bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Pharmacology of GW280430A in Humans
Authors: Belmont Matthew R. , Lien Cynthia A. , Tjan Joseph , Bradley Eleanor , Stein Brenna , Patel Sanjay S. , Savarese John J.
Published: March 2004

Background

An ultrashort-acting nondepolarizing neuromuscular blocking agent that could be an alternative to succinylcholine has been the focus of a concerted effort in the field of muscle relaxants. GW280430A showed a promising pharmacodynamic profile in preclinical work and a wide margin of safety and so was selected for study in humans.

Methods

Thirty-one volunteers participated in this study, which determined the dose producing 95% block (ED95) and the safety and pharmacodynamics of increasing ED95 multiples. Anesthesia was induced and maintained with propofol, midazolam, and fentanyl. Neuromuscular transmission was measured at the adductor pollicis using ulnar nerve stimulation, and responses were recorded continuously by standard mechanomyographic monitoring.

Results

The ED95 for GW280430A is 0.19 mg/kg. The time to onset of 90% block ranged from 1.3 to 2.1 min, depending on the dose. Clinical durations ranged from 4.7 to 10.1 min and increased with increasing dose. Five to 95% and 25-75% recovery rates were approximately 7 and 3 min, respectively, and were independent of the dose administered. Transient cardiovascular side effects were observed at doses beginning at 3 x ED95 and above and were suggestive of histamine release. Most volunteers receiving 4 x ED95 exhibited plasma histamine concentrations indicative of significant histamine release.

Conclusions

GW280430A has a rapid onset and ultrashort duration of action. The recovery rate is rapid, predictable, and independent of dose. Doses at least up to 2.5 x ED95 seem to be free of side effects and seem to be able to provide relaxation within 60-90 s.
Intracarotid Verapamil Decreases both Proximal and Distal Human Cerebrovascular Resistance
Authors: Joshi Shailendra , Meyers Philip M. , Pile-Spellman John , Wang Mei , Sahlein Daniel H.
Published: March 2004

Background

The authors determined the segmental effects of intracarotid verapamil in human subjects by using a novel method of measuring proximal and distal cerebrovascular resistance. Their hypothesis was that intracarotid verapamil, a calcium channel-blocking drug that augments cerebral blood flow and reverses arterial spasm, would decrease both the proximal-conductance and the distal-arteriolar resistance.

Methods

Coaxial catheters were transfemorally floated into internal carotid and middle cerebral arteries during cerebral angiography. Pressures were recorded in the femoral, internal carotid, and middle cerebral arteries. Hemispheric cerebral blood flow was measured by the intracarotid Xe injection technique. Cerebrovascular resistance was measured for the proximal and distal arteries. Cerebral blood flow and hemodynamic data were recorded during intracarotid infusion of saline and verapamil (1 mg/min) for 5 min. Transcranial Doppler blood flow velocity in the middle cerebral artery was also recorded.

Results

Intracarotid verapamil increased in 133Xe cerebral blood flow from 43 +/- 11 to 59 +/- 11 ml.100 g(-1).min(-1) (P = 0.001; n = 9). The cerebrovascular resistance measured for the proximal and distal arteries decreased from 0.17 +/- 0.95 to 0.12 +/- 0.75 and from 1.63 +/- 0.78 to 1.03 +/- 0.33 mmHg.ml(-1).100 g(-1).min(-1) (P < 0.01), respectively. The calculated proximal-conductive and distal-arteriolar (pial plus parenchymal) resistances showed a similar decrease. Transcranial Doppler measurements (n = 5) underestimated the effects of intracarotid verapamil that were consistent with an increase in middle cerebral artery diameter.

Conclusions

Intracarotid verapamil decreases both the proximal-conductance and the distal-arteriolar resistance. Furthermore, it is feasible to investigate segmental effects of drugs in human subjects by measuring changes in pressure gradients within the cerebral arteries and simultaneous Xe cerebral blood flow measurements.
Mixed-effects Modeling of the Influence of Alfentanil on Propofol Pharmacokinetics
Authors: Mertens Martijn J. , Olofsen Erik , Burm Anton G. L. , Bovill James G. , Vuyk Jaap
Published: March 2004

Background

The influence of alfentanil on the pharmacokinetics of propofol is poorly understood. Therefore, the authors studied the effect of a pseudo-steady state concentration of alfentanil on the pharmacokinetics of propofol.

Methods

The pharmacokinetics of propofol were studied on two occasions in eight male volunteers in a randomized crossover manner with a 3-week interval. While volunteers breathed 30% O2 in air, 1 mg/kg intravenous propofol was given in 1 min, followed by 3 mg.kg(-1).h(-1) for 59 min (sessions A and B). During session B, a target-controlled infusion of alfentanil (target concentration, 80 ng/ml) was given from 10 min before the start until 6 h after termination of the propofol infusion. Blood pressure, cardiac output, electrocardiogram, respiratory rate, oxygen saturation, and end-tidal carbon dioxide were monitored. Venous blood samples for determination of the blood propofol and plasma alfentanil concentration were collected until 6 h after termination of the propofol infusion. Nonlinear mixed-effects population pharmacokinetic models examining the influence of alfentanil and hemodynamic parameters on propofol pharmacokinetics were constructed.

