bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perceptions of illness and its development in patients with multiple sclerosis: a prospective cohort study
Authors: Lerdal Anners , Celius Elisabeth Gulowsen , Moum Torbjørn 
Published: November 2008

AbstractTitle.  Perceptions of illness and its development in patients with multiple sclerosis: a prospective cohort study. Aim.  This paper is a report of a study to examine the degree to which socio‐demographic variables, clinical variables and health‐related quality of life are related to perceptions of disease severity and changes in disease severity in patients with multiple sclerosis.Background.  Studies have shown that patients with multiple sclerosis report lower quality of life than the general population.Method.  Questionnaires measuring health‐related quality of life and perceived multiple sclerosis severity were mailed twice, 1 year apart, in May/June of 2000 and 2001, (t1 and t2), to patients with confirmed multiple sclerosis in Oslo, Norway (n = 502). Clinical data about disease onset and course were retrieved from the Oslo City Multiple Sclerosis Registry.Findings.  Among the 313 (62·4%) people who responded at both times, those with primary progressive disease course reported higher perceived multiple sclerosis severity (P < 0·001), more mental health problems (P = 0·004) and lower physical functioning (P < 0·001) than those with a relapsing remitting/secondary progressive disease course. Patients with primary progressive disease course reported higher mean scores for multiple sclerosis severity at t2 than at t1. Multivariate regression analysis showed that social functioning was the only factor with statistically significant relationships to perceived multiple sclerosis severity among all sub‐domains of health‐related quality of life or personal factors. However, physical impairment was also independently related to patients’ ratings of changes in multiple sclerosis severity during the year and illness severity 1 year later.Conclusion.  In addition to patients’ physical impairment, healthcare workers should pay special attention to issues related to their social functioning.
The need for systems change: reflections on knowledge translation and organizational change
Authors: Kitson Alison L. 
Published: November 2008

AbstractTitle. The need for systems change: reflections on knowledge translation and organizational change.Background. Despite over 40 years’ work on general systems theory, informed by critical social science, there is a mismatch between the theories used to explain and influence clinical practice in nursing and the way in which transferring new knowledge into practice is articulated.Data sources. The analysis and emerging propositions were based on a critique of seminal texts published in English up to 2008 covering critical social science, action science, diffusion of innovations, practice development and the management of innovations.Discussion. There is an implicit adherence to the world view that healthcare systems operate like machines, and much of the science generated around knowledge translation research tends to be logico‐deductive. This is in direct contrast to the prevailing arguments of general systems theorists, who view the system more as an organism. Five propositions are posited: knowledge translation is a necessary but not sufficient mechanism to transform systems; the ‘system‐as‐machine’ metaphor is profoundly unhelpful to knowledge translation; the healthcare system is best viewed as a complex entity; successful innovation is a function of the level of local autonomy experienced by individuals, teams and the unit involved; innovation is most effective when it involves key stakeholders.Conclusion. The purposeful integration of systems theory with knowledge translation theories and models may enable the application of research and new knowledge to practice to be speeded up.
The factor structure of clinical symptoms in mixed and manic episodes prior to and after antipsychotic treatment
Authors: Harvey Philip D , Endicott Jean M , Loebel Antony D 
Published: November 2008

