bluuebunny/crossref_metadata_2025 huggingface dataset:
Sorting of a nonmuscle tropomyosin to a novel cytoskeletal compartment in skeletal muscle results in muscular dystrophy
Authors: Kee Anthony J. , Schevzov Galina , Nair-Shalliker Visalini , Robinson C. Stephen , Vrhovski Bernadette , Ghoddusi Majid , Qiu Min Ru , Lin Jim J.-C. , Weinberger Ron , Gunning Peter W. , Hardeman Edna C.
Published: August 2004

Tropomyosin (Tm) is a key component of the actin cytoskeleton and >40 isoforms have been described in mammals. In addition to the isoforms in the sarcomere, we now report the existence of two nonsarcomeric (NS) isoforms in skeletal muscle. These isoforms are excluded from the thin filament of the sarcomere and are localized to a novel Z-line adjacent structure. Immunostained cross sections indicate that one Tm defines a Z-line adjacent structure common to all myofibers, whereas the second Tm defines a spatially distinct structure unique to muscles that undergo chronic or repetitive contractions. When a Tm (Tm3) that is normally absent from muscle was expressed in mice it became associated with the Z-line adjacent structure. These mice display a muscular dystrophy and ragged-red fiber phenotype, suggestive of disruption of the membrane-associated cytoskeletal network. Our findings raise the possibility that mutations in these tropomyosin and these structures may underpin these types of myopathies.
Angiotensin II (AT1) Receptors and NADPH Oxidase Regulate Cl− Current Elicited by β1 Integrin Stretch in Rabbit Ventricular Myocytes
Authors: Browe David M. , Baumgarten Clive M.
Published: August 2004

Direct stretch of β1 integrin activates an outwardly rectifying, tamoxifen-sensitive Cl− current (Cl− SAC) via focal adhesion kinase (FAK) and/or Src. The characteristics of Cl− SAC resemble those of the volume-sensitive Cl− current, ICl,swell. Because myocyte stretch releases angiotensin II (AngII), which binds AT1 receptors (AT1R) and stimulates FAK and Src in an autocrine-paracrine loop, we tested whether AT1R and their downstream signaling cascade participate in mechanotransduction. Paramagnetic beads coated with mAb for β1-integrin were applied to myocytes and pulled upward with an electromagnet while recording whole-cell anion current. Losartan (5 μM), an AT1R competitive antagonist, blocked Cl− SAC but did not significantly alter the background Cl− current in the absence of integrin stretch. AT1R signaling is mediated largely by H2O2 produced from superoxide generated by sarcolemmal NADPH oxidase. Diphenyleneiodonium (DPI, 60 μM), a potent NADPH oxidase inhibitor, rapidly and completely blocked both Cl− SAC elicited by stretch and the background Cl− current. A structurally unrelated NADPH oxidase inhibitor, 4-(2-aminoethyl) benzenesulfonyl fluoride (AEBSF, 0.5 and 2 mM), also rapidly and completely blocked Cl− SAC as well as a large fraction of the background Cl− current. With continuing integrin stretch, Cl− SAC recovered upon washout of AEBSF (2 mM). In the absence of stretch, exogenous AngII (5 nM) activated an outwardly rectifying Cl− current that was rapidly and completely blocked by DPI (60 μM). Moreover, exogenous H2O2 (10, 100, and 500 μM), the eventual product of NADPH oxidase activity, also activated Cl− SAC in the absence of stretch, whereas catalase (1,000 U/ml), an H2O2 scavenger, attenuated the response to stretch. Application of H2O2 during NADPH oxidase inhibition by either DPI (60 μM) or AEBSF (0.5 mM) did not fully reactivate Cl− SAC, however. These results suggest that stretch of β1-integrin in cardiac myocytes elicits Cl− SAC by activating AT1R and NADPH oxidase and, thereby, producing reactive oxygen species. In addition, NADPH oxidase may be intimately coupled to the channel responsible for Cl− SAC, providing a second regulatory pathway.
Using Total Fluorescence Increase (Signal Mass) to Determine the Ca2+ Current Underlying Localized Ca2+ Events
Authors: Zou Hui , Lifshitz Lawrence M. , Tuft Richard A. , Fogarty Kevin E. , Singer Joshua J.
Published: August 2004

The feasibility of determining localized Ca2+ influx using only wide-field fluorescence images was explored by imaging (using fluo-3) single channel Ca2+ fluorescence transients (SCCaFTs), due to Ca2+ entry through single openings of Ca2+-permeable ion channels, while recording unitary channel currents. Since the image obtained with wide-field optics is an integration of both in-focus and out-of-focus light, the total fluorescence increase (ΔFtotal or “signal mass”) associated with a SCCaFT can be measured directly from the image by adding together the fluorescence increase due to Ca2+ influx in all of the pixels. The assumptions necessary for obtaining the signal mass from confocal linescan images are not required. Two- and three-dimensional imaging was used to show that ΔFtotal is essentially independent of the position of the channel with respect to the focal plane of the microscope. The relationship between Ca2+ influx and ΔFtotal was obtained using SCCaFTs from plasma membrane caffeine-activated cation channels when Ca2+ was the only charge carrier of the inward current. This relationship was found to be linear, with the value of the slope (or converting factor) affected by the particular imaging system set-up, the experimental conditions, and the properties of the fluorescent indicator, including its binding capacity with respect to other cellular buffers. The converting factor was used to estimate the Ca2+ current passing through caffeine-activated channels in near physiological saline and to estimate the endogenous buffer binding capacity. In addition, it allowed a more accurate estimate of the Ca2+ current underlying Ca2+ sparks resulting from Ca2+ release from intracellular stores via ryanodine receptors in the same preparation.
How Source Content Determines Intracellular Ca2+ Release Kinetics. Simultaneous Measurement of [Ca2+] Transients and [H+] Displacement in Skeletal Muscle
Authors: Pizarro Gonzalo , Ríos Eduardo
Published: August 2004