Results

A two-compartment model, including a lag time accounting for the venous blood sampling, adequately described the concentration-time curves of propofol. Alfentanil decreased the elimination clearance of propofol from 2.1 l/min to 1.9 l/min, the distribution clearance from 2.7 l/min to 2.0 l/min, and the peripheral volume of distribution from 179 l to 141 l. Scaling the pharmacokinetic parameters to cardiac output, heart rate, and plasma alfentanil concentration significantly improved the model.

Conclusions

Alfentanil alters the pharmacokinetics of propofol. Cardiac output and heart rate have an important influence on the pharmacokinetics of propofol.
Nerve Injury Induces a Tonic Bilateral μ-Opioid Receptor–mediated Inhibitory Effect on Mechanical Allodynia in Mice
Authors: Mansikka Heikki , Zhao Chengshui , Sheth Rishi N. , Sora Ichiro , Uhl George , Raja Srinivasa N.
Published: March 2004

Background

Mice lacking the mu-opioid receptor gene have been used to characterize the role of mu-opioid receptors in nociception and the analgesic actions of opioid agonists. In this study, the authors determined the role of mu-opioid receptors in neuropathic pain behaviors and the effectiveness of mu- and kappa-opioid receptor agonists on this behavior in mice.

Methods

The authors studied the behavioral responses of mu-opioid receptor knockout and wild-type mice to thermal and mechanical stimuli before and after neuropathic pain induced by unilateral ligation and section of the L5 spinal nerve. Response to mechanical stimuli was evaluated by determining the frequency of hind paw withdrawal to repetitive stimulation using a series of von Frey monofilaments. Thermal hyperalgesia was assessed by determining the paw withdrawal latencies to radiant heat and frequency of hind paw withdrawal to cooling stimuli. The effects of systemic morphine, the kappa-opioid agonist U50488H, and naloxone on responses to mechanical and thermal stimuli were also studied in spinal nerve-injured mice.

Results

After spinal nerve injury, wild-type mice developed increased responsiveness to mechanical, heat, and cooling stimuli ipsilateral to nerve injury. mu-Opioid receptor knockout mice not only had more prominent mechanical allodynia in the nerve-injured paw, but also expressed contralateral allodynia to mechanical stimuli. Hyperalgesia to thermal stimuli was similar between mu-opioid knockout and wild-type animals. Morphine decreased mechanical allodynia dose dependently (3-30 mg/kg subcutaneous) in wild-type mice--an effect that was attenuated in the heterozygous mice and absent in the homozygous mu-opioid knockout mice. The kappa-opioid agonist U50488H (3-10 mg/kg subcutaneous) attenuated mechanical allodynia in wild-type, heterozygous, and homozygous mu-opioid mice. Naloxone in wild-type mice resulted in enhanced ipsilateral and contralateral allodynia to mechanical stimuli that resembled the pain behavior observed in mu-opioid receptor knockout mice.

Conclusions

The authors' observations indicate that (1) unilateral nerve injury induces a bilateral tonic activation of endogenous mu-opioid receptor-mediated inhibition that attenuates mechanical allodynia but not thermal hyperalgesia, (2) both mu- and kappa-opioid agonists attenuate neuropathic pain in mice, and (3) the antihyperalgesic actions of morphine are mediated primarily via mu-opioid receptors.
Effects of Alcohol on Verbal Processing: An Event‐Related Potential Study
Authors: Marinkovic Ksenija , Halgren Eric , Maltzman Irving
Published: March 2004

Abstract:Background:Behavioral studies suggest that alcohol intoxication impairs the speed and accuracy of word recognition and categorization, but alcohol's effects on the brain during verbal cognitive processing are not adequately understood. Using event‐related potentials (ERP) and a word‐recognition paradigm, this study investigated the effects of alcohol intoxication on prelexical, semantic, and mnemonic aspects of verbal processing.

Methods:Concurrent measures of ERPs and skin conductance responses were obtained in a word‐repetition priming task and permitted a comparison of the effects of alcohol on the central and autonomic physiologic systems. Social drinkers participated in all four cells of the within‐subjects balanced placebo design, in which the effects of alcohol and information as to the beverage content (expectancy) were manipulated. The average peak blood alcohol level peaked at 0.045%.

Results:None of the manipulations affected behavioral performance, and expectancy had no effect on any of the measures. In contrast, alcohol ingestion attenuated the temporoparietal N180, suggesting an impairment in prelexical pattern‐recognition processes. Alcohol significantly increased the amplitude of N450 and the latency of P580, particularly on trials evoking sympathetic arousal as measured with skin conductance responses.

Conclusions:Although behavioral measures were unaffected, ERPs showed that a moderately low alcohol dose affected verbal processing during both early, prelexical and late, semantic stages. Alcohol significantly increased the difficulty of semantic access and integration, as reflected in larger N450 amplitude and longer P580 latency. This effect was particularly prominent on arousal‐related trials, suggesting that alcohol impairs processes that modulate cognitive functioning. The lack of an interaction between the factors of repetition and beverage suggests that a moderately low alcohol dose exerts these effects via the semantic and integration systems rather than via memory processes.
Effects of Ethanol Administration and Induction of Anxiety‐Related Affective States on the Acoustic Startle Reflex in Sons of Alcohol‐Dependent Fathers
Authors: Zimmermann Ulrich , Spring Konstanze , Wittchen Hans‐Ulrich , Holsboer Florian
Published: March 2004

Abstract: Background: The high rate of comorbidity between alcoholism and anxiety disorders suggests some causal link. This study used the startle reflex to investigate whether increased reactivity to stimuli inducing fear or related affective states might be one mechanism by which a family genetic risk promotes the development of alcohol use disorders.