Background:  While the factor structure of clinical symptoms in schizophrenia has been examined and provided crucial information about the illness, there is much less information available in bipolar disorder. This study examined the structure of symptoms of bipolar disorder at an unmedicated baseline assessment and after double‐blind treatment with ziprasidone, haloperidol, or placebo. We hypothesized, consistent with recent studies of schizophrenia, that the factor structure after treatment would be similar to the structure of untreated symptoms at study baseline.Methods:  Hospitalized patients with manic (n = 363) or mixed (n = 71) bipolar episodes were rated with the Hamilton Depression Rating Scale (HAM‐D) and the Mania Rating Scale [(MRS); derived from the Schedule for Affective Disorders and Schizophrenia – Change Bipolar Scale]. After 21 days of double‐blind treatment, all patients were again rated with the MRS and HAM‐D.Results:  Exploratory orthogonal factor analysis (varimax rotation) including both HAM‐D total scores and the MRS items found different five‐factor solutions for mixed and manic patients at the unmedicated baseline assessment. Confirmatory modeling indicated that these models, with some modifications, fit the data well. At the endpoint, however, a single‐factor solution was found for mixed and manic groups.Implications:  Symptomatology in bipolar disorder is multifactorial in an acute and unmedicated state, with slightly different factor structures for mixed and manic episodes. Following treatment, a single severity dimension is detected. These results suggest that symptom dimensions in mania may be different from those seen in schizophrenia, where different elements of symptoms have been proven to have different functional correlates and treatment response.
Verapamil augmentation of lithium treatment improves outcome in mania unresponsive to lithium alone: preliminary findings and a discussion of therapeutic mechanisms
Authors: Mallinger Alan G , Thase Michael E , Haskett Roger , Buttenfield Joan , Luckenbaugh David A , Frank Ellen , Kupfer David J , Manji Husseini K 
Published: November 2008

Objectives: Attenuation of protein kinase C (PKC) is a mechanism common to both established (lithium, valproate) and some novel (tamoxifen) antimanic agents. Verapamil, although primarily known as a calcium channel blocker, also has PKC inhibitory activity. Verapamil has shown antimanic activity in some but not all studies. Therefore, we investigated verapamil, used alone or as an adjunctive treatment, in manic patients who did not respond to an initial adequate trial of lithium.Methods: Each study phase lasted three weeks. Subjects were treated openly with lithium in Phase 1 (n = 45). Those who failed to respond were randomly assigned to double‐blind treatment in Phase 2 with either verapamil (n = 10) or continued‐lithium (n = 8). Phase 2 nonresponders (n = 10) were assigned to combined verapamil/lithium in Phase 3.Results: Response in Phase 2 did not differ significantly between verapamil and continued‐lithium. During Phase 3, response to combined treatment was significantly better than overall response to monotherapy in Phase 2 (Fisher’s Exact test, p = 0.043). Mania ratings improved during combined treatment in Phase 3 by 88.2% (linear mixed model analysis,F = 4.34, p = 0.013), compared with 10.5% improvement during Phase 2.Conclusions: In this preliminary investigation, verapamil monotherapy did not demonstrate antimanic efficacy. By contrast, the combination of verapamil plus lithium was highly efficacious. Our findings thus suggest that verapamil may have potential utility as an adjunct to lithium. This effect may be mediated by additive actions on PKC inhibition, which may be an important mechanism for antimanic agents in general.
A functional MRI study of Theory of Mind in euthymic bipolar disorder patients
Authors: Malhi Gin S , Lagopoulos Jim , Das Pritha , Moss Kirsteen , Berk Michael , Coulston Carissa M 
Published: November 2008

Objectives:  To determine the neural responses invoked in Theory of Mind (ToM) in euthymic bipolar patients as compared with healthy subjects.Methods:  This study examined 20 euthymic bipolar patients (11 males and 9 females) and 20 suitably matched healthy subjects using functional magnetic resonance imaging (fMRI) while subjects were engaged in a ToM task. Within‐scanner eye movements were monitored to ensure task engagement. The activation paradigm involved observing ToM and random‐motion animated sequences in a block design. Both within group (ToM versus random motion) and random effects between group analyses were performed on fMRI data using the BrainVoyager software package. Demographic and clinical data, along with subject ratings of fMRI stimuli, were collated and analysed.Results:  Patients were compromised in their ability to appropriately rate the ToM stimuli and assess them for intention as compared to healthy subjects. This was reflected in the fact that patients had few within‐group significant activations in response to ToM animated sequences, namely, the left anterior cingulate, and precuneus and cuneus bilaterally. In contrast, robust activations in response to ToM animated sequences in healthy subjects were widespread and involved regions recognized for mental state reasoning, in particular the insula, inferior frontal, supramarginal and angular gyri, and temporal cortex. The between‐group random effects analysis exclusively favoured the healthy subjects, with many activations occurring in regions overlapping with those found in the within‐group analyses.Conclusions:  The findings of this novel neuroimaging study suggest that in a social context, euthymic bipolar patients, though seemingly well and capable of engaging aspects of ToM, are perhaps constrained in their ability to mentalize fully, and furthermore cannot reliably adopt an alternate cognitive perspective when appropriate. Impairment of this capacity, though subtle, may in effect compromise their ability to understand the emotions and intentions of others, and also may limit appreciation of their own illness and symptoms. Such a deficit in bipolar disorder perhaps impacts upon interpersonal relationships and adversely affects social cognition and clinical functioning. The potential implications of this putative mentalizing compromise in euthymic patients with bipolar disorder are substantial, both for the individual and for understanding the neural substrate of the illness, and therefore warrant further investigation.
Divergent selection and phenotypic plasticity during incipient speciation in Lake Victoria cichlid fish
Authors: MAGALHAES I. S. , MWAIKO S. , SCHNEIDER M. V. , SEEHAUSEN O. 
Published: November 2008

