bluuebunny/crossref_metadata_2025 huggingface dataset:
Hemolysis Estimation in a Centrifugal Blood Pump Using a Tensor‐based Measure
Authors: Arora Dhruv , Behr Marek , Pasquali Matteo
Published: July 2006

Abstract:  Hemolysis in the GYRO centrifugal blood pump, under development at the Baylor College of Medicine, Houston, TX, is numerically predicted using the newly proposed tensor‐based blood‐damage model, as well as a traditional model. Three typical operating conditions for the pump are simulated with a special‐purpose finite element‐based flow solver, and a novel approach for tracing the pathlines in discretely represented time‐varying flow in a complex domain is presented, and 271 pathlines are traced through the pump. Hemolysis is computed along the pathlines, and the accumulated hemolysis at the outflow is converted into standard clinical units. The cumulative hemolysis at the outlet of the pump is weighted with the flow rate associated with the pathlines, and a temporal average is obtained by releasing the tracer particles at different time intervals. Numerical predictions are compared to experimental hemolysis studies performed according to the American Society for Testing and Materials standards at the Baylor College of Medicine. The tensor‐based blood‐damage model is found to match very well with the experimental results, whereas the traditional model overpredicts the hemolysis. The success of the tensor‐based blood‐damage model is attributed to its construction, which accounts for blood‐specific physical properties and phenomena. Hemolysis values at the typical operating conditions of the pump are found to be within the clinically accepted range.
Tissue Engineering of Heart Valves In Vivo Using Bone Marrow‐derived Cells
Authors: Kim Sang‐Soo , Lim Sang‐Hyun , Hong Yoo‐Sun , Cho Seung‐Woo , Ryu Ju Hee , Chang Byung‐Chul , Choi Cha Yong , Kim Byung‐Soo
Published: July 2006

Abstract:  In this study, we tissue‐engineered heart valves in vivo using autologous bone marrow‐derived cells (BMCs). Canine BMCs were differentiated into endothelial cell (EC)‐like cells and myofibroblast (MF)‐like cells. Decellularized porcine pulmonary valves were seeded with BMCs and implanted to abdominal aorta and pulmonary valve of bone marrow donor dogs. Histological examination of the explants identified the regeneration of valvular structures expressing CD31 and smooth muscle α‐actin, indicating the presence of EC‐like and MF‐like cells in the grafts at 3 and 1 week, respectively, after implantation. Fluorescent microscopic examinations identified the presence of fluorescently labeled cells in the explants, indicating that the implanted BMCs survived and participated in the heart valve reconstitution. This study reports, for the first time, on tissue engineering of heart valve in vivo using BMCs.
A Novel Femoral Arterial Cannula to Prevent Limb Ischemia During Cardiopulmonary Support: Preliminary Report of Experimental and Clinical Experiences
Authors: Matsui Yoshiro , Shimura Shinichiro , Suto Yukio , Fukase Satoshi , Tanaka Akihito , Sasaki Shigeyuki
Published: July 2006

Abstract:  Distal limb ischemia may occur as a serious complication related to the use of femoral cannulation during veno‐arterial cardiopulmonary support (CPS). We developed a simple cannula for femoral arterial cannulation with two holes in the side wall, which could provide the distal limb blood flow without additional cannulation or surgical procedure. This cannula can be inserted into the femoral artery by routine Seldinger technique. The distal blood flow from the side holes can be confirmed by Doppler detector without specialized techniques. In porcine experimental model, the distance between the position where the blood flow was first detected and those where the blood leakage took place was at least more than 10 mm. When this cannula and its side holes were adequately positioned, the mean distal limb flow ranged from 75 to 90 mL/min under CPS at a flow of 1.5 L/min. We employed this cannula for six patients in clinical settings. Three patients showed a good distal limb blood flow at the introduction position without its adjustment. The other three patients showed distal limb ischemia at the introduction position, but the limb ischemia was soon recovered after a slight adjustment of its position. There was no blood leakage from the percutaneous entry into the artery in all cases. We currently use this cannula as the first choice for patients undergoing a prolonged CPS.
Stem Damage During Implantation of Modular Hip Prostheses
Authors: Varini Elena , Cristofolini Luca , Viceconti Marco , Traina Francesco
Published: July 2006

Abstract:  Modular hip prostheses are commonly used today. Dedicated surgical auxiliary instrumentation is indispensable. A correct coupling between the prosthesis and the instrument is necessary to avoid damage. Based on a specific commercial design (AnCAFit, Wright Cremascoli Ortho, Toulon, France), the aim of this work was to assess if stem holders of modular prostheses can induce any stem damage, and if so, to identify the features that provide minimal damage. Two different stem holder connector designs were investigated. The surface of the stem cavity was inspected to identify the damage caused by the use of the two connectors after a simulated surgical handling. Both connectors induced some damage, with significantly more damage being caused by a supposedly improved design. Scars due to contact with the stem holder were observed on the stem cavity surface. This may be sufficient to trigger increased fretting damage during service life, causing the production of fretting debris.
Clinical Implications of Headache in Lacunar Stroke: Relevance of Site of Infarct
Authors: Arboix Adrià , Grau‐Olivares Marta , García‐Eroles Luis , Massons Joan , Comes Emili , Targa Cecilia
Published: July 2006

Objective.—To assess whether the infarction topography influenced upon the incidence of headache and the likelihood of neurological recovery in lacunar infarction.

Background.—The relationship between topography of infarction and the incidence of headache as well as the influence of headache on neurological outcome in patients with lacunar stroke are still unclear.

