bluuebunny/crossref_metadata_2025 huggingface dataset:
APOE ε3 Gene Transfer Attenuates Brain Damage after Experimental Stroke
Authors: McColl Barry W , McGregor Ailsa L , Wong Andrew , Harris Julian D , Amalfitano Andrea , Magnoni Sandra , Baker Andrew H , Dickson George , Horsburgh Karen
Published: June 2006

Apolipoprotein E (apoE, protein; APOE, gene) is the major lipid-transport protein in the brain and plays an important role in modulating the outcome and regenerative processes after acute brain injury. The aim of the present study was to determine if gene transfer of the ε3 form of APOE improves outcome in a murine model of transient focal cerebral ischaemia. Mice received an intrastriatal injection of vehicle, a second-generation adenoviral vector containing the green fluorescent protein gene (Ad-GFP) or a vector containing the APOE ε3 gene (Ad- APOE) 3 days before 60 mins focal ischaemia. Green fluorescent protein expression was observed in cells throughout the striatum and subcortical white matter indicating successful gene transfer and expression. ApoE levels in the brain were significantly increased after Ad- APOE compared with Ad-GFP or vehicle treatment. Ad- APOE treatment reduced the volume of ischaemic damage by 50% compared with Ad-GFP or vehicle treatment (13±3 versus 29±4 versus 27±5 mm3). The extent of postischaemic apoE immunoreactivity was enhanced in Ad- APOE compared with Ad-GFP or vehicle treated mice. These results show the ability of APOE gene transfer to markedly improve outcome after cerebral ischaemia and suggest that modulating apoE levels may be a potential strategy in human stroke therapy.
Ernährung hochbetagter Menschen in Geriatrie und Altenhilfe
Authors: Menebröcker Claudia
Published: June 2006

Der Alternsprozess ist mit zahlreichen physiologischen und physischen Veränderungen verbunden, die eine direkte Auswirkung auf die Ernährungssituation haben. Im Vordergrund der Maßnahmen stehen die Verhinderung von Mangelernährung und der Erhalt der Mobilität. Der Beitrag zeigt grundsätzliche Aspekte aber auch konkrete Beispiele für das Speisen- und Getränkeangebot in stationären Einrichtungen auf.
Knowledge: Climbing the Learning Ladder to a ‘Phenomenological’ View
Authors: Resca Andrea
Published: June 2006

Attempts to summarise Claudio Ciborra's work through a single theme cannot succeed due to its breadth and the ease in which he moved between subjects. This paper is a tentative attempt to discover a common theme in his work, with the notion of knowledge identified as an appropriate starting point. Encompassing learning and rationality, the theme of knowledge has been persistent and evolving in Ciborra's work, with three knowledge combinations reflecting its development: knowledge-rationality, knowledge-learning and everyday-knowledge. The first combination depicts rationality as a catalyst in the pursuit of specific objectives that determine knowledge. Ciborra continued his exploration of knowledge by theorising that background knowledge structure objectives were the basis of sense-making and organisational action, while short-term knowledge structure was required to address developing situations. This introduced and provided the foundation for the knowledge-learning combination. Ciborra's final knowledge combination was predicated on the interpretation of reality as created by the experiences of the individual, including participation in organisational life where feelings, moods and the totality of existence is expressed, delineating the everyday-knowledge combination in the process. Ciborra utilised these and other approaches like the learning ladder in his investigation of complex multilayered subjects like information systems, undertaken from among others, a phenomenological vantage point that shaped many of his key contributions.
RNAi-mediated silencing of estrogen receptor α in the ventromedial nucleus of hypothalamus abolishes female sexual behaviors
Authors: Musatov Sergei , Chen Walter , Pfaff Donald W. , Kaplitt Michael G. , Ogawa Sonoko
Published: June 2006

Estrogen receptor α (ERα) plays a major role in the regulation of neuroendocrine functions and behaviors by estrogens. Although the generation of ERα knockout mice advanced our knowledge of ERα functions, gene deletion using this method is global and potentially confounded by developmental consequences. To achieve a site-specific knockdown of ERα in the normally developed adult brain, we have generated an adeno-associated virus vector expressing a small hairpin RNA targeting ERα. After bilateral injection of this vector into the hypothalamic ventromedial nucleus in ovariectomized female mice, expression levels of ERα as well as the estrogen-inducible progesterone receptor were profoundly reduced despite the continued presence of this receptor elsewhere in the brain. Functionally, silencing of ERα in the ventromedial nucleus abolished female proceptive and receptive sexual behaviors while enhancing rejection behavior. These results provide evidence that adeno-associated virus-mediated long-term knockdown of genes can be used to delineate their effects on complex behaviors in discrete brain regions.
The acute myeloid leukemia fusion protein AML1-ETO targets E proteins via a paired amphipathic helix-like TBP-associated factor homology domain
Authors: Plevin Michael J. , Zhang Jinsong , Guo Chun , Roeder Robert G. , Ikura Mitsuhiko
Published: June 2006