AbstractDivergent selection acting on several different traits that cause multidimensional shifts are supposed to promote speciation, but the outcome of this process is highly dependent on the balance between the strength of selection vs. gene flow. Here, we studied a pair of sister species of Lake Victoria cichlids at a location where they hybridize and tested the hypothesis that divergent selection acting on several traits can maintain phenotypic differentiation despite gene flow. To explore the possible role of selection we tested for correlations between phenotypes and environment and compared phenotypic divergence (PST) with that based on neutral markers (FST). We found indications for disruptive selection acting on male breeding colour and divergent selection acting on several morphological traits. By performing common garden experiments we also separated the environmental and heritable components of divergence and found evidence for phenotypic plasticity in some morphological traits contributing to species differences.
Long‐Time Exposure of Mouse Embryos to the Sperm Produces High Levels of Reactive Oxygen Species in Culture Medium and Relates to Poor Embryo Development
Authors: Enkhmaa D , Kasai T , Hoshi K 
Published: November 2008

ContentsSmall amounts of reactive oxygen species (ROS), metabolites of oxygen, are necessary for sperm‐fertilizing capability. However, in excessive levels, their role in infertility has been extensively studied. The conventional in vitro fertilization (IVF) method employs a prolonged co‐incubation of gametes for 16–18 h to reach fertilization. However, it has been shown that this long period might create high levels of ROS. We aimed at finding out whether ROS increases in vitro during prolonged incubation with fertilized oocytes and whether high level of ROS relates to poor embryo development. To confirm if levels of ROS relate to length of time, we measured the ROS levels in fertilization medium (FM), which contained mouse embryos exposed to spermatozoa. To evaluate the contribution of sperm in production of ROS, we measured the ROS in the medium with only sperm. The measurements were performed by chemiluminescence assay using luminol as a probe after 4 and 18 h of incubation separately. The ROS levels were significantly increased after 18 h as compared with 4 h (p < 0.0001). Moreover, ROS in the medium with only sperm was also increased after 18 h (p < 0.0001), demonstrating that they were generated either by spermatozoa or as a result of possible reaction of sperm with medium during prolonged incubation. In addition, we compared embryo development after 2, 4, 6, 8, 10, 12 and 18 h of incubation. The number of degenerated embryos exposed to sperm for 12 and 18 h was significantly higher than those exposed for 4 or 6 h (p < 0.01). These results demonstrate that ROS concentrations appear to be related to the length of incubation time, and their excessive levels have a negative effect on embryo development. We suggest reducing incubation time to at least 4 h.
A Scanning Electron Microscopy Study of Frozen / Thawed Dog Sperm During In Vitro Gamete Interaction
Authors: Palomino J , De los Reyes M 
Published: November 2008