In skeletal muscle, the waveform of Ca2+ release under clamp depolarization exhibits an early peak. Its decay reflects an inactivation, which locally corresponds to the termination of Ca2+ sparks, and is crucial for rapid control. In cardiac muscle, both the frequency of spontaneous sparks (i.e., their activation) and their termination appear to be strongly dependent on the Ca2+ content in the sarcoplasmic reticulum (SR). In skeletal muscle, no such role is established. Seeking a robust measurement of Ca2+ release and a way to reliably modify the SR content, we combined in the same cells the “EGTA/phenol red” method (Pape et al., 1995) to evaluate Ca2+ release, with the “removal” method (Melzer et al., 1987) to evaluate release flux. The cytosol of voltage-clamped frog fibers was equilibrated with EGTA (36 mM), antipyrylazo III, and phenol red, and absorbance changes were monitored simultaneously at three wavelengths, affording largely independent evaluations of Δ[H+] and Δ[Ca2+] from which the amount of released Ca2+ and the release flux were independently derived. Both methods yielded mutually consistent evaluations of flux. While the removal method gave a better kinetic picture of the release waveform, EGTA/phenol red provided continuous reproducible measures of calcium in the SR (CaSR). Steady release permeability (P), reached at the end of a 120-ms pulse, increased as CaSR was progressively reduced by a prior conditioning pulse, reaching 2.34-fold at 25% of resting CaSR (four cells). Peak P, reached early during a pulse, increased proportionally much less with SR depletion, decreasing at very low CaSR. The increase in steady P upon depletion was associated with a slowing of the rate of decay of P after the peak (i.e., a slower inactivation of Ca2+ release). These results are consistent with a major inhibitory effect of cytosolic (rather than intra-SR) Ca2+ on the activity of Ca2+ release channels.
A Cyclic Nucleotide Modulated Prokaryotic K+ Channel
Authors: Nimigean Crina M. , Shane Tania , Miller Christopher
Published: August 2004

A search of prokaryotic genomes uncovered a gene from Mesorhizobium loti homologous to eukaryotic K+ channels of the S4 superfamily that also carry a cyclic nucleotide binding domain at the COOH terminus. The gene was cloned from genomic DNA, and the protein, denoted MloK1, was overexpressed in Escherichia coli and purified. Gel filtration analysis revealed a heterogeneous distribution of protein sizes which, upon inclusion of cyclic nucleotide, coalesces into a homogeneous population, eluting at the size expected for a homotetramer. As followed by a radioactive 86Rb+ flux assay, the putative channel protein catalyzes ionic flux with a selectivity expected for a K+ channel. Ion transport is stimulated by cAMP and cGMP at submicromolar concentrations. Since this bacterial homologue does not have the “C-linker” sequence found in all eukaryotic S4-type cyclic nucleotide-modulated ion channels, these results show that this four-helix structure is not a general requirement for transducing the cyclic nucleotide-binding signal to channel opening.
Sclerosing Epithelioid Fibrosarcomas Involving the Neuraxis: Report of Three Cases
Authors: Bilsky Mark H. , Schefler Amy C. , Sandberg David I. , Dunkel Ira J. , Rosenblum Marc K.
Published: September 2004

OBJECTIVE AND IMPORTANCE

Sclerosing epithelioid fibrosarcoma (SEF) is a rare mesenchymal neoplasm composed of rounded, vimentin-immunoreactive tumor cells disposed in nests and cords within a hyalinized collagenous matrix. Most examples arise in the deep skeletal muscles of adults. The cases recorded to date have been characterized by protracted clinical evolutions with a tendency for stubborn local recurrence, followed by late metastasis. Accordingly, SEF has been regarded as a low-grade sarcoma. A single instance of brain and vertebral metastasis has been described. We report three examples of SEF distinguished by primary involvement of the neuraxis at initial presentation.

CLINICAL PRESENTATION

Two tumors had intracranial, calvarial and extracalvarial, soft-tissue components, whereas the third tumor manifested as a paraspinal mass with extension into the T12–L1 neural foramen and invasion of the T12 nerve root.

INTERVENTION

All three affected patients experienced local recurrence and distant metastasis after resection of the primary site. These complications appeared early in the disease course in two cases. In no case was there a response to adjuvant chemotherapy or radiotherapy.

CONCLUSION

Our experience indicates that SEFs arising along the neuraxis may demonstrate unexpectedly aggressive clinical behavior, compared with those arising in the more typical location of deep skeletal muscles.
Modified Malis Bayonet Forceps Aids Application of the Cyberonics Vagus Nerve Stimulator Electrode: Technical Note
Authors: Carey Michael E. , Kutz Scott
Published: September 2004

OBJECTIVE

To notify neurosurgeons about a modified bayonet forceps that aids application of the vagus nerve stimulating electrode.

METHODS

The manufacturer (Codman & Shurtleff, Inc., Raynham, MA) extended the tips of an upward-angled Malis bayonet forceps from 2 mm to 6 mm.