Up to 15% of acute myeloid leukemias (AMLs) are characterized by the abnormal expression of the eight-twenty-one (ETO) transcriptional corepressor within an AML1-ETO fusion protein. The t(8;21) chromosomal translocation serves not only to disrupt WT AML1 function but also to introduce ETO activity during hematopoiesis. AML1-ETO was recently shown to inhibit E protein transactivation by physically displacing WT coactivator proteins in an interaction mediated by ETO. Here, we present the 3D solution structure of the human ETO TAFH (eTAFH) domain implicated in AML1-ETO:E protein interactions and report an unexpected fold similarity to paired amphipathic helix domains from the transcriptional corepressor Sin3. We identify and characterize a conserved surface on eTAFH that is essential for ETO:E protein recognition and show that the mutation of key conserved residues at this site alleviates ETO-based silencing of E protein transactivation. Our results address uncharacterized aspects of the corepression mechanism of ETO and suggest that eTAFH may serve to recruit ETO (or AML1-ETO) to DNA-bound transcription factors. Together, these findings imply that a cofactor exchange mechanism, analogous to that described for E protein inhibition, may represent a common mode of action for ETO.
Green primary explosives: 5-Nitrotetrazolato-
N
2
-ferrate hierarchies
Authors: Huynh My Hang V. , Coburn Michael D. , Meyer Thomas J. , Wetzler Modi
Published: June 2006

The sensitive explosives used in initiating devices like primers and detonators are called primary explosives. Successful detonations of secondary explosives are accomplished by suitable sources of initiation energy that is transmitted directly from the primaries or through secondary explosive boosters. Reliable initiating mechanisms are available in numerous forms of primers and detonators depending upon the nature of the secondary explosives. The technology of initiation devices used for military and civilian purposes continues to expand owing to variations in initiating method, chemical composition, quantity, sensitivity, explosive performance, and other necessary built-in mechanisms. Although the most widely used primaries contain toxic lead azide and lead styphnate, mixtures of thermally unstable primaries, like diazodinitrophenol and tetracene, or poisonous agents, like antimony sulfide and barium nitrate, are also used. Novel environmentally friendly primary explosives are expanded here to include cat[Fe
II
(NT)
3
(H
2
O)
3
], cat
2
[Fe
II
(NT)
4
(H
2
O)
2
], cat
3
[Fe
II
(NT)
5
(H
2
O)], and cat
4
[Fe
II
(NT)
6
] with cat = cation and NT
−
= 5-nitrotetrazolato-
N
2
. With available alkaline, alkaline earth, and organic cations as partners, four series of 5-nitrotetrazolato-
N
2
-ferrate hierarchies have been prepared that provide a plethora of green primaries with diverse initiating sensitivity and explosive performance. They hold great promise for replacing not only toxic lead primaries but also thermally unstable primaries and poisonous agents. Strategies are also described for the systematic preparation of coordination complex green primaries based on appropriate selection of ligands, metals, and synthetic procedures. These strategies allow for maximum versatility in initiating sensitivity and explosive performance while retaining properties required for green primaries.
The QseC sensor kinase: A bacterial adrenergic receptor
Authors: Clarke Marcie B. , Hughes David T. , Zhu Chengru , Boedeker Edgar C. , Sperandio Vanessa
Published: June 2006

Quorum sensing is a cell-to-cell signaling mechanism in which bacteria respond to hormone-like molecules called autoinducers (AIs). The AI-3 quorum-sensing system is also involved in interkingdom signaling with the eukaryotic hormones epinephrine/norepinephrine. This signaling activates transcription of virulence genes in enterohemorrhagic
Escherichia coli
O157:H7. However, this signaling system has never been shown to be involved in virulence
in vivo
, and the bacterial receptor for these signals had not been identified. Here, we show that the QseC sensor kinase is a bacterial receptor for the host epinephrine/norepinephrine and the AI-3 produced by the gastrointestinal microbial flora. We also found that an α-adrenergic antagonist can specifically block the QseC response to these signals. Furthermore, we demonstrated that a
qseC
mutant is attenuated for virulence in a rabbit animal model, underscoring the importance of this signaling system in virulence
in vivo
. Finally, an
in silico
search found that the periplasmic sensing domain of QseC is conserved among several bacterial species. Thus, QseC is a bacterial adrenergic receptor that activates virulence genes in response to interkingdom cross-signaling. We anticipate that these studies will be a starting point in understanding bacterial–host hormone signaling at the biochemical level. Given the role that this system plays in bacterial virulence, further characterization of this unique signaling mechanism may be important for developing novel classes of antimicrobials.
Accuracy of Healthcare Worker Recall and Medical Record Review for Identifying Infectious Exposures to Hospitalized Patients
Authors: Aquino M. , Raboud J. M. , McGeer A. , Green K. , Chow R. , Dimoulas P. , Loeb M. , Scales D.
Published: June 2006

Objective.

To determine the validity of using healthcare worker (HCW) recall of patient interactions and medical record review for contact tracing in a critical care setting.

Design.

Trained observers recorded the interactions of nurses, respiratory therapists, and service assistants with study patients in a medical-surgical intensive care unit. These observers' records were used as the reference standard to test the criterion validity of using HCW recall data or medical record review data to identify exposure characteristics. We assessed the effects of previous quarantine of the HCW (because of possible exposure) and the availability of patients' medical records for use as memory aids on the accuracy of HCW recall.

Setting.

A 10-bed medical-surgical intensive care unit at Mount Sinai Hospital in Toronto, Ontario.

Patients.

Thirty-six HCWs observed caring for 16 patients, for a total of 55 healthcare worker shifts.

Results.

Recall accuracy was better among HCWs who were provided with patient medical records as memory aids (P<.01). However, HCWs tended to overestimate exposures when they used patient medical records as memory aids. For 6 of 26 procedures or care activities, this tendency to overestimate was statistically significant (P<.05). Most HCWs with true exposures were identified by means of this technique, despite the overestimations. Documentation of the activities of the 4 service assistants could not be found in any of the patients' medical records. Similarly, the interactions between 6 (19%) of 32 other patient–HCW pairs were not recorded in patients' medical records.

Conclusions.