Methods: Thirty‐one sons of alcoholics (PH+) were recruited from the participants of a longitudinal epidemiologic survey representative of the Munich area population between 18 and 25 years. Thirty male low‐risk participants without parental alcoholism (PH−) were matched for age and history of psychiatric disorders. The baseline acoustic startle reflex was elicited before and after subjects drank 0.6 g/kg ethanol or placebo in a randomized, double‐blind, placebo‐controlled crossover design. Thereafter, the startle response was investigated while the subjects’ affective state was manipulated by announcement of aversive electric finger stimuli to induce fear potentiation and by presentation of photographic slides previously rated to be pleasant, unpleasant, or neutral in their emotional valence.

Results: Plain startle response was lower in PH+ than PH− participants and was equally dampened by alcohol in PH+ and PH− subjects. Threat of finger shocks increased the startle response to the same extent in both groups. This fear potentiation effect was significantly attenuated by alcohol given on the second experimental day but not if alcohol was administered first and placebo on the second day. Pleasant and unpleasant slides decreased and increased startle response, respectively, and this effect was influenced by neither risk group nor alcohol.

Conclusions: The acoustic startle reflex seems to be reduced in sons of alcoholics. The nonsignificant results during startle modification do not support the concept of increased reactivity to anxiety‐related environmental stimuli as a mechanism promoting alcohol use disorders in subjects at increased family genetic risk for alcoholism.
The ultrastructure of the developing replication site in foot-and-mouth disease virus-infected BHK-38 cells
Authors: Monaghan Paul , Cook Hannah , Jackson Terry , Ryan Martin , Wileman Tom
Published: March 2004

Foot-and-mouth disease virus (FMDV) is the type species of theAphthovirusgenus of thePicornaviridae. Infection by picornaviruses results in a major rearrangement of the host cell membranes to create vesicular structures where virus genome replication takes place. In this report, using fluorescence and electron microscopy, membrane rearrangements in the cytoplasm of FMDV-infected BHK-38 cells are documented. At 1·5–2·0 h post-infection, free ribosomes, fragmented rough endoplasmic reticulum, Golgi and smooth membrane-bound vesicles accumulated on one side of the nucleus. Newly synthesized viral RNA was localized to this region of the cell. The changes seen in FMDV-infected cells distinguish this virus from other members of thePicornaviridae, such as poliovirus. Firstly, the collapse of cellular organelles to one side of the cell has not previously been observed for other picornaviruses. Secondly, the membrane vesicles, induced by FMDV, appear distinct from those induced by other picornaviruses such as poliovirus and echovirus 11 since they are relatively few in number and do not aggregate into densely packed clusters. Additionally, the proportion of vesicles with double membranes is considerably lower in FMDV-infected cells. These differences did not result from the use of BHK-38 cells in this study, as infection of these cells by another picornavirus, bovine enterovirus (a close relative of poliovirus), resulted in morphological changes similar to those reported for poliovirus-infected cells. With conventional fixation, FMDV particles were not seen; however, following high-pressure freezing and freeze-substitution, many clusters of virus-like particles were seen.
The central region of human immunodeficiency virus type 1 p6 protein (Gag residues S14–I31) is dispensable for the virus in vitro
Authors: Bleiber Gabriela , Peters Solange , Martinez Raquel , Cmarko Dusan , Meylan Pascal , Telenti Amalio
Published: March 2004

The human immunodeficiency virus type 1 p6 region encodes p6Gagand the transframe p6Polprotein. The Gag frame encodes an N-terminal late assembly L domain and a C-terminal Vpr binding domain. In the Pol frame, substitution at a C-terminal motif decreases protease autocleavage. The role of the highly polymorphic central region of p6, comprising amino acids S14–I31 (p6Gag) and R20–D39 (p6Pol), is unclear. Analysis of this central region demonstrated that 35 % of p6Gagappears to be dispensable for virus propagationin vitroand smaller deletion and insertion polymorphisms can be toleratedin vivo. Extensive Pol deletion (ΔR20–D39, 42 % of p6Pol) did not alter protease autocleavage.
Productive human herpesvirus 6 infection causes aberrant accumulation of p53 and prevents apoptosis
Authors: Takemoto Masaya , Mori Yasuko , Ueda Keiji , Kondo Kazuhiro , Yamanishi Koichi
Published: March 2004

