bluuebunny/crossref_metadata_2025 huggingface dataset:
`The stress of dying': the role of heat shock proteins in the regulation of apoptosis
Authors: Beere Helen M.
Published: May 2004

Heat shock proteins (Hsps) are a family of highly homologous chaperone proteins that are induced in response to environmental, physical and chemical stresses and that limit the consequences of damage and facilitate cellular recovery. The underlying ability of Hsps to maintain cell survival correlates with an inhibition of caspase activation and apoptosis that can, but does not always, depend upon their chaperoning activities. Several mechanisms proposed to account for these observations impact on both the `intrinsic', mitochondria-dependent and the `extrinsic', death-receptor-mediated pathways to apoptosis. Hsps can inhibit the activity of pro-apoptotic Bcl-2 proteins to prevent permeabilization of the outer mitochondrial membrane and release of apoptogenic factors. The disruption of apoptosome formation represents another mechanism by which Hsps can prevent caspase activation and induction of apoptosis. Several signaling cascades involved in the regulation of key elements within the apoptotic cascade are also subject to modulation by Hsps, including those involving JNK, NF-κB and AKT. The coordinated activities of the Hsps thus modulate multiple events within apoptotic pathways to help sustain cell survival following damaging stimuli.
Hofmeister Ion Effects on the Phase Diagrams of Water-Propylene Glycol Propyl Ethers
Authors: Bauduin Pierre , Wattebled Laurent , Touraud Didier , Kunz Werner
Published: May 2004

The influence of different salts on the lower critical solution temperature (LCST) of mixtures of propylene glycol propyl ether and of dipropylene glycol propyl ether with water was determined experimentally. It was observed that the temperature shifts follow precisely the same Hofmeister series for anions that was originally found for salting-in and salting-out effects for protein solutions. The results are similar to the observations found for mixtures of water with non-ionic surfactants. In the case of dipropylene glycol propyl ether mixtures with water, temperature dependent phase diagrams in the presence of one salting-in (NaSCN) and one salting-out (Na2SO4) salt were measured at a fixed salt concentration in water of 0.041 M. The results can be qualitatively understood by assuming a different hydrophobicity for both types of salts. They further hint at a strong degree of solute determined cooperative water structure.
The Liquid Structure of Various Nitriles andN,N-Dimethylformamide Studied by the X-Ray Diffraction Method Using a CCD Detector
Authors: Katayama Misaki , Komori Kohei , Ozutsumi Kazuhiko , Ohtaki Hitoshi
Published: May 2004

The liquid structure of acetonitrile (AN), propionitrile (PN), acrylonitrile (ACN), and benzonitrile (BN) was investigated by the transmission mode X-ray diffraction method with a newly developed CCD detector at room temperature and one atmospheric pressure. The nitriles were shielded in a thin wall glass tube. The reduced intensities,si(s), extracted from the measured intensities were compared with those obtained by the X-ray diffraction measurements with the θ–θ type reflection mode for benzonitrile andN,N-dimethylformamide (DMF) as the reference. In all the nitriles it was found that molecules are arrayed in the zigzag form as found in previous studies for AN. The non-bonding N···C (nitrile carbon) distance between the anti-parallel adjacent molecules was 340 pm for all nitriles. The intermolecular C···C distance between next neighbour molecules was 420 pm for CH2···CH2in AN, 430 pm for CH3···CH3in PN, 425 pm for CH···CH in ACN, and 390 pm for C6H5···C6H5in BN. The short C6H5···C6H5distance was explained in terms of theπ–πstacking interactions of the aromatic rings. DMF molecules interact each other through dipole–dipole interactions, and the O···C distance of 320 pm at the O···H–CO– interaction through the formyl proton may partly contribute to the intermolecular interactions. The distance between parallel DMF molecules in a plane was estimated to be 743 pm. The diffraction data were well explained in terms of a weak layered structure of DMF, and the layers were separated by about 365 pm.
Single Ionic Volumes in Acetonitrile–Organic Cosolvent Mixtures at 298.15 K
Authors: Piekarski Henryk , Piekarska Alina , Kubalczyk Kinga
Published: May 2004

Densities of binary nonaqueous mixtures of acetonitrile (AN) with 2-methoxyethanol (ME), N,N-dimethylacetamide (DMA) and propylene carbonate (PC) were determined over the whole composition range at 298.15 K. The excess molar volumes and the partial molar volumes of both components were calculated from these data. Densities of solutions of NaI, NaBPh4 and Ph4PI in solvent mixtures AN + ME and AN + DMA and of NaI solutions in mixtures of AN + PC were measured over the whole composition range of the mixed solvents at an electrolyte concentration equal 0.05 mol dm−3. From these densities, apparent molar volumes of electrolytes and ions were evaluated and analyzed. The relationship between the apparent molar volumes of ions and (κT
/ε) parameter was tested and discussed.
Brownian Simulations Contribution to the Study of Ionic Dynamics in Aqueous Solutions
Authors: Jardat Marie , Turq Pierre
Published: May 2004