RESULTS

The modified bayonet tips, when placed under the vagus nerve, extend well beyond the edge of the usual vagus nerve to easily accept the electrode lead.

CONCLUSION

The modified bayonet forceps and depicted wrapping sequence shorten electrode wrapping time.
Olfactory Ensheathing Cells: Bridging the Gap in Spinal Cord Injury
Authors: Bartolomei Juan C. , Greer Charles A.
Published: September 2004

SPINAL CORD INJURY (SCI) continues to be an insidious and challenging problem for scientists and clinicians. Recent neuroscientific advances have changed the pessimistic notion that axons are not capable of significant extension after transection. The challenges of recovering from SCI have been broadly divided into four areas: 1) cell survival; 2) axon regeneration (growth); 3) correct targeting by growing axons; and 4) establishment of correct and functional synaptic appositions. After acute SCI, there seems to be a therapeutic window of opportunity within which the devastating consequences of the secondary injury can be ameliorated. This is supported by several observations in which apoptotic glial cells have been identified up to 1 week after acute SCI. Moreover, autopsy studies have identified anatomically preserved but unmyelinated axons that could potentially subserve normal physiological properties. These observations suggest that therapeutic strategies after SCI can be directed into two broad modalities: 1) prevention or amelioration of the secondary injury, and 2) restorative or regenerative interventions. Intraspinal transplants have been used after SCI as a means for restoring the severed neuraxis. Fetal cell transplants and, more recently, progenitor cells have been used to restore intraspinal circuitry or to serve as relay for damaged axons. In an attempt to remyelinate anatomically preserved but physiologically disrupted axons, newer therapeutic interventions have incorporated the transplantation of myelinating cells, such as Schwann cells, oligodendrocytes, and olfactory ensheathing cells. Of these cells, the olfactory ensheathing cells have become a more favorable candidate for extensive remyelination and axonal regeneration. Olfactory ensheathing cells are found along the full length of the olfactory nerve, from the basal lamina of the epithelium to the olfactory bulb, crossing the peripheral nervous system-central nervous system junction. In vitro, these cells promote robust axonal growth, in part through cell adhesion molecules and possibly by secretion of neurotrophic growth factors that support axonal elongation and extension. In animal models of SCI, transplantation of ensheathing cells supports axonal remyelination and extensive migration throughout the length of the spinal cord. Although the specific properties of these cells that govern enhanced axon regeneration remain to be elucidated, it seems certain that they will contribute to the establishment of new horizons in SCI research.
Multiple Interstitial Substances Measured by Microdialysis in Patients with Subarachnoid Hemorrhage
Authors: Staub Frank , Graf Rudolf , Gabel Paula , Köchling Matthias , Klug Norfrid , Heiss Wolf-Dieter
Published: September 2004

OBJECTIVE

Intracerebral microdialysis is a tool to monitor metabolic disturbances in the brains of patients with severe head injuries or subarachnoid hemorrhage (SAH). In the search for putative indicators of primary and secondary brain damage, we measured multiple metabolites in the dialysates of patients with SAH, to elucidate their significance for the outcomes of the patients as well as their temporal profiles of liberation after the insult.

METHODS

Microdialysis probes were placed, with a ventriculostomy catheter for drainage of cerebrospinal fluid, into a frontal lobe of 10 patients with aneurysmal SAH, for 4.6 ± 0.5 days. Amino acids, metabolites of glycolysis, purines, catecholamines, and nitric oxide oxidation byproducts were measured by high-performance liquid chromatography. Spearman's correlation coefficient and Student's t test were used to compare the levels of the metabolites with the outcomes of the patients, as assessed using the Glasgow Outcome Scale, 3 months after the ictus.

RESULTS

For patients with unfavorable outcomes (Glasgow Outcome Scale scores of 1–3), which were primarily associated with the development of large infarctions, dialysate levels of excitatory amino acids increased up to 30-fold, those of lactate up to 10-fold, and those of nitrite up to 5-fold, compared with normal levels observed for patients with favorable outcomes (Glasgow Outcome Scale scores of 4 or 5). When average peak concentrations in the dialysates of patients with favorable and unfavorable outcomes were compared, significantly higher levels of excitatory amino acids, taurine, lactate, and nitrite, but not of purines and catecholamines, were observed for those with poor outcomes (P < 0.05). With respect to the temporal profiles of the average metabolite concentrations, the significantly increased levels of amino acids observed for patients with poor outcomes followed a biphasic course, with maximal concentrations on the first and second days or the seventh day after the insult (P < 0.01).

CONCLUSION

These data confirm the usefulness of excitatory amino acids and lactate as major parameters for neurochemical monitoring for patients threatened by acute cerebral disorders. Other substances, such as taurine and nitrite, were also demonstrated to be potentially predictive. Release of these substances into the extracellular fluid of the brain might be particularly relevant for the development of secondary brain damage after SAH, e.g., infarction or brain swelling.
Signal peptide prediction based on analysis of experimentally verified cleavage sites
Authors: Zhang Zemin , Henzel William J.
Published: September 2004

A number of computational tools are available for detecting signal peptides, but their abilities to locate the signal peptide cleavage sites vary significantly and are often less than satisfactory. We characterized a set of 270 secreted recombinant human proteins by automated Edman analysis and used the verified cleavage sites to evaluate the success rate of a number of computational prediction programs. An examination of the frequency of amino acid in the N‐terminal region of the data set showed a preference of proline and glutamine but a bias against tyrosine. The data set was compared to the SWISS‐PROT database and revealed a high percentage of discrepancies with cleavage site annotations that were computationally generated. The best program for predicting signal sequences was found to be SignalP 2.0‐NN with an accuracy of 78.1% for cleavage site recognition. The new data set can be utilized for refining prediction algorithms, and we have built an improved version of profile hidden Markov model for signal peptides based on the new data.
Sedimentation velocity studies of the high–molecular weight aggregates of the HIV gp41 ectodomain
Authors: Jacobs Amy , Hartman Kari , Laue Thomas , Caffrey Michael
Published: September 2004