p53 plays an important role in tumour suppression in cells exposed to some genotoxic stresses. We found that the p53 protein level was increased in a variety of cell lines infected with human herpesvirus 6 (HHV-6). Because the elevation in p53 began very soon after infection (4 h) and did not occur with UV-inactivated virus infection, it appeared to require the expression of one or more viral immediate-early (IE) genes. To elucidate the mechanism of p53 induction, we investigated its regulation at the protein level. Pulse–chase analysis showed that the stability of p53 increased in HHV-6-infected cells. In addition, the ubiquitination of p53 decreased after infection, indicating that the stability of p53 was increased through deubiquitination. We showed by confocal microscopy that the additional p53 mainly localized to the cytoplasm and that p53 was retained in the cytoplasm even after UV irradiation, but that it translocated into the nucleus in mock-infected cells. Furthermore, DNA fragmentation analysis, a terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) assay and annexin V staining showed that infected cells were resistant to UV-induced apoptosis. These results lead us to propose that HHV-6 has a mechanism for retaining p53 within the cytoplasm and protects the infected cells from apoptosis.
Classical swine fever virus induces proinflammatory cytokines and tissue factor expression and inhibits apoptosis and interferon synthesis during the establishment of long-term infection of porcine vascular endothelial cells
Authors: Bensaude Emmanuelle , Turner Jane L. E. , Wakeley Philip R. , Sweetman David A. , Pardieu Claire , Drew Trevor W. , Wileman Thomas , Powell Penelope P.
Published: March 2004

Infection with virulent strains of classical swine fever virus (CSFV) results in an acute haemorrhagic disease of pigs, characterized by disseminated intravascular coagulation, thrombocytopenia and immunosuppression, whereas for less virulent isolates infection can become chronic. In view of the haemorrhagic pathology of the disease, the effects of the virus on vascular endothelial cells was studied by using relative quantitative PCR and ELISA. Following infection, there was an initial and short-lived increase in the transcript levels of the proinflammatory cytokines interleukins 1, 6 and 8 at 3 h followed by a second more sustained increase 24 h post-infection. Transcription levels for the coagulation factor, tissue factor and vascular endothelial cell growth factor involved in endothelial cell permeability were also increased. Increases in these factors correlated with activation of the transcription factor NF-κB. Interestingly, the virus produced a chronic infection of endothelial cells and infected cells were unable to produce type I interferon. Infected cells were also protected from apoptosis induced by synthetic ouble-stranded RNA. These results demonstrate that, in common with the related pestivirus bovine viral diarrhoea virus, CSFV can actively block anti-viral and apoptotic responses and this may contribute to virus persistence. They also point to a central role for infection of vascular endothelial cells during the pathogenesis of the disease, where a proinflammatory and procoagulant endothelium induced by the virus may disrupt the haemostatic balance and lead to the coagulation and thrombosis seen in acute disease.
Heterologous expression of the modified coat protein of Cowpea chlorotic mottle bromovirus results in the assembly of protein cages with altered architectures and function
Authors: Brumfield Susan , Willits Deborah , Tang Liang , Johnson John E. , Douglas Trevor , Young Mark
Published: March 2004

We have developed methods for producing viral-based protein cages in high yield that are amenable to genetic modification. Expression of the structural protein ofCowpea chlorotic mottle bromovirus(CCMV) using the yeast-basedPichia pastorisheterologous expression system resulted in the assembly of particles that were visibly indistinguishable from virus particles produced in the natural host. We have shown that a collection of non-infectious CCMV coat protein mutants expressed in theP. pastorissystem assemble into viral protein cages with altered architectures and function. This provides an alternative to other heterologous expression systems for production of viral structural proteins in which expression has resulted in unassembled cages. Heterologous expression inP. pastorisfurther enhances the development of viral-based protein cages as biotemplates for nanotechnology and for future studies examining details of icosahedral virus assembly.
Mutational analysis of the R33-encoded G protein-coupled receptor of rat cytomegalovirus: identification of amino acid residues critical for cellular localization and ligand-independent signalling
Authors: Gruijthuijsen Yvonne K. , Beuken Erik V. H. , Smit Martine J. , Leurs Rob , Bruggeman Cathrien A. , Vink Cornelis
Published: March 2004

The rat cytomegalovirus (RCMV)R33gene encodes a G protein-coupled receptor (GPCR), pR33, which possesses agonist-independent, constitutive signalling activity. To characterize this activity further, we generated a series of point and deletion mutants of pR33. Both expression of and signalling by the mutants was evaluated. Several point mutants were generated that contained modifications in the NRY motif. This motif, at aa 130–132 of pR33, is the counterpart of the common DRY motif of GPCRs, which is known to be involved in G protein coupling. We found that mutation of the asparagine residue within the NRY motif of pR33 (N130) to aspartic acid resulted in a mutant (N130D) with similar signalling characteristics to the wild-type (WT) protein, indicating that N130is not the determinant of constitutive activity of pR33. Interestingly, a mutant carrying an alanine at aa 130 (N130A) was severely impaired in Gq/11-mediated, constitutive activation of phospholipase C, whereas it displayed similar levels of activity to pR33 in Gi/0-mediated signalling. Another protein that contained a modified NRY motif, R131A, did not show constitutive activity, whereas mutants Y132F and Y132A displayed similar activities to the WT receptor. This indicated that residue R131is critical for pR33 functionin vitro, whereas Y132is not. Finally, we identified two consecutive arginines within the C-terminal tails of both pR33 and its homologue from human CMV, pUL33, which are important for correct cell-surface expression of these receptors.
Modernising government workplaces: towards evidence, as well as experience
Authors: Pullen Wim , Bradley Stephen
Published: March 2004

Based on a presentation entitled “Modernising government workplaces”, looks at how modernisation can help in increasing productivity in the workplace. Examines public buildings as economic and social assets and factors of productivity while taking into account the work of the Commission for Architecture and the Built Environment (CABE). Concludes that CABE should set up an independent research body that produces evidence‐based knowledge, applied in educational programmes at universities, commercial training bodies and professional institutes, and which provides evidence‐based knowledge, not just experience‐based learning.
Serviced offices: owner capabilities for FM coordination
Authors: Bröchner Jan , Olsson Henrik , Sinik Davor
Published: March 2004