We review some results concerning the dynamics of ionic solutions that we have recently obtained by Brownian dynamics simulations; we also present new results concerning the dynamical behavior of asymmetrical electrolytes (1–10 and 2–20 electrolytes). The Brownian dynamics treats the solution in the framework of the continuous solvent model, with a ‘soft-core’ version of the primitive model. Both direct interactions and hydrodynamic interactions between solutes are taken into account in the calculations. The method allows one to obtain the self-diffusion coefficient of each ion and the electrical conductivity of the solution. The computed transport coefficients are in good agreement with experimental determinations in various cases (in aqueous solutions of 1–1 electrolytes as well as in aqueous solutions of micelles). We show that hydrodynamic interactions must be taken into account to obtain electrical conductivities in agreement with experiments. The effect of hydrodynamic interactions on the self-diffusion is also striking, especially in solutions of asymmetrical electrolytes. If this effect remains weak in simple electrolyte solutions and for small ions in 1–20 and 2–20 electrolyte solutions, it is great for macroions in latter solutions (increase of about 15 to 40%).
Effects of Polarization on the Extents and Kinetics of Adsorption of Ionic and Neutral Aromatic Heterocyclics Exhibiting Orientation Transitions at a Porous C Electrode
Authors: Conway Brian E. , Niu Jianjun
Published: May 2004

Comparative investigations of the adsorption and electrosorption of the heterocyclic compounds, pyridine, 1,4-pyrazine and 1-quinoline, and their orientation behaviours in an high specific-area C-cloth/H2O interphase, directly related to the replacement of preadsorbed and field-oriented solvent (H2O) molecules by oriented adsorbates themselves, have been carried out by means of in situ UV spectrophotometry conducted under positive or negative electric polarization at the C-cloth as an electrode. Surface charge, dipole moment of the adsorbate, polarization mode, acidity of the solution (leading to cation formation) and hydrophilic/hydrophobic properties of the adsorbed molecules in relation to the solvent (H2O vs. non-aqueous) are found to have important influences on these processes and hence govern the experimentally measurable extents and rates of their adsorption. The adsorption and orientation effects were indicated by evaluation of surface-dipole potential changes represented by Esin and Markov (EM)-type effects. Different adsorption and orientation processes amongst the three adsorbates, together with the possible rearrangement of the adsorbed molecules, were revealed by changes of the observed EM effects. The preferred adsorption/electrosorption behaviour arises by either “combined adsorption” (CAD) (i.e. combination of adsorption on open-circuit with electrosorption upon subsequent polarization) or by “alternate polarization electrosorption” (APE) (i.e. electrosorption by periodically reversed direction of polarization, between positive and negative, in one adsorption experiment). Negative-current polarization in a single transient also led to similar results for effective adsorptive removal of 1-quinoline from aqueous solution. Major differences of adsorption arise between neutral pyridine and its cation in acidic solution, including the effect of electrode polarization.
Musical Forces and Melodic Expectations: Comparing Computer Models and Experimental Results
Authors: Larson Steve
Published: May 2004

Recent work on "musical forces" asserts that experienced listeners of tonal music not only talk about music in terms used to describe physical motion, but actually experience musical motion as if it were shaped by quantifiable analogues of physical gravity, magnetism, and inertia. This article presents a theory of melodic expectation based on that assertion, describes two computer models of aspects of that theory, and finds strong support for that theory in comparisons of the behavior of those models with the behavior of participants in several experiments. The following summary statement of the theory is explained and illustrated in the article: Experienced listeners of tonal music expect completions in which the musical forces of gravity, magnetism, and inertia control operations on alphabets in hierarchies of embellishment whose stepwise displacements of auralized traces create simple closed shapes. A "single-level" computer program models the operation of these musical forces on a single level of musical structure. Given a melodic beginning in a certain key, the model not only produces almost the same responses as experimental participants, but it also rates them in a similar way; the computer model gives higher ratings to responses that participants sing more often. In fact, the completions generated by this model match note-for-note the entire completions sung by participants in several psychological studies as often as the completions of any one of those participants matches those of the other participants. A "multilevel" computer program models the operation of these musical forces on multiple hierarchical levels. When the multilevel model is given a melodic beginning and a hierarchical description of its embellishment structure (i.e., a Schenkerian analysis of it), the model produces responses that reflect the operation of musical forces on all the levels of that hierarchical structure. Statistical analyses of the results of a number of experiments test hypotheses arising from the computer models' algorithm (S. Larson, 1993a) for the interaction of musical forces as well as from F. Lerdahl's similar (1996) algorithm. Further statistical analysis contrasts the explanatory power of the theory of musical forces with that of E. Narmour's (1990, 1992) implication-realization model. The striking agreement between computer-generated responses and experimental results suggests that the theory captures some important aspects of melodic expectation. Furthermore, the fact that these data can be modeled well by the interaction of constantly acting but contextually determined musical forces gives support to the idea that we experience musical motions metaphorically in terms of our experience of physical motions.
The Relative Perceptual Salience of Tn and TnI
Authors: Samplaski Art
Published: May 2004

Trained musicians rated the similarity of 24 instances of set classes [0137/0467] and [0157/0267] at three different transposition levels and two different spacing types. Stringent criteria for retention of participants, to ensure greater reliability and predictive power, resulted in a final count of 30 participants. Participants' data were analyzed by using multidimensional scaling and additive tree methods. A three-dimensional multidimensional scaling solution showed clear effects for spacing type and transposition level (Tn). Additive tree analysis showed no grouping according to set-class type, but rather according to pitch height of inner voices or ordered location of semitones. The results are consistent with the hypothesis that even musicians with significant experience of atonal music do not use the equivalence relation TnI in making similarity judgments.
Modeling Perceived Emotion With Continuous Musical Features
Authors: Schubert Emery
Published: May 2004