Accumulation of the HIV envelope protein gp41 is observed in the brain tissues of patients suffering from HIV‐associated dementia. Previously, we have shown by electron microscopy that the extracellular domain of SIV gp41, which is analogous to that of HIV, forms high–molecular weight aggregates in vitro, and we have postulated that such high–molecular weight aggregates are responsible for neurological damage in a manner similar to protein deposition diseases such as Alzheimer's and the prion diseases. In this manuscript, we have characterized the self‐association of the HIV gp41 ectodomain by sedimentation velocity. We show that discreet species of the gp41 high–molecular weight aggregates are present. The maximum population occurs at 20 S, which corresponds to ∼5 trimers of gp41, suggesting that five trimers are required for nucleation of the high–molecular weight aggregates. The concentration dependence of the gp41 self‐association indicates that it occurs by mass action. The temperature dependence of gp41 self‐association suggests that it is driven by entropy, indicating that intermolecular hydrophobic interactions between trimers of gp41 are driving the association.
Computed tomography evaluation of cavitary necrosis in complicated childhood pneumonia
Authors: Koşucu P , Ahmetoğlu A , Çay A , İmamoğlu M , Özdemir O , Dinç H , Sarihan H , Gümele HR
Published: September 2004

The purpose of the present study was to retrospectively investigate the chest radiograph (CR) and CT findings of childhood pneumonia complicated by cavitary necrosis, and to evaluate the role of CT in decision‐making for surgical intervention. Chest CT was performed in 51 patients presenting with persistent or progressive pneumonia, respiratory distress and sepsis despite 7−10 days of appropriate antibiotic treatment and closed tube drainage. Chest radiograph and CT findings were retrospectively evaluated in 23 patients (45%) with cavitary necrosis. Chest radiographs showed consolidation in 19 of 23 patients, cavitation in five patients, parapneumonic effusions in 17 patients and air−fluid levels in the pleural space in one patient. The CT scans demonstrated consolidation and cavitary necrosis in all patients. There were parapneumonic effusions in all patients with concomitant loculated collections in six patients. Twenty‐two of 23 patients had pleural thickening. In seven patients there were air−fluid levels in the pleural space. In five of these patients, CT scans demonstrated bronchopleural fistulae. On the basis of the CT and clinical findings, 11 patients underwent surgical intervention. Computed tomography is superior to CR for demonstrating cavitary necrosis complicating pneumonia, and other parenchymal and pleural complications. It also has a crucial decision‐making role for surgery.
Bladder pheochromocytoma encountered on sonography
Authors: Çeliktaş M , Okur N , Aikimbaev KS , Binokay F , Sert M , Akgül E
Published: September 2004

Pheochromocytomas of the bladder are rare neoplasms, constituting <0.06% of all vesical tumours. Common presenting features of this tumour include episodes of sweating, hypertension, haematuria and postmicturition syncope. We describe a case of bladder pheochromocytoma in a 66‐year‐old man whose only symptom of macroscopic haematuria was initially assessed with ultrasonography. Clinical presentation highlights the need for a high index of suspicion during sonographic evaluation of bladder neoplasms because such tumours might present without symptoms of adrenergic excess.
What can national data sets tell us about inclusion and pupil achievement?
Authors: Florian Lani , Rouse Martyn , Black‐Hawkins Kristine , Jull Stephen
Published: September 2004

Recent developments in the Department for Education and Skills (DfES) have produced a national pupil database (NPD) that contains information about the attainments of individual pupils. Every child in the country has been allocated a unique pupil number (UPN), which means that the academic progress of individuals can be tracked over time. It is possible to combine data on attainment with the demographic information which is obtained from the pupil level annual schools census (PLASC). These innovations make it possible to combine ‘value added’ information about pupil progress from one key stage of education to the next with data from the PLASC, which contains pupil background information, to produce a single matched data set. Thus the NPD and the PLASC are able to provide much of the necessary information to explore issues of individual pupil performance over their school careers. Notably, more specific information about the academic achievement of pupils who are described as having ‘special educational needs’ is now available. Lani Florian, lecturer in inclusion and special educational needs, Martyn Rouse, senior lecturer in inclusion and special educational needs, Kristine Black‐Hawkins, senior research associate, and Stephen Jull, research associate, are all based at the University of Cambridge Faculty of Education. In this article, drawing on their work in the ‘Inclusion and Achievement Project’, they explore the problems and possibilities for researching issues of pupil achievement and inclusion through the use of these new national data sets.
Transition planning and the needs of young people and their carers: the alumni project
Authors: Smart Melanie
Published: September 2004

Melanie Smart is a research associate at Sunfield School, Worcestershire, and a trainee clinical psychologist. In this article, she reports the results of a small‐scale survey which looked at the views of 17 parents whose children with severe and/or complex learning difficulties had made the transition from a residential special school to an adult placement. Pa rents were asked their retrospective views on the transition planning process; their own involvement; and how the adult placement met the needs of their children.