Methods.—In a cohort of 387 patients with neuroimaging‐proven acute lacunar infarction collected from a prospective hospital‐based stroke registry over a 12‐year period, 43 patients (11.1%) presented with headache within a 72‐hour interval of stroke onset.

Results.—Headache was more common in deep brain gray matter or brainstem lacunar infarction than in supratentorial white matter lacunar infarction (14.9% vs 8%, P < .033), but lacunar infarctions in the supratentorial white matter had less frequently absence of limitation at discharge (15.1% vs 25.1%, P < .013). In deep brain gray matter or brainstem lacunar infarction, early neurological recovery decreased from 26.2% to 19.2% when headache was present at stroke onset. In the multivariate analysis, dysarthria‐clumsy hand and absence of headache in deep brain gray matter or brainstem lacunar infarction were independent predictors of favorable outcome.

Conclusions.—In patients with lacunar infarction, headache at stroke onset was more common in deep brain gray matter or brainstem topographies than in supratentorial white matter lesions. In deep brain gray matter or brainstem lacunar infarctions, early neurological recovery was less likely when headache was present.
Language Lateralization in Temporal Lobe Epilepsy: A Comparison between fMRI and the Wada Test
Authors: Benke Thomas , Köylü Bülent , Visani Pamela , Karner Elfriede , Brenneis Christian , Bartha Lisa , Trinka Eugen , Trieb Thomas , Felber Stephan , Bauer Gerhard , Chemelli Andreas , Willmes Klaus
Published: July 2006

Summary:  Purpose: Recent studies have claimed that language functional magnetic resonance imaging (fMRI) can identify language lateralization in patients with temporal lobe epilepsy (TLE) and that fMRI‐based findings are highly concordant with the conventional assessment procedure of speech dominance, the intracarotid amobarbital test (IAT).

Methods: To establish the power of language fMRI to detect language lateralization during presurgical assessment, we compared the findings of a semantic decision paradigm with the results of a standard IAT in 68 patients with chronic intractable right and left temporal lobe epilepsy (rTLE, n = 28; lTLE, n = 40) who consecutively underwent a presurgical evaluation program. The patient group also included 14 (20.6%) subjects with atypical (bilateral or right hemisphere) speech. Four raters used a visual analysis procedure to determine the laterality of speech‐related activation individually for each patient.

Results: Overall congruence between fMRI‐based laterality and the laterality quotient of the IAT was 89.3% in rTLE and 72.5% in lTLE patients. Concordance was best in rTLE patients with left speech. In lTLE patients, language fMRI identified atypical, right hemisphere speech dominance in every case, but missed left hemisphere speech dominance in 17.2%. Frontal activations had higher concordance with the IAT than did activations in temporoparietal or combined regions of interest (ROIs). Because of methodologic problems, recognition of bilateral speech was difficult.

Conclusions: These data provide evidence that language fMRI as used in the present study has limited correlation with the IAT, especially in patients with lTLE and with mixed speech dominance. Further refinements regarding the paradigms and analysis procedures will be needed to improve the contribution of language fMRI for presurgical assessment.
Facial Emotion Recognition after Curative Nondominant Temporal Lobectomy in Patients with Mesial Temporal Sclerosis
Authors: McClelland Shearwood , Garcia Rebeca E. , Peraza Daniel M. , Shih Tina T. , Hirsch Lawrence J. , Hirsch Joy , Goodman Robert R.
Published: July 2006

Summary: Purpose:The right (nondominant) amygdala is crucial for processing facial emotion recognition (FER). Patients with temporal lobe epilepsy (TLE) associated with mesial temporal sclerosis (MTS) often incur right amygdalar damage, resulting in impaired FER if TLE onset occurred before age 6 years. Consequently, early right mesiotemporal insult has been hypothesized to impair plasticity, resulting in FER deficits, whereas damage after age 5 years results in no deficit. The authors performed this study to test this hypothesis in a uniformly seizure‐free postsurgical population.

Methods:Controls (n = 10), early‐onset patients (n = 7), and late‐onset patients (n = 5) were recruited. All patients had nondominant anteromedial temporal lobectomy (AMTL), Wada‐confirmed left‐hemisphere language dominance and memory support, MTS on both preoperative MRI and biopsy, and were Engel class I 5 years postoperatively. By using a standardized (Ekman and Friesen) human face series, subjects were asked to match the affect of one of two faces to that of a simultaneously presented target face. Target faces expressed fear, anger, or happiness.

Results:Statistical analysis revealed that the early‐onset group had significantly impaired FER (measured by percentage of faces correct) for fear (p = 0.036), whereas the FER of the late‐onset group for fear was comparable to that of controls. FER for anger and happiness was comparable across all three groups.

Conclusions:Despite seizure control/freedom after AMTL, early TLE onset continues to impair FER for frightened expressions (but not for angry or happy expression), whereas late TLE onset does not impair FER, with no indication that AMTL resulted in FER impairment. These results indicate that proper development of the right amygdala is necessary for optimal fear recognition, with other neural processes unable to compensate for early amygdalar damage.
Quality of Care for Acute Myocardial Infarction in Elderly Patients with Alcohol‐Related Diagnoses
Authors: Fiellin David A. , O'Connor Patrick G. , Wang Yongfei , Radford Martha J. , Krumholz Harlan M.
Published: July 2006

Background: Elderly adults with alcohol‐related diagnoses represent a vulnerable population that may receive lower quality of treatment during hospitalization for acute myocardial infarction. We sought to determine whether elderly patients with alcohol‐related diagnoses are less likely to receive standard indicators of quality care for acute myocardial infarction.