The relationship between musical features and perceived emotion was investigated by using continuous response methodology and time-series analysis. Sixty-seven participants responded to four pieces of Romantic music expressing different emotions. Responses were sampled once per second on a two-dimensional emotion space (happy-sad valence and aroused-sleepy). Musical feature variables of loudness, tempo, melodic contour, texture, and spectral centroid (related to perceived timbral sharpness) were coded. Musical feature variables were differenced and used as predictors in two univariate linear regression models of valence and arousal for each of the four pieces. Further adjustments were made to the models to correct for serial correlation. The models explained from 33% to 73% of variation in univariate perceived emotion. Changes in loudness and tempo were associated positively with changes in arousal, but loudness was dominant. Melodic contour varied positively with valence, though this finding was not conclusive. Texture and spectral centroid did not produce consistent predictions. This methodology facilitates a more ecologically valid investigation of emotion in music and, importantly in the present study, enabled the approximate identification of the lag between musical features and perceived emotion. Responses were made 1 to 3 s after a change in the causal musical event, with sudden changes in loudness producing response lags from zero (nearly instantaneous) to 1 s. Other findings, interactions, and ramifications of the methodology are also discussed.
Sound Source Identification: The Possible Role of Timbre Transformations
Authors: Handel Stephen , Erickson Molly L.
Published: May 2004

Timbre is typically investigated as a perceptual attribute that differentiates instruments at one pitch. Yet the perceptual usefulness of timbre is that it allows listeners to recognize one instrument at different pitches. Using stimuli produced across the playing range by three wind instruments from two categories, woodwind and brass, we measured listeners' judgments of instrumental timbre across pitch in a dissimilarity task and measured listeners' ability to identify stimuli as being produced by the same or different instrument in a three-note oddball task. The resulting multidimensional scaling representation showed that Dimension 1 correlated with pitch, whereas Dimension 2 correlated with spectral centroid and separated the instrumental stimuli into the categories woodwind and brass. For three-note sequences, the task was extremely difficult for the woodwind pair, with listeners typically choosing the most dissimilarly pitched stimulus as coming from the oddball source. In contrast, the three-note sequences were easy for the woodwind-brass pairs. The results from these experiments illustrate the difficulty of extrapolating the timbre of a sound source across large differences in pitch.
Finnish Sleep-Preachers: An Example of Women's Spiritual Power
Authors: Stjerna Kirsi
Published: May 2004

ABSTRACT: A remarkable number of women leaders and teachers in the history of Christianity have relied on the ‘supernatural,’ spiritual authority received through extraordinary religious experiences. Among them were the Finnish ‘sleep-preachers,’ laywomen who felt called to preach and prophesy while asleep. This article introduces the most famous of these preachers, Helena Konttinen (1871-1916), and through her story discusses the phenomenon of sleep-preaching in turn-of-the-century Finland. Links are made to similar individuals earlier in Christianity, such as medieval mystics and Victorian Spiritualists, and to evidence from other women-led religions. Special attention is paid to the issues of gender and authority as related to religious experience and empowerment in explaining these pioneering women's rise, emancipation and contributions as lay theologians and unofficial ministers who significantly influenced grassroots religiosity in Finland.
Radical Religion in Finland?
Authors: Kaplan Jeffrey
Published: May 2004

ABSTRACT: This article examines the various new religious movements which are currently active in Finland. The somewhat ironic title of the article refers to the remarkable homogeneity of the Finnish religious field. In Finland, more than 80 percent of Finns profess membership in the Evangelical Lutheran Church of Finland. Yet underneath the surface of Finnish religious homogeneity, there exists a vibrant current of mysticism, a willingness to borrow and adapt foreign religious ideas, and currents of both fundamentalism and millennialism. “Radical Religion in Finland?” seeks to provide the necessary historical context to introduce the small but vibrant world of alternative spirituality in contemporary Finland.
“Showtime” in Texas: Social Production of the Branch Davidian Trials
Authors: Richardson James T.
Published: May 2004

ABSTRACT: This article analyzes the two major legal trials involving surviving members of the Branch Davidian sect that was involved in the fiery conflagration outside of Waco, Texas, in 1993. The criminal trial, which took place in 1994, and the wrongful death civil trial against the federal government, which occurred in 2000, are analyzed from the perspectives of the sociology of law and deviance theory. The analysis presumes that both trials were social productions designed to present a certain definition of the situation and the parties involved in that situation. Using the analogy of the trials as socially produced dramas, this article describes the ways that discretion operated within a judicial system acting in a normative role, with special attention paid to the role of the judge in both cases.
Why Waco Has Not Gone Away: Critical Incidents and Cultural Trauma
Authors: Docherty Jayne Seminare
Published: May 2004

ABSTRACT: Eight years after the 1993 standoff between federal law enforcement agents and the Branch Davidians, “Waco” has become a shorthand reference to the tragedy that claimed the lives of more than eighty people. After internal investigations by the Department of the Treasury and the Department of Justice, two trials, two sets of congressional hearings, the publication of numerous books and articles, and the production of documentary films, we are no closer to bringing closure to Waco than we were in 1993. To understand why Waco has not gone away, it is useful to combine a model of conflict that focuses attention on the motivational power of symbols and narrative with a model of trauma that operates at the collective and not just the individual level.
The Movement for the Restoration of the Ten Commandments of God
Authors: Mayer Jean-François
Published: May 2004