Melanie Smart's findings indicate that the majority of parents were very much involved in the planning process, although they reported struggling to get consistency of approach and basic information. The young people themselves were found to be marginalised in the planning process, with very few being involved in any decision making. Most parents were happy with the eventual placement, but those who had concerns were still pushing for basic services and care. Of those who had suffered placement breakdowns, the major factor was lack of consistency of approach and failure to use prior information about the child.

This survey shows that parents and their learning disabled children experience difficulties in the transition process. There seems to be a distinct lack of person‐centred planning, particularly with this user group, by both child and adult services. Parents are vital to this type of planning approach, particularly when the young people themselves cannot voice their needs or advocate their own rights to quality service provision. Melanie Smart argues that parents need access to better quality information and reassurance that their children will receive the services they deserve as young adults. The various agencies, she asserts, need to work together to ensure that the transition process is effective.
Relationship between arterial blood gas values, pulmonary function tests and treadmill exercise testing parameters in patients with COPD
Authors: YAZICI Mehmet , ARBAK Peri , BALBAY Oner , MADEN Emin , ERBAS Mete , ERBILEN Enver , ALBAYRAK Sinan , AKDEMIR Ramazan , UYAN Cihangir
Published: September 2004

Objective:  There have been controversial reports regarding the relationship between exercise tolerance and resting pulmonary function in patients with COPD. The aim of this study was to examine the relationship between resting pulmonary function tests (rPFT) and cardiopulmonary exercise testing parameters (CETP) and their value in estimating exercise tolerance of patients.

Methodology:  In total, 45 patients with COPD (nine females, 36 males; mean age 61.2 ± 11.2) and 21 healthy subjects (four females, 17 males; mean age 60.3 ± 9.7) as a control group were studied. COPD patients (group I) were divided into three subgroups according to their FEV1 (mild/group II: FEV1 60–79% of predicted; moderate/group III: FEV1 40–59%; severe/group IV: FEV1 < 40%). In controls FEV1 was ≥ 80%.

Results:  There were significant correlations between FEV1 and CETP in group III (maximal O2 consumption (mVO2), r= 0.35, P < 0.005; total treadmill time (TTT), r= 0.31, P < 0.01; total metabolic equivalent values (TMET), r= 0.29, P < 0.01)) and in group IV (mVO2, r= 0.49, P < 0.001; TTT, r= 0.45, P < 0.005; TMET, r= 0.31, P < 0.01; peak heart rate (pHR), r= 0.29, P < 0.02; frequency of ventricular extrasystole (fVES), r=−0.27, P < 0.05). Additionally, in group IV there were significant correlations between PaO2 and CETP (mVO2, r= 0.41, P < 0.02; TTT, r= 0.38, P < 0.03; TMET, r= 0.31, P < 0.05; pHR, r= 0.29, P < 0.05; fVES, r=−0.28, P < 0.05).

Conclusion:  There are significant correlations of resting FEV1% predicted and PaO2 values with CETP in patients with moderate and severe COPD and these parameters may also have a role as indicators of exercise tolerance in these COPD patients.
MAKING UP HISTORY: A COMMENT ON PRATTEN1
Authors: Weintraub E. Roy
Published: September 2004

Stephen Pratten's critique of mathematical formalism in the discipline of economics does not provide an adequate definition of formalism and his use of the term bears little resemblance to common mathematical usage. Furthermore, Pratten abuses the history of economics by inventing an imaginary tradition of opposition to formalism among Cambridge economists.
RETHINKING TAX POLICIES: NEW IDEAS FROM A DEAD ECONOMIST
Authors: Wickman Kurt , Lingle Christopher
Published: September 2004

Economic analysis of tax policy has tended to follow a macro approach in which the state is the focal point and the individual taxpayer is marginalised. An alternative micro approach, exemplified by the classic work of Wicksell, leads to an analysis of the seemingly inexorable growth of the public sector in a democracy and the constitutional constraints necessary to safeguard economic prosperity and individual liberty.
WHAT MONETARY POLICY CAN DO: THE CLARIFIED APPROACH OF THE ECB
Authors: Schönwitz Dietrich
Published: September 2004

In the confirmed and clarified monetary strategy of the ECB, money still plays a prominent role. Regarding inflation as a monetary phenomenon and concentrating on price stability the ECB rejects an activist monetary policy. However, public and open discussion may contribute to further improvement of transparency and predictability of the ECB's operations.
PRINCIPLES OF POLITICS APPLICABLE TO ALL GOVERNMENTS BY BENJAMIN CONSTANT1
Authors: O'Keeffe Dennis
Published: September 2004

In this review of Constant's Principles of Politics Applicable to All Governments, Constant's belief in liberal economics and the importance of tradition is analysed.
HOSPITAL PERSONNEL'S PERCEPTION AND KNOWLEDGE OF HOSPITAL ACQUIRED INFECTION CONTROL
Authors: Paul AL , Shaw SP , Rozanski EA
Published: September 2004

Hospital acquired infections (HAI) are a major source of morbidity and mortality in human and veterinary hospitals. Research in human hospitals has shown that well focused staff education is an important step in limiting the development of HAI. Our hospital currently has no training program with respect to HAI. The purpose of this study was to evaluate the general knowledge of hospital staff concerning HAI as the first step in developing a hospital wide education program. Ninety doctors and technicians were given a questionnaire containing 15 questions about HAI. The questionnaires were hand distributed and immediately completed. Ten of the questions tested knowledge of HAI, while five questions concerned the individual's perception of HAI in our hospital. Answers were given as a range from strongly agree to strongly disagree or in the form of multiple choice.