Methods: We conducted a retrospective cohort analysis using administrative and medical record data from the Cooperative Cardiovascular Project. Subjects were Medicare beneficiaries with a confirmed principal discharge diagnosis of acute myocardial infarction from all acute care hospitals in the United States over an 8‐month period. Our primary outcome was the receipt of 7 guideline‐recommended care measures among all eligible patients and patients who were ideal candidates for a given measure.

Results: In all, 1,284 (1%) of the 155,026 eligible patients met criteria for an alcohol‐related diagnosis. Among the alcohol‐related diagnoses, 1,077/1,284 (84%) were for the diagnoses of alcohol dependence or alcohol abuse. Patients with alcohol‐related diagnoses were less likely than those without alcohol‐related diagnoses to receive β‐blockers at the time of discharge (55% vs. 60%, p=0.02). We found no other significant differences in performance of the quality indicators after stratifying by indication and adjustment for baseline characteristics.

Conclusions: Alcohol‐related diagnoses are not a barrier to receiving most quality of care measures in elderly patients hospitalized for acute myocardial infarction.
Validity of Transdermal Alcohol Monitoring: Fixed and Self‐Regulated Dosing
Authors: Sakai Joseph T. , Mikulich‐Gilbertson Susan K. , Long Robert J. , Crowley Thomas J.
Published: July 2006

Background: To study the validity of transdermal assessment of alcohol concentration measured by a lightweight, noninvasive device.

Methods: Subjects wore a 227‐g anklet that sensed transdermal alcohol concentrations (TACs) every 15 to 30 minutes, downloading results to a remote computer each day. Twenty‐four subjects entered a laboratory and received a dose of 0, 0.28, or 0.56 g/kg of ethanol. Breath alcohol concentrations (BrAC) and TAC were measured every 15 to 30 minutes Twenty others [10 alcohol dependent (AD) and 10 not (NAD)] in the community who wore the anklet for 8 days kept a drinking log and provided a BrAC sample each day.

Results: In the laboratory, no zero‐dose subject, and every subject receiving alcohol, had alcohol‐positive TACs. The device distinguished low‐ and high‐alcohol–dosing groups using peak (t14=3.37; p<0.01) and area under the curve (t14=3.42; p<0.01) of TACs. Within dosing groups, average TAC curves were broader (right‐shifted) and had lower peaks than average BrAC curves. For community participants, self‐reported number of drinks (t18=−3.77; p<0.01), area under the TAC curve (t9.5=−3.56; p<0.01), and mean TAC (t9.9=−3.35; p<0.01) all significantly distinguished the AD and NAD groups. However, individual transdermal readings were not reliably quantitatively equivalent to simultaneously obtained breath results.

Conclusions: Within the limits of the laboratory study, the device consistently detected consumption of approximately 2 standard drinks. On average, the device shows discriminative validity as a semiquantitative measure of alcohol consumption but individual readings often are not equivalent to simultaneous BrACs.
Sedative and GABAergic Effects of Ethanol on Male and Female Rats
Authors: Cha Young May , Li Qiang , Wilson Wilkie A. , Swartzwelder H. Scott
Published: July 2006

Background: Women consume less alcohol than men, and yet they are more susceptible than men to the negative medical consequences of alcohol use, such as cirrhosis of the liver, cardiac disease, and cognitive impairments. This sex difference is also reflected in animal studies, in which male and female rats differ on both behavioral and electrophysiological measures. Given that one significant difference between males and females is the cycling fluctuations of the sex hormones, this study aimed to compare the relative sensitivity of adolescent and adult rats of both sexes and varying estrous stages to the behavioral and electrophysiological effects of ethanol.

Methods: Adult female rats were lavaged daily for estrous cycle assessment. Following administration of 5 g/kg ethanol, adolescent and adult male and female animals were observed for loss of the righting reflex. Then, using whole‐cell recording, we tested the response of spontaneous, gamma‐aminobutyric acid (GABAA) receptor‐mediated inhibitory postsynaptic currents (sIPSCs) in hippocampal slices from drug‐naïve adult male and female rats.

Results: Consistent with previous findings, adolescent animals were less sensitive than adults to the effect of ethanol on the righting reflex. In addition, adult proestrous and diestrous female rats were less sensitive than male rats to the sedative effects of ethanol. Finally, ethanol increased the frequency of sIPSCs in hippocampal pyramidal neurons and did so more potently in cells from male rats than in those from female rats.

Conclusions: Female animals are less sensitive to the behavioral sedative effects of ethanol than adult male rats, and the effect is pronounced in the proestrous and diestrous states. This sex difference may be related to differential sensitivity of GABA receptor–mediated central nervous system function to ethanol in females.
Gene by Environment Interaction: The −159C/T Polymorphism in the Promoter Region of the CD14 Gene Modifies the Effect of Alcohol Consumption on Serum IgE Levels
Authors: Campos Joaquin , Gude Francisco , Quinteiro Celsa , Vidal Carmen , Gonzalez‐Quintela Arturo
Published: July 2006

Background: Serum IgE is increased in heavy drinkers. Endotoxin mediates most of the immunological alterations associated with heavy drinking. The −159C/T polymorphism in the promoter region of the gene encoding CD14 (an endotoxin receptor) is associated with serum IgE levels in different populations.

Aim: To investigate the possible interaction between alcohol intake and the −159C/T polymorphism in the promoter region of the CD14 gene for serum IgE levels.

