithelial Injury
Authors: Kudoh Ichidai , Ohtake Mika , Nishizawa Hideo , Kurahashi Kiyoyasu , Hattori Satoshi , Okumura Fukuichiro , Pittet Jean-Francois , Wiener-Kronish Jeanine
Published: November 2003

Background

Acid instillation into one lung is known to cause an increase in the permeability of the endothelium to protein in both the instilled and the contralateral lungs. Activated neutrophils are believed to be involved in causing this increased permeability. Pentoxifylline, a drug used in clinical practice, has multiple effects on neutrophils, including inhibition of phagocytosis, degranulation, and superoxide generation. This study investigated whether pretreatment with pentoxifylline would protect the alveolar epithelium or lung endothelium from injury.

Methods

The effect of acid instillation into one lung of anesthetized rabbits using several quantitative parameters was investigated. The quantification of the bidirectional movement of the alveolar (125I-albumin) and the circulating protein tracers (131I-albumin) was used as a measurement of the permeabilities of the lung epithelium and the lung endothelium in the acid-instilled lung. Bronchoalveolar lavage and measurement of the entry of the circulating protein tracer were used to assess the permeabilities of these barriers in the noninstilled lung.

Results

The instillation of HCl (pH 1.25, 1.2 ml/kg) into the right lung resulted in an increase in the protein permeability of the right lung's alveolar epithelium and endothelium as well as an increase in the permeability to protein of the left lung's endothelium. Pentoxifylline pretreatment attenuated the increase in the endothelial permeability of both lungs by 50% and restored the PaO2/FIO2 to normal in the pretreated animals exposed to acid injury.

Conclusions

Acid aspiration causes a dramatic increase in the alveolar epithelial permeability of the acid-instilled lung, but the permeability of the alveolar epithelium of the contralateral lung remains normal. In contrast, unilateral acid instillation causes an increase in the permeability of the endothelium of both lungs. The increase in endothelial permeability can be attenuated by pretreatment with pentoxifylline administration, and this leads to restoration of normal gas exchange.
Effects of Sevoflurane on Contractile Responses and Electrophysiologic Properties in Canine Single Cardiac Myocytes
Authors: Hatakeyama Noboru , Momose Yasunori , Ito Yusuke
Published: November 2003

Background

The effects of sevoflurane was examined on the contractile response, membrane potential, membrane ionic currents, and intracellular cyclic adenosine monophosphate (cAMP) in canine single ventricular myocytes.

Methods

Contraction was measured by a video-edge detector, and membrane ionic currents were recorded using whole-cell voltage clamp technique. Intracellular cAMP was measured with radioimmunoassay method.

Results

Sevoflurane (1.0-4.0%) decreased the contraction of single ventricular cells in a dose-dependent and reversible manner. Also, sevoflurane decreased the action potential plateau and shortened the duration of action potential. Sevoflurane reduced the peak Ca2+ currents (ICa) but did not show the use-dependent block. On the other hand, sevoflurane slightly reduced the Na+ currents (INa) only at a high concentration (4.0%). Intracellular cAMP concentration was reduced only at 4.0% sevoflurane.

Conclusions

The negative inotropic effect of sevoflurane is mediated via the inhibition of ICa in canine ventricular myocyte but not associated with reduced intracellular cAMP except at a high dose (4.0%).
Myocardial Effects of Propofol in Hamsters with Hypertrophic Cardiomyopathy
Authors: Riou Bruno , Lejay Marc , Lecarpentier Yves , Viars Pierre
Published: November 2003

Background

Propofol is a short-acting intravenous induction agent that induces cardiovascular depression but without significant effect on intrinsic myocardial contractility in various species. However, its effects on diseased myocardium remain unknown.

Methods

The effects of propofol (1, 3, and 10 micrograms.ml-1) on the intrinsic contractility of left ventricular papillary muscles from normal hamsters and those with hypertrophic cardiomyopathy (strain BIO 14.6, aged 6 months) were investigated in vitro (Krebs-Henseleit solution, 29 degrees C, pH 7.40, Ca++ 2.5 mmol.l-1, stimulation frequency 3/min).