Owners of multi‐tenant office buildings pursue various strategies for providing bundles of services to building users. In order to study what determines patterns of bundling, 12 Swedish owners were interviewed in 2002. Strategies were found to depend on the size of their property holdings, where those who held less than 100,000m2 differed from large property owners. There is also a difference between owners that have a tradition of providing construction and property‐related services and owners with their main activities in the financial sector. These patterns can be explained by considering transaction costs arising from services coordination and by referring to the dynamics of learning and competence in owner organizations. It is suggested that service‐offering owners should increase their competence for monitoring service delivery. Some property owners may benefit more from developing the competence needed for a sole provider coordinated strategy.
Electrical Stimulation of the Anterior Nucleus of the Thalamus for the Treatment of Intractable Epilepsy
Authors: Kerrigan John F. , Litt Brian , Fisher Robert S. , Cranstoun Stephen , French Jacqueline A. , Blum David E. , Dichter Marc , Shetter Andrew , Baltuch Gordon , Jaggi Jurg , Krone Selma , Brodie MaryAnn , Rise Mark , Graves Nina
Published: March 2004

Summary:  Purpose: Animal studies and sporadic case reports in human subjects have suggested that intermittent electrical stimulation of the anterior nucleus of the thalamus reduces seizure activity. We embarked on an open‐label pilot study to determine initial safety and tolerability of bilateral stimulation of the anterior nucleus of the thalamus (ANT), to determine a range of appropriate stimulation parameters, and to begin to gather pilot efficacy data.

Methods: We report an open‐label pilot study of intermittent electrical stimulation of the anterior nucleus of the thalamus in five patients (three men, two women; age range, 24–47 years), with follow‐up between 6 and 36 months. All patients had intractable partial epilepsy. Four of the five patients also had secondarily generalized seizures. Stimulation was delivered by bilateral implantable, programmable devices by using an intermittent, relatively high‐frequency protocol. Stimulation parameters were 100 cycles per second with charge‐balanced alternating current; pulse width, 90 ms; and voltages ranging between 1.0 and 10.0 V. Seizure counts were monitored and compared with preimplantation baseline.

Results: Four of the five patients showed clinically and statistically significant improvement with respect to the severity of their seizures, specifically with respect to the frequency of secondarily generalized tonic–clonic seizures and complex partial seizures associated with falls. One patient showed a statistically significant reduction in total seizure frequency. No adverse events could clearly be attributed to stimulation. None of the patients could determine whether the stimulator was on or off at these parameters.

Conclusions: Electrical stimulation of the ANT appears to be well tolerated. Preliminary evidence suggests clinical improvement in seizure control in this small group of intractable patients. Further controlled study of deep brain stimulation of the anterior nucleus is warranted.
Daytime Sleepiness in Epilepsy Patients Receiving Topiramate Monotherapy
Authors: Bonanni Enrica , Galli Renato , Maestri Michelangelo , Pizzanelli Chiara , Fabbrini Monica , Manca Maria Laura , Iudice Alfonso , Murri Luigi
Published: March 2004

Summary:  Purpose: Limited research has focused to date on objective neurophysiological evaluation of daytime sleepiness in patients treated with newer antiepileptic drugs (AEDs), especially when used as monotherapy. This study was aimed at assessing occurrence of daytime sleepiness in newly diagnosed, drug‐naïve patients with partial epilepsy receiving initial topiramate (TPM) monotherapy.

Methods: Daytime vigilance was assessed in 14 consecutive, newly diagnosed and never medicated adult patients with focal epilepsy, receiving monotherapy with TPM. At baseline and 2 months after slowly titrated therapy with TPM, 200 mg/day, patients underwent the Multiple Sleep Latency Test (MSLT), visual simple and choice reaction times (VRT), and self‐rated their own degree of sleepiness with the Epworth Sleepiness Scale. A group of 14 age‐ and gender‐matched healthy volunteers served as controls.

Results: At baseline, mean daytime sleep latencies on the MSLT were comparable in patients and in controls. Two months after TPM monotherapy, MSLT scores did not significantly change in patients as compared with pretreatment values. Accordingly, subjective daytime sleepiness and VRTs, which were comparable in controls and in untreated patients at baseline, did not change in patients after TPM monotherapy.

Conclusions: Study results suggest that an initial short‐course monotherapy with TPM, 200 mg/day, does not impair daytime vigilance in newly diagnosed adult patients with partial seizures.
Controlled serial grinding for high‐resolution three‐dimensional reconstruction
Authors: Chinga G. , JohnSen P. O. , O. DiSerud
Published: March 2004

This work reports an improved preparation procedure for acquiring SEM images for three‐dimensional (3D) reconstruction. The images are acquired consecutively after serial grinding and polishing. Ugelstad beads are used as landmarks for registration purposes and for determining the thickness of the abraded sections. An estimation of the bead sizes necessary for suitable thickness quantification at the corresponding spatial resolution and uncertainty is given. Shape‐based interpolation is used for filling the gaps between the cross‐sections. An indication of the distance between cross‐sections necessary for good interpolation is also given. An example of a 3D reconstructed paper volume is presented. The method is suitable for preparation of fibre and paper as well as other materials.
The Law of One Price: A Canada/U.S. exploration
Authors: Baldwin John R. , Yan Beiling
Published: March 2004