Methods: A total of 415 individuals (51.6% males, median age 50 years, range 18–92 years) were studied. A total of 140 individuals were alcohol abstainers, 112 were moderate drinkers (1–280 g/week), and 163 were heavy drinkers (>280 g/week). Main determinations included the CD14/−159C/T genotype, a panel of skin prick tests, total serum IgE, and specific serum IgE against common aeroallergens (Phadiatop test).

Results: Heavy drinking was associated with increased total serum IgE values and with positive specific serum IgE to common aeroallergens, but the association was stronger in carriers of the CD14/−159C allele (either CC homozygotes or CT heterozygotes) than in CD14/−159TT homozygotes. Both additive and multiplicative interactions between heavy drinking and the CD14/−159C allele for total and specific serum IgE values was still present after adjusting for potential confounders. Neither alcohol consumption nor the CD14/−159 genotype was associated with skin prick test positivity.

Conclusions: The CD14/−159C/T polymorphism modifies the effect of alcohol consumption on serum IgE levels.
Rapid Induction of Apoptosis in Gastrulating Mouse Embryos by Ethanol and Its Prevention by HB‐EGF
Authors: Kilburn Brian A. , Chiang Po Jen , Wang Jun , Flentke George R. , Smith Susan M. , Armant D. Randall
Published: July 2006

Background:Ethanol exposure during gastrulation and early neurulation induces apoptosis within certain embryonic cell populations, leading to craniofacial and neurological defects. There is currently little information about the initial kinetics of ethanol‐induced apoptosis, and interest in the ability of endogenous survival factors to moderate apoptosis is growing. Ethanol alters intracellular signaling, leading to cell death in chick embryos, suggesting that apoptosis could occur rapidly and that signaling pathways activated by survival factors might reduce apoptosis.

Methods:Pregnant mice were intubated with 1, 2, or 4 g/kg ethanol on day 7.5 of embryogenesis (E7.5) 1, 3, or 6, hours before harvesting gastrulation‐stage embryos. Control animals received maltose/dextran. Blood alcohol concentrations (BAC) were determined by gas chromatography. E7.5 embryos isolated from untreated dams were cultured in vitro for 1 or 3 hr with 0 or 400 mg% ethanol and 0 or 5 nM heparin‐binding epidermal growth factor (EGF)‐like growth factor (HB‐EGF). Apoptosis was quantified using fluorescence microscopy to detect annexin V binding and DNA fragmentation [terminal deoxynucleotidyl transferase‐mediated dUTP‐Xnickendlabeling (TUNEL)] in whole‐mount or sectioned embryos.

Results:Both annexin V binding and TUNEL were elevated (p<0.05) in embryos exposed in utero to 1 g/kg ethanol for 3 hours, increasing linearly with time and ethanol concentration. Apoptosis increased (p<0.05) in all germ cell layers. Mice treated with 4 g/kg sustained BAC of 400 mg% for nearly 3 hours, significantly increasing apoptosis within the first hour. Cultured embryos exposed to 400 mg% ethanol displayed 2‐ to 3‐fold more TUNEL than vehicle‐treated embryos (p<0.05); however, exogenous HB‐EGF prevented apoptosis.

Conclusions:Ethanol rapidly produced apoptosis in gastrulation‐stage embryos, consistent with induction by intracellular signaling. The ethanol‐induced apoptotic pathway was blocked by the endogenous survival factor, HB‐EGF. Differences in the expression of survival factors within individual embryos could be partly responsible for variations in the teratogenic effects of ethanol among offspring exposed prenatally.
Effects of Chronic Alcohol and Repeated Deprivations on Dopamine D1 and D2 Receptor Levels in the Extended Amygdala of Inbred Alcohol‐Preferring Rats
Authors: Sari Youssef , Bell Richard L. , Zhou Feng C.
Published: July 2006

Background:Dopaminergic (DA) activity in the extended amygdala (EA) has been known to play a pivotal role in mediating drug and alcohol addiction. Alterations of DA activity within the EA after chronic exposure to alcohol or substances of abuse are considered a major mechanism for the development of alcoholism and addiction. To date, it is not clear how different patterns of chronic alcohol drinking affect DA receptor levels. Therefore, the current studies investigated the effects of chronic ethanol consumption, with or without deprivations, on D1 and D2 receptor densities within the EA.

Methods:Inbred alcohol‐preferring (iP) rats were divided into 3 groups with the following treatments: (1) water for 14 weeks; (2) continuous alcohol (C‐Alc) for 14 weeks [24‐hour concurrent access to 15 and 30% (v/v) ethanol]; or (3) repeatedly deprived of alcohol (RD‐Alc) (24‐hour concurrent access to 15 and 30% ethanol for 6 weeks, followed by 2 cycles of 2 weeks of deprivation of and 2 weeks of reexposure to ethanol access). At the end of 14 weeks, the rats were killed for autoradiographic labeling of D1 and D2 receptors.

Results:Compared with the water control group, both the C‐Alc and the RD‐Alc groups displayed increases in D1 receptor binding density in the anterior region of the Acb core, whereas the RD‐Alc group displayed additional increases in D1 receptor binding density in anterior regions of the lateral and intercalated nuclei of the amygdala. Additionally, both C‐Alc and RD‐Alc rats displayed increases in D2 receptor binding density in anterior regions of the Acb shell and core, whereas RD‐Alc rats displayed additional increases in D2 receptor binding density in the dorsal striatum.