Results

Cardiac hypertrophy (143 +/- 13%, P < 0.001) was observed in cardiomyopathic hamsters. The contractility of papillary muscles from hamsters with cardiomyopathy was less than that of controls, as shown by the decrease in maximum shortening velocity (-29%, P < 0.03) and active isometric force (-51%, P < 0.001). Propofol did not induce any significant effect on contraction, relaxation, and contraction-relaxation coupling under low and high loads in normal hamsters. The effects of propofol were not significantly different between normal hamsters and those with cardiomyopathy. A slight but significant increase in maximum unloaded shortening velocity was observed in cardiomyopathic hamsters at 3 micrograms.ml-1 (4 +/- 6%, P < 0.05) and 10 micrograms.ml-1 (7 +/- 6%, P < 0.05).

Conclusions

Propofol did not modify intrinsic myocardial contractility in normal hamsters, and no significant differences were observed between normal and cardiomyopathic hamsters. These results may be useful because, unlike propofol, most anesthetics decrease myocardial contractility. Nevertheless, indirect cardiac effects of propofol may be more important than its direct cardiac effects in patients with impaired cardiac function.
Effect of Vasoconstrictive Agents Added to Lidocaine on Intravenous Lidocaine-induced Convulsions in Rats
Authors: Yokoyama Masataka , Hirakawa Masahisa , Goto Hiroshi
Published: November 2003

Background

Epinephrine is reported to decrease the threshold of intravenous lidocaine-induced convulsions. However, the mechanism underlying this effect is not clear. Therefore, we carried out a study to examine the role of vasopressor-induced hypertension.

Methods

Fifty-six awake Wistar rats were assigned to seven groups of eight. All groups received a continuous intravenous infusion of lidocaine at a rate of 4 mg.kg-1.min-1 until generalized convulsions occurred. The control group (group C) received plain lidocaine. The acute hypertensive groups received lidocaine with epinephrine (group E), norepinephrine (group N), or phenylephrine (group P) to increase mean arterial blood pressure (MAP) to 150 +/- 5 mmHg. Sodium nitroprusside (SNP) was added to prevent an increase in mean arterial pressure in the remaining three groups (vasopressor-SNP groups).

Results

The acute hypertensive groups required significantly smaller cumulative doses of lidocaine to produce convulsions compared with control (C = 41.5 +/- 2.9 > E = 24.1 +/- 2.7, N = 27.1 +/- 2.8, P = 26.7 +/- 2.5 mg.kg-1; values are mean +/- SD, P < 0.01). In addition, plasma lidocaine concentrations (C = 11.0 +/- 0.7 > E = 7.4 +/- 0.5, N = 7.9 +/- 0.6, P = 8.1 +/- 0.8 micrograms.ml-1, P < 0.01) and brain lidocaine concentrations (C = 50.9 +/- 4.5 > E = 32.6 +/- 4.2, N = 34.5 +/- 4.8, P = 37.1 +/- 4.5 micrograms.g-1, P < 0.01) were less in the acute hypertensive groups at the onset of convulsions. In the vasopressor-SNP groups, the plasma and brain lidocaine concentrations at the onset of convulsions returned to the control values, although epinephrine and norepinephrine, but not phenylephrine, still decreased cumulative convulsant doses of lidocaine significantly (P < 0.01) compared with control (E + SNP = 30.8 +/- 2.9 < N + SNP = 34.8 +/- 2.8, P < 0.01) < P + SNP = 40.2 +/- 3.0 mg.kg-1, P < 0.01). The brain/plasma concentration ratios were similar for the seven groups.

Conclusions

An equal degree of acute hypertension induced by these three different vasopressors may play a role in reducing the threshold (plasma and brain lidocaine concentrations) as well as the cumulative convulsant doses associated with lidocaine-induced convulsions.
Effects of Perioperative Dexmedetomidine Infusion in Patients Undergoing Vascular Surgery
Authors: Talke P. , Li J. , Jain U. , Leung J. , Drasner K. , Hollenberg M. , Mangano D. T.
Published: November 2003

Background

Dexmedetomidine, a highly selective alpha 2-adrenergic agonist, increases perioperative hemodynamic stability in healthy patients but decreases blood pressure and heart rate. The goal of this study was to evaluate, in a preliminary manner, the hemodynamic effects of perioperatively administered dexmedetomidine in surgical patients at high risk for coronary artery disease.