ContentsThe aim of this work was to study the effects of cryopreservation on the binding and penetration of dog spermatozoa to the zona pellucida (ZP) by scanning electron microscopy (SEM). The sperm‐rich fraction of six ejaculates from five dogs was divided into two aliquots and washed by centrifugation. One aliquot was processed as fresh control sample and the other aliquot frozen in Tris‐fructose extender. Gamete interaction was assessed using in vitro matured bitch oocytes, which were co‐incubated for up to 3 h. At hourly intervals after the start of co‐incubation, in vitro fertilized (IVF) oocytes were processed by SEM. The results were analysed statistically using the anova test. Differences in binding and penetration of the spermatozoa to the ZP occurred; a lower proportion of oocytes with spermatozoa bound to ZP was observed using frozen sperm (p < 0.05) than with fresh sperm (61%, 57% and 53% vs 42%, 40% and 44% at 1, 2 and 3 h, respectively). The percentage of ZP penetration by fresh sperm was directly proportional to the time of co‐incubation (9%, 25% and 34%; p < 0.05); in contrast, no differences were observed in the penetration rate with frozen‐thawed sperm (21%, 17% and 21%). More acrosome reacted sperm were observed in frozen sperm than in fresh sperm on the surface of the ZP. The differences in the percentage of binding and penetration between fresh and frozen sperm during the co‐culture could indicate that the time course of penetration is faster in frozen‐thawed dog spermatozoa than in fresh sperm, but that fresh spermatozoa can penetrate more oocytes over a given period of time, which may be related to their reacted or non‐reacted initial status.
Night‐time frequency, sleep disturbance and general health‐related quality of life: Is there a relation?
Authors: Yoshimura Koji , Oka Yasunori , Kamoto Toshiyuki , Tsukamoto Taiji , Oshiro Kiyoshi , Suzukamo Yoshimi , Kinukawa Naoko , Ogawa Osamu 
Published: November 2008

Objectives:  We conducted a community‐based study to determine the relationship among night‐time frequency, sleep disturbance and general health‐related quality of life (GHQL).Methods:  A total of 2271 participants, men and women, aged 41–70 and randomly selected in three Japanese towns completed a postal questionnaire survey. This questionnaire included: the International Prostate Symptom Score, the overall incontinence score of the International Consultation of Incontinence Questionnaire Short Form for lower urinary tract symptoms, the Pittsburg Sleep Quality Index for sleep problems, the Medical Outcome Study Short Form‐8 for GHQL, and medical history of disease, cigarette smoking, and alcohol consumption. A multiple regression model was used for statistical analysis, and P < 0.05 was considered significant.Results:  Although night‐time frequency by itself was closely associated with most aspects of GHQL, this association disappeared in four domains (general health perception, vitality, mental health and emotional role) and in the two summary scores of the Medical Outcome Study Short Form‐8 after inclusion of the influence of sleep problems represented by the total score on the Pittsburg Sleep Quality Index. However, three domains (physical function, physical role, and social function) remained significantly associated with night‐time frequency. Sleep problems were by far the worst risk factor for the deterioration of GHQL.Conclusions:  Night‐time frequency appeared to be associated with GHQL mainly by affecting sleep conditions, a symptom that independently influenced some aspects of GHQL.
Intravesical alkalinized lidocaine (PSD597) offers sustained relief from symptoms of interstitial cystitis and painful bladder syndrome
Authors: Nickel J. Curtis , Moldwin Robert , Lee Soledad , Davis Edward L. , Henry Richard A. , Wyllie Michael G. 
Published: November 2008