Conclusion:The results of this study indicate that 14‐week extended alcohol drinking with continuous chronic or repeated deprivations increase binding sites of D1 and D2 receptors in specific regions of the EA with greater sensitivity in the anterior regions. The repeated deprivation has greater effect on altering D1 and D2 receptor binding sites in the Acb, dorsal striatum, and subamygdala regions. The current result indicates that the two drinking paradigms may have common as well as differential mechanisms on alteration of dopamine receptor–binding sites in specific regions of the EA.
Alcohol Prices, Beverage Quality, and the Demand for Alcohol: Quality Substitutions and Price Elasticities
Authors: Gruenewald Paul J. , Ponicki William R. , Holder Harold D. , Romelsjö Anders
Published: July 2006

Background:Although the published literature on alcohol beverage taxes, prices, sales, and related problems treats alcoholic beverages as a simple good, alcohol is a complex good composed of different beverage types (i.e., beer, wine, and spirits) and quality brands (e.g., high‐, medium‐, and low‐quality beers). As a complex good, consumers may make substitutions between purchases of different beverage types and brands in response to price increases. For this reason, the availability of a broad range of beverage prices provides opportunities for consumers to mitigate the effects of average price increases through quality substitutions; a change in beverage choice in response to price increases to maintain consumption.

Methods:Using Swedish price and sales data provided by Systembolaget for the years 1984 through 1994, this study assessed the relationships between alcohol beverage prices, beverage quality, and alcohol sales. The study examined price effects on alcohol consumption using seemingly unrelated regression equations to model the impacts of price increases within 9 empirically defined quality classes across beverage types. The models enabled statistical assessments of both own‐price and cross‐price effects between types and classes.

Results:The results of these analyses showed that consumers respond to price increases by altering their total consumption and by varying their brand choices. Significant reductions in sales were observed in response to price increases, but these effects were mitigated by significant substitutions between quality classes.

Conclusions:The findings suggest that the net impacts of purposeful price policy to reduce consumption will depend on how such policies affect the range of prices across beverage brands.
Moderate Alcohol Intake in Humans Attenuates Monocyte Inflammatory Responses: Inhibition of Nuclear Regulatory Factor Kappa B and Induction of Interleukin 10
Authors: Mandrekar Pranoti , Catalano Donna , White Bernadette , Szabo Gyongyi
Published: July 2006

Background: In contrast to the deleterious effects of chronic excessive alcohol consumption on the liver and cardiovascular system, modest alcohol intake, such as 1 to 2 drinks per day, has benefits on cardiovascular mortality. Little is known about the length of time or the amounts of alcohol consumed that may cause alterations in inflammatory cells such as monocytes that are crucial to atherosclerotic vascular disease. Here, we determine in vivo effects of acute alcohol consumption on inflammatory cytokine production and nuclear regulatory factor κB (NF‐κB) binding in human monocytes.

Methods: Human blood monocytes were isolated by plastic adherence before and after acute alcohol consumption (2 ml vodka/kg body weight). Lipopolysaccharide (LPS)‐ and superantigen‐induced tumor necrosis factor α (TNF α), interleukin (IL)‐1β, and IL‐10 production were then determined in monocytes by ELISA. Nuclear regulatory factor‐κB activity of monocytes before and after alcohol consumption was estimated by electromobility shift assay and promoter‐driven reporter activity. IκBα was determined by Western blotting in the cytoplasmic extracts.

Results: Eighteen hours after moderate alcohol consumption, we found a significant reduction in monocyte production of inflammatory mediators, TNF‐α and IL‐1β, in response to LPS or staphylococcal enterotoxin B stimulation. Acute alcohol consumption inhibited LPS‐induced DNA binding of the p65/p50 NF‐κB in monocytes that regulates the expression of both the TNF‐α and the IL‐1β genes. Consistent with this, acute alcohol treatment (25 mM) significantly reduced LPS‐induced activation of an NF‐κB‐driven reporter gene suggesting inhibition of this proinflammatory signaling pathway. Further, LPS‐induced IκBα degradation was not affected by acute alcohol consumption indicating an IκBα‐independent mechanism, as observed earlier in the in vitro acute alcohol studies. In contrast, monocyte production of the anti‐inflammatory cytokine, IL‐10, was augmented by acute alcohol intake.

Conclusions: Our findings suggest that acute alcohol consumption has dual anti‐inflammatory effects that involve augmentation of IL‐10 and attenuation of monocyte inflammatory responses involving inhibition of NF‐κB. These mechanisms may contribute to the beneficial effects of moderate alcohol use on atherosclerosis.
Analysis of Metallothionein Brain Gene Expression in Relation to Ethanol Preference in Mice Using Cosegregation and Gene Knockouts
Authors: Loney Kimberly D. , Uddin Raihan K. , Singh Shiva M.
Published: July 2006

Background: Metallothioneins (MTs) are ubiquitously expressed intracellular proteins that bind heavy metals and are involved in cytoprotection against several types of stress agents including chemicals, hormones, and oxidants. We have previously reported 1 isoform, MT‐II, as a possible candidate gene for ethanol (EtOH) preference (EP) determination in mice.

Methods: Semiquantitative RT‐PCR was used to determine brain mRNA levels of MT‐I and MT‐III in 4 inbred mouse strains with variable EP. Following this, cosegregation of MT‐II brain expression with EP was analyzed in F2 mice from 2 intercrosses (C57BL/6J × BALB/cJ and C57BL/6J × DBA/2J). Studies on MT‐I/MT‐II knockout (KO) mice were also undertaken to further explore this relationship.