ABSTRACT: The article provides a summary of some aspects of ongoing research about the Movement for the Restoration of the Ten Commandments of God (MRTCG), which caused some 780 deaths in Uganda in March 2000. The MRTCG emerged out of a wider milieu of Ugandan popular Catholicism; the turmoils experienced by Uganda and the spread of AIDS gave an added impetus to Marian visionary activities and apocalyptic predictions. From its very beginning, the MRTCG showed suspicion toward the mainline Roman Catholic hierarchy and was characterized by a “selective traditionalism.” Regarding the endtime, it seems that the movement had consistently predicted the end of the present generation at the close of 2000 (and not 1999), followed by a New Earth with typical millenarian features. The events of March 2000 were carefully planned. What is still missing is a well-founded explanation of the massive use of violence during the last weeks of the group's existence (some 444 people murdered and dumped in secret mass graves in addition to the final conflagration in which hundreds died), and especially a possible theological justification for such actions.
“Going Native in Reverse”: The Insider as Researcher in British Wicca
Authors: Pearson Jo
Published: May 2004

ABSTRACT: This article concentrates on Wicca as the focus for a study of researching initiatory religion as an insider. Some problems associated with the study of such religions are addressed in a critical examination of earlier research by Tanya Luhrmann, before attempting to establish how the researcher can enter such a field and undertake effective fieldwork with integrity, without dishonoring the mode of entry (initiation) and the trust of the researched community. Some of the problems which can occur in the study of an initiatory religion such as Wicca, and ways in which these might be mitigated, are briefly explored. The article closes with an assessment of the insider/outsider position suggesting that, rather than being essentially problematic, such a position can in fact be advantageous to the researcher, the research, and the researched community.
Lives-Long Learning: The Effects of Reincarnation Belief on Everyday Life in England
Authors: Walter Tony , Waterhouse Helen
Published: May 2004

ABSTRACT: A sizeable minority of Westerners who have no particular connection with Eastern or New Age religions nevertheless claim to believe in reincarnation. Does this belief affect their practical morality and how they think about suffering and injustice? An interview study conducted in England mapped the range of meanings such people give to reincarnation, and found: 1) Karma was widely referred to, but in the context of Western notions of self-improvement; there was little recognition of the possibility of bad karma leading to ‘downward mobility’ in the next life, and little linking of karma to everyday action; 2) Reincarnation enabled respondents to make sense of suffering and injustice, but in a rather general way; 3) Despite the sample's elderly bias, reincarnation was not widely reported as a comfort in illness and bereavement. The authors conclude that, outside of a culture or formal religion that embraces it, relatively high levels of personal interest in reincarnation can coincide with rather insubstantial effects on everyday morality, though individuals can and do use it to think about problems of suffering and injustice.
The Heart of the Secret: A Personal and Scholarly Encounter with Shakta Tantrism in Siddha Yoga
Authors: Caldwell Sarah
Published: May 2004

ABSTRACT: This article suggests two apparently contradictory theses: namely that Swami Muktananda (1908–1982) was an enlightened teacher and practitioner of an esoteric form of Tantric sexual yoga, and that he also engaged in actions that were not ethical, legal, or liberatory with many disciples. These two theses are brought into creative tension through a developing Tantric hermeneutic. In discussing secrecy and power, the article addresses critical cultural, feminist, and psychological issues about sexual abuse and the importation of Asian religious traditions into contemporary American society, and argues that what has happened in the recent history of Siddha Yoga arises directly out of Tantra's long history of dissimulation and secrecy. I suggest that a hybrid scholarly sensibility might emerge out of the secret heart of the Tantric teachings, itself offering a way forward in the study of such traditions.
Comparison of Risperidone with Olanzapine in Elderly Patients with Dementia and Psychosis
Authors: Ellingrod Vicki L. , Schultz Susan K. , Ekstam‐Smith Karen , Kutscher Eric , Turvey Carolyn , Arndt Stephan
Published: May 2004

Study Objectives. To compare the effects of risperidone and olanzapine on cognition in elderly patients with dementia and psychosis, and to compare the side effects of these drugs.Design. Single‐blind, multicenter, observational study.

Setting. Four rural nursing care facilities.

Patients. Nineteen elderly patients with dementia and psychosis.

Intervention. Eleven patients were treated with risperidone, eight with olanzapine.

Measurements and Main Results. Rating assessments were completed at baseline, 1 month, and 2 months. Simple paired and unpaired t tests determined between‐ and within‐group differences. Social functioning, including activities of daily living, improved over baseline in both groups (p=0.03). Cognition declined significantly (p<0.05) in the risperidone group; comparatively more side effects occurred and blood pressure decreased (p<0.05) in the olanzapine group. When compared with each group cross‐sectionally at baseline and end point, however, the two groups did not differ significantly.