Data collected from follow-up interviews with HCWs in which they are provided with patient medical records as memory aids should be adequate for contact tracing and for determining exposure histories. Neither follow-up interviews nor medical record review alone provide sufficient data for these purposes.
Dissemination of IMP-1 Metallo-β-Lactamase–Producing Acinetobacter Species in a Brazilian Teaching Hospital
Authors: Tognim Maria C. B. , Gales Ana C. , Penteado Andréia P. , Silbert Suzane , Sader Hélio S.
Published: June 2006

Objective.

To evaluate the emergence and dissemination of metallo-β-lactamase (MBL)–producing Acinetobacter species.

Design.

All carbapenem-resistant Acinetobacter strains (1 strain per patient) collected during the period 1993–2001 were evaluated.

Setting.

A Brazilian tertiary care teaching hospital (Hospital São Paulo, São Paulo).

Methods.

Seventy-three strains of carbapenem-resistant Acinetobacter species were recovered from the organism bank of the hospital. All isolates were tested for antimicrobial susceptibility by broth microdilution methods, and the production of MBL was initially assessed by phenotypic tests (MBL Etest strip and a disk approximation test). The MBL enzymes were identified by polymerase chain reaction using primers for blaIMP’, blaVIM’, and blaSPM’ followed by gene sequencing. Genetic similarity among the carbapenem-resistant strains was evaluated by automated ribotyping.

Results.

Only colistin and ampicillin-sulbactam showed reasonable in vitro activity against carbapenem-resistant isolates (97% and 74% of isolates susceptible, respectively). More than half of the isolates (55%) had a positive MBL phenotypic test result and a positive polymerase chain reaction result for blaIMP_1 The proportion of IMP-1–producing Acinetobacter isolates among carbapenem-resistant strains increased from 0% in the 1993-1997 period to 29% in 1998 and 100% in the 1999-2001 period. No carbapenem-resistant Acinetobacter isolates that harbored blaVIM or blaSPM were detected. Molecular typing results revealed 20 ribogroups among carbapenem-resistant isolates. During the study period of 1994-2001, we identified 2 major ribogroups, 52-1 (MBL-negative and MBL-positive strains) and 60-7 (MBL-positive strains), that had a coefficient of similarity of 0.85 or higher.

Conclusions.

Our results indicate that IMP-1–producing strains of Acinetobacter emerged in our institution in 1998. Since then, production of this MBL was detected not only in the major ribogroups of carbapenem-resistant Acinetobacter species but also among isolates that belonged to 17 distinct ribogroups, indicating that this important mechanism of antimicrobial resistance was disseminated among distinct clones.
Control ofLegionella pneumophilaContamination in a Respiratory Hydrotherapy System With Sulfurous Spa Water
Authors: Leoni E. , Sacchetti R. , Zanetti F. , Legnani P. P.
Published: June 2006

Objective.

To evaluate the effectiveness of different disinfection treatments in a spa water system contaminated byLegionella pneumophilaand associated with a case ofLegionellapneumonia.

Design.

During an 18-month period, the spa water was analyzed by taking samples from the well, the recirculation line, and the final distribution devices (nebulizers and nasal irrigators). Various attempts were made to eradicateLegionellaorganisms by chemical and thermal shock. The final protocol consisted of heat shock treatment at 70°C-75°C for 3 hours, 2 nights per week, followed by a lowering of the water temperature to 30°C ± 1°C for use in the plant. In addition, 3 times a week superheated steam (at a pressure of 1 atmosphere) was introduced for 1 hour into the nebulization machines.

Setting.

A spa at which sulfurous water was used for hydrotherapy by means of aerosol and nasal irrigation.

Patient.

A 74-year-old woman with legionnaires disease.

Results.

After the case of infection occurred,L. pneumophilawas isolated from the recirculation line at a concentration of 400,000 cfu/L and from the nebulizers and nasal irrigators at levels ranging from 3,300 to 1,800,000 cfu/L. The colonizing organisms consisted of a mixture ofL. pneumophilaserogroup 1 (12%) and serogroup 5 (88%). The shock treatment with chlorine dioxide and peracetic acid resulted in the eradication ofLegionellaorganisms from the recirculation line but not from the water generated from the final distribution devices. After the restructuring of the plant and the application of thermal shock protocol, an evaluation after 12 months revealed no evidence ofLegionellacontamination.

Conclusion.

To preventLegionellacolonization, disinfection treatment is effective if associated with carefully selected materials, good circuit design, and good maintenance practices.
Acquisition of Multidrug-ResistantSerratia marcescensby Critically Ill Patients Who Consumed Tap Water During Receipt of Oral Medication
Authors: Horcajada Juan P. , Martinez Jose Antonio , Alcón Amalia , Marco Francesc , Lazzari Elisa De , Matos Anastacio de , Zaragoza Magda , Sallés Montse , Zavala Elisabeth , Mensa Josep
Published: June 2006

We describe an outbreak of multidrug-resistantSerratia marcescensinfection and colonization involving adults admitted to a surgical intensive care unit. Examination of the outbreak revealed epidemiological evidence that consumption of tap water from a contaminated faucet during receipt of oral medication was the mechanism ofS. marcescensacquisition.
Hospital-Acquired Pneumonia in the Intensive Care Units of Polish Hospitals
Authors: Wójkowska-Mach Jadwiga , Bulanda Małgorzata , Różańska Anna , Kochan Piotr , Heczko Piotr B.
Published: June 2006

We analyzed the epidemiological characteristics of pneumonia in intensive care units of Polish hospitals. Among 11,587 patients, there were 191 cases of hospital-acquired pneumonia (HAP). The incidence of HAP was 5.6%, and that of ventilator-associated pneumonia (VAP) was 17.9%. The overall mortality rate was 12.6%, and the mortality rate for patients who received artificial ventilation was 15.0%. The predominant organisms causing HAP and VAP were Pseudomonas aeruginosa and Escherichia coli, and 21.1% of Staphylococcus aureus isolates were resistant to methicillin.
Risk Factors for Surgical Site Infection in Children
Authors: Casanova Juan Francisco , Herruzo Rafael , Díez Jesús
Published: June 2006

Objectives.