Results: Our results suggest that MT‐I is responsive to EtOH, with no evidence of basal‐level differences between strains. Conversely, MT‐III shows no EtOH response, yet indicates a possible strain‐specific feature with C57BL/6J having the lowest levels of brain MT‐III. Metallothionein‐II expression cosegregates with EP in F2 mice from a C57BL/6J (preferring) and DBA/2J (avoiding) intercross. Although F2 mice from a cross with C57BL/6J and BALB/cJ (avoiding) strains follow a similar pattern, the results are not statistically significant. Metallothionein‐I/MT‐II knockout (MT‐KO) mice appear to have smaller litter sizes as well as higher weight compared with controls (129S1/SvImJ) and also show a slight increase in EP.

Conclusions: Metallothionein‐II remains the primary candidate of the mouse MT gene family for involvement in EP. Its effect on EP appears to be dependent on the genetic background. Such conclusions are based on results from C57BL/6J, BALB/cJ, DBA/2J, and 129 inbred mouse strains. Evidence also points to shared neural pathways involved in weight gain and obesity. The complex interactions between MT‐II, EP, and weight gain/obesity remain to be studied.
The Alcohol Clamp: Applications, Challenges, and New Directions – An RSA 2004 Symposium Summary
Authors: Ramchandani Vijay A. , O'Connor Sean , Neumark Yehuda , Zimmermann Ulrich S. , Morzorati Sandra L. , de Wit Harriet
Published: July 2006

This article summarizes the proceedings of a symposium organized and cochaired by Vijay Ramchandani and Sean O'Connor and presented at the 2004 Research Society on Alcoholism meeting in Vancouver, BC, Canada. The objectives of this symposium were: (1) to provide a rationale for the development and use of the alcohol clamp and the requirements for its use in alcohol challenge studies; (2) to highlight recent studies conducted using the alcohol clamp to identify sources of variation in the pharmacokinetics and pharmacodynamics of alcohol, as well as to address important research questions related to the relationship between the response to alcohol and the risk for alcoholism; and (3) to provide a perspective on progress, address limitations of the clamp, and identify new directions for alcohol challenge research. The symposium began with an introduction and overview of the alcohol clamp, by Vijay Ramchandani. This was followed by 4 presentations that highlighted recent studies conducted using the clamp including: (1) determination of the influence of alcohol dehydrogenase polymorphisms on alcohol elimination rates in a male Jewish population, by Yehuda Neumark; (2) examination of family history of alcoholism, recent drinking history, and levels and rates of administration as determinants of the response to alcohol and risk for alcoholism, by Sean O'Connor; (3) evaluation of the time course of ethanol intoxication on neuroendocrine function in humans, by Ulrich Zimmermann; and (4) a study of the effects of steady‐state blood alcohol levels on auditory event‐related potentials in rats, by Sandra Morzorati. Harriet de Wit summarized and discussed the research presented at the symposium and provided her perspective on future directions for research using the alcohol clamp.
Dispersion of the Corrected QT and JT Interval in the Electrocardiogram of Alcoholic Patients
Authors: C̆orović Naima , Duraković Zijad , Mis̆igoj‐Duraković Marjeta
Published: July 2006

Background: The aim of this study was to analyze the corrected QT interval (QTc), its dispersion (QTcd), and the QT interval index (QTcI) and to compare it with the corrected JT interval (JTc), its dispersion (JTcd), and the JT interval index (JTcI) in long‐term alcoholic users, by investigating the ventricular activation until the completion of repolarization.

Methods: The study of ECGs was performed on a selected group of 49 male white alcoholic patients, mean age 53.51±4.78 years. The control group was pair‐matched. The analysis of ECGs was performed according to the Minnesota Code, and Bazett's formula gave the values of the corrected QT interval and JT interval.

Results: The results of the descriptive statistics in the group of alcoholics showed a range of the QTcd of 12.0 to 103.0 milliseconds, mean 44.2±18.6 milliseconds, compared with 5.0 to 68.0 milliseconds, mean 23.8±11.1 milliseconds, in the control group (p<0.0001). The range of JTcd in the alcoholic patients was 11.0 to 88.0 milliseconds, mean 43.0±18.3 milliseconds, compared with 5.0 to 66.0 milliseconds, mean 22.8±12.1 milliseconds, in the control group (p<0.0001). The QTc from 422.0 to 480.0 milliseconds was obtained in 69.4% of the alcoholic patients and 32.6% of the controls. The QTc over 480.0 milliseconds was found in 24.5% of the alcoholic patients, but was not recorded among the controls at all (p<0.0001). The QTcd over 50.0 milliseconds was registered in 34.7% of the alcoholic patients, while in the controls a QTcd above 50 milliseconds was found in 2.0% (p<0.0001). The mean values of QT were markedly higher in the alcoholic patients (p<0.01) than in the controls. The same was the case with the values of QTd, QTI, QTcd, and QTcI (p<0.0001). Also, the mean values of JTd, JTI, JTc, JTcd, and JTcI were significantly higher in the alcoholic patients than in the controls (p<0.0001). The mean value of JT, although higher in the alcoholic patients, did not significantly differ between the examined groups (p=0.1002). The odds ratio estimated for prolonged QTc and for enlarged QTcd in the alcoholics versus the controls was 31.625 and 25.500 (p<0.0001), respectively.