Conclusion. Improvements in social functioning in all 19 patients suggest that both risperidone and olanzapine may help improve functioning in elderly patients with dementia and psychosis. Cognitive and side effect profiles of these drugs may differ substantially. Further study is needed to determine patient subpopulations who may be able to tolerate one drug over another.
Sudden Irreversible Sensory‐Neural Hearing Loss in a Patient with Diabetes Receiving Amikacin as an Antibiotic‐Heparin Lock
Authors: Saxena Anil K. , Panhotra B. R. , Naguib Mohammed
Published: May 2004

Gram‐negative septicemia due to central venous catheter‐related infection is a leading cause of mortality and morbidity among patients who undergo hemodialysis. Antibiotic‐heparin locks are valuable for preserving access sites and lowering the cost and inconvenience associated with central venous catheter replacement and surgical interventions. The optimal duration of use of an antibiotic‐heparin lock is unknown. Prolonged use of an amikacin‐heparin lock may lead to severe irreversible sensory‐neural hearing loss. Patients at risk for this complication should be monitored for its emergence to facilitate early detection. A 43‐year‐old man with diabetic end‐stage renal disease received hemodialysis through a permanent catheter. After 16 weeks of using an amikacin‐heparin lock, he suddenly developed sensory‐neural hearing loss of 40 dB, which affected high frequencies. His condition progressed relentlessly within 1 week despite immediate discontinuation of the amikacin‐heparin lock. The patient developed severe irreversible hearing loss below 80 dB for both high and low frequencies.
Linezolid‐Induced Anemia and Thrombocytopenia
Authors: Waldrep Travis W. , Skiest Daniel J.
Published: May 2004

Linezolid, a fluorinated oxazolidinone, is the first of a new class of antimicrobials designed to target resistant gram‐positive cocci. Hematologic adverse effects, including reversible thrombocytopenia, were reported during phase III comparator‐controlled trials. A 66‐year‐old man developed sternal osteomyelitis due to methicillin‐resistant Staphylococcus aureus after undergoing coronary artery bypass graft surgery. Methicillin‐resistant S. aureus bacteremia developed after several surgical debridements and courses of vancomycin failed to improve the patient's condition. Oral linezolid 600 mg twice/day was begun; 17 days later, a complete blood count revealed that his hematocrit had decreased from 37.4% to 24.8%, and his platelet count had decreased from 234 times 103/mm3 to 149 times 103/mm3. Both values returned to normal after linezolid was discontinued. Complete blood counts should be monitored closely in patients taking linezolid, especially if therapy continues for more than 14 days.
Possible Ergotamine‐Caffeine—Associated Delirium
Authors: Gulbranson Scott H. , Mock Roy E. , Wolfrey Jeffrey D.
Published: May 2004

An elderly patient with a history of chronic migraine was hospitalized with systolic hypertension and significant mental status changes, including increasing confusion, combative behavior, and remarkably detailed auditory hallucinations of several weeks' duration. Daily increased consumption of a product containing ergotamine 1 mg and caffeine 100 mg coincided with both onset and increasing severity of symptoms. To our knowledge, this is the first case reported in the contemporary literature of severe mental status changes and hallucination possibly due to ergotamine‐caffeine.
Extended‐Spectrum β‐Lactamases: Frequency, Risk Factors, and Outcomes
Authors: Einhorn Allison E. , Neuhauser Melinda M. , Bearden David T. , Quinn John P. , Pendland Susan L.
Published: May 2004

Study Objective. To determine epidemiologic factors of extended‐spectrum β‐lactamase (ESBL)‐producing Escherichia coli or Klebsiella pneumoniae in a nonoutbreak setting.

Design. Retrospective analysis.

Setting. University teaching hospital.

Patients. Fifty‐seven patients with cultures of presumed ESBL‐producing (i.e., ceftazidime‐resistant) E. coli or K. pneumoniae.

Interventions. To determine overall frequency, institutional antibiograms from 1991–1999 were examined for percentage of isolates with ceftazidime resistance. Medical records from January 1997–June 2000 were reviewed for patient demographics, comorbidities, culture site, antimicrobial therapy, and clinical and microbiologic outcomes.

Measurements and Main Results. From 1991–1999, frequency increased from undetectable to 4% for ceftazidime‐resistant E. coli and from 2% to 6% for ceftazidime‐resistant K. pneumoniae. Seventy‐one isolates were identified in the 57 patients with presumed ESBL‐producing E. coli or K. pneumonia. Fifty‐one isolates (72%) were E. coli, with urine the primary site of infection (62%). Eighty‐six percent of patients had known risk factors for infection due to ESBL‐producing organisms, including hospitalization (37 patients) and residence in long‐term care facilities (12 patients). However, in 14% (8 patients), the infection was community acquired in patients who resided at home.

Conclusion. In addition to known populations at risk, ambulatory patients with chronic conditions represent another patient population that may harbor ESBL‐producing organisms.
Maintenance of Low‐Density Lipoprotein Goal with Step‐Down Pravastatin Therapy
Authors: Graham Maqual R. , Lindsey Cameron C. , Kennedy James A.
Published: May 2004

Study Objective. To determine whether patients who had achieved their National Cholesterol Education Program (NCEP)‐derived goals for low‐density lipoprotein (LDL) cholesterol with pravastatin would benefit from step‐down therapy.

Design. Prospective, randomized, open‐label study.

Setting. Kansas City Veterans Affairs Medical Center.

Patients. One hundred four men who were taking pravastatin once/day and had maintained their NCEP‐defined LDL goal for at least 3 months.

Intervention. Fifty‐three patients were randomized to group 1, for which the dosing frequency was changed from daily to every other day, and 51 patients were randomized to group 2, for which the daily dose was halved.