To assess the appropriateness of using the indices developed by the Study on the Efficacy of Nosocomial Infection Control (SENIC) and the National Nosocomial Infections Surveillance (NNIS) project to determine risk factors for surgical site infection (SSI) in children and, if not appropriate, to explore the factors related to SSI in children so these factors could be used in a risk index for pediatric patients.

Design.

Cohort study during more than 4 years.

Setting.

La Paz University Hospital, a national reference center that serves Health Area 5 of Madrid, Spain, which has approximately 500,000 inhabitants.

Patients.

Convenience sample consisting of the 3,646 children admitted for surgery who had a postsurgical stay of more than 2 days.

Results.

A model with 8 predictive factors (degree of surgical contamination; duration of surgery; type of surgery; use of a peripheral venous catheter, central venous catheter, or urinary catheter; number of diagnoses; and SSI exposition time) was created. Its relation to the SSI rate was better than that of the SENIC or NNIS indices. Its sensitivity, specificity, and area under the receiver–operating characteristic curve were higher than that of the SENIC index.

Conclusions.

The model that we created seems to be more adequate for predicting SSI and evaluating pediatric patients' intrinsic risk than the SENIC and NNIS indices.
Characteristics of Programs Involving Canine Visitation of Hospitalized People in Ontario
Authors: Lefebvre Sandra L. , Waltner-Toews David , Peregrine Andrew , Reid-Smith Richard , Hodge Leslie , Weese J. Scott
Published: June 2006

Objective.

To determine the distribution of canine-visitation programs in Ontario and to characterize the nature of the programs the dogs are affiliated with.

Design.

A cross-sectional survey of hospitals in Ontario was used to determine whether they permitted dogs to visit patients and, if so, where the dogs originated. On the basis of this information, dog owners were then contacted through their respective associations and interviewed using a standardized questionnaire.

Setting.

A cross-section of hospitals in Ontario.

Participants.

A total of 223 (97%) of the 231 hospitals surveyed responded. Ninety owners of 102 visitation dogs were interviewed.

Results.

A total of 201 (90%) of the 223 hospitals indicated that dogs were permitted in their facilities. Origins ranged from national therapy-dog agencies to the patients' families. Acute care wards were 5.1 times as likely than other wards to disallow animals (95% confidence interval, 2.2-12.2;P<.001). According to the 90 dog owners included in the study, the screening protocols that dogs were required to pass to participate in their respective visitation programs were highly variable, as were the owners' infection control practices. Eighteen owners (20%) said they did not practice any infection control. Sixty-six owners (73%) allowed their dogs on patients' beds, and 71 (79%) let their dogs lick patients. Thirty-six owners (40%) were unable to name one zoonotic disease that may be transmitted from their dog.

Conclusions.

Although canine-visitation programs have become standard practice in nonacute human healthcare facilities, infection control and dog-screening practices are highly variable and potentially deficient. Hospital staff, visitation groups, pet owners, and veterinarians need to work together to protect both people and pets.
Dog Bite Transmission of Antibiotic-Resistant Bacteria to a Human
Authors: Johnson Jennifer K. , Perencevich Eli N. , Lincalis Durry P. , Venezia Richard A.
Published: June 2006

The prevalence of multidrug-resistant bacteria in the community is increasing, and companion animals serve as a potential reservoir for such bacteria. This report describes a case of a companion dog that was treated with multiple courses of antibiotics for a chronic illness and transmitted multidrug-resistant bacteria to a human through a bite.
Increasing Antibiotic Resistance Among Isolates ofEscherichia coliRecovered From Inpatients and Outpatients in a Saudi Arabian Hospital
Authors: Al-Tawfiq Jaffar A.
Published: June 2006

Objective.

To study the pattern of antibiotic resistance amongEscherichia coliand the trend in resistance during a 6-year period in a Saudi Arabian hospital.

Design.

Retrospective in vitro surveillance study of the antibiotic susceptibility pattern amongE. coliisolates recovered from outpatients and from inpatients.

Setting.

A general hospital in Saudi Arabia.

Patients.

All patients with a culture positive forE. coliduring a 6-year study period.

Results.

A statistically significant increase in antibiotic resistance was observed among outpatient and inpatient isolates ofE, coli.Inpatient isolates were more likely to be resistant to antimicrobial agents. Among isolates from outpatients, 50% were resistant to ampicillin, 33% were resistant to trimethoprim-sulfamethoxazole (TMP-SMZ), and 14% were resistant to ciprofloxacin. Among isolates from inpatients, 63% were resistant to ampicillin, 44% were resistant to TMP-SMZ, and 33% were resistant to ciprofloxacin. There was a low rate of resistance to imipenem (0.3% of isolates), amikacin (2%), and nitrofurantoin (2.4%-6.5%). Resistance to ceftazidime was detected in 9% of outpatient isolates and 17% of inpatient isolates. Multidrug resistance was defined as resistance to 2 or more classes of antibiotics. Multidrug resistance was detected in 2.0%-28.1% of outpatient isolates and 7.4%-39.6% of inpatient isolates, depending on the combination of antimicrobials tested. More isolates were resistant to ampicillin plus TMP-SMZ than to any other combination of antimicrobials.

Conclusion.