Conclusions: Persons who consume various alcoholic beverages excessively and for a long time have significantly higher dispersions of the QTc and JTc, intervals and they have a significantly higher estimation of relative risk for the prolonged QTc interval and higher QTc dispersion than the control group, i.e., higher risk of arrhythmias.
Chronic Intermittent Ethanol Exposure During Adolescence Blocks Ethanol‐Induced Inhibition of Spontaneously Active Hippocampal Pyramidal Neurons
Authors: Tokunaga Sayaka , Silvers Janelle M. , Matthews Douglas B.
Published: July 2006

Background: Binge alcohol drinking among adolescents has been a serious public health problem. A model of binge alcohol, chronic intermittent ethanol exposure (CIEE), during adolescence significantly attenuates ethanol‐induced spatial memory deficits in rats. However, the attenuation was absent following a 12‐day ethanol‐free period. Since spatial memory is hippocampal dependent, a reduction in ethanol‐induced spatial memory impairments may be due to a reduction in the ability of ethanol to inhibit the firing rate of single hippocampal pyramidal neurons following CIEE.

Methods: Beginning on postnatal day 30 (P30), male adolescent Sprague‐Dawley rats (Harlan) were administered 5.0 g/kg ethanol (n=10, CIEE‐treated group) or an equivolume saline (n=10, CISE‐treated group) every 48 hours for 20 days. Single hippocampal pyramidal neurons from 5 CIEE‐treated rats and 5 CISE‐treated rats were recorded on the day following completion of the chronic intermittent exposure procedure (animals now P50). Additionally, neurons from 5 CIEE‐treated rats and 5 CISE‐treated rats were recorded 12 days after the completion of the chronic intermittent exposure procedure (animals now P62).

Results: Ethanol exposure during adolescence completely blocked ethanol‐induced inhibition of hippocampal pyramidal neurons in rats that were CIEE exposed. However, the effect of CIEE on hippocampal neurophysiology was time dependent. Specifically, neurons recorded from CIEE‐treated rats after a 12‐day ethanol‐free period had similar maximal inhibition as neurons from CISE‐treated animals, although the time to reach inhibition was significantly greater in neurons from CIEE‐treated rats.

Conclusion: Chronic ethanol exposure during adolescence produces a reduction, or tolerance, to ethanol‐induced inhibition of hippocampal pyramidal neural activity. Although the tolerance was greatly reversed after a 12‐day ethanol‐free period, neurons from CIEE animals inhibited slower than neurons from CISE animals. Since the hippocampus is known to be involved not only in spatial memory, but also in many other types of memory formation, the altered hippocampal functions because of CIEE during adolescence should be taken as a serious warning for society.
Short‐ and Long‐Term Outcome and Factors Predicting Survival After Surgical Tube Cystostomy for Treatment of Obstructive Urolithiasis in Small Ruminants
Authors: EWOLDT JENNIFER M. , ANDERSON DAVID E. , MIESNER MATT D. , SAVILLE WILLIAM J.
Published: July 2006

Objective—To evaluate outcome of small ruminants after tube cystostomy without urethral flushing.

Study Design—Retrospective clinical study.

Animals—Small ruminants (n=63; 50 goats, 13 sheep).

Methods—Medical records (January 1996–October 2003) for all small ruminants undergoing tube cystostomy were analyzed. Signalment, laboratory data, intraoperative findings, urolith type, and postoperative outcome were compared. Long‐term follow‐up was obtained at 6 and ≥12 months postoperatively.

Results—Most animals were castrated males. Pygmy goats were overrepresented. Mean time to normal urination after tube cystostomy was 11 days, and mean hospitalization was 14 days. Seventy‐six percent of animals were successfully treated with tube cystostomy (90% of those discharged from hospital). Short‐ and long‐term survival was good for those animals with follow‐up data. Reobstruction occurred in <20% of animals at 6 and 12 months. Goats, castrated males, and animals with normal serum potassium, no fluid in the abdomen, or no urethral process amputation were more likely to survive. Stone type, bladder appearance, and age at castration were not associated with outcome.

Conclusion—Surgical tube cystostomy without urethral flushing is an effective technique for resolution of obstructive urolithiasis in small ruminants.

Clinical Relevance—Goats, small ruminants with an intact urethral process, absence of abdominal fluid, and serum potassium concentration <5.2 mEq/L at admission were all associated with survival after tube cystostomy. Castrated males may also be more likely to survive. These factors should be considered in management of small ruminants with urolithiasis.
A Clinical Evaluation of a Headless, Titanium, Variable‐Pitched, Tapered, Compression Screw for Repair of Nondisplaced Lateral Condylar Fractures in Thoroughbred Racehorses
Authors: GALUPPO LARRY D. , SIMPSON EDWIN L. , GREENMAN SYLVIA L. , DOWD JOSEPH P. , FERRARO GREGORY L. , MEAGHER DENNIS M.
Published: July 2006

Objective— To report clinical evaluation of headless compression screws for repair of metacarpal/metatarsal (MC/MT3) condylar fractures in horses.

Study Design— Retrospective case study.

Sample Population— Racing Thoroughbreds (n=16) with nondisplaced lateral condylar fractures of MC/MT 3.

Methods— Medical records (1999–2004) of horses with nondisplaced longitudinal fractures of the lateral condyle of MC/MT3 were reviewed. Pre‐operative variables retrieved were: patient age, gender, limb involvement, injury occurrence, fracture length, and width, evidence of palmar comminution and degenerative joint disease, number of pre‐injury starts, and pre‐injury earnings. Post‐operative variables retrieved were: surgical complications, surgical time, number of race starts, and post‐operative earnings.

Results— MC3 (n=11) and MT3 (5) nondisplaced longitudinal fractures of the lateral condyle were repaired with Acutrak® Equine (AE) screws. Left front limb fractures were most common (8) followed by left hind (5) and right front (3). Nine fractures occurred during training and 7 during racing; 4 fractures had palmar comminution. No surgical complications occurred. Of 15 horses that returned to training, 11 (73%) raced 306±67 days after injury and had greater mean (±SD) post‐injury earnings/start ($5290.00±$8124.00) than pre‐injury ($4971.00±$2842.00). Screw removal was not required in any horse.