The paper examines whether arbitrage tends to equalize commodity prices for internationally traded homogenous products. It also investigates whether the increasing integration of North American markets has reduced price differences over time, and tests the validity of the so‐called Law of One Price. We find that price differences for homogenous tradables between Canada and the U.S. are smaller than those for differentiated tradables and non‐tradables, and are statistically insignificant over the period 1985 to 1999. We find no support for the notion that the increasing integration of North American markets due to trade liberalization has reduced price differences between Canada and the United States. Instead, the shifts in the price differences (expressed in the same currency) generally reflected fluctuations in the exchange rate. Canadian prices adapt with a lag to U.S. price changes that are brought about by changes in the exchange rate.
CD8+ T cells with parasite‐specific cytotoxic activity and a Tc1 profile of cytokine and chemokine secretion develop in experimental visceral leishmaniasis
Authors: Tsagozis Panagiotis , Karagouni Evdokia , Dotsika Eleni
Published: March 2004

Recently, a prominent role for CD8+ T cells in immunity against pathogens has emerged. The mode of action of CD8+ T cells in murine visceral leishmaniasis and their contribution to the clearance of the parasite has been addressed in the present study. We showed that during the course of experimental infection cytotoxic clones specific for Leishmania infantum antigens developed in the spleen of susceptible BALB/c mice, showed an activated phenotype and became susceptible to apoptotic cell death late in the course of the disease. CD8+ T cells exhibited considerable cytotoxic activity against cells expressing Leishmania antigens. This activity was mediated by both the perforin and the Fas/FasL pathway, as judged from in vitro and in vivo assays. The CD8+ T cells also up‐regulated mRNAs for cytokines (IFN‐γ and TNF‐α) and C‐C chemokines (RANTES and MIP‐1α), which have a major role in immunity against the pathogen. CD8+ T‐cells thus displayed a Tc1 pattern of differentiation. In conclusion, CD8+ T cells appear to play multiple roles in an experimental model of visceral leishmaniasis comprising both cytotoxic activity and secretion of cytokines and chemokines.
What Makes a Good Family‐Centered Partnership Between Women and Their Practitioners? A Qualitative Study
Authors: Gramling Lou , Hickman Kathleen , Bennett Sharon
Published: March 2004

Abstract:  Background: Family‐centered maternity care is an approach based on mutually beneficial partnerships between health care providers and families. It offers new ways of thinking about the relationship among childbearing women, their families, and health caregivers. This study was designed to identify health care practices that promoted or limited a family‐centered philosophy. Methods: A qualitative design, using reflexive interviews and focus groups, investigated the perspectives of 34, primarily African American women who used maternity services at a large urban hospital; some women traveled from rural areas for delivery. Inductive data analysis was conducted on the transcribed audiotapes of the interviews and groups. Results: Barriers to family‐centered maternity care were categorized as issues in coordination of services among health caregivers, patient‐health caregiver relationships and systems, and access to services. Facilitators of family‐centered maternity care were identified as perceived response to high‐risk patients, health‐related support outside the hospital, and special resources. Narratives, or personal stories told by the women, were used to illustrate barriers and facilitators. Conclusions: Education about family‐centered maternity care is vitally important for health caregivers. In clinical situations, each childbearing woman and her family should be treated as if they are extraordinary. In this way, practitioners can alter routines that cause the woman and her family to lose individualized care. (BIRTH 31:1 March 2004)
The epidemiology of ischaemic colitis
Authors: Higgins P. D. R. , Davis K. J. , Laine L.
Published: March 2004

Background : Ischaemic colitis has been associated with co‐morbid conditions, medications, vascular surgery and advanced age in case reports and case series. Few data exist on the baseline incidence in the general population or on the increased risk imposed by these risk factors.

Aim : To systematically review the literature regarding the incidence, prevalence and risk factors for ischaemic colitis.

Methods : Searches of bibliographic databases were performed independently by two investigators. Studies were included if they used population‐based samples, disease‐specific population samples or case–control population‐based samples of adults with ischaemic colitis, and reported the incidence, prevalence or risk factors for ischaemic colitis. Eligible articles were reviewed and data were abstracted in a duplicate, independent manner.

Results : Four studies were identified that reported the general population incidence and four that reported the disease‐specific population incidence. The incidence of ischaemic colitis in general populations ranged from 4.5 to 44 cases per 100 000 person‐years. The risk was increased two‐ to four‐fold by either prevalent irritable bowel syndrome or chronic obstructive pulmonary disease. The risk was also increased in females and in subjects of 65 years and older.