With respect to their perception of HAI, 66% of technicians and 50% of doctors believed that they possess a good working knowledge of HAI. Several areas for improvement in hospital staff knowledge were identified. Technicians were more likely than doctors to incorrectly believe that 1) routine environmental cultures are effective at preventing HAI (percent correct answer: technicians 30%, doctors 52%), 2) that all animals that aspirated gastric contents under anesthesia develop clinical evidence of pneumonia (percent correct answer: technicians 55%, doctors 84%), and 3) that animals with an indwelling urinary catheter should be treated with prophylactic antibiotics (percent correct answer: technicians 51%, doctors 90%). In addition, doctors were more likely to identify Amikacin as the antibiotic of choice for patients with HAI in our hospital (percent correct answer: technicians 27%, doctors 79%). Neither group was able to adequately identify the patients in the ICU as the primary reservoir for the multi‐drug resistant pathogens that cause HAI (percent correct answer: technicians 20%, doctors 15%). The discrepancy in knowledge between the two groups is likely explained by attendance of faculty, residents, and interns at one or more continuing education rounds sessions where HAI were discussed. This finding is contrary to what is frequently found in human hospitals where the nursing staff typically demonstrates superior knowledge of HAI when compared to doctors.

The results of this study demonstrate that knowledge of HAI is not optimal in both the doctors and technicians in our hospital. Further better focused efforts are warranted to address the educational shortcomings evidenced by this study.
SERIAL DETERMINATION OF ANTIOXIDANT CAPACITY IN DOGS WITH NATURALLY OCCURRING GASTRIC DILATION‐VOLVULUS
Authors: Walker TG , Chan DL , Rozanski EA , De Laforcade AM , Freeman LM
Published: September 2004

The ischemia‐reperfusion seen in dogs with gastric dilatation‐volvulus (GDV) could cause oxidative stress, decrease antioxidant capacity, and predispose patients to higher morbidity and mortality. Elevated lactate levels in dogs with GDV have been previously found to be a negative prognostic indicator. The purpose of this study was to serially evaluate oxidant and antioxidant concentrations in dogs with GDV and to determine if there is a correlation between the degree of antioxidant depletion and lactate levels.

Dogs presenting to the Tufts Emergency Service that had not been treated with corticosteroids or fluids prior to admission and were not receiving antioxidant supplementation were eligible for the study. Blood samples were collected at the time of initial catheter placement pre‐operatively (Time 0), and then 24 and 48 hours after surgery. The samples were analyzed for concentrations of oxidants [malondialdehyde (MDA), oxygen radical trapping capacity (ORAC) and F2 isoprostanes] and antioxidants (α‐tocopherol, γ ‐tocopherol, vitamin C, and glutathione peroxidase). ANOVA with repeated measures was used to evaluate differences in the variables over the 48‐hour period and Pearson correlation analysis was used to assess the relationship between 2 continuous variables.

To date, 8 dogs have been enrolled in the study (1 female and 7 males, with a mean age of 8.0±2.2 years). All dogs have survived to discharge. The chart below indicates differences in parameters measured during hospitalization.

Variable
Time 0 median (range)
24 hours median (range)
48 hours median (range)
P Value

MDA (nmol/L)
0.725 (0.532–1.250)
0.500 (0.423–0.870)
0.512 (0.388–0.890)
0.008

α‐tocopherol (ug/ml)
16.350 (3.800–29.400)
11.300 (6.760–30.800)
12.950 (7.850–40.400)
0.000

γ‐tocopherol (ug/ml)
0.402 (0.138–0.776)
0.293 (0.000–0.500)
0.300 (0.000–0.503)
0.501

Mean plasma lactate upon admission was 4.3 mmol/L (range 2.1–7.2 mmol/L). There was a positive correlation between γ‐tocopherol and lactate (r=0.784, P=0.012) but there were no correlations between lactate and MDA or α‐tocopherol. Additional dogs are currently being enrolled in the study and analyses of the other variables (ORAC, F2 isoprostanes, vitamin C, and glutathione peroxidase) are pending. These preliminary results support the hypothesis of alterations in oxidant and antioxidant parameters in dogs with GDV.
EFFECTS OF 3 SEDATIVE COMBINATIONS ON FRACTIONAL SHORTENING IN NORMAL CATS
Authors: Day TK , Downs BL
Published: September 2004

Objective: To determine if 1) administration of a neuroleptanalgesia sedative combination (hydromorphone‐diazepam) would result in alteration of heart rate and fractional shortening parameters and 2) if administration of a neuroleptanalgesia sedative combination (hydromorphone‐diazepam) prior to administration of a dissociative sedative combination (ketamine‐diazepam) would blunt increases in heart rate and fractional shortening parameters previously reported with the use of dissociative‐based sedation.

Design: Single blinded, randomized, crossover design.

Animals: Eleven privately owned healthy cats with normal echocardiograms.

Procedure: All cats received each of the following injections with at least one week separating each treatment: Treatment A (TA) – saline IM followed in 15 minutes by diazepam (0.2 mg/kg IM) and hydromorphone (0.2 mg/kg IM) combined in the same syringe; Treatment B (TB) – saline IM followed in 15 minutes by ketamine (6 mg/kg IM) and diazepam (0.2 mg/kg IM) combined in the same syringe; Treatment C (TC) – diazepam and hydromorphone combined in the same syringe followed in 15 minutes by ketamine and diazepam combined in the same syringe. Echocardiograms were performed using the right parasternal position 15 minutes after the second injection. Heart rate (HR) and parameters to determine fractional shortening (FS) in the short axis view were recorded in triplicate for each treatment group. An analysis of variance for repeated measures with a Fisher's LSD protected t‐test was used for statistical analysis.