Measurements and Main Results. Fasting lipid profiles and hepatic transaminase levels were analyzed at baseline, 2 months, and 4 months. Lifestyle, concomitant drug therapy, adverse events, weight, and compliance were noted at baseline and month 4. Thirty‐one patients (58%) from group 1 and 22 patients (43%) from group 2 did not remain at their LDL goal after step‐down pravastatin therapy. Mean LDL at study end was 113 mg/dl for group 1 and 104 mg/dl for group 2 (p=0.04).

Conclusion. More than half (51%) of the patients enrolled did not remain at their LDL goal with step‐down pravastatin therapy. Therefore, we do not recommend a step‐down approach for patients who have achieved their LDL goals. If a clinician decides, however, to attempt dosage reduction, the preferred regimen appears to be to halve the current dose once/day (vs administering the current dose every other day). A fasting lipid profile should be evaluated at 2 months and 4 months after step‐down therapy begins to ensure that desired outcomes are achieved.
A Review of Vasopeptidase Inhibitors: A New Modality in the Treatment of Hypertension and Chronic Heart Failure
Authors: Nathisuwan Surakit , Talbert Robert L.
Published: May 2004

Vasopeptidase inhibitors are a group of agents capable of inhibiting neutral endopeptidase and angiotensin‐converting enzymes, which leads to potentiation of natriuretic peptide actions and suppression of the renin‐angiotensin‐aldosterone system. With this distinctively characteristic mechanism, these agents have emerged as a new drug class for management of hypertension and heart failure. Several vasopeptidase inhibitors are under clinical investigation. Omapatrilat is the most studied agent in this class. Clinical studies of omapatrilat in hypertension have consistently shown the agent's effectiveness in a variety of patient populations. In patients with heart failure, omapatrilat significantly improved neurohormonal and hemodynamic status. Long‐term effects of omapatrilat in patients with heart failure recently were compared with those of conventional therapy in a large phase II trial. Results of the study appear promising. Large clinical trials are ongoing, and additional information regarding safety and efficacy from these studies may help define the place in therapy for this agent.
Endothelin‐1 and Endothelin Receptor Antagonists as Potential Cardiovascular Therapeutic Agents
Authors: Ergul Adviye
Published: May 2004

Endothelin (ET)‐1 is an endothelium‐derived peptide with potent vasoconstrictor and proliferative properties. The ET system is activated in several cardiovascular disease states associated with functional and structural vascular changes, including hypertension and heart failure. The two ET receptor subtypes are known as ETAR and ETBR. The former is located mainly on vascular smooth muscle cells and is responsible for mediating vasoconstriction and proliferation. The latter is present predominantly on endothelial cells and mediates vasorelaxation as well as ET‐1 clearance. Activation of smooth muscle ETBR causes vasoconstriction. Selective ETAR antagonists as well as nonselective ETAR‐ETBR antagonists have been developed. Studies with animal models and early‐phase clinical trials provided strong evidence that these agents are effective in the treatment of heart failure, essential hypertension, pulmonary hypertension, and atherosclerosis. However, the complexity of biologic effects mediated by two different receptor subtypes complicates therapy with selective versus nonselective ET receptor antagonists. In addition to subtype selectivity and potency, changes in receptor subtype distribution under different pathologic conditions and different patient populations will play a crucial role in the evaluation of these potentially therapeutic drugs.
Dose Proportionality of Three Different Doses of Tibolone
Authors: Timmer Cees J. , Houwing Natalie S.
Published: May 2004

Study Objective. To assess dose proportionality of tibolone tablets after multiple oral administration.

Design. Open‐label, randomized, three‐period crossover study.

Setting. Department of Drug Metabolism and Kinetics, N.V. Organon, Oss, The Netherlands.

Subjects. Twenty‐seven postmenopausal women aged 65 years or younger.

Intervention. Subjects received tibolone 1.25, 2.5, or 5.0 mg once/day for 7 days.

Measurements and Main Results. Plasma concentrations of tibolone and its three primary metabolites were assayed. Steady state was attained by day 5. Elimination half‐life for 3α‐hydroxytibolone was 7.2–8.5 hours. At steady state, the dose‐normalized peak concentration and area under the curve satisfied bioequivalence requirements for the 1.25‐ and 2.5‐mg doses, but not fully for the 5.0‐mg dose. Parameters were proportionally slightly lower for the 5.0‐mg dose compared with the 1.25‐ and 2.5‐mg doses.

Conclusion. Proportional bioequivalence was established for the 1.25‐ and 2.5‐mg doses, but not between the 5.0‐mg dose and the two lower doses of tibolone.
Conversion of Recent‐Onset Atrial Fibrillation with Intravenous Amiodarone: A Meta‐Analysis of Randomized Controlled Trials
Authors: Hilleman Daniel E. , Spinler Sarah A.
Published: May 2004

Study Objective. To evaluate efficacy and safety of intravenous amiodarone for conversion of recent‐onset atrial fibrillation.

Data Sources. MEDLINE search of published, randomized, controlled trials assessing the efficacy and safety of intravenous amiodarone in recent‐onset (< 7 days) atrial fibrillation, supplemented with searches of reference lists of identified articles and bibliographies of secondary and tertiary review articles.