Conclusions : Ischaemic colitis is uncommon in the general population. The effect sizes of the most commonly reported risk factors have not been adequately quantified in population‐based studies.
Hepatitis vaccination in patients with chronic liver disease
Authors: Reiss G. , Keeffe E. B.
Published: March 2004

Evidence regarding the outcomes of viral super‐infection in patients with chronic liver disease and practical strategies for hepatitis A and B vaccination of these individuals are reviewed. Patients with acute hepatitis A and chronic hepatitis B have a more severe clinical course and a higher death rate compared with otherwise healthy individuals with hepatitis A, and these differences are most pronounced in older patients and those with histological evidence of chronic hepatitis or cirrhosis, rather than in asymptomatic hepatitis B carriers. Patients with acute hepatitis A super‐infection and chronic hepatitis C have an increased risk of fulminant hepatitis and death. In addition, patients with other chronic liver diseases also appear to be at increased risk for more severe disease with superimposed hepatitis A. Patients with chronic hepatitis B and hepatitis C virus co‐infection have more severe laboratory abnormalities, more severe histological disease, a greater frequency of cirrhosis and complications of cirrhosis, and a higher incidence of hepatocellular carcinoma. Vaccines for both hepatitis A and B are safe and effective if used early in the course of chronic liver disease. Hepatitis A and B vaccination should be part of the routine management of patients with chronic liver disease, preferably as early as possible in the natural course of their disease.
Different presentation of hepatitis B‐related hepatocellular carcinoma in a cohort of 1863 young and old patients — implications for screening
Authors: Lam C.‐M. , Chan A. O. O. , Ho P. , Ng I. O.‐L. , Lo C. M. , Liu C. L. , Poon R. T. P. , Fan S. T.
Published: March 2004

Aim : To compare the clinico‐pathological features of hepatitis B virus‐related hepatocellular carcinoma in young and old patients.

Methods : The clinico‐pathological characteristics of hepatitis B virus‐related hepatocellular carcinoma were compared in 1863 consecutive patients (121 patients, ≤40 years; 1742 patients, > 40 years) seen at a single institution over the last 13 years.

Results : Young patients presented more often with pain (P < 0.0001), hepatomegaly (P = 0.01) and ruptured hepatocellular carcinoma (P = 0.02), whereas old patients presented with ankle oedema (P = 0.001), ascites (P = 0.002) and by routine screening (P = 0.035). Liver function, Child–Pugh grading and indocyanine green test were better preserved in young patients. They also had a higher α‐foetoprotein concentration (P = 0.001), larger tumour size (P = 0.001) and more frequent metastasis (P = 0.008), but a similar surgical resection rate (33.6% vs. 28%), to old patients. There was no difference between the two groups in the overall post‐resection survival rate, but there was a shorter survival in young patients with unresectable disease (3.6 months vs. 4.6 months, P = 0.004).

Conclusion : Young patients with hepatocellular carcinoma often show a later presentation, but a higher resectability rate and similar survival rates, than old patients. The screening programme should include young hepatitis B virus carriers, even in the absence of cirrhosis.
Living with an elephant: Growing up with parental substance misuse
Authors: Kroll Brynna
Published: March 2004

Although parental substance misuse is now a focus of concern in child welfare practice, we know little about what it is really like for children who grow up in families where adult drug and/or alcohol use is an issue. Set against a backdrop of research links between parental substance misuse and child maltreatment, this article examines a number of studies that focus on the experiences of children and young people in this context. Emerging themes are identified which provide insight into the world of children for whom a substance is, effectively, a family member –‘the elephant in the living room’– and the implications for practice, particularly in relation to children's visibility, disclosure and confidentiality, are considered. It is argued that a focus on the ‘elephant’ often leads to children remaining ‘invisible’ to those whose role it is to ensure their welfare.
Patterns of injury in patients with radiographic occult fracture of neck of femur as determined by magnetic resonance imaging
Authors: Galloway Howard R , Meikle Grant R , Despois Mervyn
Published: March 2004

The purpose of the present study was to review retrospectively our experience with MRI in patients over the age of 50 who present to the emergency department with inability to weight bear following a fall and whose initial radiographs were normal. The study was designed to establish the incidence and pattern of bone and soft tissue injuries in these patients and to determine whether MRI could provide predictive information regarding length of hospital stay. The present study demonstrated the practicality of a protocol using MRI to obtain rapid definitive diagnosis in patients with occult fractures of the pelvic ring and neck of femur. The present study also suggests that significant prognostic information with regard to length of hospital stay can be obtained from an early MRI scan.
Intensity‐modulated radiotherapy: Examples of its utility in head and neck cancer
Authors: Porceddu Sandro , Hope Geoff , Wills Julie , Cramb Jim , Rischin Danny , Corry June , Peters Lester
Published: March 2004

Intensity‐modulated radiotherapy (IMRT) has been available at Peter MaCallum Cancer Centre (PMCC) since November 2000. The present report illustrates two cases of our early experience with IMRT. Case 1 is a 66‐year‐old man with a T1N2M0 nasopharyngeal carcinoma treated with chemo‐radiotherapy using parotid‐sparing IMRT. Fourteen months following treatment he remains in complete remission, with salivary function assessed using a xerostomia‐specific quality of life questionnaire, having returned to near pretreatment levels by 12 months. Case 2 is a 70‐year‐old man with a T4N0M0 base of tongue squamous cell carcinoma treated with chemo‐radiotherapy after refusing radical surgery. He had received subtotal nodal irradiation to 36 Gy in 1994 for Hodgkins disease stage IIA. A radical dose was still achievable despite previous irradiation without exceeding unacceptable spinal cord dose with IMRT. He remains in complete remission 14 months from his initial presentation without evidence of neurological toxicity. Intensity‐modulated radiotherapy allows sparing of critical normal structures in the head and neck without compromising dose to the tumour. It is, therefore, desirable for several clinical applications and essential in some, if unacceptable compromises are not to be made.
Abdominal cerebrospinal fluid pseudocyst
Authors: Pathi Ramon , Sage Michael , Slavotinek John , Hanieh Ahmad
Published: March 2004