The prevalence of antibiotic resistance among outpatient and inpatientE. coliisolates increased during the study period. The rates of antibiotic resistance were statistically significantly higher among inpatient isolates, compared with outpatient isolates. These findings call for wiser use of antibiotics and continued surveillance of antibiotic resistance.
Comparison of Unit-Specific and Hospital-Wide Antibiograms Potential Implications for Selection of Empirical Antimicrobial Therapy
Authors: Binkley Shawn , Fishman Neil O. , LaRosa Lori A. , Marr Ann Marie , Nachamkin Irving , Wordell David , Bilker Warren B. , Lautenbach Ebbing
Published: June 2006

Objective.

To identify differences between unit-specific and hospital-wide antibiograms and to determine the potential impact of these differences on selection of empirical antimicrobial therapy.

Setting.

A 625-bed tertiary care medical center.

Methods.

Antimicrobial susceptibility results were collected for all inpatient clinical bacterial isolates recovered over a 3-year period; isolates were categorized by the hospital location of the patient at the time of sampling and by the anatomic site from which the isolate was recovered. Antibiograms from each unit were compiled for the most commonly isolated organisms and were compared to the hospital-wide antibiogram.

Results.

A total of 9,970 bacterial isolates were evaluated in this study, including 2,646 enterococcal isolates, 2,806 S. aureus isolates, 2,795 E. coli isolates, and 1,723 Pseudomonas aeruginosa isolates. The percentages of bacterial isolates resistant to antimicrobials were significantly higher in the medical ICU and surgical ICU than the hospital-wide antibiogram would have predicted, whereas the percentages of isolates susceptible to antimicrobials were significantly higher in the non-ICU units, compared with the hospital overall. However, on general medicine units, the prevalence of susceptibility to levofloxacin was significantly lower than that for the hospital overall.

Conclusions.

Unit-specific antibiograms are important for making informed decisions about empirical antimicrobial therapy, because the hospital-wide antibiogram may mask important differences in susceptibility rates across different units. These differences may have important implications for selecting the optimal empirical antimicrobial therapy.
Interscalene Brachial Plexus Block: Can the Risk of Entering the Spinal Canal Be Reduced?
Authors: Sardesai Anand M. , Patel Roger , Denny Nicholas M. , Menon David K. , Dixon Adrian K. , Herrick Martin J. , Harrop-Griffiths Alan W.
Published: June 2006

Background

Spinal cord damage during interscalene brachial plexus block has been attributed to needle entry into the spinal canal. The purpose of this study was to identify the angles and depths of needle insertion that increase the likelihood of such an event, using the traditional classic interscalene approach and two more proximal entry points.

Method

Magnetic resonance images of the neck from 10 healthy volunteers were used to obtain the three-dimensional spatial coordinates of three skin markers and the right-sided cervical nerves at the exiting neural foramina. The distance of the intervertebral foramina from the skin markers and the angles of the needle vector and the foramina were calculated.

Results

The distance from the skin to the intervertebral foramen may be as short as 2.5 cm with the classic approach. A caudal angulation greater than 50 degrees seemed to eliminate the risk of needle entry through the foramen.

Conclusion

With the classic approach to the interscalene block, there is a greater possibility of the needle passing through the intervertebral foramen if the needle is advanced too deeply. More proximal entry points and techniques that use a more steeply angled needle may reduce the risk of entry into the spinal space.
Cerebral State Index during Propofol Anesthesia
Authors: Jensen Erik W. , Litvan Hector , Revuelta Miren , Rodriguez Bernardo E. , Caminal Pere , Martinez Pablo , Vereecke Hugo , Struys Michel M. R. F.
Published: June 2006

Background

The objective of this study was to prospectively test the Cerebral State Index designed for measuring the depth of anesthesia. The Cerebral State Index is calculated using a fuzzy logic combination of four subparameters of the electroencephalographic signal. The performance of the Cerebral State Index was compared with that of the Bispectral Index and the A-Line ARX Index.

Methods

This study applied raw data from two previously published clinical protocols. The patients in protocol 1 were given a continuous propofol infusion, 300 ml/h, until 80% of burst suppression occurred. In protocol 2, a stepwise increased target-controlled infusion of propofol was administered to patients until loss of response to noxious stimuli while the Observer's Assessment of Alertness and Sedation was registered every 4 min. The Cerebral State Index was calculated off-line from the recorded electroencephalographic data. The Spearman rank correlation coefficient between electronic indices and the effect site concentration of propofol was calculated along with the prediction probability of each index to predict the Observer's Assessment of Alertness and Sedation level.

Results

The Spearman rank correlation coefficients between the Cerebral State Index, Bispectral Index, and A-Line ARX Index and the propofol effect site concentration were -0.94, -0.89, and -0.82, respectively, in protocol 1, whereas the prediction probability values between the Cerebral State Index, Bispectral Index, and A-Line ARX Index and the Observer's Assessment of Alertness and Sedation score in protocol 2 were 0.92, 0.93, and 0.91, respectively.

Conclusion

The Cerebral State Index detects well the graduated levels of propofol anesthesia when compared with the propofol effect site concentration and the Observer's Assessment of Alertness and Sedation score.
Naloxone Reversal of Buprenorphine-induced Respiratory Depression
Authors: van Dorp Eveline , Yassen Ashraf , Sarton Elise , Romberg Raymonda , Olofsen Erik , Teppema Luc , Danhof Meindert , Dahan Albert
Published: June 2006

Background

The objective of this investigation was to examine the ability of the opioid antagonist naloxone to reverse respiratory depression produced by the mu-opioid analgesic, buprenorphine, in healthy volunteers. The studies were designed in light of the claims that buprenorphine is relatively resistant to the effects of naloxone.