Conclusion— The AE screw is a viable option for repair of nondisplaced lateral condylar MC/MT3 fractures in Thoroughbred racehorses.

Clinical Relevance— Adequate stability of nondisplaced lateral condylar fractures can be achieved with a headless tapered compression screw while avoiding impingement on the collateral ligaments and joint capsule of the fetlock joint.
Laparoscopic Obliteration of the Nephrosplenic Space Using Polypropylene Mesh in Five Horses
Authors: EPSTEIN KIRA L. , PARENTE ERIC J.
Published: July 2006

Objective—To report a laparoscopic technique for insertion of polypropylene mesh in the nephrosplenic space in horses and evaluate outcome.

Study Design—Descriptive experimental study.

Animals—Five healthy mature horses.

Methods—One laparoscope and 2 instrument portals were made on the left side of the horse. The nephrosplenic space was measured and appropriately sized polypropylene mesh was inserted and attached to the dorsolateral splenic capsule and perirenal fascia using helical titanium coils. All horses had repeat laparoscopy 4 weeks later and were necropsied at intervals 4–14 weeks after mesh placement.

Results—Mean time for laparoscopic mesh placement was 104 minutes. None of the horses had signs of colic and at 4 weeks all mesh implants were covered by fibrous tissue. One horse had a descending colon mesenteric adhesion to the mesh. At necropsy, the fibrous tissue covering the mesh had adhered to itself and pulled the splenic capsule and perirenal fascia into close apposition. Each mesh implant was firmly adhered to the spleen, nephrosplenic ligament, and perirenal fascia.

Conclusions—Laparoscopic mesh placement was easily performed, well tolerated, and provided excellent fibrous obliteration of the nephrosplenic space. The single important complication observed was a mesenteric adhesion of the descending colon to the mesh in 1 horse.

Clinical Relevance—Laparoscopic placement of polypropylene mesh leads to obliteration of the nephrosplenic space within 4 weeks and should prevent entrapment of viscera in the nephrosplenic space.
Induction of a Barrier Membrane to Facilitate Reconstruction of Massive Segmental Diaphyseal Bone Defects: An Ovine Model
Authors: VIATEAU VÉRONIQUE , GUILLEMIN GENEVIÈVE , CALANDO YOLANDE , LOGEART DELPHINE , OUDINA KARIM , SEDEL LAURENT , HANNOUCHE DIDIER , BOUSSON VALÉRIE , PETITE HERVÉ
Published: July 2006

Objectives—To report an ovine model that can be used to evaluate the efficacy of bone substitutes for repair of segmental diaphyseal bone defects.

Study Design—Experimental study.

Animals—Eleven 2‐year‐old Pré‐Alpes Sheep.

Methods—Mid‐diaphyseal metatarsal bone defects (25 mm long) were stabilized by a dynamic compression plate over a polymethylmethacrylate (PMMA) cement spacer, and by external coaptation. The PMMA spacer was removed at 6 weeks by incising the encapsulating membrane. The defect remained unfilled (Group 1; n=5) or was filled with morselized autologous corticocancellous graft (Group 2; n=6), the membrane sutured closed, and external coaptation applied for 6 months, when healing was evaluated.

Results—Radiographic, computed tomographic, and histologic examinations at 6 months after the 2nd surgery revealed non‐union in ungrafted defects whereas grafted defects showed bone healing. The induced membrane had blood vessels, CBFA1+ cells, and very few macrophages entrapped in a collagenous tissue positive for type I collagen.

Conclusion—This ovine metatarsal defect model resulted in a critical‐size defect (non‐union) that healed when grafted. The PMMA‐induced membrane constrained the graft, was well vascularized, and may have osteogenic properties.

Clinical Relevance—This model may be useful to evaluate new strategies in bone tissue engineering because the PMMA‐induced membrane may help confine bone morphogenetic proteins, skeletal stem cells, or other agents to the defect cavity where they could be useful to enhance bone formation.
Change in Tibial Plateau Angle After Tibial Plateau Leveling Osteotomy in Dogs
Authors: MOELLER E. MICHAEL , CROSS ALAN R. , RAPOFF ANDREW J.
Published: July 2006

Objective— To determine the change in tibial plateau angle (TPA) during healing after tibial plateau leveling osteotomy (TPLO) performed for cranial cruciate ligament insufficiency in dogs and to examine factors that may be associated with the change.

Study Design— Retrospective study.

Study Population— One hundred and forty‐nine canine stifles after TPLO procedure.

Methods— Records of dogs that had TPLO were reviewed. Patient age, weight, sex, breed, pre‐ and postoperative TPA, recheck TPA, time to recheck, type of implant used, and radiographic evidence of healing were analyzed.

Results— Mean time to recheck evaluation was 46 days (range, 28–65 days). Mean difference between immediate postoperative and recheck TPA measurements was 1.5° (range, −3 to 9°). Recheck TPA was a significantly greater (numerically higher) than immediate postoperative TPA (P<.0001). There was no significant effect of patient weight, type of plate used, or healing status of the osteotomy at the time of recheck. No correlation between pre‐ or postoperative TPA angles and change in TPA angle was detected.

Conclusions— TPA changes during osteotomy healing after TPLO, but factors influencing this change were not identified.

Clinical Relevance— TPA may increase during healing after TPLO despite apparently adequate osteotomy fixation. The clinical relevance of this increase is unknown but is likely minimal.