Results: Fractional shortening was significantly increased in each treatment group compared to baseline (p<0.05). There was a significant increase in FS between TA and TB (p<0.05), TA and TC (p<0.05), but not between TB and TC (p=0.9). Heart rate was not significantly increased between baseline and TA. There was a significant increase in HR between baseline and both TB and TC (p<0.05), but not between TB and TC (p<0.05)

Conclusion: The increase in fractional shortening induced by dissociative‐based chemical restraint in normal cats is not blunted by the prior administration of a neuroleptanalgesia combination. The increase in fractional shortening following administration of the neuroleptanalgesia combination may have been due to an indirect increase in sympathetic tone (stress response).
EFFICACY OF GASTRIC ACID‐LOWERING THERAPY IN THE DOG
Authors: Bersenas AME , Mathews KA
Published: September 2004

Introduction: Gastric acid suppression is a recommended therapy for gastric ulceration. Human studies suggest that optimal healing of duodenal ulcers occurs at gastric pH >3 for 75% of the day. The objective of this study was to evaluate the efficacy of 4 gastric acid suppressants at recommended veterinary doses. Drug effect was based on the 24‐hour median pH and the percentage of time that the intragastric pH ≥3 in a 24 hour period.

Methods: The study was conducted in 12 healthy Beagle dogs and was a double‐blind, randomized, multiple cross‐over comparison of a placebo (saline IV q12 h), ranitidine 2 mg/kg IV q12 h, famotidine 0.5 mg/kg IV q12 h, pantoprazole 1 mg/kg IV q24 h, and omeprazole (unblinded) ∼1 mg/kg PO q24 h. Continuous 24‐hour intragastric pH measurements were obtained via PEG tube. Prior to drug testing, 24‐hour pH measurements were recorded in fasted and fed dogs. Thereafter, dogs were fed standardized meals throughout the remainder of the study period. Drugs were administered for 1 week with a one‐week washout period between tests. Data were obtained on Day 0 (baseline), Day 2 and Day 6 of treatment. Following the randomized study, famotidine 0.5 mg/kg IV q8 h and omeprazole ∼1 mg/kg + bicarbonate q12 h via PEG tube were evaluated in 6 dogs, respectively. Appropriate statistical analyses were applied to calculate the 24‐hour median pH and percentage of time that the test drug maintained intragastric pH≥3 over 24 hours.

Results: The 24‐hour median pH of fasted dogs was 4.44 vs. fed dogs 1.30 (p<0.0001). The % time pH≥3: fasted dogs 66.0% vs. fed dogs 13.3% (p<0.0001). The 24‐hour median pH was (bold denotes significance when compared to saline) ‐ saline pH 1.81, ranitidine Day 2–pH 2.53, Day 6–pH 2.05, famotidine Day 2–pH 2.83, Day 6–pH 3.68, pantoprazole Day 2–pH 3.11, Day 6–pH 3.49, omeprazole Day 2–pH 3.86, Day 6–pH 4.09. The % time pH≥3: saline 32.9%; ranitidine day 2 – 44.6%, Day 6 – 37.2%; famotidine: Day 2 – 48.9%, Day 6 – 60.1%; pantoprazole: Day 2 – 54.2%, Day 6 – 59.1%; omeprazole: Day 2 – 66.9%, Day 6 – 70.2%. The 24‐hour median pH of omeprazole + bicarbonate q12 h was 4.7 on Day 2 and 4.9 on Day 6; the % time pH ≥3 was 90.9% on Day 2 and 78.4% on Day 6, respectively. No significant difference was noted in any parameter comparing famotidine q8 h and q12 h.

Conclusions: Fasted dogs had a significantly higher pH than fed dogs. Omeprazole was the only drug tested that approached the potential therapeutic efficacy for healing of duodenal ulcers when assessed by criteria for human patients. Variation existed amongst dogs in all drugs tested.
EPIDURAL ANALGESIA WITH TRAMADOL AND MORPHINE IN A DONKEY WITH ONCOLOGIC PAIN
Authors: Faleiros Rafael R. , Alves Geraldo Eleno S. , Andrade Vinicios G. , Matos Maria Rachel F. , De Marval Cyril A. , Braga Cleyton E. , Natalini Cláudio C.
Published: September 2004