A case of an abdominal cerebrospinal fluid (CSF) pseudocyst in a patient with a ventriculoperitoneal shunt is reported to illustrate this known but rare complication. In the setting of a VP shunt, the frequency of abdominal CSF pseudocyst formation is approximately 3.2%, often being precipitated by a recent inflammatory or infective process or recent surgery. Larger pseudocysts tend to be sterile, whereas smaller pseudocysts are more often infected. Ultrasound and CT each have characteristic findings.
Focal nodular hyperplasia in a child with hemihypertrophy and multiple cutaneous vascular malformations
Authors: Al‐Attar M , Verma R , Shannon RS , McKeever PA , Rickett A
Published: March 2004

A case of focal nodular hyperplasia of the liver occurring in a 9‐year‐old girl with musculoskeletal hemihypertrophy and multiple cutaneous capillary haemangiomata is described. The child presented because of limb length discrepancy and was found to have a large mass in the liver. Imaging showed a mass of similar characteristics to normal liver tissue. Prominent vascular supply to the liver was also seen. We present this case to emphasize the important diagnosis of focal nodular hyperplasia, which may occur in syndromic form in children with typical cutaneous and skeletal manifestations.
Primary nasal lymphoma, NK/T‐cell type: Report of two cases with similar presentation but different outcome
Authors: Loong Susan , Soong Yoke Lim , Tham Ivan , Lee Khai Mun
Published: March 2004

Two cases of natural killer (NK)/T‐cell primary nasal lymphoma with similar clinical presentations are reported, for comparison and contrast, to highlight the clinical issues and challenges posed by this unusual disease, its aggressiveness being matched only by its rarity. Presenting as a lesion in the nasal cavity with histological features of malignant lymphoma, primary nasal lymphoma is an uncommon extranodal lymphoma, which poses problems in both diagnosis and management. In people of oriental descent, the common cell subtype is NK/T‐cell. Although it is generally thought that combination treatment with chemotherapy and radiation is the best management for early stage non‐Hodgkin's lymphoma (NHL), there is still debate as to whether combined therapy is optimal treatment for this particular subtype of NHL, given that it responds less well to conventional chemotherapy. Herein we report two patients to illustrate these controversies.
Parotid gland as an initial site of metastasis
Authors: Borg Martin F
Published: March 2004

The parotid gland is an uncommon site of metastasis from carcinomas arising outside the head and neck region. Involvement of the parotid gland as an initial site of metastasis or presentation is rare. The present case report is the first, to our knowledge, to describe the management and outcome of an elderly man whose first presentation of an asymptomatic squamous cell carcinoma of the lung was that of a rapidly growing fungating left parotid mass.
Towards a philosophic theory of nursing
Authors: Kikuchi June F.
Published: March 2004

AbstractRecently, Edwards and Liaschenko questioned the validity of an argument put forward by Dr Søren Holm and Joseph Dunne concerning the impossibility of a theory of nursing. Taking into consideration the premises of the argument, I describe how Maritain's conception of philosophy allows for the possibility of a theory of nursing conceived as a philosophy of nursing art that is both practical and propositional in nature. As well, I identify how the philosophy of nursing art guides nursing art in developing and applying other kinds of artistic practical nursing knowledge: artistic nursing rules and artistic prudential nursing judgements. Finally, the relationship of ethical knowledge to artistic practical nursing knowledge is set down.
Analysing interpretation and reinterpreting analysis: exploring the logic of critical reflection
Authors: Freshwater Dawn , Avis Mark
Published: March 2004

Abstract This paper examines the distinction that is sometimes drawn between analysis and interpretation in the context of qualitative research, and the processes of critical analysis that underpin reflective practice. The authors consider the complementary logical processes involved in analysis and interpretation, and propose a cycle of reductive, inductive and hypothetico‐deductive testing that is both rational and creative. The authors argue that the goal of critical reflection and qualitative data analysis is not to produce knowledge that can be justified in terms of ‘correspondence’ to ‘reality’. Instead we propose a pragmatic, coherence view of knowledge that emphasizes the centrality of dialogue with texts, evidence, beliefs and practice. We conclude that evidence and belief are inextricably linked and that combined processes of reductive, inductive and hypothetico‐deductive logic need to be used in a transparent manner to establish the credibility of an interpretation. Although there is no clear demarcation between what is found and what is constructed, a commitment to coherence is the basis of a pragmatic theory of knowledge.
Self‐transcendence: Lonergan's key to integration of nursing theory, research, and practice
Authors: Perry Donna J.
Published: March 2004

Abstract This paper proposes that the philosophy of Bernard Lonergan can provide insight into the challenge of integrating nursing theory, research and practice. The author discusses Lonergan's work in regard to reflective understanding, authenticity and the human person as a subject of consciously developing unity. This is followed by a discussion of two key elements in Lonergan's work that relate to nursing: the subject–object challenge of nursing inquiry and common sense vs. scientific knowledge. The author suggests that integration of nursing theory, science and practice may be achieved through self‐transcendence.