Methods

Twenty-four vascular surgery patients received a continuous infusion of placebo or one of three doses of dexmedetomidine, targeting plasma concentrations of 0.15 ng/ml (low dose), 0.30 ng/ml (medium dose), or 0.45 ng/ml (high dose) from 1 h before induction of anesthesia until 48 h postoperatively. All patients received standardized anesthesia and hemodynamic management. Blood pressure, heart rate, and Holter ECG were monitored; additional monitoring included continuous 12-lead ECG preoperatively, anesthetic concentrations and myocardial wall motion (echocardiography) intraoperatively, and cardiac enzymes postoperatively.

Results

Preoperatively, there was a decrease in heart rate (low dose 11%, medium dose 5%, high dose 20%) and systolic blood pressure (low dose 3%, medium dose 12%, high dose 20%) in patients receiving dexmedetomidine. Intraoperatively, dexmedetomidine groups required more vasoactive medications to maintain hemodynamics within predetermined limits. Postoperatively, demedetomidine groups had less tachycardia (minutes/monitored hours) than the placebo group (placebo 23 min/h; low dose 9 min/h, P = 0.006; medium dose 0.5 min/h, P = 0.004; high dose 2.3 min/h, P = 0.004). Bradycardia was rare in all groups. There were no myocardial infarctions or discernible trends in the laboratory results.

Conclusions

Infusion of dexmedetomidine up to a targeted plasma concentration of 0.45 ng/ml appears to benefit perioperative hemodynamic management of surgical patients undergoing vascular surgery but required greater intraoperative pharmacologic intervention to support blood pressure and heart rate.
Comparison of the Neuromuscular Blocking Effect of Atracurium and Vecuronium on the Adductor Pollicis and the Geniohyoid Muscle in Humans
Authors: D'Honneur G. , Guignard B. , Slavov V. , Ruggler R. , Duvaldestin P.
Published: November 2003

Background

Residual paralysis of suprahyoid muscles may occur when the adductor pollicis response has completely recovered after the administration of a neuromuscular blocking agent. The response of the geniohyoid muscle to intubating doses of muscle relaxants is evaluated and compared to that of adductor pollicis.

Methods

Sixteen patients undergoing elective surgery under general anesthesia were given 5-7 mg.kg-1 thiopental and 2 micrograms.kg-1 fentanyl intravenously for induction of anesthesia. Eight (half) patients then received 0.5 mg.kg-1 atracurium, and the other eight received 0.1 mg.kg-1 vecuronium. The evoked response (twitch height, TH) of the adductor pollicis was monitored by measuring the integrated electromyographic response (AP EMG) on one limb and the mechanical response, using a force transducer (AP force), on the other. The activity of geniohyoid muscle (GH EMG) was measured using submental percutaneous electrodes. The following variables were measured: maximal TH depression; onset time for neuromuscular blockade to 50%, 90%, and maximal TH depression (OT50, OT90, and OTmax); times between administration of neuromuscular blocking agent and TH recovery to 10%, 25%, 50%, 75%, and 90% of control; and time for return of train-of-four ratio to return to 0.7.

Results

The principal findings were (1) OTmax was significantly (P < 0.01) shorter for geniohyoid than for adductor pollicis after either atracurium or vecuronium (OTmax was 216, 256, and 175 s for AP force, AP EMG, and GH EMG, with atracurium and 181, 199, and 144 s with vecuronium, respectively), and (2) the evoked EMG of geniohyoid recovered at the same speed as the EMG of adductor pollicis after an intubating dose of atracurium or vecuronium (recovery of TH to 75% of control at 50, 48, 42 min with AP force, AP EMG, and GH EMG with atracurium and 46, 45, and 42 min with vecuronium, respectively).

Conclusions

Once the adductor pollicis response has returned to normal values after a single intubating dose of atracurium or vecuronium, the risk of residual depression of the TH of the geniohyoid muscle, one of the principal muscles contributing to airway patency, appears unlikely.