Study Selection. The identified trials were eligible for meta‐analysis if they met the following criteria: patients had recent‐onset atrial fibrillation; patients were randomized to intravenous amiodarone, placebo, or another antiarrhythmic agent; no other antiarrhythmic agent except digoxin was administered simultaneously with intravenous amiodarone or other active treatments; the number and percentage of conversions to sinus rhythm after treatment began were reported; and the number and type of adverse drug reactions occurring after treatment began were reported.

Results. Eighteen randomized controlled trials, including active control cohorts and placebo cohorts, met inclusion criteria. Atrial fibrillation was spontaneous in 13 trials, postoperative in 4, and combined spontaneous and postoperative in 1. A total of 550 patients received intravenous amiodarone, 451 received other antiarrhythmic therapy, and 202 received placebo. Unadjusted averages for cardioversion were as follows: intravenous amiodarone, 417 (76%) of 550 patients; other antiarrhythmics, 324 (72%) of 451 patients; and placebo, 121 (60%) of 202 patients. Pooled estimates of cardioversion for active cohort studies were 72.1% for intravenous amiodarone and 71.9% for other antiarrhythmics (p=0.84). Pooled estimates of cardioversion for placebo cohort studies were 82.4% for intravenous amiodarone and 59.7% for placebo (p=0.03). Unadjusted averages for adverse event rates were intravenous amiodarone, 94 (17%) of 550 patients; other antiarrhythmics, 63 (14%) of 451 patients; and placebo, 23 (11%) of 202 patients. Pooled estimates of adverse event rates for active cohort studies were 12.2% for intravenous amiodarone and 14.0% for other antiarrhythmics (p=0.64). Pooled estimates of adverse event rates for placebo cohort studies were 26.8% for intravenous amiodarone and 10.8% for placebo (p=0.02). The most common adverse drug reactions reported with intravenous amiodarone were infusion phlebitis, bradycardia, and hypotension.

Conclusion. The efficacy and safety profile of intravenous amiodarone is similar to that of other antiarrhythmics for cardioversion of recent‐onset atrial fibrillation. Intravenous amiodarone is significantly more effective than placebo but is associated with significantly higher frequency of adverse events, although most were not considered to be dose limiting.
The Effect of an Antimicrobial Formulary Change on Hospital Resistance Patterns
Authors: Empey Kerry M. , Rapp Robert P. , Evans Martin E.
Published: May 2004

A university hospital formulary change that was designed to reduce the use of the third‐generation cephalosporins ceftazidime and cefotaxime and replace them with the so‐called “fourth‐generation” cephalosporin cefepime was evaluated. A retrospective review of antibiotic use and antimicrobial resistance during two 6‐month periods before and after the formulary change was performed. All hospital patients with vancomycin‐resistant Enterococcus (VRE), ceftazidime‐resistant Klebsiella pneumoniae (CRKP), methicillin‐resistant Staphylococcus aureus (MRSA), piperacillin‐resistant Pseudomonas aeruginosa (PRPA), and ceftazidime‐resistant P. aeruginosa (CRPA) infections were included in the study. Ceftazidime use decreased from 9600 g to 99 g, and cefotaxime use decreased from 6314 g to 732 g, which represented a combined decrease of 89%. Use of cefepime increased from 0 g to 5396 g. Infections from CRKP decreased from 13% to 3%, PRPA infections decreased from 22% to 14%, and CRPA infections decreased from 25% to 15% (p<0.05 for all). Infections from MRSA dropped insignificantly, and VRE infections increased significantly. Substituting cefepime for ceftazidime and cefotaxime while reducing the overall use of cephalosporins appears to decrease rates of CRKP, PRPA, and CRPA.
The Effect of Sepsis During Parenteral Nutrition on Hepatic Microsomal Function in Rats
Authors: Dickerson Roland N. , Charland Scott L.
Published: May 2004

Study Objective. To investigate the effect of sepsis during parenteral nutrition on hepatic cytochrome P450 (CYP) activity in rats.

Design. Prospective, randomized, controlled study.

Setting. University‐based animal research laboratory.

Animals. Twenty adult male Sprague‐Dawley rats.

Intervention. The animals were cannulated intravenously and randomized to receive parenteral nutrition (PN), intravenous live Escherichia coli 4 × 108 colony‐forming units/100 g body weight for 2 consecutive days with PN (PNEC), or chow (CH).

Measurements and Main Results. Both PN alone and PNEC resulted in a progressive decline in hepatic CYP concentration compared with CH (0.53 ± 0.10, 0.41 ± 0.17, and 0.35 ± 0.14 nmol/mg microsomal protein, respectively, p<0.05). Parenteral nutrition alone was associated with a 57% decrease in isoenzyme ethoxycoumarin‐O‐deethylase activity (ECOD) compared with CH, but sepsis did not further decrease ECOD activity any more than PN alone (0.103 ± 0.049, 0.044 ± 0.018, and 0.050 ± 0.020 nmol/mg microsomal protein/min, respectively, p<0.05).

Conclusion. Hepatic CYP concentration declines with PN and is further decreased when compounded by sepsis. The disproportional decrease in ECOD activity relative to CYP concentration with PN is unchanged by sepsis, indicating a selective alteration in hepatic isoenzymes by PN.
Comparison of Two Needle Sizes for Subcutaneous Administration of Enoxaparin: Effects on Size of Hematomas and Pain on Injection
Authors: Robb Dawn M. , Kanji Zahra
Published: May 2004

Study Objective. To determine whether use of a smaller needle size for subcutaneous injection of enoxaparin would reduce the size of injection‐site hematomas and/or decrease the pain of injection.