An 8‐year‐old Pêga breed donkey that presented with a history of persistent enlargement of the right leg was diagnosed with a rhabdomyosarcoma by surgical exploration and biopsy. The tumoral mass involved the medial and posterior aspects of the thigh. At presentation, the donkey was extremely painful and reluctant to walk. Initial physical examination showed a heart rate of 60 beats/min, respiratory rate of 32 breaths/min, and a rectal temperature of 100.2°F. Venous blood was collected for a CBC and biochemistry. Postoperative care included antibiotic (potassium penicillin and gentamicin) and anti‐inflammatory (phenylbutazone and dexamethasone). The donkey was very painful in the immediate postoperative period and developed dehiscence of the incision. It was unable to bear weight on the affected limb, very reluctant to walk, and lying down in sternal recumbency most of the time. Heart and respiratory rates ranged from 60 to 90 and 20 to 32, respectively. Because of the poor prognosis, euthanasia was indicated but the owner decided to keep the donkey alive to try semen collection. In order to improve life quality and making the semen collection possible, the anti‐inflammatory therapy was stopped and an analgesic therapy with epidural opioids was selected. A 20‐gauge epidural catheter was inserted in the first intercoccygeal space through an epidural Huber point needle. With the purpose of reaching the lumbosacral area, 20 cm of the catheter was advanced cranially from the needle tip. During 3 days, a combination of morphine (0.1 mg/kg) and tramadol (0.5 mg/kg) was administered daily with a total volume of 20 ml. During the first 24 hours after the first administration, heart rate ranged from 62 to 64 and respiratory rate from 20 to 24. It was not observed to have any adverse effect. The donkey improved during treatment standing most of the time and eating better. It was easier to hand walk, although it was not completely able to bear weight in the affected limb. Even during treatment, the donkey reacted intensely when the surgical area in the caudal aspect of the thigh was manipulated. On the forth day, it tried to copulate and semen was successfully collected by manipulation of the penis. As the semen was not classified as good enough to be frozen, the donkey was euthanatized. On post‐mortem examination, the position of the catheter in the epidural canal was observed and 20 ml of methylene blue solution injected through the catheter before euthanasia. It was enough to totally stain the segment of epidural canal from the first intercoccygeal space to the lumbosacral joint. The opioid epidural analgesic therapy reported here was considered to be efficient to treat the painful condition of the donkey, but it was not able to completely abolish the pain.
CLINICAL EFFECTS OF KETAMINE INFUSIONS IN AWAKE HORSES
Authors: Fielding C. Langdon , Brumbaugh Gordon W. , Matthews Nora S. , Peck Kenneth E. , Roussel Allen J.
Published: September 2004

The primary classes of drugs used for pain control in horses include the non‐steroidal anti‐inflammatory drugs (NSAIDS), the alpha‐2 agonists, and the opiates, but each of these drug classes has significant adverse effects. Ketamine hydrochloride is a non‐competitive antagonist at N‐methyl D‐aspartate (NMDA) receptors in the spinal cord and has been used in both dogs and humans to provide analgesia. The purpose of this study was to identify a safe administration rate for a continuous infusion of ketamine to awake horses and describe the clinical effects of this infusion. Six horses were administered a continuous infusion of ketamine hydrochloride at a low dose (0.4 mg/kg/hr) and high dose (0.8 mg/kg/hr). Each infusion took place over 6 hours and the horses were monitored during infusion as well as for the 6 hours post‐infusion. The following parameters were evaluated: heart rate, blood pressure, respiratory rate, activity level, and analgesic thresholds. Both the low dose and high dose rates were tolerated well by all horses with no signs of excitation or discomfort. Post‐infusion heart rate and mean arterial blood pressure were significantly decreased as compared to pre‐infusion values (p=0.02 and p=0.02, respectively) A significant increase in analgesic threshold was not identified.

Subanesthetic infusions of ketamine to awake horses appear to be well tolerated and cause only mild changes in clinical parameters. Further research is needed to evaluate the analgesic potential of these infusions.
DEVELOPMENT OF ANTIBIOTIC RESISTANCE IN ESCHERICHIA COLI FROM DOGS IN THE INTENSIVE CARE UNIT WITH INCREASED DURATION OF STAY
Authors: Ogeer‐Gyles J , Mathews KA , Prescott J , Boerlin P
Published: September 2004

Introduction: Antibiotic resistance develops in human patients in the intensive care unit (ICU) with increased duration of stay. The major selection factor is the use of antimicrobial agents. The hypothesis tested in this study was that antimicrobial resistance in fecal E. coli isolated from dogs increased with increased length of stay in the ICU.

Methods: E. coli were isolated from rectal swabs collected on days 0 (D0, day of admission to the ICU), 3 (D3), 6 (D6), and 9 (D9) from all dogs housed in the ICU for 3 or more days. The E. coli were tested for resistance to nalidixic acid, enrofloxacin, cephalothin, cefoxitin, cefotaxime, ceftiofur, trimethoprim‐sulfa, chloramphenicol, gentamicin, tetracycline, ampicillin and amoxicillin/clavulanate. Thirty‐two patients were included in the study, 17 with D0‐D3 and 15 with D0‐D6 E. coli isolates. Five E. coli strains were isolated each sampling day and tested for antimicrobial susceptibility, resulting in a total of 60 outcomes per day per dog. The proportion of positive outcomes (resistance) was calculated for each day up to D6. Univariate ANOVA analysis was used to analyze the data.

Results: The proportion of positive outcomes (resistance) increased from 9.3% on D0 to 14.7% on D3 to 27.9% on D6. Resistance to the frequently used ampicillin increased in a linear manner with increased duration of stay. The proportion of ampicillin‐resistant colonies increased from 19.6% on D0 to 39.1% on D3 to 68.7% on D6 (p=0.001). Resistance to the infrequently used amoxicillin/clavulanic acid, also increased significantly (p=0.026) and linearly. The increase in resistance to enrofloxacin was significant (p=0.046); but the increase in resistance to the precursor, nalidixic acid, was highly significant (p=0.020). No change in resistance to gentamicin was found. The remaining antibiotics tested showed an insignificant increase in resistance.

Conclusions: Resistance to antibiotics increased in dogs with duration of stay in the ICU for 3 or more days. This linear trend was most significant with penicillin‐based beta‐lactams, which are frequently used in the ICU. Consequently, critically ill dogs may be at increased risk for developing opportunistic infections, caused by multi‐drug resistant organisms.