Methods

In a first attempt, the effect of an intravenous bolus dose of 0.8 mg naloxone was assessed on 0.2 mg buprenorphine-induced respiratory depression. Next, the effect of increasing naloxone doses (0.5-7 mg, given over 30 min) on 0.2 mg buprenorphine-induced respiratory depression was tested. Subsequently, continuous naloxone infusions were applied to reverse respiratory depression from 0.2 and 0.4 mg buprenorphine. All doses are per 70 kg. Respiration was measured against a background of constant increased end-tidal carbon dioxide concentration.

Results

An intravenous naloxone dose of 0.8 mg had no effect on respiratory depression from buprenorphine. Increasing doses of naloxone given over 30 min produced full reversal of buprenorphine effect in the dose range of 2-4 mg naloxone. Further increasing the naloxone dose (doses of 5 mg or greater) caused a decline in reversal activity. Naloxone bolus doses of 2-3 mg, followed by a continuous infusion of 4 mg/h, caused full reversal within 40-60 min of both 0.2 and 0.4 mg buprenorphine-induced respiratory depression.

Conclusions

Reversal of buprenorphine effect is possible but depends on the buprenorphine dose and the correct naloxone dose window. Because respiratory depression from buprenorphine may outlast the effects of naloxone boluses or short infusions, a continuous infusion of naloxone may be required to maintain reversal of respiratory depression.
Selective γ-Aminobutyric Acid Type A Receptor Antagonism Reverses Isoflurane Ischemic Neuroprotection
Authors: Elsersy Hazem , Mixco Javier , Sheng Huaxin , Pearlstein Robert D. , Warner David S.
Published: June 2006

Background

Isoflurane provides protection against severe forebrain ischemia in the rat. The authors hypothesized that this is attributable to interaction with the gamma-aminobutyric acid type A (GABAA) receptor resulting in altered time to onset of ischemic hippocampal depolarization.

Methods

Organotypic hippocampal slices were subjected to oxygen-glucose deprivation in the presence of isoflurane and combinations of GABAA (bicuculline) and GABAB (phaclofen) receptor antagonists. Cell death was measured. Rats were subjected to severe forebrain ischemia while anesthetized with fentanyl-nitrous oxide or 1.4% isoflurane. In the isoflurane group, rats also received intravenous bicuculline (0, 1, or 2 mg/kg). Neurologic and histologic outcomes and time to depolarization were assessed.

Results

In slices, 2% isoflurane caused near-complete protection against oxygen-glucose deprivation. This was unaffected by coadministration of phaclofen but largely reversed by bicuculline. The GABAA agonist muscimol was also protective, having an effect equivalent to 1% isoflurane. In rats, isoflurane (0 mg bicuculline) improved neurologic and histologic outcome versus fentanyl-nitrous oxide (CA1 percentage of alive neurons: fentanyl-nitrous oxide, 15 +/- 7; isoflurane, 61 +/- 24). The isoflurane effect was reversed in a dose-dependent manner by bicuculline (CA1 percentage alive: 1 mg/kg, 44 +/- 22; 2 mg/kg, 21 +/- 15). Time to depolarization was delayed with isoflurane versus fentanyl-nitrous oxide (137 vs. 80 s) but was not affected by bicuculline (149 s). In contrast, postischemic time to repolarization was more rapid with fentanyl-nitrous oxide or isoflurane plus bicuculline versus isoflurane alone.

Conclusions

These studies are consistent with the hypothesis that the GABAA receptor serves as a major site of action for isoflurane neuroprotection both in vitro and in vivo. However, the mechanism by which this interaction confers in vivo protection cannot be attributed to effects on the duration of ischemic depolarization.
Biologically Variable Ventilation Improves Oxygenation and Respiratory Mechanics during One-lung Ventilation
Authors: McMullen Michael C. , Girling Linda G. , Graham M Ruth , Mutch W Alan C.
Published: June 2006

Background

Hypoxemia is common during one-lung ventilation (OLV). Atelectasis contributes to the problem. Biologically variable ventilation (BVV), using microprocessors to reinstitute physiologic variability to respiratory rate and tidal volume, has been shown to be advantageous over conventional monotonous control mode ventilation (CMV) in improving oxygenation during the period of lung reinflation after OLV in an experimental model. Here, using a porcine model, the authors compared BVV with CMV during OLV to assess gas exchange and respiratory mechanics.

Methods

Eight pigs (25-30 kg) were studied in each of two groups. After induction of anesthesia-tidal volume 12 ml/kg with CMV and surgical intervention-tidal volume was reduced to 9 ml/kg. OLV was initiated with an endobronchial blocker, and the animals were randomly allocated to either continue CMV or switch to BVV for 90 min. After OLV, a recruitment maneuver was undertaken, and both lungs were ventilated for a further 60 min. At predetermined intervals, hemodynamics, respiratory gases (arterial, venous, and end-tidal samples) and mechanics (airway pressures, static and dynamic compliances) were measured. Derived indices (pulmonary vascular resistance, shunt fraction, and dead space ventilation) were calculated.

Results

By 15 min of OLV, arterial oxygen tension was greater in the BVV group (group x time interaction, P = 0.003), and shunt fraction was lower with BVV from 30 to 90 min (group effect, P = 0.0004). From 60 to 90 min, arterial carbon dioxide tension was lower with BVV (group x time interaction, P = 0.0001) and dead space ventilation was less from 60 to 90 min (group x time interaction, P = 0.0001). Static compliance was greater by 60 min of BVV and remained greater during return to ventilation of both lungs (group effect, P = 0.0001).