Design. Prospective, randomized trial.

Setting. Community hospital in North Vancouver, British Columbia, Canada.

Patients. One hundred twenty‐four patients with unstable angina or non‐Q‐wave myocardial infarction who were administered enoxaparin for anticoagulation.

Intervention. Each patient was randomly assigned to one of two groups. One group received enoxaparin injections with a 30–gauge, 5/16–inch insulin syringe, and the other group was injected with a 26–gauge, 3/8–inch tuberculin syringe.

Measurements and Main Results. Participating nurses used standard measuring tape to determine the largest diameter of each hematoma. Pain was assessed with a 10–unit numeric scale. The two groups did not differ significantly with regard to either the mean size of the largest hematoma/patient (4.2 cm in the insulin‐syringe group vs 3.8 cm in the tuberculin‐syringe group, p=0.68) or the mean pain score (0.3 in the insulin‐syringe group vs 0.5 in the tuberculin‐syringe group, p=0.10).

Conclusions. Use of a 30–gauge, 5/16–inch insulin syringe instead of a 26–gauge, 3/8–inch tuberculin syringe does not significantly reduce either hematoma size or pain of injection. A larger study is required to determine whether needle size affects the frequency of hematoma formation. (Pharmacotherapy 2002;22(9):1105–1109)
Daily Dosing versus Alternate‐Day Dosing of Simvastatin in Patients with Hypercholesterolemia
Authors: Copher Heather R. , Stewart Robert D.
Published: May 2004

Study Objective. To compare the efficacy of daily simvastatin administration with that of alternate‐day therapy at double the daily dose.

Design. Nonrandomized, before‐after comparison trial.

Setting. Outpatient clinic of a Veterans Affairs medical center. Patients. Fifteen men with hyperlipidemia.

Intervention. The simvastatin regimen for patients with a low‐density lipoprotein cholesterol (LDL) level at their established National Cholesterol Education Program goal was converted from daily dosing to double the daily dose given every other day for 8 weeks.

Measurements and Main Results. Baseline laboratory values were obtained for patients receiving daily simvastatin therapy. After 8 weeks of alternate‐day therapy, follow‐up laboratory values were obtained and assessed for efficacy and toxicity. The LDL‐lowering effect of the daily dosing regimen was compared with that of the alternate‐day dosing regimen. Paired t tests were computed to compare LDL concentrations before and after the study using a 95% confidence interval. No statistically significant difference was observed.

Conclusion. Alternate‐day dosing of simvastatin may be an effective alternative to daily dosing. (Pharmacotherapy 2002;22(9):1110–1116)
Fluticasone Is Associated with Lower Asthma‐Related Costs than Leukotriene Modifiers in a Real‐World Analysis
Authors: Armstrong Edward P. , Malone Daniel C.
Published: May 2004

Study Objective. To compare the impact of fluticasone propionate versus three leukotriene modifiers—montelukast, zafirlukast, and zileuton—on the cost of asthma within a managed care organization.

Design. Retrospective quasi‐experimental comparison.

Setting. Managed care organization with approximately 350,000 enrollees.

Patients. Three hundred forty‐seven patients with asthma who received at least two prescriptions for either fluticasone or a leukotriene modifier. Patients receiving both fluticasone and a leukotriene modifier were excluded.

Measurements and Main Results. Multivariate analysis was used to compare total asthma‐related costs between treatment groups. A significant difference in total asthma‐related costs was found between patients receiving fluticasone (adjusted mean cost $511) compared with those receiving a leukotriene modifier ($1092; p=0.0001). Other significant predictors of postindex asthma‐related costs were pre‐index asthma‐related costs, a severity adjustment score, and the diagnosis of chronic obstructive pulmonary disease. Patients taking a leukotriene modifier obtained more short‐acting β‐agonists than patients receiving fluticasone (6.49 ± 4.05 vs 4.30 ± 3.41, p<0.0001). A survival analysis of time to receive any additional controller therapy revealed that patients receiving fluticasone were significantly less likely to receive another controller than were those receiving a leukotriene modifier (p=0.0014).

Conclusion. These results suggest that fluticasone is associated with lower asthma‐related costs than leukotriene modifiers. (Pharmacotherapy 2002;22(9):1117–1123)
Formoterol Therapy for Chronic Obstructive Pulmonary Disease: A Review of the Literature
Authors: Friedman Mitchell , Cioppa Giovanni Della , Kottakis John
Published: May 2004

Numerous clinical trials have investigated the use of formoterol, a long‐acting β2–agonist, for the treatment of chronic obstructive pulmonary disease (COPD). Formoterol provides bronchodilation as rapidly as albuterol, yet its efficacy and duration of action are similar to those of salmeterol. It demonstrates better spirometric efficacy than either ipratropium or theophylline alone, and its efficacy improves when administered in combination with ipratropium. Formoterol improves patients' quality of life and has a good safety profile. It is better tolerated than theophylline and has a similar tolerability to albuterol, salmeterol, and ipratropium. In short, formoterol is a bronchodilator with rapid onset of action and prolonged duration of action with a favorable efficacy, safety, and tolerability profile when used in patients with COPD. It provides a valid therapeutic option in the pharmacologic treatment of this disease.