OBJECTIVETo assess the immediate and sustained relief of the symptoms of interstitial cystitis/painful bladder syndrome (IC/PBlS) after a consecutive 5‐day course of treatment with intravesical alkalinized lidocaine (PSD597), and to characterize the pharmacokinetics of single and multiple doses of intravesical PSD597 in a subgroup of patients.PATIENTS AND METHODSIn all, 102 adult patients (99 women) with a clinical diagnosis of IC/PBlS were randomized from 19 centres in the USA and Canada to receive a daily intravesical instillation of PSD597 (200 mg lidocaine, alkalinized with a sequential instillation of 8.4% sodium bicarbonate solution, to a final volume of 10 mL) or placebo (double‐blind), for 5 consecutive days. Patients were followed at intervals up to 29 days after the first instillation. Efficacy was assessed by changes in the Global Response Assessment (GRA), Likert scales for bladder pain, urgency and frequency, and validated O’Leary‐Sant IC symptom and problem indices.RESULTSSignificantly more patients treated with PSD597 rated their overall bladder symptoms as moderately or markedly improved on the GRA scale 3 days after completing the 5‐day course of treatment (30% and 9.6%, respectively, for patients treated with PSD597 and placebo;P = 0.012). The treatment effects were also maintained beyond the end of treatment and are further supported by the secondary endpoints, including symptom and problem indices. The peak serum lidocaine concentration during the study was <2 µg/mL, and well below the toxic level (>5 µg/mL).CONCLUSIONThis preliminary study showed that PSD597 was effective for providing sustained amelioration of symptoms of IC/PBlS beyond the acute treatment phase. The drug was safe, well tolerated and devoid of the systemic side‐effects often experienced with oral drug administration. Long‐term studies are needed to determine the optimum regimen to maintain this favourable treatment effect.
Evaluating and grading cystographic leakage: correlation with clinical outcomes in patients undergoing robotic prostatectomy
Authors: Patil Nilesh , Krane Louis , Javed Khurram , Williams Todd , Bhandari Mahendra , Menon Mani 
Published: November 2008

OBJECTIVETo classify cystographically detected urinary leaks in patients undergoing computer‐assisted (robotic) radical prostatectomy (RP) and to evaluate its effect on postoperative outcomes.PATIENTS AND METHODSBetween October 2001 and October 2007, 3327 patients had a RP using a technique described previously. The data were entered prospectively into an approved database. Before catheter removal, all patients had a gravity cystogram taken 7 days after RP. All patients who had a detectable urinary leak on cystography were stratified into three groups by two independent radiologists using a previously described grading system. Patients were evaluated with a validated International Prostate Symptom Score at 3‐, 6‐, 9‐ and 12‐month intervals after RP. The continence status was determined based on a patient‐reported questionnaire. Medical records in these patients were reviewed for the presence of complications requiring secondary interventions.RESULTSIn all, 287 patients (8.6%) had a detectable leak on cystography, of which 179 (62.4%), 84 (29.3%) and 24 (8.4%) were grades I, II and III, respectively. Of the patients with a detectable leak 70% were continent within 3 months and 94% had no involuntary urinary leakage at 1 year. Eight of 287 (2.8%) patients required a secondary intervention to correct bladder neck contracture. All eight of these patients had a grade II or III leak on cystography.CONCLUSIONThe presence of a urinary leak might delay the time to continence, but has no adverse effect on long‐term urinary control. Quantifying the gradation of leakage according to the described classification might provide the clinician with prognostic information about patients at risk for future interventions.
Evidence for durable kidney stone prevention over several decades
Authors: Parks Joan H. , Coe Fredric L. 
Published: November 2008

OBJECTIVETo analyse three outcomes of stone prevention strategies in one clinic devoted to that activity since 1969, i.e. stone recurrence rates, stone‐related procedures and 24‐h urinary stone risk factor, to assess whether such treatment can be maintained over long periods.PATIENTS AND METHODSWe selected 2509 patients with at least one laboratory follow‐up after initial clinical and laboratory evaluation. We divided them into five time cohorts of 5, 10, 15, 20 and >20 years of follow‐up. Rates of new stones and stone‐related procedures, and 24‐h urinary stone risk factors were compared between the cohorts using analysis of variance and general linear modelling.RESULTSStone rates and rates of stone‐related procedures declined in all five cohorts, as did 24‐h urinary stone risk indices. We found no diminution of treatment effects for any of these three over time.CONCLUSIONThose patients who remained under active care had significant reductions in stone recurrence and rates of stone‐related urological procedures for up to >20 years. However, only a small fraction of patients who entered the clinic remained for such long periods. Urine testing substantiates impressive and sustained reductions in supersaturation, the principle driving force for stone formation. Overall, for those patients willing to remain in continuous treatment for periods of up to three decades, medical stone prevention appears to be effective in maintaining low recurrence and procedure rates.