Conclusions

In this model of OLV, BVV resulted in superior gas exchange and respiratory mechanics when compared with CMV. Improved static compliance persisted with restoration of two-lung ventilation.
Distinct Roles for Sarcolemmal and Mitochondrial Adenosine Triphosphate-sensitive Potassium Channels in Isoflurane-induced Protection against Oxidative Stress
Authors: Marinovic Jasna , Bosnjak Zeljko J. , Stadnicka Anna
Published: June 2006

Background

Cardiac preconditioning, including that induced by halogenated anesthetics, is an innate protective mechanism against ischemia-reperfusion injury. The adenosine triphosphate-sensitive potassium (K(ATP)) channels are considered essential in preconditioning mechanism. However, it is unclear whether K(ATP) channels are triggers initiating the preconditioning signaling, and/or effectors responsible for the cardioprotective memory and activated during ischemia-reperfusion.

Methods

Adult rat cardiomyocytes were exposed to oxidative stress with 200 microM H(2)O(2) and 100 microM FeSO4. Myocyte survival was determined based on morphologic characteristics and trypan blue exclusion. To induce preconditioning, the myocytes were pretreated with isoflurane. The involvement of sarcolemmal and mitochondrial K(ATP) channels was investigated using specific inhibitors HMR-1098 and 5-hydroxydecanoic acid. Data are expressed as mean +/- SD.

Results

Oxidative stress induced cell death in 47 +/- 14% of myocytes. Pretreatment with isoflurane attenuated this effect to 26 +/- 8%. Blockade of the sarcolemmal K(ATP) channels abolished the protection by isoflurane pretreatment when HMR-1098 was applied throughout the experiment (50 +/- 21%) or only during oxidative stress (50 +/- 12%), but not when applied during isoflurane pretreatment (29 +/- 13%). Inhibition of the mitochondrial K(ATP) channels abolished cardioprotection irrespective of the timing of 5-hydroxydecanoic acid application. Cell death was 42 +/- 23, 45 +/- 23, and 46 +/- 22% when 5-hydroxydecanoic acid was applied throughout the experiment, only during isoflurane pretreatment, or only during oxidative stress, respectively.

Conclusion

The authors conclude that both sarcolemmal and mitochondrial K(ATP) channels play essential and distinct roles in protection afforded by isoflurane. Sarcolemmal K(ATP) channel seems to act as an effector of preconditioning, whereas mitochondrial K(ATP) channel plays a dual role as a trigger and an effector.
Low-dose Intravenous Ketamine Potentiates Epidural Analgesia after Thoracotomy
Authors: Suzuki Manzo , Haraguti Syuji , Sugimoto Kikuzo , Kikutani Takehiko , Shimada Yoichi , Sakamoto Atsuhiro
Published: June 2006

Background

Ketamine potentiates intravenous or epidural morphine analgesia. The authors hypothesized that very-low-dose ketamine infusion reduces acute and long-term postthoracotomy pain.

Methods

Forty-nine patients scheduled to undergo open thoracotomy were randomly assigned to receive one of two anesthesia regimens: continuous epidural infusion of ropivacaine and morphine, along with intravenous infusion of ketamine (0.05 mg . kg(-1) . h(-1) [approximately 3 mg/h], ketamine group, n = 24) or placebo (saline, control group, n = 25). Epidural analgesia was continued for 2 days after surgery, and infusion of ketamine or placebo was continued for 3 days. Pain was assessed at 6, 12, 24, and 48 h after surgery. Patients were asked about their pain, abnormal sensation on the wound, and inconvenience in daily life at 7 days and 1, 3, and 6 months after surgery.

Results

The visual analog scale scores for pain at rest and on coughing 24 and 48 h after thoracotomy were lower in the ketamine group than in the control group (pain at rest, 9 +/- 11 vs. 25 +/- 20 and 9 +/- 11 vs. 18 +/- 13; pain on coughing, 26 +/- 16 vs. 50 +/- 17 and 30 +/- 18 vs. 43 +/- 18, mean +/- SD; P = 0.002 and P = 0.01, P < 0.0001 and P = 0.02, respectively). The numerical rating scale scores for baseline pain 1 and 3 months after thoracotomy were significantly lower in the ketamine group (0.5 [0-4] vs. 2 [0-5] and 0 [0-5] vs. 1.5 [0-6], median [range], respectively; P = 0.02). Three months after surgery, a higher number of control patients were taking pain medication (2 vs. 9; P = 0.03).

Conclusions

Very-low-dose ketamine (0.05 mg . kg(-1) . h(-1)) potentiated morphine-ropivacaine analgesia and reduced postthoracotomy pain.
Effects of Bupivacaine and Tetrodotoxin on Carrageenan-induced Hind Paw Inflammation in Rats (Part 2)
Authors: Beloeil Hélène , Ji Ru-Rong , Berde Charles B.
Published: June 2006

Background

The authors previously showed that bupivacaine and tetrodotoxin via contralateral or ipsilateral sciatic block, but not systemically, attenuate local edema and hyperalgesia induced by carrageenan hind paw injection in rats. Bupivacaine, by all three routes, suppressed systemic cytokine activation, whereas tetrodotoxin was ineffective by all three routes. In the current study, the authors examined cytokine and p38 mitogen-activated protein kinase (MAPK) activation in lumbar dorsal root ganglia (DRGs) and spinal cord after carrageenan paw injections and sciatic blocks with either bupivacaine or tetrodotoxin.

Methods

Ten groups of rats (n = 3-5) received injections in the following sites: right or left hind paw or right forepaw (carrageenan or saline) and left sciatic block (with epinephrine plus bupivacaine, tetrodotoxin, or saline; repeated 6 h later). Fifteen hours later, tumor necrosis factor alpha, interleukin 1beta, p38 MAPK, and phosphorylated p38 MAPK were measured by enzyme-linked immunosorbent assay in DRGs and in the spinal cord.

Results

Carrageenan-induced hind paw inflammation enhanced tumor necrosis factor-alpha and interleukin-1beta production in bilateral DRGs and spinal cord and enhanced p38 MAPK activation in bilateral DRGs. These pathways were not activated after forepaw injection of carrageenan, suggesting a segmental mechanism. Neither bupivacaine nor tetrodotoxin inhibited cytokine and p38 MAPK activation after carrageenan injection.

Conclusion

Ipsilateral or contralateral sciatic blockade using either bupivacaine or tetrodotoxin does not inhibit carrageenan-induced activation of cytokines and p-38 MAPK in spinal cord and DRGs. Possible explanations may include incomplete degrees of conduction blockade or afferent signaling via saphenous nerves.
Cerebrospinal Fluid and Spinal Cord Distribution of Baclofen and Bupivacaine during Slow Intrathecal Infusion in Pigs
Authors: Bernards Christopher M.
Published: June 2006

Background

Increasing numbers of patients are receiving chronic intrathecal infusions of local anesthetics, baclofen, opioids, and other analgesics via implanted pumps. These infusions typically deliver drugs at rates measured in microliters per hour. However, to date, there have been no studies aimed at characterizing drug distribution within cerebrospinal fluid (CSF) and spinal cord during these slow infusion rates. Therefore, this study was designed to address this knowledge gap.

Methods

Anesthetized pigs were instrumented with eight intrathecal microdialysis probes placed at multiple points along the neuroaxis in both the anterior and posterior intrathecal space to permit continuous CSF sampling for measurement of bupivacaine and baclofen concentrations. Animals were divided into three groups and received bupivacaine and baclofen infusions at 20 or 1,000 microl/h or as a 1,000-microl bolus over 5 min every hour. Drug administration continued for 8 h, at which time the animals were killed, and the spinal cord was removed and divided into 1-cm-long sections that were further divided into anterior and posterior portions for measurement of bupivacaine and baclofen concentrations.

Results

In all groups, drug concentration in CSF and spinal cord decreased rapidly as a function of distance from the site of administration, with most drug found within a few centimeters. In addition, there were significant anterior-posterior differences in both CSF and spinal cord drug concentrations.

Conclusions

During slow intrathecal infusion, drug distribution in CSF and spinal cord is severely limited in all groups, although significantly more so in the 20-microl/h infusion group.
Molecular Mechanisms Transducing the Anesthetic, Analgesic, and Organ-protective Actions of Xenon
Authors: Preckel Benedikt , Weber Nina C. , Sanders Robert D. , Maze Mervyn , Schlack Wolfgang , Warltier David C.
Published: June 2006

The anesthetic properties of xenon have been known for more than 50 yr, and the safety and efficacy of xenon inhalational anesthesia has been demonstrated in several recent clinical studies. In addition, xenon demonstrates many favorable pharmacodynamic and pharmacokinetic properties, which could be used in certain niche clinical settings such as cardiopulmonary bypass. This inert gas is capable of interacting with a variety of molecular targets, and some of them are also modulated in anesthesia-relevant brain regions. Besides these anesthetic and analgesic effects, xenon has been shown to exert substantial organoprotective properties, especially in the brain and the heart. Several experimental studies have demonstrated a reduction in cerebral and myocardial infarction after xenon application. Whether this translates to a clinical benefit must be determined because preservation of myocardial and cerebral function may outweigh the significant cost of xenon administration. Clinical trials to assess the impact of xenon in settings with a high probability of injury such as cardiopulmonary bypass and neonatal asphyxia should be designed and underpinned with investigation of the molecular targets that transduce these effects.
Myocardial Ischemia Revisited
Authors: Slogoff Stephen , Keats Arthur S. , Raja Srinivasa N.
Published: June 2006

Does perioperative myocardial ischemia lead to postoperative myocardial infarction? By Stephen Slogoff and Arthur S. Keats. Anesthesiology 1985; 62:107-14. Reprinted with permission. To determine if a relationship exists between perioperative myocardial ischemia (ST segment depression greater than or equal to 0.1 mV) and postoperative myocardial infarction (PMI), nonparticipating observers recorded all electrocardiographic, hemodynamic, and other events between arrival of patients in the operating room and onset of cardiopulmonary bypass during 1,023 elective coronary artery bypass operations (CABG). The roles of preoperative patient characteristics, quality of the operation limited by disease as rated by the surgeon and duration of ischemic cardiac arrest as risk factors for PMI also were quantified. Electrocardiographic ischemia occurred in 36.9% of all patients, with almost half the episodes occurring before induction of anesthesia. PMI was almost three times as frequent in patients with ischemia (6.9% vs. 2.5%) and was independent of when ischemia occurred. Ischemia was related significantly to tachycardia but not hypertension nor hypotension and was frequent in the absence of any hemodynamic abnormalities. The anesthesiologist whose patients had the highest rate of tachycardia and ischemia had the highest rate of PMI. Although neither single nor multiple preoperative patient characteristics related to PMI, suboptimal quality of operation and prolonged ischemic cardiac arrest increased the likelihood of PMI independent of the occurrence of myocardial ischemia. The authors conclude that perioperative myocardial ischemia is common in patients undergoing CABG, occurs randomly as well as in response to hemodynamic abnormalities, and is one of three independent risk factors the authors identified as related to PMI. PMI is unrelated to preoperative patient characteristics such as ejection fraction and left main coronary artery disease, and its frequency will relate primarily to perioperative management rather than patient selection.